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SARS-CoV-2 present significantly longer in stool than in respiratory, serum samples
A study from China showed that the presence of SARS-CoV-2 lasts significantly longer in stool samples from COVID-19 patients than in respiratory and serum samples.
However, the virus also persists longer with higher loads and later peaks in the respiratory tissue of patients with severe disease than in those with mild disease, according to an analysis of 96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection.
The retrospective study cohort data were collected from Jan. 19 to March 20 at a designated hospital for patients with COVID-19 in Zhejiang province. Among the patients, 22 had mild disease, and 74 had severe disease, according to the researchers.
Infection was confirmed in all patients by testing sputum and saliva samples. Viral RNA was detected in the stool of 59% of the patients and in the serum of 41% of patients. Only one of the patients had a positive urine sample. The median duration of virus in stool (22 days) was significantly longer than in respiratory (18 days; P = .002) and serum samples (16 days; P < .001).
In addition, the median duration of virus in the respiratory samples of patients with severe disease (21 days) was significantly longer than in patients with mild disease (14 days; P = .04).
“In the mild group, the viral loads peaked in respiratory samples in the second week from disease onset, whereas viral load continued to be high during the third week in the severe group,” the authors stated.
Virus duration was also longer in patients older than 60 years and in men.
The longer duration of SARS-CoV-2 in stool samples highlights the need to strengthen the management of stool samples in the prevention and control of the epidemic, especially for patients in the later stages of the disease, the authors advised.
“Compared with patients with mild disease, those with severe disease showed longer duration of SARS-CoV-2 in respiratory samples, higher viral load, and a later shedding peak. These findings suggest that reducing viral loads through clinical means and strengthening management during each stage of severe disease should help to prevent the spread of the virus,” the researchers concluded.
The study was funded by the China National Mega-Projects for Infectious Diseases and the National Natural Science Foundation of China. The authors reported they had no disclosures.
SOURCE: Zheng S et al. BMJ. 2020;369:m1443.
A study from China showed that the presence of SARS-CoV-2 lasts significantly longer in stool samples from COVID-19 patients than in respiratory and serum samples.
However, the virus also persists longer with higher loads and later peaks in the respiratory tissue of patients with severe disease than in those with mild disease, according to an analysis of 96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection.
The retrospective study cohort data were collected from Jan. 19 to March 20 at a designated hospital for patients with COVID-19 in Zhejiang province. Among the patients, 22 had mild disease, and 74 had severe disease, according to the researchers.
Infection was confirmed in all patients by testing sputum and saliva samples. Viral RNA was detected in the stool of 59% of the patients and in the serum of 41% of patients. Only one of the patients had a positive urine sample. The median duration of virus in stool (22 days) was significantly longer than in respiratory (18 days; P = .002) and serum samples (16 days; P < .001).
In addition, the median duration of virus in the respiratory samples of patients with severe disease (21 days) was significantly longer than in patients with mild disease (14 days; P = .04).
“In the mild group, the viral loads peaked in respiratory samples in the second week from disease onset, whereas viral load continued to be high during the third week in the severe group,” the authors stated.
Virus duration was also longer in patients older than 60 years and in men.
The longer duration of SARS-CoV-2 in stool samples highlights the need to strengthen the management of stool samples in the prevention and control of the epidemic, especially for patients in the later stages of the disease, the authors advised.
“Compared with patients with mild disease, those with severe disease showed longer duration of SARS-CoV-2 in respiratory samples, higher viral load, and a later shedding peak. These findings suggest that reducing viral loads through clinical means and strengthening management during each stage of severe disease should help to prevent the spread of the virus,” the researchers concluded.
The study was funded by the China National Mega-Projects for Infectious Diseases and the National Natural Science Foundation of China. The authors reported they had no disclosures.
SOURCE: Zheng S et al. BMJ. 2020;369:m1443.
A study from China showed that the presence of SARS-CoV-2 lasts significantly longer in stool samples from COVID-19 patients than in respiratory and serum samples.
However, the virus also persists longer with higher loads and later peaks in the respiratory tissue of patients with severe disease than in those with mild disease, according to an analysis of 96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection.
The retrospective study cohort data were collected from Jan. 19 to March 20 at a designated hospital for patients with COVID-19 in Zhejiang province. Among the patients, 22 had mild disease, and 74 had severe disease, according to the researchers.
Infection was confirmed in all patients by testing sputum and saliva samples. Viral RNA was detected in the stool of 59% of the patients and in the serum of 41% of patients. Only one of the patients had a positive urine sample. The median duration of virus in stool (22 days) was significantly longer than in respiratory (18 days; P = .002) and serum samples (16 days; P < .001).
In addition, the median duration of virus in the respiratory samples of patients with severe disease (21 days) was significantly longer than in patients with mild disease (14 days; P = .04).
“In the mild group, the viral loads peaked in respiratory samples in the second week from disease onset, whereas viral load continued to be high during the third week in the severe group,” the authors stated.
Virus duration was also longer in patients older than 60 years and in men.
The longer duration of SARS-CoV-2 in stool samples highlights the need to strengthen the management of stool samples in the prevention and control of the epidemic, especially for patients in the later stages of the disease, the authors advised.
“Compared with patients with mild disease, those with severe disease showed longer duration of SARS-CoV-2 in respiratory samples, higher viral load, and a later shedding peak. These findings suggest that reducing viral loads through clinical means and strengthening management during each stage of severe disease should help to prevent the spread of the virus,” the researchers concluded.
The study was funded by the China National Mega-Projects for Infectious Diseases and the National Natural Science Foundation of China. The authors reported they had no disclosures.
SOURCE: Zheng S et al. BMJ. 2020;369:m1443.
FROM THE BRITISH MEDICAL JOURNAL
Undeterred during COVID-19, hospital chaplains transform delivery of spiritual care
The first time that the Rev. Michael Mercier, BCC (a board-certified chaplain), provided spiritual care for a patient hospitalized with COVID-19 in March, he found himself engaged in a bit of soul-searching. Even though he donned a mask, gloves, and gown, he could get no closer than the hospital room doorway to interact with the patient because of infection-control measures.
“It went against all my natural instincts and my experience as a chaplain,” said Rev. Mercier, who serves as director of spiritual care for Rhode Island Hospital, Hasbro Children’s Hospital, Miriam Hospital, and Newport Hospital, which are operated by Lifespan, Rhode Island’s largest health system. “The first instinct is to be physically present in the room with the person who’s dying, to have the family gathered around the bedside.”
Prior to standing in the doorway that day, he’d been on the phone with family members, “just listening to their fear and their anxiety that they could not be with their loved one when their loved one was dying,” he said. “I validated their feelings. I also urged them to work with me and the nurse to bring a phone into the room, hold it to the patient’s ear, and they were able to say their goodbyes and how much they loved the person.”
The patient was a devout Roman Catholic, he added, and the family requested that the Prayer of Commendation and the Apostolic Pardon be performed. Rev. Mercier arranged for a Catholic priest to carry out this request. “The nurse told the patient what was going on, and the priest offered the prayers and the rituals from the doorway,” Rev. Mercier said. “It was a surreal experience. For me, it was almost entirely phone based, and it was mostly with the family because the patient couldn’t talk too much.”
To add to the sense of detachment in a situation like that, doctors, nurses, and chaplains caring for COVID-19 patients are wearing masks and face shields, and sometimes the sickest patients are intubated, which can complicate efforts to communicate. “I’m surprised at how we find the mask as somewhat of a barrier,” said Carolanne B. Hauck, BCC, director of chaplaincy care & education and volunteer services at Lancaster (Pa.) General Hospital, which is part of the Penn Medicine system. “By that I mean, often for us, sitting at the bedside and really being able to see someone’s face and have them see our face – with our masks, that’s just not happening. We’re also having briefer visits when we’re visiting with COVID patients.”
COVID-19 may have quarantined some traditional ways of providing spiritual care, but hospital chaplains are relying on technology more than ever in their efforts to meet the needs of patients and their families, including the use of iPads, FaceTime, and video conferencing programs like Zoom and BlueJeans.
“We’ve used Zoom to talk with family members that live out of state,” Rev. Mercier said. “Most of the time, I get an invitation to join a Zoom meeting, but now I need to become proficient in utilizing Zoom to set up those end-of-life family meetings. There’s a lot of learning on the fly, how to use these technologies in a way that’s helpful for everybody. That’s the biggest thing I’m learning: Connection is connection during this time of high stress and anxiety, and we just have to get creative.”
Despite the “disembodied” nature of technology, patients and their families have expressed gratitude to chaplains for their efforts to facilitate connections between loved ones and to be “a guide on the side,” as Mary Wetsch-Johnson, BCC, put it. She recalled one phone conversation with the daughter of a man with COVID-19 who was placed on comfort measures. “She said her dad was like the dad on the TV series Father Knows Best, just a kind-hearted, loving, wonderful man,” said Ms. Wetsch-Johnson, a chaplain at CHI Franciscan Health, which operates 10 acute-care hospitals in the Puget Sound region of Washington state. “She was able to describe him in a way that I felt like I knew him. She talked about the discord they had in their family and how they’re processing through that, and about her own personal journey with grief and loss. She then asked me for information about funeral homes, and I provided her with information. At the end of it, she said, ‘I did not know that I needed you today, but you are exactly what I needed.’ ”
Hospital chaplains may be using smartphones and other gadgets to communicate with patients and their families more than they did in the pre-COVID-19 world, but their basic job has not changed, said Rabbi Neal J. Loevinger, BCC, director of spiritual care services at Vassar Brothers Medical Center in Poughkeepsie, N.Y., part of a seven-hospital system operated by Nuvance Health. “We offer the hope of a caring presence,” said Rabbi Loevinger, who is also a member of the board of directors for Neshama: Association of Jewish Chaplains. “If someone is in a hole, our job is to climb down into the hole with them and say, ‘We’re going to get out of this hole together.’ We can’t promise that someone’s going to get better. We can’t promise that everything’s going to be all right. What we can promise is that we will not abandon you. We can promise that there will be someone accompanying you in any way we can through this crisis.”
Ms. Hauck remembered a phone conversation with the granddaughter of a patient hospitalized with COVID-19 who was nearing the end of her life. The granddaughter told her a story about how her grandmother and her best friend made a pact with each other that, when one was dying, the other would come to her side and pray the Rosary with her. “The granddaughter got tearful and said, ‘That can’t happen now,’ ” said Ms. Hauck, who oversees a staff of 9 chaplains and 10 per diem chaplains. “I made a promise that I would do my best to be at the bedside and pray the Rosary with her grandmother.”
The nurses were aware of the request, and about a day later, Ms. Hauck received a call at 1 a.m., indicating that the patient was close to dying. She drove to Lancaster General, put on her personal protective equipment, made it to the patient’s bedside, and began to pray the Rosary with her, with a nurse in the room. “The nurse said to me, ‘Carolanne, all of her stats are going up,’ and the patient actually became a little more alert,” she recalled. “We talked a little bit, and I asked, ‘Would you like to pray the Rosary now?’ She shook her head yes, and said, ‘Hail Mary, full of grace ...’ and those were the last words that she spoke. I finished the prayers for her, and then she died. It was very meaningful knowing that I could honor that wish for her, but more importantly, that I could do that for the family, who otherwise would have been at her side saying the Rosary with her. We have a recognition of how hard it is to leave someone at the hospital and not be at their bedside.”
Hospital chaplains are also supporting interdisciplinary teams of physicians, nurses, and other staff, as they navigate the provision of care in the wake of a pandemic. “They are under a great deal of stress – not only from being at work but with all the role changes that have happened in their home life,” Ms. Wetsch-Johnson said. “Some of them now are being the teacher at home and having to care for children. They have a lot that they come in with. My job is to help them so that they can go do their job. Regularly what I do is check in with the units and ask, ‘How are you doing today? What’s going on for you?’ Because people need to know that someone’s there to be with them and walk with them and listen to them.”
In the spirit of being present for their staff, she and her colleagues established “respite rooms” at CHI Franciscan hospitals, where workers can decompress and get recentered before returning to work. “We usually have water and snacks in there for them, and some type of soothing music,” Ms. Wetsch-Johnson said. “There is also literature on breathing exercises and stretching exercises. We’re also inviting people to write little notes of hope and gratitude, and they’re putting those up for each other. It’s important that we keep supporting them as they support the patients. Personally, I also round with our physicians, because they carry a lot with them, just as much as any other staff. I check in with dietary and environmental services. Everybody’s giving in their own unique way; that helps this whole health care system keep going.”
On any given day, it’s not uncommon for hospital staff members to spontaneously pull aside chaplains to vent, pray, or just to talk. “They process their own fears and anxieties about working in this kind of environment,” Rev. Mercier said. “They’re scared for themselves. They think, ‘Could I get the virus? Could I spread the virus to my family?’ Or, they may express the care and concern they have for their patients. Oftentimes, it’s a mixture of both. Those spontaneous conversations are often the most powerful.”
Ms. Hauck noted that some nurses and clinicians at Lancaster General Hospital “are doing work they may have not done before,” she said. “Some of them are experiencing death for the first time, so we help them to navigate that. One of the best things we can do is hear the anxiety they have or the sadness they have when a patient dies. Also, maybe the frustration that they couldn’t do more in some cases and helping them to see that sometimes their best is good enough.”
She recalled one younger patient with COVID-19 who fell seriously ill. “It was really affecting a lot of people on the unit because of the patient’s age,” she said. “When we saw that the patient was getting better and would be discharged, there was such a sense of relief. I’m not sure that patient will ever understand how that helped us. It was comforting to us to know that people are getting better. It is something we celebrate.”
As chaplains adjust to their “new normal,” carving out time for self-care is key. Ms. Hauck and her staff periodically meet on Zoom with a psychotherapist “who understands what we do, asks us really good questions, and reminds us to take care of ourselves,” she said. “Personally, I’m making sure I get my exercise in, I pack a healthy lunch. We do check in with each other. Part of our handoff at every shift provides for an opportunity to debrief about how your day was.”
Rev. Mercier’s self check-in includes deep-breathing meditation and reciting certain prayers throughout the day. “The deep breathing helps me center and refocus with my body, while the prayers remind me of my connection to the Divine,” he said. “It also reminds me that in the midst of the fear and the anxiety, I fear for myself. It’s hard not to be concerned that I could be infected. I have a family at home and could spread this to them. The prayer practices are a reminder to me that it’s okay to feel those fears and anxieties. Sometimes the spiritual practice helps me find that place of acceptance. That enables me to keep moving forward.”
Ms. Wetsch-Johnson described the sense of upendedness caused by the COVID-19 pandemic as a “ripple in the water that’s going to have long-lasting effects on the delivery of health care. People are taking the time to listen to one another. I’ve seen people in all departments be more compassionate with one another. I’ve seen managers go out of their way to make sure their staff are deeply cared for. I think that will have a ripple effect. That’s my hope, that we will continue to be more compassionate, more loving, and more understanding.”
Rabbi Loevinger hopes that even the most reticent physicians remember that chaplains serve as their advocate, too, especially during times of crisis. “This has been a time of unprecedented ethical wrestling in our hospitals, where there’s been a real concern that doctors, nurses, and respiratory therapists are going to be faced with morally distressing situations regarding insufficient PPE, or insufficient ventilator or dialysis machine supply to support everybody that needs to be supported,” he said. “Chaplains are a key part of the process of making ethical decisions, but also supporting physicians who are in distress over [being in] situations they never had imagined. Physicians don’t like to talk about the fact that a lot of the decisions they make are really heartbreaking. But if chaplains understand anything, it’s that being brokenhearted is part of the human condition, and that we can be part of the answer for keeping physicians morally and spiritually grounded in their work. We always invite that conversation.”
For Rev. Mercier, serving in a time of crisis reminds him of the importance of providing care as a team, “not just for patients and families, but for one another,” he said. “One of the lessons we can learn is, how can we build that connection with one another, to support and care for one another? How can we make sure that no one feels alone while working in the hospital?”
He draws inspiration from a saying credited to St. John of the Cross, which reads, “I saw the river through which every soul must pass, and the name of that river is suffering. I saw the boat that carries each soul across that river, and the name of that boat is love.”
“It’s that image that’s sticking with me, not just for myself as a chaplain but for all of my colleagues in the hospital,” said Rev. Mercier, who also pastors Tabernacle Baptist Church in Hope, R.I. “We’re in that river with the patients right now, suffering, and we’re doing our best to help them get to the other side – whatever the other side may look like.”
Correction, 4/30/20: An earlier version of the caption for the photo with Mary Wetsch-Johnson misstated the location. The photo was taken outside St. Elizabeth Hospital in Enumclaw, Wash.
The first time that the Rev. Michael Mercier, BCC (a board-certified chaplain), provided spiritual care for a patient hospitalized with COVID-19 in March, he found himself engaged in a bit of soul-searching. Even though he donned a mask, gloves, and gown, he could get no closer than the hospital room doorway to interact with the patient because of infection-control measures.
“It went against all my natural instincts and my experience as a chaplain,” said Rev. Mercier, who serves as director of spiritual care for Rhode Island Hospital, Hasbro Children’s Hospital, Miriam Hospital, and Newport Hospital, which are operated by Lifespan, Rhode Island’s largest health system. “The first instinct is to be physically present in the room with the person who’s dying, to have the family gathered around the bedside.”
Prior to standing in the doorway that day, he’d been on the phone with family members, “just listening to their fear and their anxiety that they could not be with their loved one when their loved one was dying,” he said. “I validated their feelings. I also urged them to work with me and the nurse to bring a phone into the room, hold it to the patient’s ear, and they were able to say their goodbyes and how much they loved the person.”
The patient was a devout Roman Catholic, he added, and the family requested that the Prayer of Commendation and the Apostolic Pardon be performed. Rev. Mercier arranged for a Catholic priest to carry out this request. “The nurse told the patient what was going on, and the priest offered the prayers and the rituals from the doorway,” Rev. Mercier said. “It was a surreal experience. For me, it was almost entirely phone based, and it was mostly with the family because the patient couldn’t talk too much.”
To add to the sense of detachment in a situation like that, doctors, nurses, and chaplains caring for COVID-19 patients are wearing masks and face shields, and sometimes the sickest patients are intubated, which can complicate efforts to communicate. “I’m surprised at how we find the mask as somewhat of a barrier,” said Carolanne B. Hauck, BCC, director of chaplaincy care & education and volunteer services at Lancaster (Pa.) General Hospital, which is part of the Penn Medicine system. “By that I mean, often for us, sitting at the bedside and really being able to see someone’s face and have them see our face – with our masks, that’s just not happening. We’re also having briefer visits when we’re visiting with COVID patients.”
COVID-19 may have quarantined some traditional ways of providing spiritual care, but hospital chaplains are relying on technology more than ever in their efforts to meet the needs of patients and their families, including the use of iPads, FaceTime, and video conferencing programs like Zoom and BlueJeans.
“We’ve used Zoom to talk with family members that live out of state,” Rev. Mercier said. “Most of the time, I get an invitation to join a Zoom meeting, but now I need to become proficient in utilizing Zoom to set up those end-of-life family meetings. There’s a lot of learning on the fly, how to use these technologies in a way that’s helpful for everybody. That’s the biggest thing I’m learning: Connection is connection during this time of high stress and anxiety, and we just have to get creative.”
Despite the “disembodied” nature of technology, patients and their families have expressed gratitude to chaplains for their efforts to facilitate connections between loved ones and to be “a guide on the side,” as Mary Wetsch-Johnson, BCC, put it. She recalled one phone conversation with the daughter of a man with COVID-19 who was placed on comfort measures. “She said her dad was like the dad on the TV series Father Knows Best, just a kind-hearted, loving, wonderful man,” said Ms. Wetsch-Johnson, a chaplain at CHI Franciscan Health, which operates 10 acute-care hospitals in the Puget Sound region of Washington state. “She was able to describe him in a way that I felt like I knew him. She talked about the discord they had in their family and how they’re processing through that, and about her own personal journey with grief and loss. She then asked me for information about funeral homes, and I provided her with information. At the end of it, she said, ‘I did not know that I needed you today, but you are exactly what I needed.’ ”
Hospital chaplains may be using smartphones and other gadgets to communicate with patients and their families more than they did in the pre-COVID-19 world, but their basic job has not changed, said Rabbi Neal J. Loevinger, BCC, director of spiritual care services at Vassar Brothers Medical Center in Poughkeepsie, N.Y., part of a seven-hospital system operated by Nuvance Health. “We offer the hope of a caring presence,” said Rabbi Loevinger, who is also a member of the board of directors for Neshama: Association of Jewish Chaplains. “If someone is in a hole, our job is to climb down into the hole with them and say, ‘We’re going to get out of this hole together.’ We can’t promise that someone’s going to get better. We can’t promise that everything’s going to be all right. What we can promise is that we will not abandon you. We can promise that there will be someone accompanying you in any way we can through this crisis.”
Ms. Hauck remembered a phone conversation with the granddaughter of a patient hospitalized with COVID-19 who was nearing the end of her life. The granddaughter told her a story about how her grandmother and her best friend made a pact with each other that, when one was dying, the other would come to her side and pray the Rosary with her. “The granddaughter got tearful and said, ‘That can’t happen now,’ ” said Ms. Hauck, who oversees a staff of 9 chaplains and 10 per diem chaplains. “I made a promise that I would do my best to be at the bedside and pray the Rosary with her grandmother.”
The nurses were aware of the request, and about a day later, Ms. Hauck received a call at 1 a.m., indicating that the patient was close to dying. She drove to Lancaster General, put on her personal protective equipment, made it to the patient’s bedside, and began to pray the Rosary with her, with a nurse in the room. “The nurse said to me, ‘Carolanne, all of her stats are going up,’ and the patient actually became a little more alert,” she recalled. “We talked a little bit, and I asked, ‘Would you like to pray the Rosary now?’ She shook her head yes, and said, ‘Hail Mary, full of grace ...’ and those were the last words that she spoke. I finished the prayers for her, and then she died. It was very meaningful knowing that I could honor that wish for her, but more importantly, that I could do that for the family, who otherwise would have been at her side saying the Rosary with her. We have a recognition of how hard it is to leave someone at the hospital and not be at their bedside.”
Hospital chaplains are also supporting interdisciplinary teams of physicians, nurses, and other staff, as they navigate the provision of care in the wake of a pandemic. “They are under a great deal of stress – not only from being at work but with all the role changes that have happened in their home life,” Ms. Wetsch-Johnson said. “Some of them now are being the teacher at home and having to care for children. They have a lot that they come in with. My job is to help them so that they can go do their job. Regularly what I do is check in with the units and ask, ‘How are you doing today? What’s going on for you?’ Because people need to know that someone’s there to be with them and walk with them and listen to them.”
In the spirit of being present for their staff, she and her colleagues established “respite rooms” at CHI Franciscan hospitals, where workers can decompress and get recentered before returning to work. “We usually have water and snacks in there for them, and some type of soothing music,” Ms. Wetsch-Johnson said. “There is also literature on breathing exercises and stretching exercises. We’re also inviting people to write little notes of hope and gratitude, and they’re putting those up for each other. It’s important that we keep supporting them as they support the patients. Personally, I also round with our physicians, because they carry a lot with them, just as much as any other staff. I check in with dietary and environmental services. Everybody’s giving in their own unique way; that helps this whole health care system keep going.”
On any given day, it’s not uncommon for hospital staff members to spontaneously pull aside chaplains to vent, pray, or just to talk. “They process their own fears and anxieties about working in this kind of environment,” Rev. Mercier said. “They’re scared for themselves. They think, ‘Could I get the virus? Could I spread the virus to my family?’ Or, they may express the care and concern they have for their patients. Oftentimes, it’s a mixture of both. Those spontaneous conversations are often the most powerful.”
Ms. Hauck noted that some nurses and clinicians at Lancaster General Hospital “are doing work they may have not done before,” she said. “Some of them are experiencing death for the first time, so we help them to navigate that. One of the best things we can do is hear the anxiety they have or the sadness they have when a patient dies. Also, maybe the frustration that they couldn’t do more in some cases and helping them to see that sometimes their best is good enough.”
She recalled one younger patient with COVID-19 who fell seriously ill. “It was really affecting a lot of people on the unit because of the patient’s age,” she said. “When we saw that the patient was getting better and would be discharged, there was such a sense of relief. I’m not sure that patient will ever understand how that helped us. It was comforting to us to know that people are getting better. It is something we celebrate.”
As chaplains adjust to their “new normal,” carving out time for self-care is key. Ms. Hauck and her staff periodically meet on Zoom with a psychotherapist “who understands what we do, asks us really good questions, and reminds us to take care of ourselves,” she said. “Personally, I’m making sure I get my exercise in, I pack a healthy lunch. We do check in with each other. Part of our handoff at every shift provides for an opportunity to debrief about how your day was.”
Rev. Mercier’s self check-in includes deep-breathing meditation and reciting certain prayers throughout the day. “The deep breathing helps me center and refocus with my body, while the prayers remind me of my connection to the Divine,” he said. “It also reminds me that in the midst of the fear and the anxiety, I fear for myself. It’s hard not to be concerned that I could be infected. I have a family at home and could spread this to them. The prayer practices are a reminder to me that it’s okay to feel those fears and anxieties. Sometimes the spiritual practice helps me find that place of acceptance. That enables me to keep moving forward.”
Ms. Wetsch-Johnson described the sense of upendedness caused by the COVID-19 pandemic as a “ripple in the water that’s going to have long-lasting effects on the delivery of health care. People are taking the time to listen to one another. I’ve seen people in all departments be more compassionate with one another. I’ve seen managers go out of their way to make sure their staff are deeply cared for. I think that will have a ripple effect. That’s my hope, that we will continue to be more compassionate, more loving, and more understanding.”
Rabbi Loevinger hopes that even the most reticent physicians remember that chaplains serve as their advocate, too, especially during times of crisis. “This has been a time of unprecedented ethical wrestling in our hospitals, where there’s been a real concern that doctors, nurses, and respiratory therapists are going to be faced with morally distressing situations regarding insufficient PPE, or insufficient ventilator or dialysis machine supply to support everybody that needs to be supported,” he said. “Chaplains are a key part of the process of making ethical decisions, but also supporting physicians who are in distress over [being in] situations they never had imagined. Physicians don’t like to talk about the fact that a lot of the decisions they make are really heartbreaking. But if chaplains understand anything, it’s that being brokenhearted is part of the human condition, and that we can be part of the answer for keeping physicians morally and spiritually grounded in their work. We always invite that conversation.”
For Rev. Mercier, serving in a time of crisis reminds him of the importance of providing care as a team, “not just for patients and families, but for one another,” he said. “One of the lessons we can learn is, how can we build that connection with one another, to support and care for one another? How can we make sure that no one feels alone while working in the hospital?”
He draws inspiration from a saying credited to St. John of the Cross, which reads, “I saw the river through which every soul must pass, and the name of that river is suffering. I saw the boat that carries each soul across that river, and the name of that boat is love.”
“It’s that image that’s sticking with me, not just for myself as a chaplain but for all of my colleagues in the hospital,” said Rev. Mercier, who also pastors Tabernacle Baptist Church in Hope, R.I. “We’re in that river with the patients right now, suffering, and we’re doing our best to help them get to the other side – whatever the other side may look like.”
Correction, 4/30/20: An earlier version of the caption for the photo with Mary Wetsch-Johnson misstated the location. The photo was taken outside St. Elizabeth Hospital in Enumclaw, Wash.
The first time that the Rev. Michael Mercier, BCC (a board-certified chaplain), provided spiritual care for a patient hospitalized with COVID-19 in March, he found himself engaged in a bit of soul-searching. Even though he donned a mask, gloves, and gown, he could get no closer than the hospital room doorway to interact with the patient because of infection-control measures.
“It went against all my natural instincts and my experience as a chaplain,” said Rev. Mercier, who serves as director of spiritual care for Rhode Island Hospital, Hasbro Children’s Hospital, Miriam Hospital, and Newport Hospital, which are operated by Lifespan, Rhode Island’s largest health system. “The first instinct is to be physically present in the room with the person who’s dying, to have the family gathered around the bedside.”
Prior to standing in the doorway that day, he’d been on the phone with family members, “just listening to their fear and their anxiety that they could not be with their loved one when their loved one was dying,” he said. “I validated their feelings. I also urged them to work with me and the nurse to bring a phone into the room, hold it to the patient’s ear, and they were able to say their goodbyes and how much they loved the person.”
The patient was a devout Roman Catholic, he added, and the family requested that the Prayer of Commendation and the Apostolic Pardon be performed. Rev. Mercier arranged for a Catholic priest to carry out this request. “The nurse told the patient what was going on, and the priest offered the prayers and the rituals from the doorway,” Rev. Mercier said. “It was a surreal experience. For me, it was almost entirely phone based, and it was mostly with the family because the patient couldn’t talk too much.”
To add to the sense of detachment in a situation like that, doctors, nurses, and chaplains caring for COVID-19 patients are wearing masks and face shields, and sometimes the sickest patients are intubated, which can complicate efforts to communicate. “I’m surprised at how we find the mask as somewhat of a barrier,” said Carolanne B. Hauck, BCC, director of chaplaincy care & education and volunteer services at Lancaster (Pa.) General Hospital, which is part of the Penn Medicine system. “By that I mean, often for us, sitting at the bedside and really being able to see someone’s face and have them see our face – with our masks, that’s just not happening. We’re also having briefer visits when we’re visiting with COVID patients.”
COVID-19 may have quarantined some traditional ways of providing spiritual care, but hospital chaplains are relying on technology more than ever in their efforts to meet the needs of patients and their families, including the use of iPads, FaceTime, and video conferencing programs like Zoom and BlueJeans.
“We’ve used Zoom to talk with family members that live out of state,” Rev. Mercier said. “Most of the time, I get an invitation to join a Zoom meeting, but now I need to become proficient in utilizing Zoom to set up those end-of-life family meetings. There’s a lot of learning on the fly, how to use these technologies in a way that’s helpful for everybody. That’s the biggest thing I’m learning: Connection is connection during this time of high stress and anxiety, and we just have to get creative.”
Despite the “disembodied” nature of technology, patients and their families have expressed gratitude to chaplains for their efforts to facilitate connections between loved ones and to be “a guide on the side,” as Mary Wetsch-Johnson, BCC, put it. She recalled one phone conversation with the daughter of a man with COVID-19 who was placed on comfort measures. “She said her dad was like the dad on the TV series Father Knows Best, just a kind-hearted, loving, wonderful man,” said Ms. Wetsch-Johnson, a chaplain at CHI Franciscan Health, which operates 10 acute-care hospitals in the Puget Sound region of Washington state. “She was able to describe him in a way that I felt like I knew him. She talked about the discord they had in their family and how they’re processing through that, and about her own personal journey with grief and loss. She then asked me for information about funeral homes, and I provided her with information. At the end of it, she said, ‘I did not know that I needed you today, but you are exactly what I needed.’ ”
Hospital chaplains may be using smartphones and other gadgets to communicate with patients and their families more than they did in the pre-COVID-19 world, but their basic job has not changed, said Rabbi Neal J. Loevinger, BCC, director of spiritual care services at Vassar Brothers Medical Center in Poughkeepsie, N.Y., part of a seven-hospital system operated by Nuvance Health. “We offer the hope of a caring presence,” said Rabbi Loevinger, who is also a member of the board of directors for Neshama: Association of Jewish Chaplains. “If someone is in a hole, our job is to climb down into the hole with them and say, ‘We’re going to get out of this hole together.’ We can’t promise that someone’s going to get better. We can’t promise that everything’s going to be all right. What we can promise is that we will not abandon you. We can promise that there will be someone accompanying you in any way we can through this crisis.”
Ms. Hauck remembered a phone conversation with the granddaughter of a patient hospitalized with COVID-19 who was nearing the end of her life. The granddaughter told her a story about how her grandmother and her best friend made a pact with each other that, when one was dying, the other would come to her side and pray the Rosary with her. “The granddaughter got tearful and said, ‘That can’t happen now,’ ” said Ms. Hauck, who oversees a staff of 9 chaplains and 10 per diem chaplains. “I made a promise that I would do my best to be at the bedside and pray the Rosary with her grandmother.”
The nurses were aware of the request, and about a day later, Ms. Hauck received a call at 1 a.m., indicating that the patient was close to dying. She drove to Lancaster General, put on her personal protective equipment, made it to the patient’s bedside, and began to pray the Rosary with her, with a nurse in the room. “The nurse said to me, ‘Carolanne, all of her stats are going up,’ and the patient actually became a little more alert,” she recalled. “We talked a little bit, and I asked, ‘Would you like to pray the Rosary now?’ She shook her head yes, and said, ‘Hail Mary, full of grace ...’ and those were the last words that she spoke. I finished the prayers for her, and then she died. It was very meaningful knowing that I could honor that wish for her, but more importantly, that I could do that for the family, who otherwise would have been at her side saying the Rosary with her. We have a recognition of how hard it is to leave someone at the hospital and not be at their bedside.”
Hospital chaplains are also supporting interdisciplinary teams of physicians, nurses, and other staff, as they navigate the provision of care in the wake of a pandemic. “They are under a great deal of stress – not only from being at work but with all the role changes that have happened in their home life,” Ms. Wetsch-Johnson said. “Some of them now are being the teacher at home and having to care for children. They have a lot that they come in with. My job is to help them so that they can go do their job. Regularly what I do is check in with the units and ask, ‘How are you doing today? What’s going on for you?’ Because people need to know that someone’s there to be with them and walk with them and listen to them.”
In the spirit of being present for their staff, she and her colleagues established “respite rooms” at CHI Franciscan hospitals, where workers can decompress and get recentered before returning to work. “We usually have water and snacks in there for them, and some type of soothing music,” Ms. Wetsch-Johnson said. “There is also literature on breathing exercises and stretching exercises. We’re also inviting people to write little notes of hope and gratitude, and they’re putting those up for each other. It’s important that we keep supporting them as they support the patients. Personally, I also round with our physicians, because they carry a lot with them, just as much as any other staff. I check in with dietary and environmental services. Everybody’s giving in their own unique way; that helps this whole health care system keep going.”
On any given day, it’s not uncommon for hospital staff members to spontaneously pull aside chaplains to vent, pray, or just to talk. “They process their own fears and anxieties about working in this kind of environment,” Rev. Mercier said. “They’re scared for themselves. They think, ‘Could I get the virus? Could I spread the virus to my family?’ Or, they may express the care and concern they have for their patients. Oftentimes, it’s a mixture of both. Those spontaneous conversations are often the most powerful.”
Ms. Hauck noted that some nurses and clinicians at Lancaster General Hospital “are doing work they may have not done before,” she said. “Some of them are experiencing death for the first time, so we help them to navigate that. One of the best things we can do is hear the anxiety they have or the sadness they have when a patient dies. Also, maybe the frustration that they couldn’t do more in some cases and helping them to see that sometimes their best is good enough.”
She recalled one younger patient with COVID-19 who fell seriously ill. “It was really affecting a lot of people on the unit because of the patient’s age,” she said. “When we saw that the patient was getting better and would be discharged, there was such a sense of relief. I’m not sure that patient will ever understand how that helped us. It was comforting to us to know that people are getting better. It is something we celebrate.”
As chaplains adjust to their “new normal,” carving out time for self-care is key. Ms. Hauck and her staff periodically meet on Zoom with a psychotherapist “who understands what we do, asks us really good questions, and reminds us to take care of ourselves,” she said. “Personally, I’m making sure I get my exercise in, I pack a healthy lunch. We do check in with each other. Part of our handoff at every shift provides for an opportunity to debrief about how your day was.”
Rev. Mercier’s self check-in includes deep-breathing meditation and reciting certain prayers throughout the day. “The deep breathing helps me center and refocus with my body, while the prayers remind me of my connection to the Divine,” he said. “It also reminds me that in the midst of the fear and the anxiety, I fear for myself. It’s hard not to be concerned that I could be infected. I have a family at home and could spread this to them. The prayer practices are a reminder to me that it’s okay to feel those fears and anxieties. Sometimes the spiritual practice helps me find that place of acceptance. That enables me to keep moving forward.”
Ms. Wetsch-Johnson described the sense of upendedness caused by the COVID-19 pandemic as a “ripple in the water that’s going to have long-lasting effects on the delivery of health care. People are taking the time to listen to one another. I’ve seen people in all departments be more compassionate with one another. I’ve seen managers go out of their way to make sure their staff are deeply cared for. I think that will have a ripple effect. That’s my hope, that we will continue to be more compassionate, more loving, and more understanding.”
Rabbi Loevinger hopes that even the most reticent physicians remember that chaplains serve as their advocate, too, especially during times of crisis. “This has been a time of unprecedented ethical wrestling in our hospitals, where there’s been a real concern that doctors, nurses, and respiratory therapists are going to be faced with morally distressing situations regarding insufficient PPE, or insufficient ventilator or dialysis machine supply to support everybody that needs to be supported,” he said. “Chaplains are a key part of the process of making ethical decisions, but also supporting physicians who are in distress over [being in] situations they never had imagined. Physicians don’t like to talk about the fact that a lot of the decisions they make are really heartbreaking. But if chaplains understand anything, it’s that being brokenhearted is part of the human condition, and that we can be part of the answer for keeping physicians morally and spiritually grounded in their work. We always invite that conversation.”
For Rev. Mercier, serving in a time of crisis reminds him of the importance of providing care as a team, “not just for patients and families, but for one another,” he said. “One of the lessons we can learn is, how can we build that connection with one another, to support and care for one another? How can we make sure that no one feels alone while working in the hospital?”
He draws inspiration from a saying credited to St. John of the Cross, which reads, “I saw the river through which every soul must pass, and the name of that river is suffering. I saw the boat that carries each soul across that river, and the name of that boat is love.”
“It’s that image that’s sticking with me, not just for myself as a chaplain but for all of my colleagues in the hospital,” said Rev. Mercier, who also pastors Tabernacle Baptist Church in Hope, R.I. “We’re in that river with the patients right now, suffering, and we’re doing our best to help them get to the other side – whatever the other side may look like.”
Correction, 4/30/20: An earlier version of the caption for the photo with Mary Wetsch-Johnson misstated the location. The photo was taken outside St. Elizabeth Hospital in Enumclaw, Wash.
COVID-19 registry tracks pregnant women, newborns
A multidisciplinary team of researchers has created a national registry to study how COVID-19 affects pregnant women and their newborns.
“Pregnant women are generally considered healthy, but they are also a vulnerable group, and we currently have no data on COVID-19 in pregnancy,” coprincipal investigator Yalda Afshar, MD, PhD, an ob.gyn. at UCLA Health in Los Angeles, said in an interview.
“We expect this registry to provide data that will be critical in helping to improve care for pregnant women during this global pandemic,” Dr. Afshar, a fellow with UCLA Biodesign, stated in a news release.
The Pregnancy Coronavirus Outcomes Registry is enrolling pregnant women and those who have been pregnant or post partum within the past 6 weeks and who have either received a confirmed diagnosis of COVID-19 or are being evaluated for COVID-19.
Women are being recruited through their health care provider. A study coordinator contacts the participants by telephone. Women can also join the registry on their own without a referral by visiting the registry website.
The registry collects data on COVID-19 symptoms, clinical course, pregnancy, and neonatal outcomes and follows women from enrollment through the second and third trimesters and the postpartum period. The goal is to follow the mothers and babies for up to 1 year.
Hundreds of women already enrolled
Dr. Afshar noted that these kinds of registries often take months to design and to receive funding, but with COVID-19, “there was no time for that. We had to get it up and running ASAP.”
She said the team has been “blown away” by how quickly people have come forward to join the registry. Within 2 weeks of going live, the registry had enrolled more than 400 participants from across the United States. “At this rate, I think we will easily get 1,000 participants in a month or so,” Dr. Afshar said.
“With the global reach of this disease, the findings resulting from this work have the potential to impact millions of lives in an entire generation,” Johnese Spisso, CEO of UCLA Health, said in the news release.
Dr. Afshar noted that, although the impact of COVID-19 on pregnancy remains unknown, history suggests the disease will make some pregnancies and deliveries more challenging. “We know that in previous outbreaks of the regular flu, for example, there have been more deaths and poorer outcomes among pregnant women compared with nonpregnant women.”
Dr. Afshar is overseeing the study with colleagues at the University of California, Los Angeles, and the University of California, San Francisco, where the registry data will be coordinated.
“In addition to gaining a better understanding of the course of the disease, we will investigate disease transmission to determine if it can be passed from a mother to her baby in utero and during the postpartum period, such as in breast milk,” UCSF’s Stephanie Gaw, MD, PhD, who is leading the biospecimen core of the study, said in the release.
Health care providers interested in more information about the registry may send an email to [email protected]. A YouTube video on the registry is also available.
Dr. Afshar disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A multidisciplinary team of researchers has created a national registry to study how COVID-19 affects pregnant women and their newborns.
“Pregnant women are generally considered healthy, but they are also a vulnerable group, and we currently have no data on COVID-19 in pregnancy,” coprincipal investigator Yalda Afshar, MD, PhD, an ob.gyn. at UCLA Health in Los Angeles, said in an interview.
“We expect this registry to provide data that will be critical in helping to improve care for pregnant women during this global pandemic,” Dr. Afshar, a fellow with UCLA Biodesign, stated in a news release.
The Pregnancy Coronavirus Outcomes Registry is enrolling pregnant women and those who have been pregnant or post partum within the past 6 weeks and who have either received a confirmed diagnosis of COVID-19 or are being evaluated for COVID-19.
Women are being recruited through their health care provider. A study coordinator contacts the participants by telephone. Women can also join the registry on their own without a referral by visiting the registry website.
The registry collects data on COVID-19 symptoms, clinical course, pregnancy, and neonatal outcomes and follows women from enrollment through the second and third trimesters and the postpartum period. The goal is to follow the mothers and babies for up to 1 year.
Hundreds of women already enrolled
Dr. Afshar noted that these kinds of registries often take months to design and to receive funding, but with COVID-19, “there was no time for that. We had to get it up and running ASAP.”
She said the team has been “blown away” by how quickly people have come forward to join the registry. Within 2 weeks of going live, the registry had enrolled more than 400 participants from across the United States. “At this rate, I think we will easily get 1,000 participants in a month or so,” Dr. Afshar said.
“With the global reach of this disease, the findings resulting from this work have the potential to impact millions of lives in an entire generation,” Johnese Spisso, CEO of UCLA Health, said in the news release.
Dr. Afshar noted that, although the impact of COVID-19 on pregnancy remains unknown, history suggests the disease will make some pregnancies and deliveries more challenging. “We know that in previous outbreaks of the regular flu, for example, there have been more deaths and poorer outcomes among pregnant women compared with nonpregnant women.”
Dr. Afshar is overseeing the study with colleagues at the University of California, Los Angeles, and the University of California, San Francisco, where the registry data will be coordinated.
“In addition to gaining a better understanding of the course of the disease, we will investigate disease transmission to determine if it can be passed from a mother to her baby in utero and during the postpartum period, such as in breast milk,” UCSF’s Stephanie Gaw, MD, PhD, who is leading the biospecimen core of the study, said in the release.
Health care providers interested in more information about the registry may send an email to [email protected]. A YouTube video on the registry is also available.
Dr. Afshar disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A multidisciplinary team of researchers has created a national registry to study how COVID-19 affects pregnant women and their newborns.
“Pregnant women are generally considered healthy, but they are also a vulnerable group, and we currently have no data on COVID-19 in pregnancy,” coprincipal investigator Yalda Afshar, MD, PhD, an ob.gyn. at UCLA Health in Los Angeles, said in an interview.
“We expect this registry to provide data that will be critical in helping to improve care for pregnant women during this global pandemic,” Dr. Afshar, a fellow with UCLA Biodesign, stated in a news release.
The Pregnancy Coronavirus Outcomes Registry is enrolling pregnant women and those who have been pregnant or post partum within the past 6 weeks and who have either received a confirmed diagnosis of COVID-19 or are being evaluated for COVID-19.
Women are being recruited through their health care provider. A study coordinator contacts the participants by telephone. Women can also join the registry on their own without a referral by visiting the registry website.
The registry collects data on COVID-19 symptoms, clinical course, pregnancy, and neonatal outcomes and follows women from enrollment through the second and third trimesters and the postpartum period. The goal is to follow the mothers and babies for up to 1 year.
Hundreds of women already enrolled
Dr. Afshar noted that these kinds of registries often take months to design and to receive funding, but with COVID-19, “there was no time for that. We had to get it up and running ASAP.”
She said the team has been “blown away” by how quickly people have come forward to join the registry. Within 2 weeks of going live, the registry had enrolled more than 400 participants from across the United States. “At this rate, I think we will easily get 1,000 participants in a month or so,” Dr. Afshar said.
“With the global reach of this disease, the findings resulting from this work have the potential to impact millions of lives in an entire generation,” Johnese Spisso, CEO of UCLA Health, said in the news release.
Dr. Afshar noted that, although the impact of COVID-19 on pregnancy remains unknown, history suggests the disease will make some pregnancies and deliveries more challenging. “We know that in previous outbreaks of the regular flu, for example, there have been more deaths and poorer outcomes among pregnant women compared with nonpregnant women.”
Dr. Afshar is overseeing the study with colleagues at the University of California, Los Angeles, and the University of California, San Francisco, where the registry data will be coordinated.
“In addition to gaining a better understanding of the course of the disease, we will investigate disease transmission to determine if it can be passed from a mother to her baby in utero and during the postpartum period, such as in breast milk,” UCSF’s Stephanie Gaw, MD, PhD, who is leading the biospecimen core of the study, said in the release.
Health care providers interested in more information about the registry may send an email to [email protected]. A YouTube video on the registry is also available.
Dr. Afshar disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
COVID-19 linked to large vessel stroke in young adults
In a rapid communication to be published online April 29 in the New England Journal of Medicine, investigators led by Thomas Oxley, MD, PhD, of the department of neurosurgery at Mount Sinai Health System, reported five cases of large vessel stroke over a 2-week period in COVID-19 patients under age 50 years. This represents a sevenfold increase in what would normally be expected.
The five cases had either no, or mild, COVID-19 symptoms.
“It’s been surprising to learn that the virus appears to cause disease through a process of blood clotting,” Dr. Oxley said in an interview.
The message for neurologists and other physicians is “we’re learning that this can disproportionally affect large vessels more than small vessels in terms of presentation of stroke,” he said.
Inflammation in the blood vessel walls may be driving thrombosis formation, Dr. Oxley added. This report joins other research pointing to this emerging phenomenon.
Recently, investigators in the Netherlands found a “remarkably high” 31% rate of thrombotic complications among 184 critical care patients with COVID-19 pneumonia.
Dr. Oxley and colleagues also suggested that, since the onset of the pandemic, fewer patients may be calling emergency services when they experience signs of a stroke. The physicians noted that two of the five cases in the report delayed calling an ambulance.
“I understand why people do not want to leave the household. I think people are more willing to ignore other [non–COVID-19] symptoms in this environment,” he said.
As previously reported, physicians in hospitals across the United States and elsewhere have reported a significant drop in stroke patients since the COVID-19 pandemic took hold, which suggests that patients may indeed be foregoing emergency care.
The observations from Dr. Oxley and colleagues call for greater awareness of the association between COVID-19 and large vessel strokes in this age group, they add.
One patient in the case series died, one remains hospitalized, two are undergoing rehabilitation, and one was discharged home as of April 24.
Dr. Oxley and colleagues dedicated their report to “our inspiring colleague Gary Sclar, MD, a stroke physician who succumbed to COVID-19 while caring for his patients.”
Dr. Oxley has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In a rapid communication to be published online April 29 in the New England Journal of Medicine, investigators led by Thomas Oxley, MD, PhD, of the department of neurosurgery at Mount Sinai Health System, reported five cases of large vessel stroke over a 2-week period in COVID-19 patients under age 50 years. This represents a sevenfold increase in what would normally be expected.
The five cases had either no, or mild, COVID-19 symptoms.
“It’s been surprising to learn that the virus appears to cause disease through a process of blood clotting,” Dr. Oxley said in an interview.
The message for neurologists and other physicians is “we’re learning that this can disproportionally affect large vessels more than small vessels in terms of presentation of stroke,” he said.
Inflammation in the blood vessel walls may be driving thrombosis formation, Dr. Oxley added. This report joins other research pointing to this emerging phenomenon.
Recently, investigators in the Netherlands found a “remarkably high” 31% rate of thrombotic complications among 184 critical care patients with COVID-19 pneumonia.
Dr. Oxley and colleagues also suggested that, since the onset of the pandemic, fewer patients may be calling emergency services when they experience signs of a stroke. The physicians noted that two of the five cases in the report delayed calling an ambulance.
“I understand why people do not want to leave the household. I think people are more willing to ignore other [non–COVID-19] symptoms in this environment,” he said.
As previously reported, physicians in hospitals across the United States and elsewhere have reported a significant drop in stroke patients since the COVID-19 pandemic took hold, which suggests that patients may indeed be foregoing emergency care.
The observations from Dr. Oxley and colleagues call for greater awareness of the association between COVID-19 and large vessel strokes in this age group, they add.
One patient in the case series died, one remains hospitalized, two are undergoing rehabilitation, and one was discharged home as of April 24.
Dr. Oxley and colleagues dedicated their report to “our inspiring colleague Gary Sclar, MD, a stroke physician who succumbed to COVID-19 while caring for his patients.”
Dr. Oxley has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In a rapid communication to be published online April 29 in the New England Journal of Medicine, investigators led by Thomas Oxley, MD, PhD, of the department of neurosurgery at Mount Sinai Health System, reported five cases of large vessel stroke over a 2-week period in COVID-19 patients under age 50 years. This represents a sevenfold increase in what would normally be expected.
The five cases had either no, or mild, COVID-19 symptoms.
“It’s been surprising to learn that the virus appears to cause disease through a process of blood clotting,” Dr. Oxley said in an interview.
The message for neurologists and other physicians is “we’re learning that this can disproportionally affect large vessels more than small vessels in terms of presentation of stroke,” he said.
Inflammation in the blood vessel walls may be driving thrombosis formation, Dr. Oxley added. This report joins other research pointing to this emerging phenomenon.
Recently, investigators in the Netherlands found a “remarkably high” 31% rate of thrombotic complications among 184 critical care patients with COVID-19 pneumonia.
Dr. Oxley and colleagues also suggested that, since the onset of the pandemic, fewer patients may be calling emergency services when they experience signs of a stroke. The physicians noted that two of the five cases in the report delayed calling an ambulance.
“I understand why people do not want to leave the household. I think people are more willing to ignore other [non–COVID-19] symptoms in this environment,” he said.
As previously reported, physicians in hospitals across the United States and elsewhere have reported a significant drop in stroke patients since the COVID-19 pandemic took hold, which suggests that patients may indeed be foregoing emergency care.
The observations from Dr. Oxley and colleagues call for greater awareness of the association between COVID-19 and large vessel strokes in this age group, they add.
One patient in the case series died, one remains hospitalized, two are undergoing rehabilitation, and one was discharged home as of April 24.
Dr. Oxley and colleagues dedicated their report to “our inspiring colleague Gary Sclar, MD, a stroke physician who succumbed to COVID-19 while caring for his patients.”
Dr. Oxley has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
COVID-19: Psychiatrists ‘more than a match’ for crisis moment
Tackling the COVID-19 crisis will require psychiatrists to muster the courage to lead, establish trust, and ultimately provide psychiatric care with competence, honesty, and compassion, said Patrice A. Harris, MD, an Atlanta-based psychiatrist who is president of the American Medical Association.
Leaders in psychiatry are uniquely positioned to combat a wave of disease misinformation, address inequities in care, and meet the logistical challenges of safely meeting patient needs as the outbreak continues, Dr. Harris said at the American Psychiatric Association annual meeting, which was held as a virtual live event.
“I believe you, we, are more than a match for this moment – a moment that requires our leadership and requires us to hold other leaders accountable as we fight this pandemic,” she said in remarks to online attendees.
Using trust to fight myths
Misinformation about COVID-19 has been “spreading rapidly, even intentionally, due to fear or political agendas,” said Dr. Harris, who became the 174th president of the AMA in June 2019.
Others believe the coronavirus crisis is a new way to force vaccinations on people who don’t want them, added Dr. Harris.
Myths, rumors, and conspiracy theories lead to “more illness and death,” she said, at a time when most Americans say they’ve lost trust in the federal government and even in other American citizens.
“Fortunately, people still trust us – their doctors,” she added. “We fight for science, we call out quackery and snake oil when we see it, [and] we are willing to counter the propaganda of the antiscience voice.”
Physicians are ranked among the most trusted professions because they are committed to seeing, acknowledging, and sharing patients’ human experience, “and of course, I believe we do that as psychiatrists more than most,” Dr. Harris said.
Fighting COVID-19 at the AMA level
During the pandemic, the AMA has advocated for adequate testing and supplies, adequate insurance coverage, and changes to current procedural technology (CPT) codes to streamline novel coronavirus testing. The AMA has also developed a free COVID-19 resource center on the JAMA Network website, Dr. Harris said, as well as guidance on protecting medical students responding to the pandemic.
The safety of health care clinicians remains a central issue for the AMA at a time when masks and other personal protective equipment (PPE) remain in short supply.
In a recent letter to Vice President Mike Pence, who is leading the White House’s coronavirus task force, AMA Executive Vice President and CEO James L. Madara, MD, urged the Trump administration to undertake a Manhattan Project–like effort to expand capacity for needed supplies.
“We will continue to call on the White House, and APA has as well, to make sure these needs are met,” Dr. Harris said.
COVID-19 and inequities in care
Because the pandemic has had dramatic effects on African American communities across the United States, AMA Chief Health Equity Officer Aletha Maybank, MD, has made recent media appearances to highlight care inequities and what can be done about them.
Meanwhile, the AMA and other physician associations have urged the Trump Administration to collect, analyze, and make available COVID-19 data by race and ethnicity: “We can’t fix a problem until we identify a problem,” Dr. Harris said in her address to the APA.
Relying on science
In a virtual address hosted by the National Press Club earlier in April, Dr. Harris made an appeal for “relying on the science and evidence” to inform COVID-19–related decisions.
Elected officials need to “affirm science, evidence, and fact in their words and actions,” while media need to be vigilant in citing credible sources and challenging those who “chose to trade in misinformation,” she said in that address.
Speaking at the APA virtual meeting, Dr. Harris spoke of an “assault on science for several years” that inspired the National Press Club address. “We wanted to remind the public of its responsibility to focus on science and the evidence, for us to turn the tide against COVID-19,” she explained.
Physician care and self-care
While the AMA urges social distancing, Dr. Harris used the term “physical distancing” in her APA address. Physical distancing emphasizes the need for stay-at-home and shelter-in-place restrictions, while recognizing the need for maintaining meaningful social interactions, she explained.
Social media use represents one “opportunity” to bridge that gap when physical proximity is not an option, she added.
Dr. Harris also stressed the need for physicians to “take time out and practice self-care” to ensure that they are recharged and able to provide optimal patient care.
“We need to be there for others, but we have to put our own masks on first,” she said.
Dr. Harris reported no financial relationships with commercial interests.
SOURCE: Harris PA. APA 2020 Virtual Meeting.
Tackling the COVID-19 crisis will require psychiatrists to muster the courage to lead, establish trust, and ultimately provide psychiatric care with competence, honesty, and compassion, said Patrice A. Harris, MD, an Atlanta-based psychiatrist who is president of the American Medical Association.
Leaders in psychiatry are uniquely positioned to combat a wave of disease misinformation, address inequities in care, and meet the logistical challenges of safely meeting patient needs as the outbreak continues, Dr. Harris said at the American Psychiatric Association annual meeting, which was held as a virtual live event.
“I believe you, we, are more than a match for this moment – a moment that requires our leadership and requires us to hold other leaders accountable as we fight this pandemic,” she said in remarks to online attendees.
Using trust to fight myths
Misinformation about COVID-19 has been “spreading rapidly, even intentionally, due to fear or political agendas,” said Dr. Harris, who became the 174th president of the AMA in June 2019.
Others believe the coronavirus crisis is a new way to force vaccinations on people who don’t want them, added Dr. Harris.
Myths, rumors, and conspiracy theories lead to “more illness and death,” she said, at a time when most Americans say they’ve lost trust in the federal government and even in other American citizens.
“Fortunately, people still trust us – their doctors,” she added. “We fight for science, we call out quackery and snake oil when we see it, [and] we are willing to counter the propaganda of the antiscience voice.”
Physicians are ranked among the most trusted professions because they are committed to seeing, acknowledging, and sharing patients’ human experience, “and of course, I believe we do that as psychiatrists more than most,” Dr. Harris said.
Fighting COVID-19 at the AMA level
During the pandemic, the AMA has advocated for adequate testing and supplies, adequate insurance coverage, and changes to current procedural technology (CPT) codes to streamline novel coronavirus testing. The AMA has also developed a free COVID-19 resource center on the JAMA Network website, Dr. Harris said, as well as guidance on protecting medical students responding to the pandemic.
The safety of health care clinicians remains a central issue for the AMA at a time when masks and other personal protective equipment (PPE) remain in short supply.
In a recent letter to Vice President Mike Pence, who is leading the White House’s coronavirus task force, AMA Executive Vice President and CEO James L. Madara, MD, urged the Trump administration to undertake a Manhattan Project–like effort to expand capacity for needed supplies.
“We will continue to call on the White House, and APA has as well, to make sure these needs are met,” Dr. Harris said.
COVID-19 and inequities in care
Because the pandemic has had dramatic effects on African American communities across the United States, AMA Chief Health Equity Officer Aletha Maybank, MD, has made recent media appearances to highlight care inequities and what can be done about them.
Meanwhile, the AMA and other physician associations have urged the Trump Administration to collect, analyze, and make available COVID-19 data by race and ethnicity: “We can’t fix a problem until we identify a problem,” Dr. Harris said in her address to the APA.
Relying on science
In a virtual address hosted by the National Press Club earlier in April, Dr. Harris made an appeal for “relying on the science and evidence” to inform COVID-19–related decisions.
Elected officials need to “affirm science, evidence, and fact in their words and actions,” while media need to be vigilant in citing credible sources and challenging those who “chose to trade in misinformation,” she said in that address.
Speaking at the APA virtual meeting, Dr. Harris spoke of an “assault on science for several years” that inspired the National Press Club address. “We wanted to remind the public of its responsibility to focus on science and the evidence, for us to turn the tide against COVID-19,” she explained.
Physician care and self-care
While the AMA urges social distancing, Dr. Harris used the term “physical distancing” in her APA address. Physical distancing emphasizes the need for stay-at-home and shelter-in-place restrictions, while recognizing the need for maintaining meaningful social interactions, she explained.
Social media use represents one “opportunity” to bridge that gap when physical proximity is not an option, she added.
Dr. Harris also stressed the need for physicians to “take time out and practice self-care” to ensure that they are recharged and able to provide optimal patient care.
“We need to be there for others, but we have to put our own masks on first,” she said.
Dr. Harris reported no financial relationships with commercial interests.
SOURCE: Harris PA. APA 2020 Virtual Meeting.
Tackling the COVID-19 crisis will require psychiatrists to muster the courage to lead, establish trust, and ultimately provide psychiatric care with competence, honesty, and compassion, said Patrice A. Harris, MD, an Atlanta-based psychiatrist who is president of the American Medical Association.
Leaders in psychiatry are uniquely positioned to combat a wave of disease misinformation, address inequities in care, and meet the logistical challenges of safely meeting patient needs as the outbreak continues, Dr. Harris said at the American Psychiatric Association annual meeting, which was held as a virtual live event.
“I believe you, we, are more than a match for this moment – a moment that requires our leadership and requires us to hold other leaders accountable as we fight this pandemic,” she said in remarks to online attendees.
Using trust to fight myths
Misinformation about COVID-19 has been “spreading rapidly, even intentionally, due to fear or political agendas,” said Dr. Harris, who became the 174th president of the AMA in June 2019.
Others believe the coronavirus crisis is a new way to force vaccinations on people who don’t want them, added Dr. Harris.
Myths, rumors, and conspiracy theories lead to “more illness and death,” she said, at a time when most Americans say they’ve lost trust in the federal government and even in other American citizens.
“Fortunately, people still trust us – their doctors,” she added. “We fight for science, we call out quackery and snake oil when we see it, [and] we are willing to counter the propaganda of the antiscience voice.”
Physicians are ranked among the most trusted professions because they are committed to seeing, acknowledging, and sharing patients’ human experience, “and of course, I believe we do that as psychiatrists more than most,” Dr. Harris said.
Fighting COVID-19 at the AMA level
During the pandemic, the AMA has advocated for adequate testing and supplies, adequate insurance coverage, and changes to current procedural technology (CPT) codes to streamline novel coronavirus testing. The AMA has also developed a free COVID-19 resource center on the JAMA Network website, Dr. Harris said, as well as guidance on protecting medical students responding to the pandemic.
The safety of health care clinicians remains a central issue for the AMA at a time when masks and other personal protective equipment (PPE) remain in short supply.
In a recent letter to Vice President Mike Pence, who is leading the White House’s coronavirus task force, AMA Executive Vice President and CEO James L. Madara, MD, urged the Trump administration to undertake a Manhattan Project–like effort to expand capacity for needed supplies.
“We will continue to call on the White House, and APA has as well, to make sure these needs are met,” Dr. Harris said.
COVID-19 and inequities in care
Because the pandemic has had dramatic effects on African American communities across the United States, AMA Chief Health Equity Officer Aletha Maybank, MD, has made recent media appearances to highlight care inequities and what can be done about them.
Meanwhile, the AMA and other physician associations have urged the Trump Administration to collect, analyze, and make available COVID-19 data by race and ethnicity: “We can’t fix a problem until we identify a problem,” Dr. Harris said in her address to the APA.
Relying on science
In a virtual address hosted by the National Press Club earlier in April, Dr. Harris made an appeal for “relying on the science and evidence” to inform COVID-19–related decisions.
Elected officials need to “affirm science, evidence, and fact in their words and actions,” while media need to be vigilant in citing credible sources and challenging those who “chose to trade in misinformation,” she said in that address.
Speaking at the APA virtual meeting, Dr. Harris spoke of an “assault on science for several years” that inspired the National Press Club address. “We wanted to remind the public of its responsibility to focus on science and the evidence, for us to turn the tide against COVID-19,” she explained.
Physician care and self-care
While the AMA urges social distancing, Dr. Harris used the term “physical distancing” in her APA address. Physical distancing emphasizes the need for stay-at-home and shelter-in-place restrictions, while recognizing the need for maintaining meaningful social interactions, she explained.
Social media use represents one “opportunity” to bridge that gap when physical proximity is not an option, she added.
Dr. Harris also stressed the need for physicians to “take time out and practice self-care” to ensure that they are recharged and able to provide optimal patient care.
“We need to be there for others, but we have to put our own masks on first,” she said.
Dr. Harris reported no financial relationships with commercial interests.
SOURCE: Harris PA. APA 2020 Virtual Meeting.
FROM APA 2020
FDA reiterates hydroxychloroquine limitations for COVID-19
The U.S. Food and Drug Administration reinforced its March guidance on when it’s permissible to use hydroxychloroquine and chloroquine to treat COVID-19 patients and on the multiple risks these drugs pose in a Safety Communication on April 24.
The new communication reiterated the agency’s position from the Emergency Use Authorization (EUA) it granted on March 28 to allow hydroxychloroquine and chloroquine treatment of COVID-19 patients only when they are hospitalized and participation in a clinical trial is “not available,” or “not feasible.” The April 24 update to the EUA noted that “the FDA is aware of reports of serious heart rhythm problems in patients with COVID-19 treated with hydroxychloroquine or chloroquine, often in combination with azithromycin and other QT-prolonging medicines. We are also aware of increased use of these medicines through outpatient prescriptions.”
In addition to reiterating the prior limitations on permissible patients for these treatment the agency also said in the new communication that “close supervision is strongly recommended, “ specifying that “we recommend initial evaluation and monitoring when using hydroxychloroquine or chloroquine under the EUA or in clinical trials that investigate these medicines for the treatment or prevention of COVID-19. Monitoring may include baseline ECG, electrolytes, renal function, and hepatic tests.” The communication also highlighted several potential serious adverse effects from hydroxychloroquine or chloroquine that include QT prolongation with increased risk in patients with renal insufficiency or failure, increased insulin levels and insulin action causing increased risk of severe hypoglycemia, hemolysis in selected patients, and interaction with other medicines that cause QT prolongation.
“If a healthcare professional is considering use of hydroxychloroquine or chloroquine to treat or prevent COVID-19, FDA recommends checking www.clinicaltrials.gov for a suitable clinical trial and consider enrolling the patient,” the statement added.
The FDA’s Safety Communication came a day after the European Medicines Agency issued a similar reminder about the risk for serious adverse effects from treatment with hydroxychloroquine and chloroquine, the need for adverse effect monitoring, and the unproven status of purported benefits from these agents.
The statement came after ongoing promotion by the Trump administration of hydroxychloroquine, in particular, for COVID-19 despite a lack of evidence.
The FDA’s communication cited recent case reports sent to the FDA, as well as published findings, and reports to the National Poison Data System that have described serious, heart-related adverse events and death in COVID-19 patients who received hydroxychloroquine and chloroquine, alone or in combination with azithromycin or another QT-prolonging drug. One recent, notable but not peer-reviewed report on 368 patients treated at any of several U.S. VA medical centers showed no apparent benefit to hospitalized COVID-19 patients treated with hydroxychloroquine and a signal for increased mortality among certain patients on this drug (medRxiv. 2020 Apr 23; doi: 10.1101/2020.04.16.20065920). Several cardiology societies have also highlighted the cardiac considerations for using these drugs in patients with COVID-19, including a summary coauthored by the presidents of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society (Circulation. 2020 Apr 8. doi: 10.1161/CIRCULATIONAHA.120.047521), and in guidance from the European Society of Cardiology.
The U.S. Food and Drug Administration reinforced its March guidance on when it’s permissible to use hydroxychloroquine and chloroquine to treat COVID-19 patients and on the multiple risks these drugs pose in a Safety Communication on April 24.
The new communication reiterated the agency’s position from the Emergency Use Authorization (EUA) it granted on March 28 to allow hydroxychloroquine and chloroquine treatment of COVID-19 patients only when they are hospitalized and participation in a clinical trial is “not available,” or “not feasible.” The April 24 update to the EUA noted that “the FDA is aware of reports of serious heart rhythm problems in patients with COVID-19 treated with hydroxychloroquine or chloroquine, often in combination with azithromycin and other QT-prolonging medicines. We are also aware of increased use of these medicines through outpatient prescriptions.”
In addition to reiterating the prior limitations on permissible patients for these treatment the agency also said in the new communication that “close supervision is strongly recommended, “ specifying that “we recommend initial evaluation and monitoring when using hydroxychloroquine or chloroquine under the EUA or in clinical trials that investigate these medicines for the treatment or prevention of COVID-19. Monitoring may include baseline ECG, electrolytes, renal function, and hepatic tests.” The communication also highlighted several potential serious adverse effects from hydroxychloroquine or chloroquine that include QT prolongation with increased risk in patients with renal insufficiency or failure, increased insulin levels and insulin action causing increased risk of severe hypoglycemia, hemolysis in selected patients, and interaction with other medicines that cause QT prolongation.
“If a healthcare professional is considering use of hydroxychloroquine or chloroquine to treat or prevent COVID-19, FDA recommends checking www.clinicaltrials.gov for a suitable clinical trial and consider enrolling the patient,” the statement added.
The FDA’s Safety Communication came a day after the European Medicines Agency issued a similar reminder about the risk for serious adverse effects from treatment with hydroxychloroquine and chloroquine, the need for adverse effect monitoring, and the unproven status of purported benefits from these agents.
The statement came after ongoing promotion by the Trump administration of hydroxychloroquine, in particular, for COVID-19 despite a lack of evidence.
The FDA’s communication cited recent case reports sent to the FDA, as well as published findings, and reports to the National Poison Data System that have described serious, heart-related adverse events and death in COVID-19 patients who received hydroxychloroquine and chloroquine, alone or in combination with azithromycin or another QT-prolonging drug. One recent, notable but not peer-reviewed report on 368 patients treated at any of several U.S. VA medical centers showed no apparent benefit to hospitalized COVID-19 patients treated with hydroxychloroquine and a signal for increased mortality among certain patients on this drug (medRxiv. 2020 Apr 23; doi: 10.1101/2020.04.16.20065920). Several cardiology societies have also highlighted the cardiac considerations for using these drugs in patients with COVID-19, including a summary coauthored by the presidents of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society (Circulation. 2020 Apr 8. doi: 10.1161/CIRCULATIONAHA.120.047521), and in guidance from the European Society of Cardiology.
The U.S. Food and Drug Administration reinforced its March guidance on when it’s permissible to use hydroxychloroquine and chloroquine to treat COVID-19 patients and on the multiple risks these drugs pose in a Safety Communication on April 24.
The new communication reiterated the agency’s position from the Emergency Use Authorization (EUA) it granted on March 28 to allow hydroxychloroquine and chloroquine treatment of COVID-19 patients only when they are hospitalized and participation in a clinical trial is “not available,” or “not feasible.” The April 24 update to the EUA noted that “the FDA is aware of reports of serious heart rhythm problems in patients with COVID-19 treated with hydroxychloroquine or chloroquine, often in combination with azithromycin and other QT-prolonging medicines. We are also aware of increased use of these medicines through outpatient prescriptions.”
In addition to reiterating the prior limitations on permissible patients for these treatment the agency also said in the new communication that “close supervision is strongly recommended, “ specifying that “we recommend initial evaluation and monitoring when using hydroxychloroquine or chloroquine under the EUA or in clinical trials that investigate these medicines for the treatment or prevention of COVID-19. Monitoring may include baseline ECG, electrolytes, renal function, and hepatic tests.” The communication also highlighted several potential serious adverse effects from hydroxychloroquine or chloroquine that include QT prolongation with increased risk in patients with renal insufficiency or failure, increased insulin levels and insulin action causing increased risk of severe hypoglycemia, hemolysis in selected patients, and interaction with other medicines that cause QT prolongation.
“If a healthcare professional is considering use of hydroxychloroquine or chloroquine to treat or prevent COVID-19, FDA recommends checking www.clinicaltrials.gov for a suitable clinical trial and consider enrolling the patient,” the statement added.
The FDA’s Safety Communication came a day after the European Medicines Agency issued a similar reminder about the risk for serious adverse effects from treatment with hydroxychloroquine and chloroquine, the need for adverse effect monitoring, and the unproven status of purported benefits from these agents.
The statement came after ongoing promotion by the Trump administration of hydroxychloroquine, in particular, for COVID-19 despite a lack of evidence.
The FDA’s communication cited recent case reports sent to the FDA, as well as published findings, and reports to the National Poison Data System that have described serious, heart-related adverse events and death in COVID-19 patients who received hydroxychloroquine and chloroquine, alone or in combination with azithromycin or another QT-prolonging drug. One recent, notable but not peer-reviewed report on 368 patients treated at any of several U.S. VA medical centers showed no apparent benefit to hospitalized COVID-19 patients treated with hydroxychloroquine and a signal for increased mortality among certain patients on this drug (medRxiv. 2020 Apr 23; doi: 10.1101/2020.04.16.20065920). Several cardiology societies have also highlighted the cardiac considerations for using these drugs in patients with COVID-19, including a summary coauthored by the presidents of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society (Circulation. 2020 Apr 8. doi: 10.1161/CIRCULATIONAHA.120.047521), and in guidance from the European Society of Cardiology.
FROM THE FDA
COVID-19: Experts call for ‘urgent’ global action to prevent suicide
A global group of suicide experts is urging governments around the world to take action to prevent a possible jump in suicide rates because of the ongoing COVID-19 pandemic.
In a commentary published online April 21 in Lancet Psychiatry, members of the International COVID-19 Suicide Prevention Research Collaboration warned that suicide rates are likely to rise as the pandemic spreads and its ensuing long-term effects on the general population, economy, and vulnerable groups emerge.
“Preventing suicide therefore needs urgent consideration. The response must capitalize on, but extend beyond, general mental health policies and practices,” the experts wrote.
The COVID-19 collaboration was started by David Gunnell, MBChB, PhD, University of Bristol, England, and includes 42 members with suicide expertise from around the world.
“We’re an ad hoc grouping of international suicide prevention researchers, research leaders, and members of larger international suicide prevention organizations. We include specialists in public health, psychiatry, psychology, and other clinical disciplines,” Dr. Gunnell said in an interview.
“Through this comment piece we hope to share our ideas and experiences about best practice, and ask others working in the field of suicide prevention at a regional, national, and international level to share our intervention and surveillance/data collection recommendations with relevant policy makers,” he added.
Lessons from the past
During times of crisis, people with existing mental health disorders may suffer worsening symptoms, whereas others may develop new mental health problems, especially depression, anxiety, and posttraumatic stress disorder (PTSD), the group notes.
There is some evidence that suicide increased in the United States during the Spanish flu pandemic of 1918 and among older people in Hong Kong during the 2003 severe acute respiratory syndrome (SARS) outbreak.
An increase in suicide related to COVID-19 is not inevitable provided preventive action is prompt, the group notes.
In their article, the group offered several potential public health responses to mitigate suicide risk associated with the COVID-19 pandemic.
These include:
- Clear care pathways for those who are suicidal.
- Remote or digital assessments for patients currently under the care of a mental health professional.
- Staff training to support new ways of working.
- Increased support for mental health helplines.
- Providing easily accessible grief counseling for those who have lost a loved one to the virus.
- Financial safety nets and labor market programs.
- Dissemination of evidence-based online interventions.
Public health responses must also ensure that those facing domestic violence have access to support and a place to go during times of crisis, they suggested.
“These are unprecedented times. The pandemic will cause distress and leave many vulnerable. Mental health consequences are likely to be present for longer and peak later than the actual pandemic. However, research evidence and the experience of national strategies provide a strong basis for suicide prevention,” the group wrote.
Dr. Gunnell said it’s hard to predict what impact the pandemic will have on suicide rates, “but given the range of concerns, it is important to be prepared and take steps to mitigate risk as much as possible.”
Concerning spike in gun sales
Eric Fleegler, MD, MPH, and colleagues from Boston Children’s Hospital and Harvard Medical School, Boston, agreed.
“The time to act is now. Both population and individual approaches are needed to reduce the risk for suicide in the coming months,” they wrote in a commentary published online April 22 in Annals of Internal Medicine.
Dr. Fleegler and colleagues are particularly concerned about a potential increase in gun-related suicides, as gun sales in the United States have “skyrocketed” during the COVID-19 pandemic.
In March, more than 2.5 million firearms were sold, including 1.5 million handguns. That’s an 85% increase in gun sales compared with March 2019 and the highest firearm sales ever recorded in the United States, they reported.
In addition, research has shown that individuals who buy handguns have a 22-fold higher rate of firearm-related suicide within the first year vs. those who don’t purchase a handgun.
“In the best of times, increased gun ownership is associated with a heightened risk for firearm-related suicide. These are not the best of times,” the authors wrote.
Dr. Fleegler and colleagues said From 2006 to 2018, firearm-related suicide rates increased by more than 25%, according to the National Center for Injury Prevention and Control. In 2018 alone, there were 24,432 firearm-related suicides in the United States.
“The United States should take policy and clinical action to avoid a potential epidemic of firearm-related suicide in the wake of the COVID-19 pandemic,” they concluded.
This research had no specific funding. Dr. Gunnell and Dr. Fleegler disclosed no relevant financial relationships .
A version of this article originally appeared on Medscape.com.
A global group of suicide experts is urging governments around the world to take action to prevent a possible jump in suicide rates because of the ongoing COVID-19 pandemic.
In a commentary published online April 21 in Lancet Psychiatry, members of the International COVID-19 Suicide Prevention Research Collaboration warned that suicide rates are likely to rise as the pandemic spreads and its ensuing long-term effects on the general population, economy, and vulnerable groups emerge.
“Preventing suicide therefore needs urgent consideration. The response must capitalize on, but extend beyond, general mental health policies and practices,” the experts wrote.
The COVID-19 collaboration was started by David Gunnell, MBChB, PhD, University of Bristol, England, and includes 42 members with suicide expertise from around the world.
“We’re an ad hoc grouping of international suicide prevention researchers, research leaders, and members of larger international suicide prevention organizations. We include specialists in public health, psychiatry, psychology, and other clinical disciplines,” Dr. Gunnell said in an interview.
“Through this comment piece we hope to share our ideas and experiences about best practice, and ask others working in the field of suicide prevention at a regional, national, and international level to share our intervention and surveillance/data collection recommendations with relevant policy makers,” he added.
Lessons from the past
During times of crisis, people with existing mental health disorders may suffer worsening symptoms, whereas others may develop new mental health problems, especially depression, anxiety, and posttraumatic stress disorder (PTSD), the group notes.
There is some evidence that suicide increased in the United States during the Spanish flu pandemic of 1918 and among older people in Hong Kong during the 2003 severe acute respiratory syndrome (SARS) outbreak.
An increase in suicide related to COVID-19 is not inevitable provided preventive action is prompt, the group notes.
In their article, the group offered several potential public health responses to mitigate suicide risk associated with the COVID-19 pandemic.
These include:
- Clear care pathways for those who are suicidal.
- Remote or digital assessments for patients currently under the care of a mental health professional.
- Staff training to support new ways of working.
- Increased support for mental health helplines.
- Providing easily accessible grief counseling for those who have lost a loved one to the virus.
- Financial safety nets and labor market programs.
- Dissemination of evidence-based online interventions.
Public health responses must also ensure that those facing domestic violence have access to support and a place to go during times of crisis, they suggested.
“These are unprecedented times. The pandemic will cause distress and leave many vulnerable. Mental health consequences are likely to be present for longer and peak later than the actual pandemic. However, research evidence and the experience of national strategies provide a strong basis for suicide prevention,” the group wrote.
Dr. Gunnell said it’s hard to predict what impact the pandemic will have on suicide rates, “but given the range of concerns, it is important to be prepared and take steps to mitigate risk as much as possible.”
Concerning spike in gun sales
Eric Fleegler, MD, MPH, and colleagues from Boston Children’s Hospital and Harvard Medical School, Boston, agreed.
“The time to act is now. Both population and individual approaches are needed to reduce the risk for suicide in the coming months,” they wrote in a commentary published online April 22 in Annals of Internal Medicine.
Dr. Fleegler and colleagues are particularly concerned about a potential increase in gun-related suicides, as gun sales in the United States have “skyrocketed” during the COVID-19 pandemic.
In March, more than 2.5 million firearms were sold, including 1.5 million handguns. That’s an 85% increase in gun sales compared with March 2019 and the highest firearm sales ever recorded in the United States, they reported.
In addition, research has shown that individuals who buy handguns have a 22-fold higher rate of firearm-related suicide within the first year vs. those who don’t purchase a handgun.
“In the best of times, increased gun ownership is associated with a heightened risk for firearm-related suicide. These are not the best of times,” the authors wrote.
Dr. Fleegler and colleagues said From 2006 to 2018, firearm-related suicide rates increased by more than 25%, according to the National Center for Injury Prevention and Control. In 2018 alone, there were 24,432 firearm-related suicides in the United States.
“The United States should take policy and clinical action to avoid a potential epidemic of firearm-related suicide in the wake of the COVID-19 pandemic,” they concluded.
This research had no specific funding. Dr. Gunnell and Dr. Fleegler disclosed no relevant financial relationships .
A version of this article originally appeared on Medscape.com.
A global group of suicide experts is urging governments around the world to take action to prevent a possible jump in suicide rates because of the ongoing COVID-19 pandemic.
In a commentary published online April 21 in Lancet Psychiatry, members of the International COVID-19 Suicide Prevention Research Collaboration warned that suicide rates are likely to rise as the pandemic spreads and its ensuing long-term effects on the general population, economy, and vulnerable groups emerge.
“Preventing suicide therefore needs urgent consideration. The response must capitalize on, but extend beyond, general mental health policies and practices,” the experts wrote.
The COVID-19 collaboration was started by David Gunnell, MBChB, PhD, University of Bristol, England, and includes 42 members with suicide expertise from around the world.
“We’re an ad hoc grouping of international suicide prevention researchers, research leaders, and members of larger international suicide prevention organizations. We include specialists in public health, psychiatry, psychology, and other clinical disciplines,” Dr. Gunnell said in an interview.
“Through this comment piece we hope to share our ideas and experiences about best practice, and ask others working in the field of suicide prevention at a regional, national, and international level to share our intervention and surveillance/data collection recommendations with relevant policy makers,” he added.
Lessons from the past
During times of crisis, people with existing mental health disorders may suffer worsening symptoms, whereas others may develop new mental health problems, especially depression, anxiety, and posttraumatic stress disorder (PTSD), the group notes.
There is some evidence that suicide increased in the United States during the Spanish flu pandemic of 1918 and among older people in Hong Kong during the 2003 severe acute respiratory syndrome (SARS) outbreak.
An increase in suicide related to COVID-19 is not inevitable provided preventive action is prompt, the group notes.
In their article, the group offered several potential public health responses to mitigate suicide risk associated with the COVID-19 pandemic.
These include:
- Clear care pathways for those who are suicidal.
- Remote or digital assessments for patients currently under the care of a mental health professional.
- Staff training to support new ways of working.
- Increased support for mental health helplines.
- Providing easily accessible grief counseling for those who have lost a loved one to the virus.
- Financial safety nets and labor market programs.
- Dissemination of evidence-based online interventions.
Public health responses must also ensure that those facing domestic violence have access to support and a place to go during times of crisis, they suggested.
“These are unprecedented times. The pandemic will cause distress and leave many vulnerable. Mental health consequences are likely to be present for longer and peak later than the actual pandemic. However, research evidence and the experience of national strategies provide a strong basis for suicide prevention,” the group wrote.
Dr. Gunnell said it’s hard to predict what impact the pandemic will have on suicide rates, “but given the range of concerns, it is important to be prepared and take steps to mitigate risk as much as possible.”
Concerning spike in gun sales
Eric Fleegler, MD, MPH, and colleagues from Boston Children’s Hospital and Harvard Medical School, Boston, agreed.
“The time to act is now. Both population and individual approaches are needed to reduce the risk for suicide in the coming months,” they wrote in a commentary published online April 22 in Annals of Internal Medicine.
Dr. Fleegler and colleagues are particularly concerned about a potential increase in gun-related suicides, as gun sales in the United States have “skyrocketed” during the COVID-19 pandemic.
In March, more than 2.5 million firearms were sold, including 1.5 million handguns. That’s an 85% increase in gun sales compared with March 2019 and the highest firearm sales ever recorded in the United States, they reported.
In addition, research has shown that individuals who buy handguns have a 22-fold higher rate of firearm-related suicide within the first year vs. those who don’t purchase a handgun.
“In the best of times, increased gun ownership is associated with a heightened risk for firearm-related suicide. These are not the best of times,” the authors wrote.
Dr. Fleegler and colleagues said From 2006 to 2018, firearm-related suicide rates increased by more than 25%, according to the National Center for Injury Prevention and Control. In 2018 alone, there were 24,432 firearm-related suicides in the United States.
“The United States should take policy and clinical action to avoid a potential epidemic of firearm-related suicide in the wake of the COVID-19 pandemic,” they concluded.
This research had no specific funding. Dr. Gunnell and Dr. Fleegler disclosed no relevant financial relationships .
A version of this article originally appeared on Medscape.com.
COVID-19: What are the major cardiovascular issues?
Acute viral myocarditis often confounds with ischemic injury
Frontline health care workers are facing escalating challenges with rapidly spreading coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.1 Hospitalists will often deal with various manifestations of acute cardiac injury, controversial withholding of ACE inhibitors (ACEI) or angiotensin receptor blockers (ARBs), arrhythmic toxicities from such drug therapies as hydroxychloroquine.
Presentation and cardiac risks from COVID-19
Patients with COVID-19 often have presented with noncardiac symptoms, usually a febrile illness associated with cough or shortness of breath. Recent reports from Italy and New York have suggested patients also can present with isolated cardiac involvement without any other symptoms that can portend a grim prognosis.2 Cardiac effects include myocarditis, acute coronary syndrome, malignant arrhythmias ultimately cardiogenic shock and cardiac arrest.3
The mortality rate correlates with older age, preexisting health conditions, and availability of medical resources. A recent meta-analysis including 53,000 COVID-19 patients found the most common comorbidities were hypertension (19%), diabetes (8 %) and cardiovascular disease (CVD) (3%).4 Half of the cases died from respiratory failure and one-third have died from concomitant respiratory and heart failure. Acute heart failure alone accounted for about 7% of cases.5
Overall mortality rate can be better understood with the largest case series to-date of COVID-19 in mainland China published by the Chinese Center for Disease Control and Prevention. The overall case-fatality rate was 2.3% (1,023 deaths among 44,672 confirmed cases), but the mortality reached 10.5% in patients with underlying CVD.6
Acute cardiac injuries in COVID-19
Acute cardiac injury (ACI) is defined as troponin elevation above the 99th percentile of the upper reference limit.7 A practical description of ACI in COVID-19 patients should also include broader definition with new abnormalities in ECG since not all patients with acute cardiac effects have developed troponin elevation.3 More recent reports showed up to 28% of hospitalized patients had a myocardial injury.3
It is not uncommon to see a patient with COVID-19 myocarditis as a mimicker of acute ST-elevation myocardial infarction (STEMI). The mechanism of ACI is unknown, though several hypotheses have been proposed based on case series and retrospective reviews. These include direct viral invasion into myocardial cells leading to myocarditis, oxygen demand-supply mismatch, acute coronary syndrome from plaque rupture, stress, or cytokine-mediated cardiomyopathy.3 The exact incidence of true MI from occlusive coronary disease in the COVID-19 population is yet unknown.
In some cases, troponin elevation may be a late manifestation of COVID-19. As coronavirus disease progressed slowly, a rapid rise of troponin was noted when patients developed acute respiratory failure after 10 days of illness. Among nonsurvivors, a steady rise in troponin was observed from day 4 through day 22.8
ACI is associated with ICU admission and mortality. Both troponin and BNP levels increased significantly during the course of hospitalization in those who ultimately died, but no such changes were evident in survivors.3 ACI was higher in nonsurvivors (59%) than in survivors (1%).8 ACI was higher in ICU patients (22%), compared with non-ICU patients (2%).9 Patients with CVD were more likely to exhibit elevation of troponin levels (54%), compared with patients without CVD (13%).3
Higher troponin levels and the presence of CVD are directly proportional to severe disease and death. Patients with elevated troponin developed more frequent complications including acute respiratory distress syndrome, malignant arrhythmias including ventricular tachycardia/ventricular fibrillation, acute coagulopathy, and acute kidney injury.3,8 Death was markedly higher in patients with elevated troponin, compared with normal levels: 60% versus 9%. Only 8% with no CVD and normal troponin died, whereas 69% of people with underlying CVD and elevated troponin died.3
The median duration from illness onset to death was 23 (8-41) days in the group with elevated troponin. Patients with CVD and escalation of troponin levels had the shortest survival of 1-5 days. The dynamic rise of cardiac biomarkers and increased incidence of malignant arrhythmias during the course of illness shows that myocardial injury played a greater role in the fatal outcome of COVID-19 than the presence of preexisting CVD itself.3
Management of acute cardiac issues in COVID-19
There are no established therapeutic options with randomized, clinical trials specific to the management of COVID-19 patients at this point. Standard supportive care and individualized treatment plan based on existing guidelines is probably the best approach. Disposition of cases and cardiac testing should be tailored, based on local protocols, availability of resources and expertise.10
There seems to be a consensus that baseline troponin levels should be obtained in all admitted patients. Repeat troponin levels can be obtained based on the severity of illness, for example, daily troponin checks are reasonable in ICU patients and every-other-day troponin testing may be reasonable in general inpatients. Routine troponin testing in minimally symptomatic or asymptomatic patients will likely not change any outcome.3,11,12
Daily ECG is reasonable in severe COVID-19. However, routine transthoracic ECGs are not reasonable, unless it will change further treatment plans. Transthoracic electrocardiograms (TTE) are reasonable in patients with significant troponin elevation, a decline in central venous oxygen saturation, new heart failure, shock, new persistent arrhythmias, or significant new ECG changes.12
Limited TTEs for a focused exam enough to answer the clinical question should be ordered to minimize the risk of viral exposure to the sonographers. Transesophageal echo will rarely be needed, and its use should be minimized to reduce direct contact exposure and because of anesthesia risks.13 Routine stress testing should not be ordered in active COVID-19 and should be deferred for outpatient evaluation, if clinically indicated, once the patient recovers from the infection.12
Myocarditis and pericarditis are potential manifestations of acute cardiac injury. Recent case reports have suggested evidence of myocarditis confirmed with cardiac MRI.11 Because of high fatality rates with cardiac involvement and no proven therapies yet, the role of routine advanced cardiac imaging such as cardiac CT, cardiac MRI, or cardiac biopsy is unclear.
Myocarditis can likely be caused either by the virus itself, or the body’s immune and inflammatory response (cytokine storm) to the virus.2,3 The use of anti-inflammatory drugs like colchicine, ibuprofen, steroids, or statins is not yet established.10,12 Drugs like remdesivir, lopinavir-ritonavir, hydroxychloroquine, chloroquine, and anti-interleukin-6 agents have been invariably used with some anecdotal success and randomized clinical trials for some of these drugs are presently undergoing.
Physicians may encounter situations to call a STEMI code or not in COVID-19 patients.2,11 Patients may have substernal pain, diffuse or regional ST elevations in ECG and reduced left ventricular dysfunction with regional wall motion abnormalities on ECG. These findings may be casued by myocarditis, acute type 1 MI, or stress-induced cardiomyopathy. Clinicians should make their judgment based on the overall pretest probability for type 1 MI, incorporating risk factor profiles and the presence of typical symptoms.
Treatment practice for questionable STEMI cases will likely vary across the country as we are learning more about the virus. Cath lab operators are at risk for COVID-19 infection through direct contact with patients. Few cardiologists were admitted after COVID-19 infections in the ICU at a New York hospital after they were involved in a acute MI case in a cath lab.14 Based on the Chinese experience, some have suggested the idea of lytic therapy first with follow-up cardiac CT to assess the recanalization of perfusion status, but at this point, this strategy remains controversial in the United States. In addition, if the patient has myocarditis instead, there will be a risk for pericardial effusion and hemorrhagic complications with lytic therapy.
Case examples
1. A 70-year-old male presents with fevers, chest pain, cough, shortness of breath. He has a history of metabolic syndrome and 30 pack-years of smoking. His ECG showed 1.5 mm ST elevation in inferior leads with reciprocal ST depressions in lateral leads, and his initial troponin is 2. Echocardiogram showed reduced left ventricle ejection fraction of 32% and inferior wall hypokinesis. He is suspected COVID-19 and his PCR result is pending. How would you manage this patient?
This patient presented with febrile illness and, but he had a very high pretest probability for obstructive coronary artery disease based on his age, male sex, and multiple risk factors. He may have a viral syndrome and it is a stressful situation for him. This may have precipitated plaque rupture causing acute MI.
Activating the STEMI pathway for emergent left heart catheterization is likely appropriate in this case. Coronary angiogram in this patient showed a 100% occluded mid-right coronary artery with a fresh thrombus. Delaying cardiac cath would have possibly led to malignant arrhythmias and death from ischemic injury. We need to be cognizant patients can die from non–COVID-related emergencies also.
2. An 18-year-old healthy male presents with cough and chest pain and has bilateral lung infiltrates. ECG showed anterolateral 2 mm ST elevations and no reciprocal ST changes. Stat TTE showed anterior wall hypokinesis and LV function 30% and his initial troponin are 0.6 (normal is < .05). The nasopharyngeal swab is sent out and his COVID result is pending. How would you manage this patient?
A young patient with no cardiovascular risk factors has a very low pretest probability for obstructive coronary disease and the likelihood of having a true ischemic MI is low even though he has significant new ST elevations. Especially with presumed COVID-19 and risk of virus exposure to the cath lab personnel, it will be prudent to manage this patient with supportive therapy including beta-blockers, ACEIs, etc. Repeat echo in 7 days before discharge showed improved LVEF 45%.
Controversy on ACEI/ARB
The SARS-CoV-2 virus enters via cell-entry receptor namely angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 is thought to have a higher affinity for ACE2 than other SARS-viruses.15
ACE2 is expressed in the heart, lungs, vasculature, and kidneys. ACEI and ARBs in animal models increase the expression of ACE2,16 though this has not been confirmed in human studies. This has led to the hypothesis that ACEI and ARBs might worsen myocarditis or precipitate the acute coronary syndrome. It has also been hypothesized that the upregulation of ACE2 is therapeutic in COVID-19 and that ARBs might be protective during infection.17
The increased ACE2 expression induced by ACEI or ARB would aggravate lung injury of patients with COVID-19. However, a previous study showed a beneficial effect of ACEI/ARB in patients admitted with viral pneumonia, as it significantly reduced the pulmonary inflammatory response and cytokine release caused by virus infection.18
Therefore, this remains an area of investigation and it is unclear how these medications affect patients with COVID-19. In a recent review, with a limited number of patients, the mortality of those treated with or without the use of ACEI/ARB did not show a significant difference in the outcome.3
Both American and European cardiology societies recommend against routine discontinuation of ACEI and ARBs in patients with COVID-19 because of risks of uncontrolled hypertension and heart failure, stroke, or heart attack.19 However, it will be reasonable to hold off in inpatients in cases of acute kidney injury, hypotension, shock, etc.12
Cardiac concern about hydroxychloroquine and chloroquine
Hydroxychloroquine (HCQ) is an antimalarial drug shown to have in vitro (but not yet in vivo) activity against diverse RNA viruses, including SARS-CoV-1.20 An expert consensus group from China suggests that chloroquine improved lung imaging and shortened disease course.21 HCQ was found to be more potent than chloroquine in inhibiting SARS-CoV-2 in vitro.22
Based on limited in vitro and anecdotal clinical data from other countries, the U.S. Food and Drug Administration recently authorized emergency use of chloroquine and HCQ in hopes of slowing the progression of the disease when a clinical trial is not available, or participation is not feasible for use of these drugs in hospitalized patients. However, with no clear benefit, there is a concern for possible risks with cardiac toxicity.
HCQ is known to cause cardiomyopathy in a dose-dependent manner over several years. Given the anticipated short duration in COVID-19, it is not an expected risk. QT-segment prolongation and torsades de pointes, especially if administered in combination with azithromycin, is possible even in short term use.23
Given above, frequent ECG monitoring is indicated for patients being treated with chloroquine or HCQ. All other QT-prolonging drugs should be discontinued. Continuous telemetry monitoring while under treatment is reasonable. HCQ should not be started if baseline QTc is > 500 msec and it should be stopped if the patient develops ventricular arrhythmias.12
Dr. Subedi is a noninvasive cardiologist for Wellspan Health System in Franklin and Cumberland counties in south central Pennsylvania. He is a clinical assistant professor of medicine at Penn State College of Medicine, Hershey, Pa. He is an active member of the critical care committee at Wellspan Chambersburg (Pa.) Hospital. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro Hospitals, all in Pennsylvania. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Areti is currently working as a hospitalist at Wellspan Chambersburg Hospital and is a member of the Wellspan pharmacy and therapeutics committee. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson.
Key points
- Acute cardiac injury or myocarditis is common among patients infected with COVID-19. Often, COVID myocarditis can mimic acute MI or stress cardiomyopathy and will present diagnostic and therapeutic challenges. On the other hand, isolated cardiac involvement can occur, even without symptoms and signs of interstitial pneumonia.
- A most important indicator of worse prediction is the degree of myocardial injury, regardless of preexisting conditions or underlying cardiovascular disease.
- Early recognition of cardiac involvement will be helpful in targeting more aggressive supportive therapies. Commonly available clinical tools like bloodwork, ECG, or echocardiogram should be adequate to diagnose carditis in most cases.
- Advanced cardiac imaging tests or cardiac biopsy are of uncertain benefits. Meticulous evaluation is needed for possible ischemic changes before taking the patient to the cardiac cath lab in order to reduce unnecessary virus exposure to the operators.
- ACEI/ARB should be continued in most cases in COVID patients based on cardiology societies’ recommendations.
- With the widespread use of antimalarial drugs like chloroquine or hydroxychloroquine, frequent ECG and continuous telemetry monitoring is reasonable to rule out ventricular arrhythmias like torsades.
- There is no specific treatment to date for acute cardiac injuries. Since there are no specific guidelines and information about the virus is rapidly changing, it will be prudent to follow common-sense approaches outlined by institutions like the Brigham and Women’s Hospital COVID-19 Critical Care clinical guidelines, which incorporate new clinical information on a daily basis ().
References
1. Rothan HA and Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020 May;109:102433. doi: 10.1016/j.jaut.2020.102433.
2. Kolata G. A heart attack? No, it was the coronavirus. New York Times 2020 Mar 27.
3. Guo T et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1017.
4. Zhao X et al. Incidence, clinical characteristics and prognostic factor of patients with COVID-19: a systematic review and meta-analysis. MedRxIV. 2020 Mar 20. doi: 10.1101/2020.03.17.20037572.
5. Ruan Q et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 Mar 3. doi: 10.1007/s00134-020-05991-x.
6. Wu Z and McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648.
7. Thygesen K et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol. 2018 Oct;72:2231-64.
8. Zhou F et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62.
9. Wang D et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020 Feb 7. doi: 10.1001/jama.2020.1585.
10. CDC: Therapeutic options for patients with COVID-19. Updated April 13, 2020.
11. Inciardi RM et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1096.
12. Brigham and Women’s Hospital COVID-19 Critical Care Clinical Guidelines.
13. American Society of Echocardiography Statement on COVID-19. 2020 Apr 1.
14. A cardiologist in Brooklyn infected with COVID-19. @jigneshpatelMD. 2020 Mar 20.
15. Paules CI et al. Coronavirus infections – more than just the common cold. JAMA. 2020 Jan 23. doi: 10.1001/jama.2020.0757.
16. Zheng YY et al. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020 May;17(5):259-60.
17. Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656.
18. Henry C et al. Impact of angiotensin-converting enzyme inhibitors and statins on viral pneumonia. Proc (Bayl Univ Med Cent). 2018 Oct 26;31(4):419-23.
19. HFSA/ACC/AHA statement addresses concerns re: Using RAAS antagonists in COVID-19. 2020 Mar 17.
20. Touret F and de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res. 2020 May;177:104762. doi: 10.1016/j.antiviral.2020.104762.
21. Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia. Chinese journal of tuberculosis and respiratory diseases. 2020 Mar 12;43(3):185-8.
22. Yao X et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Mar 9. doi: 10.1093/cid/ciaa237.
23. Devaux CA et al. New insights on the antiviral effects of chloroquine against coronavirus: What to expect for COVID-19? Int J Antimicrob Agents. 2020 Mar 12:105938. doi: 10.1016/j.ijantimicag.2020.105938.
Acute viral myocarditis often confounds with ischemic injury
Acute viral myocarditis often confounds with ischemic injury
Frontline health care workers are facing escalating challenges with rapidly spreading coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.1 Hospitalists will often deal with various manifestations of acute cardiac injury, controversial withholding of ACE inhibitors (ACEI) or angiotensin receptor blockers (ARBs), arrhythmic toxicities from such drug therapies as hydroxychloroquine.
Presentation and cardiac risks from COVID-19
Patients with COVID-19 often have presented with noncardiac symptoms, usually a febrile illness associated with cough or shortness of breath. Recent reports from Italy and New York have suggested patients also can present with isolated cardiac involvement without any other symptoms that can portend a grim prognosis.2 Cardiac effects include myocarditis, acute coronary syndrome, malignant arrhythmias ultimately cardiogenic shock and cardiac arrest.3
The mortality rate correlates with older age, preexisting health conditions, and availability of medical resources. A recent meta-analysis including 53,000 COVID-19 patients found the most common comorbidities were hypertension (19%), diabetes (8 %) and cardiovascular disease (CVD) (3%).4 Half of the cases died from respiratory failure and one-third have died from concomitant respiratory and heart failure. Acute heart failure alone accounted for about 7% of cases.5
Overall mortality rate can be better understood with the largest case series to-date of COVID-19 in mainland China published by the Chinese Center for Disease Control and Prevention. The overall case-fatality rate was 2.3% (1,023 deaths among 44,672 confirmed cases), but the mortality reached 10.5% in patients with underlying CVD.6
Acute cardiac injuries in COVID-19
Acute cardiac injury (ACI) is defined as troponin elevation above the 99th percentile of the upper reference limit.7 A practical description of ACI in COVID-19 patients should also include broader definition with new abnormalities in ECG since not all patients with acute cardiac effects have developed troponin elevation.3 More recent reports showed up to 28% of hospitalized patients had a myocardial injury.3
It is not uncommon to see a patient with COVID-19 myocarditis as a mimicker of acute ST-elevation myocardial infarction (STEMI). The mechanism of ACI is unknown, though several hypotheses have been proposed based on case series and retrospective reviews. These include direct viral invasion into myocardial cells leading to myocarditis, oxygen demand-supply mismatch, acute coronary syndrome from plaque rupture, stress, or cytokine-mediated cardiomyopathy.3 The exact incidence of true MI from occlusive coronary disease in the COVID-19 population is yet unknown.
In some cases, troponin elevation may be a late manifestation of COVID-19. As coronavirus disease progressed slowly, a rapid rise of troponin was noted when patients developed acute respiratory failure after 10 days of illness. Among nonsurvivors, a steady rise in troponin was observed from day 4 through day 22.8
ACI is associated with ICU admission and mortality. Both troponin and BNP levels increased significantly during the course of hospitalization in those who ultimately died, but no such changes were evident in survivors.3 ACI was higher in nonsurvivors (59%) than in survivors (1%).8 ACI was higher in ICU patients (22%), compared with non-ICU patients (2%).9 Patients with CVD were more likely to exhibit elevation of troponin levels (54%), compared with patients without CVD (13%).3
Higher troponin levels and the presence of CVD are directly proportional to severe disease and death. Patients with elevated troponin developed more frequent complications including acute respiratory distress syndrome, malignant arrhythmias including ventricular tachycardia/ventricular fibrillation, acute coagulopathy, and acute kidney injury.3,8 Death was markedly higher in patients with elevated troponin, compared with normal levels: 60% versus 9%. Only 8% with no CVD and normal troponin died, whereas 69% of people with underlying CVD and elevated troponin died.3
The median duration from illness onset to death was 23 (8-41) days in the group with elevated troponin. Patients with CVD and escalation of troponin levels had the shortest survival of 1-5 days. The dynamic rise of cardiac biomarkers and increased incidence of malignant arrhythmias during the course of illness shows that myocardial injury played a greater role in the fatal outcome of COVID-19 than the presence of preexisting CVD itself.3
Management of acute cardiac issues in COVID-19
There are no established therapeutic options with randomized, clinical trials specific to the management of COVID-19 patients at this point. Standard supportive care and individualized treatment plan based on existing guidelines is probably the best approach. Disposition of cases and cardiac testing should be tailored, based on local protocols, availability of resources and expertise.10
There seems to be a consensus that baseline troponin levels should be obtained in all admitted patients. Repeat troponin levels can be obtained based on the severity of illness, for example, daily troponin checks are reasonable in ICU patients and every-other-day troponin testing may be reasonable in general inpatients. Routine troponin testing in minimally symptomatic or asymptomatic patients will likely not change any outcome.3,11,12
Daily ECG is reasonable in severe COVID-19. However, routine transthoracic ECGs are not reasonable, unless it will change further treatment plans. Transthoracic electrocardiograms (TTE) are reasonable in patients with significant troponin elevation, a decline in central venous oxygen saturation, new heart failure, shock, new persistent arrhythmias, or significant new ECG changes.12
Limited TTEs for a focused exam enough to answer the clinical question should be ordered to minimize the risk of viral exposure to the sonographers. Transesophageal echo will rarely be needed, and its use should be minimized to reduce direct contact exposure and because of anesthesia risks.13 Routine stress testing should not be ordered in active COVID-19 and should be deferred for outpatient evaluation, if clinically indicated, once the patient recovers from the infection.12
Myocarditis and pericarditis are potential manifestations of acute cardiac injury. Recent case reports have suggested evidence of myocarditis confirmed with cardiac MRI.11 Because of high fatality rates with cardiac involvement and no proven therapies yet, the role of routine advanced cardiac imaging such as cardiac CT, cardiac MRI, or cardiac biopsy is unclear.
Myocarditis can likely be caused either by the virus itself, or the body’s immune and inflammatory response (cytokine storm) to the virus.2,3 The use of anti-inflammatory drugs like colchicine, ibuprofen, steroids, or statins is not yet established.10,12 Drugs like remdesivir, lopinavir-ritonavir, hydroxychloroquine, chloroquine, and anti-interleukin-6 agents have been invariably used with some anecdotal success and randomized clinical trials for some of these drugs are presently undergoing.
Physicians may encounter situations to call a STEMI code or not in COVID-19 patients.2,11 Patients may have substernal pain, diffuse or regional ST elevations in ECG and reduced left ventricular dysfunction with regional wall motion abnormalities on ECG. These findings may be casued by myocarditis, acute type 1 MI, or stress-induced cardiomyopathy. Clinicians should make their judgment based on the overall pretest probability for type 1 MI, incorporating risk factor profiles and the presence of typical symptoms.
Treatment practice for questionable STEMI cases will likely vary across the country as we are learning more about the virus. Cath lab operators are at risk for COVID-19 infection through direct contact with patients. Few cardiologists were admitted after COVID-19 infections in the ICU at a New York hospital after they were involved in a acute MI case in a cath lab.14 Based on the Chinese experience, some have suggested the idea of lytic therapy first with follow-up cardiac CT to assess the recanalization of perfusion status, but at this point, this strategy remains controversial in the United States. In addition, if the patient has myocarditis instead, there will be a risk for pericardial effusion and hemorrhagic complications with lytic therapy.
Case examples
1. A 70-year-old male presents with fevers, chest pain, cough, shortness of breath. He has a history of metabolic syndrome and 30 pack-years of smoking. His ECG showed 1.5 mm ST elevation in inferior leads with reciprocal ST depressions in lateral leads, and his initial troponin is 2. Echocardiogram showed reduced left ventricle ejection fraction of 32% and inferior wall hypokinesis. He is suspected COVID-19 and his PCR result is pending. How would you manage this patient?
This patient presented with febrile illness and, but he had a very high pretest probability for obstructive coronary artery disease based on his age, male sex, and multiple risk factors. He may have a viral syndrome and it is a stressful situation for him. This may have precipitated plaque rupture causing acute MI.
Activating the STEMI pathway for emergent left heart catheterization is likely appropriate in this case. Coronary angiogram in this patient showed a 100% occluded mid-right coronary artery with a fresh thrombus. Delaying cardiac cath would have possibly led to malignant arrhythmias and death from ischemic injury. We need to be cognizant patients can die from non–COVID-related emergencies also.
2. An 18-year-old healthy male presents with cough and chest pain and has bilateral lung infiltrates. ECG showed anterolateral 2 mm ST elevations and no reciprocal ST changes. Stat TTE showed anterior wall hypokinesis and LV function 30% and his initial troponin are 0.6 (normal is < .05). The nasopharyngeal swab is sent out and his COVID result is pending. How would you manage this patient?
A young patient with no cardiovascular risk factors has a very low pretest probability for obstructive coronary disease and the likelihood of having a true ischemic MI is low even though he has significant new ST elevations. Especially with presumed COVID-19 and risk of virus exposure to the cath lab personnel, it will be prudent to manage this patient with supportive therapy including beta-blockers, ACEIs, etc. Repeat echo in 7 days before discharge showed improved LVEF 45%.
Controversy on ACEI/ARB
The SARS-CoV-2 virus enters via cell-entry receptor namely angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 is thought to have a higher affinity for ACE2 than other SARS-viruses.15
ACE2 is expressed in the heart, lungs, vasculature, and kidneys. ACEI and ARBs in animal models increase the expression of ACE2,16 though this has not been confirmed in human studies. This has led to the hypothesis that ACEI and ARBs might worsen myocarditis or precipitate the acute coronary syndrome. It has also been hypothesized that the upregulation of ACE2 is therapeutic in COVID-19 and that ARBs might be protective during infection.17
The increased ACE2 expression induced by ACEI or ARB would aggravate lung injury of patients with COVID-19. However, a previous study showed a beneficial effect of ACEI/ARB in patients admitted with viral pneumonia, as it significantly reduced the pulmonary inflammatory response and cytokine release caused by virus infection.18
Therefore, this remains an area of investigation and it is unclear how these medications affect patients with COVID-19. In a recent review, with a limited number of patients, the mortality of those treated with or without the use of ACEI/ARB did not show a significant difference in the outcome.3
Both American and European cardiology societies recommend against routine discontinuation of ACEI and ARBs in patients with COVID-19 because of risks of uncontrolled hypertension and heart failure, stroke, or heart attack.19 However, it will be reasonable to hold off in inpatients in cases of acute kidney injury, hypotension, shock, etc.12
Cardiac concern about hydroxychloroquine and chloroquine
Hydroxychloroquine (HCQ) is an antimalarial drug shown to have in vitro (but not yet in vivo) activity against diverse RNA viruses, including SARS-CoV-1.20 An expert consensus group from China suggests that chloroquine improved lung imaging and shortened disease course.21 HCQ was found to be more potent than chloroquine in inhibiting SARS-CoV-2 in vitro.22
Based on limited in vitro and anecdotal clinical data from other countries, the U.S. Food and Drug Administration recently authorized emergency use of chloroquine and HCQ in hopes of slowing the progression of the disease when a clinical trial is not available, or participation is not feasible for use of these drugs in hospitalized patients. However, with no clear benefit, there is a concern for possible risks with cardiac toxicity.
HCQ is known to cause cardiomyopathy in a dose-dependent manner over several years. Given the anticipated short duration in COVID-19, it is not an expected risk. QT-segment prolongation and torsades de pointes, especially if administered in combination with azithromycin, is possible even in short term use.23
Given above, frequent ECG monitoring is indicated for patients being treated with chloroquine or HCQ. All other QT-prolonging drugs should be discontinued. Continuous telemetry monitoring while under treatment is reasonable. HCQ should not be started if baseline QTc is > 500 msec and it should be stopped if the patient develops ventricular arrhythmias.12
Dr. Subedi is a noninvasive cardiologist for Wellspan Health System in Franklin and Cumberland counties in south central Pennsylvania. He is a clinical assistant professor of medicine at Penn State College of Medicine, Hershey, Pa. He is an active member of the critical care committee at Wellspan Chambersburg (Pa.) Hospital. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro Hospitals, all in Pennsylvania. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Areti is currently working as a hospitalist at Wellspan Chambersburg Hospital and is a member of the Wellspan pharmacy and therapeutics committee. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson.
Key points
- Acute cardiac injury or myocarditis is common among patients infected with COVID-19. Often, COVID myocarditis can mimic acute MI or stress cardiomyopathy and will present diagnostic and therapeutic challenges. On the other hand, isolated cardiac involvement can occur, even without symptoms and signs of interstitial pneumonia.
- A most important indicator of worse prediction is the degree of myocardial injury, regardless of preexisting conditions or underlying cardiovascular disease.
- Early recognition of cardiac involvement will be helpful in targeting more aggressive supportive therapies. Commonly available clinical tools like bloodwork, ECG, or echocardiogram should be adequate to diagnose carditis in most cases.
- Advanced cardiac imaging tests or cardiac biopsy are of uncertain benefits. Meticulous evaluation is needed for possible ischemic changes before taking the patient to the cardiac cath lab in order to reduce unnecessary virus exposure to the operators.
- ACEI/ARB should be continued in most cases in COVID patients based on cardiology societies’ recommendations.
- With the widespread use of antimalarial drugs like chloroquine or hydroxychloroquine, frequent ECG and continuous telemetry monitoring is reasonable to rule out ventricular arrhythmias like torsades.
- There is no specific treatment to date for acute cardiac injuries. Since there are no specific guidelines and information about the virus is rapidly changing, it will be prudent to follow common-sense approaches outlined by institutions like the Brigham and Women’s Hospital COVID-19 Critical Care clinical guidelines, which incorporate new clinical information on a daily basis ().
References
1. Rothan HA and Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020 May;109:102433. doi: 10.1016/j.jaut.2020.102433.
2. Kolata G. A heart attack? No, it was the coronavirus. New York Times 2020 Mar 27.
3. Guo T et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1017.
4. Zhao X et al. Incidence, clinical characteristics and prognostic factor of patients with COVID-19: a systematic review and meta-analysis. MedRxIV. 2020 Mar 20. doi: 10.1101/2020.03.17.20037572.
5. Ruan Q et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 Mar 3. doi: 10.1007/s00134-020-05991-x.
6. Wu Z and McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648.
7. Thygesen K et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol. 2018 Oct;72:2231-64.
8. Zhou F et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62.
9. Wang D et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020 Feb 7. doi: 10.1001/jama.2020.1585.
10. CDC: Therapeutic options for patients with COVID-19. Updated April 13, 2020.
11. Inciardi RM et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1096.
12. Brigham and Women’s Hospital COVID-19 Critical Care Clinical Guidelines.
13. American Society of Echocardiography Statement on COVID-19. 2020 Apr 1.
14. A cardiologist in Brooklyn infected with COVID-19. @jigneshpatelMD. 2020 Mar 20.
15. Paules CI et al. Coronavirus infections – more than just the common cold. JAMA. 2020 Jan 23. doi: 10.1001/jama.2020.0757.
16. Zheng YY et al. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020 May;17(5):259-60.
17. Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656.
18. Henry C et al. Impact of angiotensin-converting enzyme inhibitors and statins on viral pneumonia. Proc (Bayl Univ Med Cent). 2018 Oct 26;31(4):419-23.
19. HFSA/ACC/AHA statement addresses concerns re: Using RAAS antagonists in COVID-19. 2020 Mar 17.
20. Touret F and de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res. 2020 May;177:104762. doi: 10.1016/j.antiviral.2020.104762.
21. Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia. Chinese journal of tuberculosis and respiratory diseases. 2020 Mar 12;43(3):185-8.
22. Yao X et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Mar 9. doi: 10.1093/cid/ciaa237.
23. Devaux CA et al. New insights on the antiviral effects of chloroquine against coronavirus: What to expect for COVID-19? Int J Antimicrob Agents. 2020 Mar 12:105938. doi: 10.1016/j.ijantimicag.2020.105938.
Frontline health care workers are facing escalating challenges with rapidly spreading coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.1 Hospitalists will often deal with various manifestations of acute cardiac injury, controversial withholding of ACE inhibitors (ACEI) or angiotensin receptor blockers (ARBs), arrhythmic toxicities from such drug therapies as hydroxychloroquine.
Presentation and cardiac risks from COVID-19
Patients with COVID-19 often have presented with noncardiac symptoms, usually a febrile illness associated with cough or shortness of breath. Recent reports from Italy and New York have suggested patients also can present with isolated cardiac involvement without any other symptoms that can portend a grim prognosis.2 Cardiac effects include myocarditis, acute coronary syndrome, malignant arrhythmias ultimately cardiogenic shock and cardiac arrest.3
The mortality rate correlates with older age, preexisting health conditions, and availability of medical resources. A recent meta-analysis including 53,000 COVID-19 patients found the most common comorbidities were hypertension (19%), diabetes (8 %) and cardiovascular disease (CVD) (3%).4 Half of the cases died from respiratory failure and one-third have died from concomitant respiratory and heart failure. Acute heart failure alone accounted for about 7% of cases.5
Overall mortality rate can be better understood with the largest case series to-date of COVID-19 in mainland China published by the Chinese Center for Disease Control and Prevention. The overall case-fatality rate was 2.3% (1,023 deaths among 44,672 confirmed cases), but the mortality reached 10.5% in patients with underlying CVD.6
Acute cardiac injuries in COVID-19
Acute cardiac injury (ACI) is defined as troponin elevation above the 99th percentile of the upper reference limit.7 A practical description of ACI in COVID-19 patients should also include broader definition with new abnormalities in ECG since not all patients with acute cardiac effects have developed troponin elevation.3 More recent reports showed up to 28% of hospitalized patients had a myocardial injury.3
It is not uncommon to see a patient with COVID-19 myocarditis as a mimicker of acute ST-elevation myocardial infarction (STEMI). The mechanism of ACI is unknown, though several hypotheses have been proposed based on case series and retrospective reviews. These include direct viral invasion into myocardial cells leading to myocarditis, oxygen demand-supply mismatch, acute coronary syndrome from plaque rupture, stress, or cytokine-mediated cardiomyopathy.3 The exact incidence of true MI from occlusive coronary disease in the COVID-19 population is yet unknown.
In some cases, troponin elevation may be a late manifestation of COVID-19. As coronavirus disease progressed slowly, a rapid rise of troponin was noted when patients developed acute respiratory failure after 10 days of illness. Among nonsurvivors, a steady rise in troponin was observed from day 4 through day 22.8
ACI is associated with ICU admission and mortality. Both troponin and BNP levels increased significantly during the course of hospitalization in those who ultimately died, but no such changes were evident in survivors.3 ACI was higher in nonsurvivors (59%) than in survivors (1%).8 ACI was higher in ICU patients (22%), compared with non-ICU patients (2%).9 Patients with CVD were more likely to exhibit elevation of troponin levels (54%), compared with patients without CVD (13%).3
Higher troponin levels and the presence of CVD are directly proportional to severe disease and death. Patients with elevated troponin developed more frequent complications including acute respiratory distress syndrome, malignant arrhythmias including ventricular tachycardia/ventricular fibrillation, acute coagulopathy, and acute kidney injury.3,8 Death was markedly higher in patients with elevated troponin, compared with normal levels: 60% versus 9%. Only 8% with no CVD and normal troponin died, whereas 69% of people with underlying CVD and elevated troponin died.3
The median duration from illness onset to death was 23 (8-41) days in the group with elevated troponin. Patients with CVD and escalation of troponin levels had the shortest survival of 1-5 days. The dynamic rise of cardiac biomarkers and increased incidence of malignant arrhythmias during the course of illness shows that myocardial injury played a greater role in the fatal outcome of COVID-19 than the presence of preexisting CVD itself.3
Management of acute cardiac issues in COVID-19
There are no established therapeutic options with randomized, clinical trials specific to the management of COVID-19 patients at this point. Standard supportive care and individualized treatment plan based on existing guidelines is probably the best approach. Disposition of cases and cardiac testing should be tailored, based on local protocols, availability of resources and expertise.10
There seems to be a consensus that baseline troponin levels should be obtained in all admitted patients. Repeat troponin levels can be obtained based on the severity of illness, for example, daily troponin checks are reasonable in ICU patients and every-other-day troponin testing may be reasonable in general inpatients. Routine troponin testing in minimally symptomatic or asymptomatic patients will likely not change any outcome.3,11,12
Daily ECG is reasonable in severe COVID-19. However, routine transthoracic ECGs are not reasonable, unless it will change further treatment plans. Transthoracic electrocardiograms (TTE) are reasonable in patients with significant troponin elevation, a decline in central venous oxygen saturation, new heart failure, shock, new persistent arrhythmias, or significant new ECG changes.12
Limited TTEs for a focused exam enough to answer the clinical question should be ordered to minimize the risk of viral exposure to the sonographers. Transesophageal echo will rarely be needed, and its use should be minimized to reduce direct contact exposure and because of anesthesia risks.13 Routine stress testing should not be ordered in active COVID-19 and should be deferred for outpatient evaluation, if clinically indicated, once the patient recovers from the infection.12
Myocarditis and pericarditis are potential manifestations of acute cardiac injury. Recent case reports have suggested evidence of myocarditis confirmed with cardiac MRI.11 Because of high fatality rates with cardiac involvement and no proven therapies yet, the role of routine advanced cardiac imaging such as cardiac CT, cardiac MRI, or cardiac biopsy is unclear.
Myocarditis can likely be caused either by the virus itself, or the body’s immune and inflammatory response (cytokine storm) to the virus.2,3 The use of anti-inflammatory drugs like colchicine, ibuprofen, steroids, or statins is not yet established.10,12 Drugs like remdesivir, lopinavir-ritonavir, hydroxychloroquine, chloroquine, and anti-interleukin-6 agents have been invariably used with some anecdotal success and randomized clinical trials for some of these drugs are presently undergoing.
Physicians may encounter situations to call a STEMI code or not in COVID-19 patients.2,11 Patients may have substernal pain, diffuse or regional ST elevations in ECG and reduced left ventricular dysfunction with regional wall motion abnormalities on ECG. These findings may be casued by myocarditis, acute type 1 MI, or stress-induced cardiomyopathy. Clinicians should make their judgment based on the overall pretest probability for type 1 MI, incorporating risk factor profiles and the presence of typical symptoms.
Treatment practice for questionable STEMI cases will likely vary across the country as we are learning more about the virus. Cath lab operators are at risk for COVID-19 infection through direct contact with patients. Few cardiologists were admitted after COVID-19 infections in the ICU at a New York hospital after they were involved in a acute MI case in a cath lab.14 Based on the Chinese experience, some have suggested the idea of lytic therapy first with follow-up cardiac CT to assess the recanalization of perfusion status, but at this point, this strategy remains controversial in the United States. In addition, if the patient has myocarditis instead, there will be a risk for pericardial effusion and hemorrhagic complications with lytic therapy.
Case examples
1. A 70-year-old male presents with fevers, chest pain, cough, shortness of breath. He has a history of metabolic syndrome and 30 pack-years of smoking. His ECG showed 1.5 mm ST elevation in inferior leads with reciprocal ST depressions in lateral leads, and his initial troponin is 2. Echocardiogram showed reduced left ventricle ejection fraction of 32% and inferior wall hypokinesis. He is suspected COVID-19 and his PCR result is pending. How would you manage this patient?
This patient presented with febrile illness and, but he had a very high pretest probability for obstructive coronary artery disease based on his age, male sex, and multiple risk factors. He may have a viral syndrome and it is a stressful situation for him. This may have precipitated plaque rupture causing acute MI.
Activating the STEMI pathway for emergent left heart catheterization is likely appropriate in this case. Coronary angiogram in this patient showed a 100% occluded mid-right coronary artery with a fresh thrombus. Delaying cardiac cath would have possibly led to malignant arrhythmias and death from ischemic injury. We need to be cognizant patients can die from non–COVID-related emergencies also.
2. An 18-year-old healthy male presents with cough and chest pain and has bilateral lung infiltrates. ECG showed anterolateral 2 mm ST elevations and no reciprocal ST changes. Stat TTE showed anterior wall hypokinesis and LV function 30% and his initial troponin are 0.6 (normal is < .05). The nasopharyngeal swab is sent out and his COVID result is pending. How would you manage this patient?
A young patient with no cardiovascular risk factors has a very low pretest probability for obstructive coronary disease and the likelihood of having a true ischemic MI is low even though he has significant new ST elevations. Especially with presumed COVID-19 and risk of virus exposure to the cath lab personnel, it will be prudent to manage this patient with supportive therapy including beta-blockers, ACEIs, etc. Repeat echo in 7 days before discharge showed improved LVEF 45%.
Controversy on ACEI/ARB
The SARS-CoV-2 virus enters via cell-entry receptor namely angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 is thought to have a higher affinity for ACE2 than other SARS-viruses.15
ACE2 is expressed in the heart, lungs, vasculature, and kidneys. ACEI and ARBs in animal models increase the expression of ACE2,16 though this has not been confirmed in human studies. This has led to the hypothesis that ACEI and ARBs might worsen myocarditis or precipitate the acute coronary syndrome. It has also been hypothesized that the upregulation of ACE2 is therapeutic in COVID-19 and that ARBs might be protective during infection.17
The increased ACE2 expression induced by ACEI or ARB would aggravate lung injury of patients with COVID-19. However, a previous study showed a beneficial effect of ACEI/ARB in patients admitted with viral pneumonia, as it significantly reduced the pulmonary inflammatory response and cytokine release caused by virus infection.18
Therefore, this remains an area of investigation and it is unclear how these medications affect patients with COVID-19. In a recent review, with a limited number of patients, the mortality of those treated with or without the use of ACEI/ARB did not show a significant difference in the outcome.3
Both American and European cardiology societies recommend against routine discontinuation of ACEI and ARBs in patients with COVID-19 because of risks of uncontrolled hypertension and heart failure, stroke, or heart attack.19 However, it will be reasonable to hold off in inpatients in cases of acute kidney injury, hypotension, shock, etc.12
Cardiac concern about hydroxychloroquine and chloroquine
Hydroxychloroquine (HCQ) is an antimalarial drug shown to have in vitro (but not yet in vivo) activity against diverse RNA viruses, including SARS-CoV-1.20 An expert consensus group from China suggests that chloroquine improved lung imaging and shortened disease course.21 HCQ was found to be more potent than chloroquine in inhibiting SARS-CoV-2 in vitro.22
Based on limited in vitro and anecdotal clinical data from other countries, the U.S. Food and Drug Administration recently authorized emergency use of chloroquine and HCQ in hopes of slowing the progression of the disease when a clinical trial is not available, or participation is not feasible for use of these drugs in hospitalized patients. However, with no clear benefit, there is a concern for possible risks with cardiac toxicity.
HCQ is known to cause cardiomyopathy in a dose-dependent manner over several years. Given the anticipated short duration in COVID-19, it is not an expected risk. QT-segment prolongation and torsades de pointes, especially if administered in combination with azithromycin, is possible even in short term use.23
Given above, frequent ECG monitoring is indicated for patients being treated with chloroquine or HCQ. All other QT-prolonging drugs should be discontinued. Continuous telemetry monitoring while under treatment is reasonable. HCQ should not be started if baseline QTc is > 500 msec and it should be stopped if the patient develops ventricular arrhythmias.12
Dr. Subedi is a noninvasive cardiologist for Wellspan Health System in Franklin and Cumberland counties in south central Pennsylvania. He is a clinical assistant professor of medicine at Penn State College of Medicine, Hershey, Pa. He is an active member of the critical care committee at Wellspan Chambersburg (Pa.) Hospital. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro Hospitals, all in Pennsylvania. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Areti is currently working as a hospitalist at Wellspan Chambersburg Hospital and is a member of the Wellspan pharmacy and therapeutics committee. Dr. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson.
Key points
- Acute cardiac injury or myocarditis is common among patients infected with COVID-19. Often, COVID myocarditis can mimic acute MI or stress cardiomyopathy and will present diagnostic and therapeutic challenges. On the other hand, isolated cardiac involvement can occur, even without symptoms and signs of interstitial pneumonia.
- A most important indicator of worse prediction is the degree of myocardial injury, regardless of preexisting conditions or underlying cardiovascular disease.
- Early recognition of cardiac involvement will be helpful in targeting more aggressive supportive therapies. Commonly available clinical tools like bloodwork, ECG, or echocardiogram should be adequate to diagnose carditis in most cases.
- Advanced cardiac imaging tests or cardiac biopsy are of uncertain benefits. Meticulous evaluation is needed for possible ischemic changes before taking the patient to the cardiac cath lab in order to reduce unnecessary virus exposure to the operators.
- ACEI/ARB should be continued in most cases in COVID patients based on cardiology societies’ recommendations.
- With the widespread use of antimalarial drugs like chloroquine or hydroxychloroquine, frequent ECG and continuous telemetry monitoring is reasonable to rule out ventricular arrhythmias like torsades.
- There is no specific treatment to date for acute cardiac injuries. Since there are no specific guidelines and information about the virus is rapidly changing, it will be prudent to follow common-sense approaches outlined by institutions like the Brigham and Women’s Hospital COVID-19 Critical Care clinical guidelines, which incorporate new clinical information on a daily basis ().
References
1. Rothan HA and Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020 May;109:102433. doi: 10.1016/j.jaut.2020.102433.
2. Kolata G. A heart attack? No, it was the coronavirus. New York Times 2020 Mar 27.
3. Guo T et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1017.
4. Zhao X et al. Incidence, clinical characteristics and prognostic factor of patients with COVID-19: a systematic review and meta-analysis. MedRxIV. 2020 Mar 20. doi: 10.1101/2020.03.17.20037572.
5. Ruan Q et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 Mar 3. doi: 10.1007/s00134-020-05991-x.
6. Wu Z and McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648.
7. Thygesen K et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol. 2018 Oct;72:2231-64.
8. Zhou F et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62.
9. Wang D et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020 Feb 7. doi: 10.1001/jama.2020.1585.
10. CDC: Therapeutic options for patients with COVID-19. Updated April 13, 2020.
11. Inciardi RM et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1096.
12. Brigham and Women’s Hospital COVID-19 Critical Care Clinical Guidelines.
13. American Society of Echocardiography Statement on COVID-19. 2020 Apr 1.
14. A cardiologist in Brooklyn infected with COVID-19. @jigneshpatelMD. 2020 Mar 20.
15. Paules CI et al. Coronavirus infections – more than just the common cold. JAMA. 2020 Jan 23. doi: 10.1001/jama.2020.0757.
16. Zheng YY et al. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020 May;17(5):259-60.
17. Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656.
18. Henry C et al. Impact of angiotensin-converting enzyme inhibitors and statins on viral pneumonia. Proc (Bayl Univ Med Cent). 2018 Oct 26;31(4):419-23.
19. HFSA/ACC/AHA statement addresses concerns re: Using RAAS antagonists in COVID-19. 2020 Mar 17.
20. Touret F and de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res. 2020 May;177:104762. doi: 10.1016/j.antiviral.2020.104762.
21. Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia. Chinese journal of tuberculosis and respiratory diseases. 2020 Mar 12;43(3):185-8.
22. Yao X et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Mar 9. doi: 10.1093/cid/ciaa237.
23. Devaux CA et al. New insights on the antiviral effects of chloroquine against coronavirus: What to expect for COVID-19? Int J Antimicrob Agents. 2020 Mar 12:105938. doi: 10.1016/j.ijantimicag.2020.105938.
Angiotensin drugs and COVID-19: More reassuring data
Initial data from one Chinese center on the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in patients hospitalized with COVID-19 appear to give some further reassurance about continued use of these drugs.
The report from one hospital in Wuhan found that among patients with hypertension hospitalized with the COVID-19 virus, there was no difference in disease severity or death rate in patients taking ACE inhibitors or ARBs and those not taking such medications.
The data were published online April 23 in JAMA Cardiology.
The study adds to another recent report in a larger number of COVID-19 patients from nine Chinese hospitals that suggested a beneficial effect of ACE inhibitors or ARBs on mortality.
Additional studies
Two other similar studies have also been recently released. Another study from China, published online March 31 in Emerging Microbes & Infections, included a small sample of 42 hospitalized patients with COVID-19 on antihypertensive therapy. Those on ACE inhibitor/ARB therapy had a lower rate of severe disease and a trend toward a lower level of IL-6 in peripheral blood. In addition, patients on ACE inhibitor/ARB therapy had increased CD3+ and CD8+ T-cell counts in peripheral blood and decreased peak viral load compared with other antihypertensive drugs.
And a preliminary study from the UK, which has not yet been peer reviewed, found that treatment with ACE inhibitors was associated with a reduced risk of rapidly deteriorating severe COVID-19 disease.
The study, available online on MedRxiv, a preprint server for health sciences, reports on 205 acute inpatients with COVID-19 at King’s College Hospital and Princess Royal University Hospital, London.
Of these, 51.2% had hypertension, 30.2% had diabetes, and 14.6% had ischemic heart disease or heart failure. Of the 37 patients on ACE inhibitors, five (14%) died or required critical care support compared with 29% (48/168) of patients not taking an ACE inhibitor.
New Wuhan study
The authors of the new article published in JAMA Cardiology, led by Juyi Li, MD, reported on a case series of 1,178 patients hospitalized with COVID-19 at the Central Hospital of Wuhan, Hubei, China, between Jan. 15 and March 15, 2020.
Patients were a median age of 55 years, and 46% were men. They had an overall in-hospital mortality rate of 11%.
Of the 1,178 patients, 362 (30.7%) had a diagnosis of hypertension. These patients were older (median age, 66 years) and had a greater prevalence of chronic diseases. Patients with hypertension also had more severe manifestations of COVID-19 compared to those without hypertension, including higher rates of acute respiratory distress syndrome and in-hospital mortality (21.3% vs. 6.5%).
Of the 362 patients with hypertension, 31.8% were taking ACE inhibitors or ARBs.
Apart from a greater prevalence of coronary artery disease, patients taking ACE inhibitors or ARBs had similar comorbidities to those not taking these medications, and also similar laboratory profile results including blood counts, inflammatory markers, renal and liver function tests, and cardiac biomarkers, although those taking ACE inhibitors/ARBs had higher levels of alkaline phosphatase.
The most commonly used antihypertensive drugs were calcium blockers. The percentage of patients with hypertension taking any drug or drug combination did not differ between those with severe and nonsevere infections and between those who survived and those who died.
Specifically regarding ACE inhibitors/ARBs, there was no difference between those with severe versus nonsevere illness in the use of ACE inhibitors (9.2% vs. 10.1%; P = .80), ARBs (24.9% vs. 21.2%; P = .40), or the composite of ACE inhibitors or ARBs (32.9% vs. 30.7%; P = .65).
Similarly, there were no differences in nonsurvivors and survivors in the use of ACE inhibitors (9.1% vs. 9.8%; P = .85); ARBs (19.5% vs. 23.9%; P = .42), or the composite of ACE inhibitors or ARBs (27.3% vs. 33.0%; P = .34).
The frequency of severe illness and death also did not differ between those treated with and without ACE inhibitors/ARBs in patients with hypertension and other various chronic conditions including coronary heart disease, cerebrovascular disease, diabetes, neurological disease, and chronic renal disease.
The authors noted that these data confirm previous reports showing that patients with hypertension have more severe illness and higher mortality rates associated with COVID-19 than those without hypertension.
But they added: “Our data provide some reassurance that ACE inhibitors/ARBs are not associated with the progression or outcome of COVID-19 hospitalizations in patients with hypertension.”
They also noted that these results support the recommendations from almost all major cardiovascular societies that patients do not discontinue ACE inhibitors or ARBs because of worries about COVID-19.
However, the authors did point out some limitations of their study, which included a small number of patients with hypertension taking ACE inhibitors or ARBs and the fact that a nonsevere disease course was still severe enough to require hospitalization. In addition, it was not clear whether ACE inhibitor/ARB treatment at baseline was maintained throughout hospitalization for all patients.
This was also an observational comparison and may be biased by differences in patients taking versus not taking ACE inhibitors or ARBs at the time of hospitalization, although the measured baseline characteristics were similar in both groups.
But the authors also highlighted the finding that, in this cohort, patients with hypertension had three times the mortality rate of all other patients hospitalized with COVID-19.
“Hypertension combined with cardiovascular and cerebrovascular disease, diabetes, and chronic kidney disease would predispose patients to an increased risk of severity and mortality of COVID-19. Therefore, patients with these underlying conditions who develop COVID-19 require particularly intensive surveillance and care,” they wrote.
Experts cautiously optimistic
Some cardiovascular experts were cautiously optimistic about these latest results.
Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, and editor-in-chief of the Journal of Clinical Hypertension, said: “This new report from Wuhan, China, gives modest reassurance that the use of ACE inhibitors or ARBs in hypertensive patients with COVID-19 disease does not increase the risk of clinical deterioration or death.
“Ongoing, more definitive studies should help resolve competing hypotheses regarding the effects of these agents: whether the increased ACE2 enzyme levels they produce can worsen outcomes by increasing access of the COVID virus to lung tissue; or whether there is a benefit linked to a protective effect of increased ACE2 on alveolar cell function,” Dr. Weber noted.
“Though the number of patients included in this new report is small, it is startling that hypertensive patients were three times as likely as nonhypertensives to have a fatal outcome, presumably reflecting vulnerability due to the cardiovascular and metabolic comorbidities associated with hypertension,” he added.
“In any case, for now, clinicians should continue treating hypertensive patients with whichever drugs, including ACE inhibitors and ARBs, best provide protection from adverse outcomes,” Dr. Weber concluded.
John McMurray, MD, professor of medical cardiology, University of Glasgow, Scotland, commented: “This study from Wuhan provides some reassurance about one of the two questions about ACEI/ARBs: Do these drugs increase susceptibility to infection? And if [the patient is] infected, do they increase the severity of infection? This study addresses the latter question and appears to suggest no increased severity.”
However, Dr. McMurray pointed out that the study had many limitations. There were only small patient numbers and the data were unadjusted, “although it looks like the ACE inhibitor/ARB treated patients were higher risk to start with.” It was an observational study, and patients were not randomized and were predominantly treated with ARBs, and not ACE inhibitors, so “we don’t know if the concerns apply equally to these two classes of drug.
“Other data published and unpublished supporting this (even showing better outcomes in patients treated with an ACE inhibitor/ARB), and, to date, any concerns about these drugs remain unsubstantiated and the guidance from medical societies to continue treatment with these agents in patients prescribed them seems wise,” Dr. McMurray added.
Franz H. Messerli, MD, professor of medicine at the University of Bern, Switzerland, commented: “The study from Wuhan is not a great study. They didn’t even do a multivariable analysis. They could have done a bit more with the data, but it still gives some reassurance.”
Dr. Messerli said it was “interesting” that 30% of the patients hospitalized with COVID-19 in the sample had hypertension. “That corresponds to the general population, so does not suggest that having hypertension increases susceptibility to infection – but it does seem to increase the risk of a bad outcome.”
Dr. Messerli noted that there are two more similar studies due to be published soon, both said to suggest either a beneficial or neutral effect of ACE inhibitors/ARBs on COVID-19 outcomes in hospitalized patients.
“This does help with confidence in prescribing these agents and reinforces the recommendations for patients to stay on these drugs,” he said.
“However, none of these studies address the infectivity issue – whether their use upregulates the ACE2 receptor, which the virus uses to gain entry to cells, thereby increasing susceptibility to the infection,” Dr. Messerli cautioned. “But the similar or better outcomes on these drugs are encouraging,” he added.
The Wuhan study was supported by the Health and Family Planning Commission of Wuhan City, China. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Initial data from one Chinese center on the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in patients hospitalized with COVID-19 appear to give some further reassurance about continued use of these drugs.
The report from one hospital in Wuhan found that among patients with hypertension hospitalized with the COVID-19 virus, there was no difference in disease severity or death rate in patients taking ACE inhibitors or ARBs and those not taking such medications.
The data were published online April 23 in JAMA Cardiology.
The study adds to another recent report in a larger number of COVID-19 patients from nine Chinese hospitals that suggested a beneficial effect of ACE inhibitors or ARBs on mortality.
Additional studies
Two other similar studies have also been recently released. Another study from China, published online March 31 in Emerging Microbes & Infections, included a small sample of 42 hospitalized patients with COVID-19 on antihypertensive therapy. Those on ACE inhibitor/ARB therapy had a lower rate of severe disease and a trend toward a lower level of IL-6 in peripheral blood. In addition, patients on ACE inhibitor/ARB therapy had increased CD3+ and CD8+ T-cell counts in peripheral blood and decreased peak viral load compared with other antihypertensive drugs.
And a preliminary study from the UK, which has not yet been peer reviewed, found that treatment with ACE inhibitors was associated with a reduced risk of rapidly deteriorating severe COVID-19 disease.
The study, available online on MedRxiv, a preprint server for health sciences, reports on 205 acute inpatients with COVID-19 at King’s College Hospital and Princess Royal University Hospital, London.
Of these, 51.2% had hypertension, 30.2% had diabetes, and 14.6% had ischemic heart disease or heart failure. Of the 37 patients on ACE inhibitors, five (14%) died or required critical care support compared with 29% (48/168) of patients not taking an ACE inhibitor.
New Wuhan study
The authors of the new article published in JAMA Cardiology, led by Juyi Li, MD, reported on a case series of 1,178 patients hospitalized with COVID-19 at the Central Hospital of Wuhan, Hubei, China, between Jan. 15 and March 15, 2020.
Patients were a median age of 55 years, and 46% were men. They had an overall in-hospital mortality rate of 11%.
Of the 1,178 patients, 362 (30.7%) had a diagnosis of hypertension. These patients were older (median age, 66 years) and had a greater prevalence of chronic diseases. Patients with hypertension also had more severe manifestations of COVID-19 compared to those without hypertension, including higher rates of acute respiratory distress syndrome and in-hospital mortality (21.3% vs. 6.5%).
Of the 362 patients with hypertension, 31.8% were taking ACE inhibitors or ARBs.
Apart from a greater prevalence of coronary artery disease, patients taking ACE inhibitors or ARBs had similar comorbidities to those not taking these medications, and also similar laboratory profile results including blood counts, inflammatory markers, renal and liver function tests, and cardiac biomarkers, although those taking ACE inhibitors/ARBs had higher levels of alkaline phosphatase.
The most commonly used antihypertensive drugs were calcium blockers. The percentage of patients with hypertension taking any drug or drug combination did not differ between those with severe and nonsevere infections and between those who survived and those who died.
Specifically regarding ACE inhibitors/ARBs, there was no difference between those with severe versus nonsevere illness in the use of ACE inhibitors (9.2% vs. 10.1%; P = .80), ARBs (24.9% vs. 21.2%; P = .40), or the composite of ACE inhibitors or ARBs (32.9% vs. 30.7%; P = .65).
Similarly, there were no differences in nonsurvivors and survivors in the use of ACE inhibitors (9.1% vs. 9.8%; P = .85); ARBs (19.5% vs. 23.9%; P = .42), or the composite of ACE inhibitors or ARBs (27.3% vs. 33.0%; P = .34).
The frequency of severe illness and death also did not differ between those treated with and without ACE inhibitors/ARBs in patients with hypertension and other various chronic conditions including coronary heart disease, cerebrovascular disease, diabetes, neurological disease, and chronic renal disease.
The authors noted that these data confirm previous reports showing that patients with hypertension have more severe illness and higher mortality rates associated with COVID-19 than those without hypertension.
But they added: “Our data provide some reassurance that ACE inhibitors/ARBs are not associated with the progression or outcome of COVID-19 hospitalizations in patients with hypertension.”
They also noted that these results support the recommendations from almost all major cardiovascular societies that patients do not discontinue ACE inhibitors or ARBs because of worries about COVID-19.
However, the authors did point out some limitations of their study, which included a small number of patients with hypertension taking ACE inhibitors or ARBs and the fact that a nonsevere disease course was still severe enough to require hospitalization. In addition, it was not clear whether ACE inhibitor/ARB treatment at baseline was maintained throughout hospitalization for all patients.
This was also an observational comparison and may be biased by differences in patients taking versus not taking ACE inhibitors or ARBs at the time of hospitalization, although the measured baseline characteristics were similar in both groups.
But the authors also highlighted the finding that, in this cohort, patients with hypertension had three times the mortality rate of all other patients hospitalized with COVID-19.
“Hypertension combined with cardiovascular and cerebrovascular disease, diabetes, and chronic kidney disease would predispose patients to an increased risk of severity and mortality of COVID-19. Therefore, patients with these underlying conditions who develop COVID-19 require particularly intensive surveillance and care,” they wrote.
Experts cautiously optimistic
Some cardiovascular experts were cautiously optimistic about these latest results.
Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, and editor-in-chief of the Journal of Clinical Hypertension, said: “This new report from Wuhan, China, gives modest reassurance that the use of ACE inhibitors or ARBs in hypertensive patients with COVID-19 disease does not increase the risk of clinical deterioration or death.
“Ongoing, more definitive studies should help resolve competing hypotheses regarding the effects of these agents: whether the increased ACE2 enzyme levels they produce can worsen outcomes by increasing access of the COVID virus to lung tissue; or whether there is a benefit linked to a protective effect of increased ACE2 on alveolar cell function,” Dr. Weber noted.
“Though the number of patients included in this new report is small, it is startling that hypertensive patients were three times as likely as nonhypertensives to have a fatal outcome, presumably reflecting vulnerability due to the cardiovascular and metabolic comorbidities associated with hypertension,” he added.
“In any case, for now, clinicians should continue treating hypertensive patients with whichever drugs, including ACE inhibitors and ARBs, best provide protection from adverse outcomes,” Dr. Weber concluded.
John McMurray, MD, professor of medical cardiology, University of Glasgow, Scotland, commented: “This study from Wuhan provides some reassurance about one of the two questions about ACEI/ARBs: Do these drugs increase susceptibility to infection? And if [the patient is] infected, do they increase the severity of infection? This study addresses the latter question and appears to suggest no increased severity.”
However, Dr. McMurray pointed out that the study had many limitations. There were only small patient numbers and the data were unadjusted, “although it looks like the ACE inhibitor/ARB treated patients were higher risk to start with.” It was an observational study, and patients were not randomized and were predominantly treated with ARBs, and not ACE inhibitors, so “we don’t know if the concerns apply equally to these two classes of drug.
“Other data published and unpublished supporting this (even showing better outcomes in patients treated with an ACE inhibitor/ARB), and, to date, any concerns about these drugs remain unsubstantiated and the guidance from medical societies to continue treatment with these agents in patients prescribed them seems wise,” Dr. McMurray added.
Franz H. Messerli, MD, professor of medicine at the University of Bern, Switzerland, commented: “The study from Wuhan is not a great study. They didn’t even do a multivariable analysis. They could have done a bit more with the data, but it still gives some reassurance.”
Dr. Messerli said it was “interesting” that 30% of the patients hospitalized with COVID-19 in the sample had hypertension. “That corresponds to the general population, so does not suggest that having hypertension increases susceptibility to infection – but it does seem to increase the risk of a bad outcome.”
Dr. Messerli noted that there are two more similar studies due to be published soon, both said to suggest either a beneficial or neutral effect of ACE inhibitors/ARBs on COVID-19 outcomes in hospitalized patients.
“This does help with confidence in prescribing these agents and reinforces the recommendations for patients to stay on these drugs,” he said.
“However, none of these studies address the infectivity issue – whether their use upregulates the ACE2 receptor, which the virus uses to gain entry to cells, thereby increasing susceptibility to the infection,” Dr. Messerli cautioned. “But the similar or better outcomes on these drugs are encouraging,” he added.
The Wuhan study was supported by the Health and Family Planning Commission of Wuhan City, China. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Initial data from one Chinese center on the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in patients hospitalized with COVID-19 appear to give some further reassurance about continued use of these drugs.
The report from one hospital in Wuhan found that among patients with hypertension hospitalized with the COVID-19 virus, there was no difference in disease severity or death rate in patients taking ACE inhibitors or ARBs and those not taking such medications.
The data were published online April 23 in JAMA Cardiology.
The study adds to another recent report in a larger number of COVID-19 patients from nine Chinese hospitals that suggested a beneficial effect of ACE inhibitors or ARBs on mortality.
Additional studies
Two other similar studies have also been recently released. Another study from China, published online March 31 in Emerging Microbes & Infections, included a small sample of 42 hospitalized patients with COVID-19 on antihypertensive therapy. Those on ACE inhibitor/ARB therapy had a lower rate of severe disease and a trend toward a lower level of IL-6 in peripheral blood. In addition, patients on ACE inhibitor/ARB therapy had increased CD3+ and CD8+ T-cell counts in peripheral blood and decreased peak viral load compared with other antihypertensive drugs.
And a preliminary study from the UK, which has not yet been peer reviewed, found that treatment with ACE inhibitors was associated with a reduced risk of rapidly deteriorating severe COVID-19 disease.
The study, available online on MedRxiv, a preprint server for health sciences, reports on 205 acute inpatients with COVID-19 at King’s College Hospital and Princess Royal University Hospital, London.
Of these, 51.2% had hypertension, 30.2% had diabetes, and 14.6% had ischemic heart disease or heart failure. Of the 37 patients on ACE inhibitors, five (14%) died or required critical care support compared with 29% (48/168) of patients not taking an ACE inhibitor.
New Wuhan study
The authors of the new article published in JAMA Cardiology, led by Juyi Li, MD, reported on a case series of 1,178 patients hospitalized with COVID-19 at the Central Hospital of Wuhan, Hubei, China, between Jan. 15 and March 15, 2020.
Patients were a median age of 55 years, and 46% were men. They had an overall in-hospital mortality rate of 11%.
Of the 1,178 patients, 362 (30.7%) had a diagnosis of hypertension. These patients were older (median age, 66 years) and had a greater prevalence of chronic diseases. Patients with hypertension also had more severe manifestations of COVID-19 compared to those without hypertension, including higher rates of acute respiratory distress syndrome and in-hospital mortality (21.3% vs. 6.5%).
Of the 362 patients with hypertension, 31.8% were taking ACE inhibitors or ARBs.
Apart from a greater prevalence of coronary artery disease, patients taking ACE inhibitors or ARBs had similar comorbidities to those not taking these medications, and also similar laboratory profile results including blood counts, inflammatory markers, renal and liver function tests, and cardiac biomarkers, although those taking ACE inhibitors/ARBs had higher levels of alkaline phosphatase.
The most commonly used antihypertensive drugs were calcium blockers. The percentage of patients with hypertension taking any drug or drug combination did not differ between those with severe and nonsevere infections and between those who survived and those who died.
Specifically regarding ACE inhibitors/ARBs, there was no difference between those with severe versus nonsevere illness in the use of ACE inhibitors (9.2% vs. 10.1%; P = .80), ARBs (24.9% vs. 21.2%; P = .40), or the composite of ACE inhibitors or ARBs (32.9% vs. 30.7%; P = .65).
Similarly, there were no differences in nonsurvivors and survivors in the use of ACE inhibitors (9.1% vs. 9.8%; P = .85); ARBs (19.5% vs. 23.9%; P = .42), or the composite of ACE inhibitors or ARBs (27.3% vs. 33.0%; P = .34).
The frequency of severe illness and death also did not differ between those treated with and without ACE inhibitors/ARBs in patients with hypertension and other various chronic conditions including coronary heart disease, cerebrovascular disease, diabetes, neurological disease, and chronic renal disease.
The authors noted that these data confirm previous reports showing that patients with hypertension have more severe illness and higher mortality rates associated with COVID-19 than those without hypertension.
But they added: “Our data provide some reassurance that ACE inhibitors/ARBs are not associated with the progression or outcome of COVID-19 hospitalizations in patients with hypertension.”
They also noted that these results support the recommendations from almost all major cardiovascular societies that patients do not discontinue ACE inhibitors or ARBs because of worries about COVID-19.
However, the authors did point out some limitations of their study, which included a small number of patients with hypertension taking ACE inhibitors or ARBs and the fact that a nonsevere disease course was still severe enough to require hospitalization. In addition, it was not clear whether ACE inhibitor/ARB treatment at baseline was maintained throughout hospitalization for all patients.
This was also an observational comparison and may be biased by differences in patients taking versus not taking ACE inhibitors or ARBs at the time of hospitalization, although the measured baseline characteristics were similar in both groups.
But the authors also highlighted the finding that, in this cohort, patients with hypertension had three times the mortality rate of all other patients hospitalized with COVID-19.
“Hypertension combined with cardiovascular and cerebrovascular disease, diabetes, and chronic kidney disease would predispose patients to an increased risk of severity and mortality of COVID-19. Therefore, patients with these underlying conditions who develop COVID-19 require particularly intensive surveillance and care,” they wrote.
Experts cautiously optimistic
Some cardiovascular experts were cautiously optimistic about these latest results.
Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, and editor-in-chief of the Journal of Clinical Hypertension, said: “This new report from Wuhan, China, gives modest reassurance that the use of ACE inhibitors or ARBs in hypertensive patients with COVID-19 disease does not increase the risk of clinical deterioration or death.
“Ongoing, more definitive studies should help resolve competing hypotheses regarding the effects of these agents: whether the increased ACE2 enzyme levels they produce can worsen outcomes by increasing access of the COVID virus to lung tissue; or whether there is a benefit linked to a protective effect of increased ACE2 on alveolar cell function,” Dr. Weber noted.
“Though the number of patients included in this new report is small, it is startling that hypertensive patients were three times as likely as nonhypertensives to have a fatal outcome, presumably reflecting vulnerability due to the cardiovascular and metabolic comorbidities associated with hypertension,” he added.
“In any case, for now, clinicians should continue treating hypertensive patients with whichever drugs, including ACE inhibitors and ARBs, best provide protection from adverse outcomes,” Dr. Weber concluded.
John McMurray, MD, professor of medical cardiology, University of Glasgow, Scotland, commented: “This study from Wuhan provides some reassurance about one of the two questions about ACEI/ARBs: Do these drugs increase susceptibility to infection? And if [the patient is] infected, do they increase the severity of infection? This study addresses the latter question and appears to suggest no increased severity.”
However, Dr. McMurray pointed out that the study had many limitations. There were only small patient numbers and the data were unadjusted, “although it looks like the ACE inhibitor/ARB treated patients were higher risk to start with.” It was an observational study, and patients were not randomized and were predominantly treated with ARBs, and not ACE inhibitors, so “we don’t know if the concerns apply equally to these two classes of drug.
“Other data published and unpublished supporting this (even showing better outcomes in patients treated with an ACE inhibitor/ARB), and, to date, any concerns about these drugs remain unsubstantiated and the guidance from medical societies to continue treatment with these agents in patients prescribed them seems wise,” Dr. McMurray added.
Franz H. Messerli, MD, professor of medicine at the University of Bern, Switzerland, commented: “The study from Wuhan is not a great study. They didn’t even do a multivariable analysis. They could have done a bit more with the data, but it still gives some reassurance.”
Dr. Messerli said it was “interesting” that 30% of the patients hospitalized with COVID-19 in the sample had hypertension. “That corresponds to the general population, so does not suggest that having hypertension increases susceptibility to infection – but it does seem to increase the risk of a bad outcome.”
Dr. Messerli noted that there are two more similar studies due to be published soon, both said to suggest either a beneficial or neutral effect of ACE inhibitors/ARBs on COVID-19 outcomes in hospitalized patients.
“This does help with confidence in prescribing these agents and reinforces the recommendations for patients to stay on these drugs,” he said.
“However, none of these studies address the infectivity issue – whether their use upregulates the ACE2 receptor, which the virus uses to gain entry to cells, thereby increasing susceptibility to the infection,” Dr. Messerli cautioned. “But the similar or better outcomes on these drugs are encouraging,” he added.
The Wuhan study was supported by the Health and Family Planning Commission of Wuhan City, China. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AUGUSTUS: After ACS or PCI, aspirin gives AFib patients scant benefit
When patients with atrial fibrillation have an acute coronary syndrome event or undergo percutaneous coronary intervention, their window of opportunity for benefiting from a triple antithrombotic regimen was, at best, about 30 days, according to a post hoc analysis of AUGUSTUS, a multicenter, randomized trial with more than 4,600 patients.
Beyond 30 days out to 180 days, the incremental benefit from reduced ischemic events fell to essentially zero, giving it a clear back seat to the ongoing, increased bleeding risk from adding a third antithrombotic drug.
Patients randomized to receive aspirin in addition to an anticoagulant, either apixaban or a vitamin K antagonist such as warfarin, and a P2Y12 inhibitor such as clopidogrel “for up to approximately 30 days” had a roughly similar decrease in severe ischemic events and increase in severe bleeding events, suggesting that even acutely the overall impact of adding aspirin on top of the other two antithrombotics was a wash, John H. Alexander, MD, said in a presentation of research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
Using aspirin as a third antithrombotic in patients with atrial fibrillation (AFib) who have also recently had either an acute coronary syndrome event (ACS) or underwent percutaneous coronary intervention (PCI), “may be reasonable,” for selected patients, but is a decision that requires careful individualization, cautioned Dr. Alexander, professor of medicine and director of Cardiovascular Research at the Duke Clinical Research Institute of Duke University, Durham, N.C.
“This is a superb secondary analysis looking at the time course of potential benefit and harm with aspirin, and they found that aspirin was beneficial only in the first 30 days. After 30 days, it’s startling and remarkable that the ischemic event curves were completely on top of each other,” commented Julia H. Indik, MD, a cardiac electrophysiologist at Banner–University Medical Center Tuscon and designated discussant for the report. “This substudy will be essential for updating the guidelines,” she predicted. “When a treatment’s benefit equals its risks,” which happened when aspirin was part of the regimen during the first 30 days, “then it’s not even a class IIb recommendation; it’s class III,” the classification used by the ACC and collaborating groups to identify treatments where net benefit and net risk are similar and hence the treatment is considered not recommended.
A key element in the analysis Dr. Alexander presented was to define a spectrum of clinical events as representing broad, intermediate, or severe ischemic or bleeding events. The severe category for bleeding events included fatal, intracranial, and any bleed rated as major by the International Society on Thrombosis and Haemostasis (ISTH) criteria, while the broad bleeding definition included all of these plus bleeds that directly resulted in hospitalization and clinically relevant nonmajor bleeds. For ischemic events, the severe group consisted of cardiovascular death, MI, stent thrombosis, and ischemic stroke, while the broad category also tallied urgent revascularizations and cardiovascular hospitalizations.
“I believe the severe bleeds and severe ischemic events we identified are roughly equal in severity,” Dr. Alexander noted. “Where I think we need more analysis is which patients have more bleeding risk and which have more ischemia risk. We need a more tailored approach to identify patient subgroups, perhaps based on angiographic characteristics, or something else,” that modifies the trade-off that, on a population level, seems very evenly balanced.
Applying this approach to scoring the severity of adverse outcomes, Dr. Alexander reported that, during the first 30 days on treatment, patients on aspirin had a net absolute gain of 1.0% in severe bleeding events, compared with placebo, and a 3.4% gain in broad bleeds, while showing a 0.9% drop in severe ischemic events but no between-group difference in the rate of broadly defined ischemic events. During days 31-180, the addition of aspirin resulted in virtually no reductions in ischemic events regardless of whether they were severe, intermediate, or broad, but adding aspirin continued to produce an excess of bleeding episodes in all three categories. The results also appeared in an article published online (Circulation. 2020 Mar 29. doi: 10.1161/CIRCULATIONAHA.120.046534).
“We did not see a time window when the ischemia risk was greater than the bleeding risk,” Dr. Alexander noted, and he also highlighted that the one option the analysis could not explore is never giving these patients any aspirin. “Patients received aspirin for some number of days before randomization,” a median of 6 days from the time of their ACS or PCI event until randomization, “so we don’t have great insight into whether no aspirin” is an reasonable option.
The AUGUSTUS trial randomized 4,614 patients with AFib and a recent ACS or PCI event at any of 492 sites in 33 countries during 2015-2018. The study’s primary endpoint was the rate of major or clinically relevant nonmajor bleeding by the ISTH criteria during 6 months on treatment, while composites of death or hospitalization, and death plus ischemic events served as secondary outcomes. All patients received an antiplatelet P2Y12 inhibitor, with 93% of patients receiving clopidogrel, and were randomized in a 2 x 2 factorial design to one of four regimens: either apixaban or a vitamin K antagonist (such as warfarin), and to aspirin or placebo. The study’s primary findings showed that using apixaban instead of a vitamin K antagonist significantly reduced bleeding events as well as the rate of death or hospitalization, but the rate of death and ischemic events was similar in the two arms. The primary AUGUSTUS finding for the aspirin versus placebo randomization was that overall throughout the study ischemic events were balanced in the these two treatment arms while aspirin boosted bleeding (N Engl J Med. 2019 Apr 18;380[16]:1509-24).
AUGUSTUS was sponsored by Bristol-Myers Squibb and Pfizer, the companies that market apixaban. Dr. Alexander has been a consultant to and received research funding from Bristol-Myers Squibb and Pfizer; has been a consultant to AbbVie, Bayer, CryoLife, CSL Behring, Novo Nordisk, Portola, Quantum Genomics, XaTek, and Zafgen; and has received research funding from Boehringer Ingelheim, CryoLife, CSL Behring, GlaxoSmithKline, and XaTek. Dr. Indik had no disclosures.
SOURCE: Alexander JH et al. ACC 2020, Abstract 409-08.
When patients with atrial fibrillation have an acute coronary syndrome event or undergo percutaneous coronary intervention, their window of opportunity for benefiting from a triple antithrombotic regimen was, at best, about 30 days, according to a post hoc analysis of AUGUSTUS, a multicenter, randomized trial with more than 4,600 patients.
Beyond 30 days out to 180 days, the incremental benefit from reduced ischemic events fell to essentially zero, giving it a clear back seat to the ongoing, increased bleeding risk from adding a third antithrombotic drug.
Patients randomized to receive aspirin in addition to an anticoagulant, either apixaban or a vitamin K antagonist such as warfarin, and a P2Y12 inhibitor such as clopidogrel “for up to approximately 30 days” had a roughly similar decrease in severe ischemic events and increase in severe bleeding events, suggesting that even acutely the overall impact of adding aspirin on top of the other two antithrombotics was a wash, John H. Alexander, MD, said in a presentation of research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
Using aspirin as a third antithrombotic in patients with atrial fibrillation (AFib) who have also recently had either an acute coronary syndrome event (ACS) or underwent percutaneous coronary intervention (PCI), “may be reasonable,” for selected patients, but is a decision that requires careful individualization, cautioned Dr. Alexander, professor of medicine and director of Cardiovascular Research at the Duke Clinical Research Institute of Duke University, Durham, N.C.
“This is a superb secondary analysis looking at the time course of potential benefit and harm with aspirin, and they found that aspirin was beneficial only in the first 30 days. After 30 days, it’s startling and remarkable that the ischemic event curves were completely on top of each other,” commented Julia H. Indik, MD, a cardiac electrophysiologist at Banner–University Medical Center Tuscon and designated discussant for the report. “This substudy will be essential for updating the guidelines,” she predicted. “When a treatment’s benefit equals its risks,” which happened when aspirin was part of the regimen during the first 30 days, “then it’s not even a class IIb recommendation; it’s class III,” the classification used by the ACC and collaborating groups to identify treatments where net benefit and net risk are similar and hence the treatment is considered not recommended.
A key element in the analysis Dr. Alexander presented was to define a spectrum of clinical events as representing broad, intermediate, or severe ischemic or bleeding events. The severe category for bleeding events included fatal, intracranial, and any bleed rated as major by the International Society on Thrombosis and Haemostasis (ISTH) criteria, while the broad bleeding definition included all of these plus bleeds that directly resulted in hospitalization and clinically relevant nonmajor bleeds. For ischemic events, the severe group consisted of cardiovascular death, MI, stent thrombosis, and ischemic stroke, while the broad category also tallied urgent revascularizations and cardiovascular hospitalizations.
“I believe the severe bleeds and severe ischemic events we identified are roughly equal in severity,” Dr. Alexander noted. “Where I think we need more analysis is which patients have more bleeding risk and which have more ischemia risk. We need a more tailored approach to identify patient subgroups, perhaps based on angiographic characteristics, or something else,” that modifies the trade-off that, on a population level, seems very evenly balanced.
Applying this approach to scoring the severity of adverse outcomes, Dr. Alexander reported that, during the first 30 days on treatment, patients on aspirin had a net absolute gain of 1.0% in severe bleeding events, compared with placebo, and a 3.4% gain in broad bleeds, while showing a 0.9% drop in severe ischemic events but no between-group difference in the rate of broadly defined ischemic events. During days 31-180, the addition of aspirin resulted in virtually no reductions in ischemic events regardless of whether they were severe, intermediate, or broad, but adding aspirin continued to produce an excess of bleeding episodes in all three categories. The results also appeared in an article published online (Circulation. 2020 Mar 29. doi: 10.1161/CIRCULATIONAHA.120.046534).
“We did not see a time window when the ischemia risk was greater than the bleeding risk,” Dr. Alexander noted, and he also highlighted that the one option the analysis could not explore is never giving these patients any aspirin. “Patients received aspirin for some number of days before randomization,” a median of 6 days from the time of their ACS or PCI event until randomization, “so we don’t have great insight into whether no aspirin” is an reasonable option.
The AUGUSTUS trial randomized 4,614 patients with AFib and a recent ACS or PCI event at any of 492 sites in 33 countries during 2015-2018. The study’s primary endpoint was the rate of major or clinically relevant nonmajor bleeding by the ISTH criteria during 6 months on treatment, while composites of death or hospitalization, and death plus ischemic events served as secondary outcomes. All patients received an antiplatelet P2Y12 inhibitor, with 93% of patients receiving clopidogrel, and were randomized in a 2 x 2 factorial design to one of four regimens: either apixaban or a vitamin K antagonist (such as warfarin), and to aspirin or placebo. The study’s primary findings showed that using apixaban instead of a vitamin K antagonist significantly reduced bleeding events as well as the rate of death or hospitalization, but the rate of death and ischemic events was similar in the two arms. The primary AUGUSTUS finding for the aspirin versus placebo randomization was that overall throughout the study ischemic events were balanced in the these two treatment arms while aspirin boosted bleeding (N Engl J Med. 2019 Apr 18;380[16]:1509-24).
AUGUSTUS was sponsored by Bristol-Myers Squibb and Pfizer, the companies that market apixaban. Dr. Alexander has been a consultant to and received research funding from Bristol-Myers Squibb and Pfizer; has been a consultant to AbbVie, Bayer, CryoLife, CSL Behring, Novo Nordisk, Portola, Quantum Genomics, XaTek, and Zafgen; and has received research funding from Boehringer Ingelheim, CryoLife, CSL Behring, GlaxoSmithKline, and XaTek. Dr. Indik had no disclosures.
SOURCE: Alexander JH et al. ACC 2020, Abstract 409-08.
When patients with atrial fibrillation have an acute coronary syndrome event or undergo percutaneous coronary intervention, their window of opportunity for benefiting from a triple antithrombotic regimen was, at best, about 30 days, according to a post hoc analysis of AUGUSTUS, a multicenter, randomized trial with more than 4,600 patients.
Beyond 30 days out to 180 days, the incremental benefit from reduced ischemic events fell to essentially zero, giving it a clear back seat to the ongoing, increased bleeding risk from adding a third antithrombotic drug.
Patients randomized to receive aspirin in addition to an anticoagulant, either apixaban or a vitamin K antagonist such as warfarin, and a P2Y12 inhibitor such as clopidogrel “for up to approximately 30 days” had a roughly similar decrease in severe ischemic events and increase in severe bleeding events, suggesting that even acutely the overall impact of adding aspirin on top of the other two antithrombotics was a wash, John H. Alexander, MD, said in a presentation of research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
Using aspirin as a third antithrombotic in patients with atrial fibrillation (AFib) who have also recently had either an acute coronary syndrome event (ACS) or underwent percutaneous coronary intervention (PCI), “may be reasonable,” for selected patients, but is a decision that requires careful individualization, cautioned Dr. Alexander, professor of medicine and director of Cardiovascular Research at the Duke Clinical Research Institute of Duke University, Durham, N.C.
“This is a superb secondary analysis looking at the time course of potential benefit and harm with aspirin, and they found that aspirin was beneficial only in the first 30 days. After 30 days, it’s startling and remarkable that the ischemic event curves were completely on top of each other,” commented Julia H. Indik, MD, a cardiac electrophysiologist at Banner–University Medical Center Tuscon and designated discussant for the report. “This substudy will be essential for updating the guidelines,” she predicted. “When a treatment’s benefit equals its risks,” which happened when aspirin was part of the regimen during the first 30 days, “then it’s not even a class IIb recommendation; it’s class III,” the classification used by the ACC and collaborating groups to identify treatments where net benefit and net risk are similar and hence the treatment is considered not recommended.
A key element in the analysis Dr. Alexander presented was to define a spectrum of clinical events as representing broad, intermediate, or severe ischemic or bleeding events. The severe category for bleeding events included fatal, intracranial, and any bleed rated as major by the International Society on Thrombosis and Haemostasis (ISTH) criteria, while the broad bleeding definition included all of these plus bleeds that directly resulted in hospitalization and clinically relevant nonmajor bleeds. For ischemic events, the severe group consisted of cardiovascular death, MI, stent thrombosis, and ischemic stroke, while the broad category also tallied urgent revascularizations and cardiovascular hospitalizations.
“I believe the severe bleeds and severe ischemic events we identified are roughly equal in severity,” Dr. Alexander noted. “Where I think we need more analysis is which patients have more bleeding risk and which have more ischemia risk. We need a more tailored approach to identify patient subgroups, perhaps based on angiographic characteristics, or something else,” that modifies the trade-off that, on a population level, seems very evenly balanced.
Applying this approach to scoring the severity of adverse outcomes, Dr. Alexander reported that, during the first 30 days on treatment, patients on aspirin had a net absolute gain of 1.0% in severe bleeding events, compared with placebo, and a 3.4% gain in broad bleeds, while showing a 0.9% drop in severe ischemic events but no between-group difference in the rate of broadly defined ischemic events. During days 31-180, the addition of aspirin resulted in virtually no reductions in ischemic events regardless of whether they were severe, intermediate, or broad, but adding aspirin continued to produce an excess of bleeding episodes in all three categories. The results also appeared in an article published online (Circulation. 2020 Mar 29. doi: 10.1161/CIRCULATIONAHA.120.046534).
“We did not see a time window when the ischemia risk was greater than the bleeding risk,” Dr. Alexander noted, and he also highlighted that the one option the analysis could not explore is never giving these patients any aspirin. “Patients received aspirin for some number of days before randomization,” a median of 6 days from the time of their ACS or PCI event until randomization, “so we don’t have great insight into whether no aspirin” is an reasonable option.
The AUGUSTUS trial randomized 4,614 patients with AFib and a recent ACS or PCI event at any of 492 sites in 33 countries during 2015-2018. The study’s primary endpoint was the rate of major or clinically relevant nonmajor bleeding by the ISTH criteria during 6 months on treatment, while composites of death or hospitalization, and death plus ischemic events served as secondary outcomes. All patients received an antiplatelet P2Y12 inhibitor, with 93% of patients receiving clopidogrel, and were randomized in a 2 x 2 factorial design to one of four regimens: either apixaban or a vitamin K antagonist (such as warfarin), and to aspirin or placebo. The study’s primary findings showed that using apixaban instead of a vitamin K antagonist significantly reduced bleeding events as well as the rate of death or hospitalization, but the rate of death and ischemic events was similar in the two arms. The primary AUGUSTUS finding for the aspirin versus placebo randomization was that overall throughout the study ischemic events were balanced in the these two treatment arms while aspirin boosted bleeding (N Engl J Med. 2019 Apr 18;380[16]:1509-24).
AUGUSTUS was sponsored by Bristol-Myers Squibb and Pfizer, the companies that market apixaban. Dr. Alexander has been a consultant to and received research funding from Bristol-Myers Squibb and Pfizer; has been a consultant to AbbVie, Bayer, CryoLife, CSL Behring, Novo Nordisk, Portola, Quantum Genomics, XaTek, and Zafgen; and has received research funding from Boehringer Ingelheim, CryoLife, CSL Behring, GlaxoSmithKline, and XaTek. Dr. Indik had no disclosures.
SOURCE: Alexander JH et al. ACC 2020, Abstract 409-08.
FROM ACC 2020