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COVID can mimic prostate cancer symptoms
This patient has a strong likelihood of aggressive prostate cancer, right? If that same patient also presents with severe, burning bone pain with no precipitating trauma to the area and rest and over-the-counter painkillers are not helping, you’d think, “check for metastases,” right?
That patient was me in late January 2023.
As a research scientist member of the American Urological Association, I knew enough to know I had to consult my urologist ASAP.
With the above symptoms, I’ll admit I was scared. Fortunately, if that’s the right word, I was no stranger to a rapid, dramatic spike in PSA. In 2021 I was temporarily living in a new city, and I wanted to form a relationship with a good local urologist. The urologist that I was referred to gave me a thorough consultation, including a vigorous digital rectal exam (DRE) and sent me across the street for a blood draw.
To my shock, my PSA had spiked over 2 points, to 9.9 from 7.8 a few months earlier. I freaked. Had my 3-cm tumor burst out into an aggressive cancer? Research on PubMed provided an array of studies showing what could cause PSA to suddenly rise, including a DRE performed 72 hours before the blood draw.1 A week later, my PSA was back down to its normal 7.6.
But in January 2023, I had none of those previously reported experiences that could suddenly trigger a spike in PSA, like a DRE or riding on a thin bicycle seat for a few hours before the lab visit.
The COVID effect
I went back to PubMed and found a new circumstance that could cause a surge in PSA: COVID-19. A recent study2 of 91 men with benign prostatic hypertrophy by researchers in Turkey found that PSA spiked from 0 to 5 points during the COVID infection period and up to 2 points higher 3 months after the infection had cleared. I had tested positive for COVID-19 in mid-December 2022, 4 weeks before my 9.9 PSA reading.
Using Google translate, I communicated with the team in Turkey and found out that the PSA spike can last up to 6 months.
That study helps explain why my PSA dropped over 1.5 points to 8.5 just 2 weeks after the 9.9 reading, with the expectation that it would return to its previous normal of 7.8 within 6 months of infection with SARS-CoV-2. To be safe, my urologist scheduled another PSA test in May, along with an updated multiparametric MRI, which may be followed by an in-bore MRI-guided biopsy of the 3-cm tumor if the mass has enlarged.
COVID-19 pain
What about my burning bone pain in my upper right humerus and right rotator cuff that was not precipitated by trauma or strain? A radiograph found no evidence of metastasis, thank goodness. And my research showed that several studies3 have found that COVID-19 can cause burning musculoskeletal pain, including enthesopathy, which is what I had per the radiology report. So my PSA spike and searing pain were likely consequences of the infection.
To avoid the risk for a gross misdiagnosis after a radical spike in PSA, the informed urologist should ask the patient if he has had COVID-19 in the previous 6 months. Overlooking that question could lead to the wrong diagnostic decisions about a rapid jump in PSA or unexplained bone pain.
References
1. Bossens MM et al. Eur J Cancer. 1995;31A:682-5.
2. Cinislioglu AE et al. Urology. 2022;159:16-21.
3. Ciaffi J et al. Joint Bone Spine. 2021;88:105158.
Dr. Keller is founder of the Keller Research Institute, Jacksonville, Fla. He reported serving as a research scientist for the American Urological Association, serving on the advisory board of Active Surveillance Patient’s International, and serving on the boards of numerous nonprofit organizations.
A version of this article first appeared on Medscape.com.
This patient has a strong likelihood of aggressive prostate cancer, right? If that same patient also presents with severe, burning bone pain with no precipitating trauma to the area and rest and over-the-counter painkillers are not helping, you’d think, “check for metastases,” right?
That patient was me in late January 2023.
As a research scientist member of the American Urological Association, I knew enough to know I had to consult my urologist ASAP.
With the above symptoms, I’ll admit I was scared. Fortunately, if that’s the right word, I was no stranger to a rapid, dramatic spike in PSA. In 2021 I was temporarily living in a new city, and I wanted to form a relationship with a good local urologist. The urologist that I was referred to gave me a thorough consultation, including a vigorous digital rectal exam (DRE) and sent me across the street for a blood draw.
To my shock, my PSA had spiked over 2 points, to 9.9 from 7.8 a few months earlier. I freaked. Had my 3-cm tumor burst out into an aggressive cancer? Research on PubMed provided an array of studies showing what could cause PSA to suddenly rise, including a DRE performed 72 hours before the blood draw.1 A week later, my PSA was back down to its normal 7.6.
But in January 2023, I had none of those previously reported experiences that could suddenly trigger a spike in PSA, like a DRE or riding on a thin bicycle seat for a few hours before the lab visit.
The COVID effect
I went back to PubMed and found a new circumstance that could cause a surge in PSA: COVID-19. A recent study2 of 91 men with benign prostatic hypertrophy by researchers in Turkey found that PSA spiked from 0 to 5 points during the COVID infection period and up to 2 points higher 3 months after the infection had cleared. I had tested positive for COVID-19 in mid-December 2022, 4 weeks before my 9.9 PSA reading.
Using Google translate, I communicated with the team in Turkey and found out that the PSA spike can last up to 6 months.
That study helps explain why my PSA dropped over 1.5 points to 8.5 just 2 weeks after the 9.9 reading, with the expectation that it would return to its previous normal of 7.8 within 6 months of infection with SARS-CoV-2. To be safe, my urologist scheduled another PSA test in May, along with an updated multiparametric MRI, which may be followed by an in-bore MRI-guided biopsy of the 3-cm tumor if the mass has enlarged.
COVID-19 pain
What about my burning bone pain in my upper right humerus and right rotator cuff that was not precipitated by trauma or strain? A radiograph found no evidence of metastasis, thank goodness. And my research showed that several studies3 have found that COVID-19 can cause burning musculoskeletal pain, including enthesopathy, which is what I had per the radiology report. So my PSA spike and searing pain were likely consequences of the infection.
To avoid the risk for a gross misdiagnosis after a radical spike in PSA, the informed urologist should ask the patient if he has had COVID-19 in the previous 6 months. Overlooking that question could lead to the wrong diagnostic decisions about a rapid jump in PSA or unexplained bone pain.
References
1. Bossens MM et al. Eur J Cancer. 1995;31A:682-5.
2. Cinislioglu AE et al. Urology. 2022;159:16-21.
3. Ciaffi J et al. Joint Bone Spine. 2021;88:105158.
Dr. Keller is founder of the Keller Research Institute, Jacksonville, Fla. He reported serving as a research scientist for the American Urological Association, serving on the advisory board of Active Surveillance Patient’s International, and serving on the boards of numerous nonprofit organizations.
A version of this article first appeared on Medscape.com.
This patient has a strong likelihood of aggressive prostate cancer, right? If that same patient also presents with severe, burning bone pain with no precipitating trauma to the area and rest and over-the-counter painkillers are not helping, you’d think, “check for metastases,” right?
That patient was me in late January 2023.
As a research scientist member of the American Urological Association, I knew enough to know I had to consult my urologist ASAP.
With the above symptoms, I’ll admit I was scared. Fortunately, if that’s the right word, I was no stranger to a rapid, dramatic spike in PSA. In 2021 I was temporarily living in a new city, and I wanted to form a relationship with a good local urologist. The urologist that I was referred to gave me a thorough consultation, including a vigorous digital rectal exam (DRE) and sent me across the street for a blood draw.
To my shock, my PSA had spiked over 2 points, to 9.9 from 7.8 a few months earlier. I freaked. Had my 3-cm tumor burst out into an aggressive cancer? Research on PubMed provided an array of studies showing what could cause PSA to suddenly rise, including a DRE performed 72 hours before the blood draw.1 A week later, my PSA was back down to its normal 7.6.
But in January 2023, I had none of those previously reported experiences that could suddenly trigger a spike in PSA, like a DRE or riding on a thin bicycle seat for a few hours before the lab visit.
The COVID effect
I went back to PubMed and found a new circumstance that could cause a surge in PSA: COVID-19. A recent study2 of 91 men with benign prostatic hypertrophy by researchers in Turkey found that PSA spiked from 0 to 5 points during the COVID infection period and up to 2 points higher 3 months after the infection had cleared. I had tested positive for COVID-19 in mid-December 2022, 4 weeks before my 9.9 PSA reading.
Using Google translate, I communicated with the team in Turkey and found out that the PSA spike can last up to 6 months.
That study helps explain why my PSA dropped over 1.5 points to 8.5 just 2 weeks after the 9.9 reading, with the expectation that it would return to its previous normal of 7.8 within 6 months of infection with SARS-CoV-2. To be safe, my urologist scheduled another PSA test in May, along with an updated multiparametric MRI, which may be followed by an in-bore MRI-guided biopsy of the 3-cm tumor if the mass has enlarged.
COVID-19 pain
What about my burning bone pain in my upper right humerus and right rotator cuff that was not precipitated by trauma or strain? A radiograph found no evidence of metastasis, thank goodness. And my research showed that several studies3 have found that COVID-19 can cause burning musculoskeletal pain, including enthesopathy, which is what I had per the radiology report. So my PSA spike and searing pain were likely consequences of the infection.
To avoid the risk for a gross misdiagnosis after a radical spike in PSA, the informed urologist should ask the patient if he has had COVID-19 in the previous 6 months. Overlooking that question could lead to the wrong diagnostic decisions about a rapid jump in PSA or unexplained bone pain.
References
1. Bossens MM et al. Eur J Cancer. 1995;31A:682-5.
2. Cinislioglu AE et al. Urology. 2022;159:16-21.
3. Ciaffi J et al. Joint Bone Spine. 2021;88:105158.
Dr. Keller is founder of the Keller Research Institute, Jacksonville, Fla. He reported serving as a research scientist for the American Urological Association, serving on the advisory board of Active Surveillance Patient’s International, and serving on the boards of numerous nonprofit organizations.
A version of this article first appeared on Medscape.com.
COVID raises risk for long-term GI complications
, a large new study indicates.
The researchers estimate that, so far, SARS-CoV-2 infections have contributed to more than 6 million new cases of GI disorders in the United States and 42 million new cases worldwide.
The diagnoses more common among patients who’ve had COVID ranged from stomach upset to acute pancreatitis, say the researchers, led by Evan Xu, a data analyst at the Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System.
Signs and symptoms of GI problems, such as constipation and diarrhea, also were more common among patients who had had the virus, the study found.
“Altogether, our results show that people with SARS-CoV-2 infection are at increased risk of gastrointestinal disorders in the post-acute phase of COVID-19,” the researchers write. “Post-COVID care should involve attention to gastrointestinal health and disease.”
The results were published online in Nature Communications.
Disease risks jump
The researchers used data from the U.S. Department of Veterans Affairs national health care databases to identify 154,068 people with confirmed COVID-19 from March 1, 2020, through Jan. 15, 2021. They used statistical modeling to compare those patients with 5.6 million patients with similar characteristics who had not been infected during the same period and an historical control group of 5.9 million patients from March 1, 2018, to Dec. 31, 2019, before the virus began to spread across the globe.
The study included hospitalized and nonhospitalized COVID patients. The majority of the study population was male, but the study included almost 1.2 million female patients.
Compared with control persons, post-COVID patients’ increased risk of a GI diagnosis and the excess disease burden at 1 year, respectively, were as follows.
- 102% for cholangitis; 0.22 per 1,000 persons
- 62% for peptic ulcer disease; 1.57 per 1,000 persons
- 54% for irritable bowel syndrome; 0.44 per 1,000 persons
- 47% for acute gastritis; 0.47 per 1,000 persons
- 46% for acute pancreatitis; 0.6 per 1,000 persons
- 36% for functional dyspepsia; 0.63 per 1,000 persons
- 35% for gastroesophageal reflux disease; 15.5 per 1,000 persons
Patients who’d had the virus were also at higher risk for GI symptoms than their COVID-free peers. Their risk was 60% higher for constipation, 58% for diarrhea, 52% for vomiting, 46% for bloating, and 44% for abdominal pain, the investigators found.
The risk of developing GI symptoms increased with COVID-19 severity and was highest for those who received intensive care because of the virus, the researchers note.
Subgroup analyses found that the risks of composite gastrointestinal outcome were evident in all subgroups based on age, race, sex, obesity, smoking, cardiovascular disease, chronic kidney disease, diabetes, hyperlipidemia, and hypertension, the authors write.
Disease burden rises
The increased numbers of GI patients with prior SARS-CoV-2 infection are altering the burden on the health care system, senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University, St. Louis, said in an interview.
The shift may be pronounced in primary care, where GI concerns should be seen as a trigger for questions about prior SARS-CoV-2 infection, Dr. Al-Aly said.
Patients may encounter longer wait times at GI clinics or may give up on trying to schedule appointments if waits become too long, he said. They may also present to emergency departments if they can’t get an outpatient appointment, he added.
Simon C. Mathews, MD, assistant professor of medicine, division of gastroenterology, Johns Hopkins Medicine, Baltimore, told this news organization that he’s seeing increased wait times since COVID emerged.
“We know that the pandemic impacted patients’ ability and willingness to seek GI care. There continues to be a long backlog for patients who are only now getting reconnected to care. As a result, our clinics are busier than ever, and our wait times for appointments are unfortunately longer than we would like,” said Dr. Mathews, who was not involved in the research.
Abdominal pain, bloating, diarrhea, and constipation continue to be among the most common symptoms Dr. Mathews sees in clinic, he said.
Kyle Staller, MD, a Massachusetts General Brigham gastroenterologist, said in an interview that it’s important to distinguish symptoms from eventual diagnoses, which lag behind.
“Are patients attributing their symptoms to COVID, or is COVID itself creating a background of inflammation or changes in the nerves that are making these symptoms more common? My suspicion is a little bit of both,” said Dr. Staller, who is director of the Gastrointestinal Motility Laboratory at Mass General, Boston.
Although his clinic is seeing patients with the GI signs and symptoms listed in the article, “we’re not seeing as much of some of the diagnoses, like peptic ulcer disease and pancreatitis,” he said. “I wonder if those may be related to some of the consequences of being critically ill in general, rather than COVID specifically. Those diagnoses I would be more skeptical about.”
Duration of symptoms unclear
It’s hard to tell patients how long their GI symptoms might last after COVID, given the relatively short time researchers have had to study the virus, said Dr. Staller, who was not involved in the research.
The symptoms he’s seeing in patients after COVID mimic those of postinfectious IBS, which literature says could last for months or years, Dr. Staller said. “But they should improve over time,” he added.
Senior author Dr. Al-Aly agreed that the duration of post-COVID GI symptoms is unclear.
“What I can tell you is that even people who got SARS-CoV-2 infection from March 2020 are still coming back for GI problems,” he said.
Unlike other symptoms of long COVID, such as brain fog, gastroenterologists fortunately know how to treat the GI disorders that evolve from SARS-CoV-2 infection, said Dr. Al-Aly, who has studied the long-term effects of the virus on the brain, kidneys, heart, and other organs.
All health care providers “need to be thinking about COVID as a risk factor for all these diseases” and should ask patients about SARS-CoV-2 infection when they take their histories, he said.
The authors, Dr. Staller, and Dr. Mathews report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a large new study indicates.
The researchers estimate that, so far, SARS-CoV-2 infections have contributed to more than 6 million new cases of GI disorders in the United States and 42 million new cases worldwide.
The diagnoses more common among patients who’ve had COVID ranged from stomach upset to acute pancreatitis, say the researchers, led by Evan Xu, a data analyst at the Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System.
Signs and symptoms of GI problems, such as constipation and diarrhea, also were more common among patients who had had the virus, the study found.
“Altogether, our results show that people with SARS-CoV-2 infection are at increased risk of gastrointestinal disorders in the post-acute phase of COVID-19,” the researchers write. “Post-COVID care should involve attention to gastrointestinal health and disease.”
The results were published online in Nature Communications.
Disease risks jump
The researchers used data from the U.S. Department of Veterans Affairs national health care databases to identify 154,068 people with confirmed COVID-19 from March 1, 2020, through Jan. 15, 2021. They used statistical modeling to compare those patients with 5.6 million patients with similar characteristics who had not been infected during the same period and an historical control group of 5.9 million patients from March 1, 2018, to Dec. 31, 2019, before the virus began to spread across the globe.
The study included hospitalized and nonhospitalized COVID patients. The majority of the study population was male, but the study included almost 1.2 million female patients.
Compared with control persons, post-COVID patients’ increased risk of a GI diagnosis and the excess disease burden at 1 year, respectively, were as follows.
- 102% for cholangitis; 0.22 per 1,000 persons
- 62% for peptic ulcer disease; 1.57 per 1,000 persons
- 54% for irritable bowel syndrome; 0.44 per 1,000 persons
- 47% for acute gastritis; 0.47 per 1,000 persons
- 46% for acute pancreatitis; 0.6 per 1,000 persons
- 36% for functional dyspepsia; 0.63 per 1,000 persons
- 35% for gastroesophageal reflux disease; 15.5 per 1,000 persons
Patients who’d had the virus were also at higher risk for GI symptoms than their COVID-free peers. Their risk was 60% higher for constipation, 58% for diarrhea, 52% for vomiting, 46% for bloating, and 44% for abdominal pain, the investigators found.
The risk of developing GI symptoms increased with COVID-19 severity and was highest for those who received intensive care because of the virus, the researchers note.
Subgroup analyses found that the risks of composite gastrointestinal outcome were evident in all subgroups based on age, race, sex, obesity, smoking, cardiovascular disease, chronic kidney disease, diabetes, hyperlipidemia, and hypertension, the authors write.
Disease burden rises
The increased numbers of GI patients with prior SARS-CoV-2 infection are altering the burden on the health care system, senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University, St. Louis, said in an interview.
The shift may be pronounced in primary care, where GI concerns should be seen as a trigger for questions about prior SARS-CoV-2 infection, Dr. Al-Aly said.
Patients may encounter longer wait times at GI clinics or may give up on trying to schedule appointments if waits become too long, he said. They may also present to emergency departments if they can’t get an outpatient appointment, he added.
Simon C. Mathews, MD, assistant professor of medicine, division of gastroenterology, Johns Hopkins Medicine, Baltimore, told this news organization that he’s seeing increased wait times since COVID emerged.
“We know that the pandemic impacted patients’ ability and willingness to seek GI care. There continues to be a long backlog for patients who are only now getting reconnected to care. As a result, our clinics are busier than ever, and our wait times for appointments are unfortunately longer than we would like,” said Dr. Mathews, who was not involved in the research.
Abdominal pain, bloating, diarrhea, and constipation continue to be among the most common symptoms Dr. Mathews sees in clinic, he said.
Kyle Staller, MD, a Massachusetts General Brigham gastroenterologist, said in an interview that it’s important to distinguish symptoms from eventual diagnoses, which lag behind.
“Are patients attributing their symptoms to COVID, or is COVID itself creating a background of inflammation or changes in the nerves that are making these symptoms more common? My suspicion is a little bit of both,” said Dr. Staller, who is director of the Gastrointestinal Motility Laboratory at Mass General, Boston.
Although his clinic is seeing patients with the GI signs and symptoms listed in the article, “we’re not seeing as much of some of the diagnoses, like peptic ulcer disease and pancreatitis,” he said. “I wonder if those may be related to some of the consequences of being critically ill in general, rather than COVID specifically. Those diagnoses I would be more skeptical about.”
Duration of symptoms unclear
It’s hard to tell patients how long their GI symptoms might last after COVID, given the relatively short time researchers have had to study the virus, said Dr. Staller, who was not involved in the research.
The symptoms he’s seeing in patients after COVID mimic those of postinfectious IBS, which literature says could last for months or years, Dr. Staller said. “But they should improve over time,” he added.
Senior author Dr. Al-Aly agreed that the duration of post-COVID GI symptoms is unclear.
“What I can tell you is that even people who got SARS-CoV-2 infection from March 2020 are still coming back for GI problems,” he said.
Unlike other symptoms of long COVID, such as brain fog, gastroenterologists fortunately know how to treat the GI disorders that evolve from SARS-CoV-2 infection, said Dr. Al-Aly, who has studied the long-term effects of the virus on the brain, kidneys, heart, and other organs.
All health care providers “need to be thinking about COVID as a risk factor for all these diseases” and should ask patients about SARS-CoV-2 infection when they take their histories, he said.
The authors, Dr. Staller, and Dr. Mathews report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a large new study indicates.
The researchers estimate that, so far, SARS-CoV-2 infections have contributed to more than 6 million new cases of GI disorders in the United States and 42 million new cases worldwide.
The diagnoses more common among patients who’ve had COVID ranged from stomach upset to acute pancreatitis, say the researchers, led by Evan Xu, a data analyst at the Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System.
Signs and symptoms of GI problems, such as constipation and diarrhea, also were more common among patients who had had the virus, the study found.
“Altogether, our results show that people with SARS-CoV-2 infection are at increased risk of gastrointestinal disorders in the post-acute phase of COVID-19,” the researchers write. “Post-COVID care should involve attention to gastrointestinal health and disease.”
The results were published online in Nature Communications.
Disease risks jump
The researchers used data from the U.S. Department of Veterans Affairs national health care databases to identify 154,068 people with confirmed COVID-19 from March 1, 2020, through Jan. 15, 2021. They used statistical modeling to compare those patients with 5.6 million patients with similar characteristics who had not been infected during the same period and an historical control group of 5.9 million patients from March 1, 2018, to Dec. 31, 2019, before the virus began to spread across the globe.
The study included hospitalized and nonhospitalized COVID patients. The majority of the study population was male, but the study included almost 1.2 million female patients.
Compared with control persons, post-COVID patients’ increased risk of a GI diagnosis and the excess disease burden at 1 year, respectively, were as follows.
- 102% for cholangitis; 0.22 per 1,000 persons
- 62% for peptic ulcer disease; 1.57 per 1,000 persons
- 54% for irritable bowel syndrome; 0.44 per 1,000 persons
- 47% for acute gastritis; 0.47 per 1,000 persons
- 46% for acute pancreatitis; 0.6 per 1,000 persons
- 36% for functional dyspepsia; 0.63 per 1,000 persons
- 35% for gastroesophageal reflux disease; 15.5 per 1,000 persons
Patients who’d had the virus were also at higher risk for GI symptoms than their COVID-free peers. Their risk was 60% higher for constipation, 58% for diarrhea, 52% for vomiting, 46% for bloating, and 44% for abdominal pain, the investigators found.
The risk of developing GI symptoms increased with COVID-19 severity and was highest for those who received intensive care because of the virus, the researchers note.
Subgroup analyses found that the risks of composite gastrointestinal outcome were evident in all subgroups based on age, race, sex, obesity, smoking, cardiovascular disease, chronic kidney disease, diabetes, hyperlipidemia, and hypertension, the authors write.
Disease burden rises
The increased numbers of GI patients with prior SARS-CoV-2 infection are altering the burden on the health care system, senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University, St. Louis, said in an interview.
The shift may be pronounced in primary care, where GI concerns should be seen as a trigger for questions about prior SARS-CoV-2 infection, Dr. Al-Aly said.
Patients may encounter longer wait times at GI clinics or may give up on trying to schedule appointments if waits become too long, he said. They may also present to emergency departments if they can’t get an outpatient appointment, he added.
Simon C. Mathews, MD, assistant professor of medicine, division of gastroenterology, Johns Hopkins Medicine, Baltimore, told this news organization that he’s seeing increased wait times since COVID emerged.
“We know that the pandemic impacted patients’ ability and willingness to seek GI care. There continues to be a long backlog for patients who are only now getting reconnected to care. As a result, our clinics are busier than ever, and our wait times for appointments are unfortunately longer than we would like,” said Dr. Mathews, who was not involved in the research.
Abdominal pain, bloating, diarrhea, and constipation continue to be among the most common symptoms Dr. Mathews sees in clinic, he said.
Kyle Staller, MD, a Massachusetts General Brigham gastroenterologist, said in an interview that it’s important to distinguish symptoms from eventual diagnoses, which lag behind.
“Are patients attributing their symptoms to COVID, or is COVID itself creating a background of inflammation or changes in the nerves that are making these symptoms more common? My suspicion is a little bit of both,” said Dr. Staller, who is director of the Gastrointestinal Motility Laboratory at Mass General, Boston.
Although his clinic is seeing patients with the GI signs and symptoms listed in the article, “we’re not seeing as much of some of the diagnoses, like peptic ulcer disease and pancreatitis,” he said. “I wonder if those may be related to some of the consequences of being critically ill in general, rather than COVID specifically. Those diagnoses I would be more skeptical about.”
Duration of symptoms unclear
It’s hard to tell patients how long their GI symptoms might last after COVID, given the relatively short time researchers have had to study the virus, said Dr. Staller, who was not involved in the research.
The symptoms he’s seeing in patients after COVID mimic those of postinfectious IBS, which literature says could last for months or years, Dr. Staller said. “But they should improve over time,” he added.
Senior author Dr. Al-Aly agreed that the duration of post-COVID GI symptoms is unclear.
“What I can tell you is that even people who got SARS-CoV-2 infection from March 2020 are still coming back for GI problems,” he said.
Unlike other symptoms of long COVID, such as brain fog, gastroenterologists fortunately know how to treat the GI disorders that evolve from SARS-CoV-2 infection, said Dr. Al-Aly, who has studied the long-term effects of the virus on the brain, kidneys, heart, and other organs.
All health care providers “need to be thinking about COVID as a risk factor for all these diseases” and should ask patients about SARS-CoV-2 infection when they take their histories, he said.
The authors, Dr. Staller, and Dr. Mathews report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NATURE COMMUNICATIONS
‘Breakthrough’ study: Diabetes drug helps prevent long COVID
with The Lancet on SSRN. The preprint hasn’t yet been peer-reviewed or published in a journal.
In particular, metformin led to a 42% drop in long COVID among people who had a mild to moderate COVID-19 infection.
“Long COVID affects millions of people, and preventing long COVID through a treatment like metformin could prevent significant disruptions in people’s lives,” said lead author Carolyn Bramante, MD, assistant professor of internal medicine and pediatrics at the University of Minnesota, Minneapolis.
Between January 2021 and February 2022, Dr. Bramante and colleagues tested three oral medications – metformin (typically used to treat type 2 diabetes), ivermectin (an antiparasitic), and fluvoxamine (an antidepressant) – in a clinical trial across the United States called COVID-OUT. The people being studied, investigators, care providers, and others involved in the study were blinded to the randomized treatments. The trial was decentralized, with no in-person contact with participants.
The researchers included patients who were aged 30-85 with overweight or obesity, had documentation of a confirmed COVID-19 infection, had fewer than 7 days of symptoms, had no known prior infection, and joined the study within 3 days of their positive test. The study included monthly follow-up for 300 days, and participants indicated whether they received a long COVID diagnosis from a medical doctor, which the researchers confirmed in medical records after participants gave consent.
The medications were prepackaged into pill boxes for fast delivery to participants and to ensure they took the correct number of each type of pill. The packages were sent via same-day courier or overnight shipping.
The metformin doses were doled out over 14 days, with 500 milligrams on the first day, 500 milligrams twice a day for the next 4 days, and then 500 milligrams in the morning and 1,000 milligrams in the evening for the remaining 9 days.
Among the 1,323 people studied, 1,125 agreed to do long-term follow-up for long COVID: 564 in the metformin group and 561 in the blinded placebo group. The average age was 45, and 56% were women, including 7% who were pregnant.
The average time from the start of symptoms to starting medication was 5 days, and 47% began taking the drug within 4 days or less. About 55% had received the primary COVID-19 vaccination series, including 5.1% who received an initial booster, before enrolling in the study.
Overall, 8.4% of participants reported that a medical provider diagnosed them with long COVID. Of those who took metformin, 6.3% developed long COVID, compared to 10.6% among those who took the identical-matched placebo.
The risk reduction for metformin was 42% versus the placebo, which was consistent across subgroups, including vaccination status and different COVID-19 variants.
When metformin was started less than 4 days after COVID-19 symptoms started, the effect was potentially even greater, with a 64% reduction, as compared with a 36% reduction among those who started metformin after 4 or more days after symptoms.
Neither ivermectin nor fluvoxamine showed any benefits for preventing long COVID.
At the same time, the study authors caution that more research is needed.
“The COVID-OUT trial does not indicate whether or not metformin would be effective at preventing long COVID if started at the time of emergency department visit or hospitalization for COVID-19, nor whether metformin would be effective as treatment in persons who already have long COVID,” they wrote. “With the burden of long COVID on society, confirmation is urgently needed in a trial that addresses our study’s limitations in order to translate these results into practice and policy.”
Several risk factors for long COVID emerged in the analysis. About 11.1% of the women had a long COVID diagnosis, compared with 4.9% of the men. Also, those who had received at least the primary vaccine series had a lower risk of developing long COVID, at 6.6%, as compared with 10.5% among the unvaccinated. Only 1 of the 57 people who received a booster shot developed long COVID.
Notably, pregnant and lactating people were included in this study, which is important given that pregnant people face higher risks for poor COVID-19 outcomes and are excluded from most nonobstetric clinical trials, the study authors wrote. In this study, they were randomized to metformin or placebo but not ivermectin or fluvoxamine due to limited research about the safety of those drugs during pregnancy and lactation.
The results are now under journal review but show findings consistent with those from other recent studies. Also, in August 2022, the authors published results from COVID-OUT that showed metformin led to a 42% reduction in hospital visits, emergency department visits, and deaths related to severe COVID-19.
“Given the lack of side effects and cost for a 2-week course, I think these data support use of metformin now,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief of Medscape, WebMD’s sister site for health care professionals.
Dr. Topol, who wasn’t involved with this study, has been a leading voice on COVID-19 research throughout the pandemic. He noted the need for more studies, including a factorial design trial to test metformin and Paxlovid, which has shown promise in preventing long COVID. Dr. Topol also wrote about the preprint in Ground Truths, his online newsletter.
“As I’ve written in the past, I don’t use the term ‘breakthrough’ lightly,” he wrote. “But to see such a pronounced benefit in the current randomized trial of metformin, in the context of its being so safe and low cost, I’d give it a breakthrough categorization.”
Another way to put it, Dr. Topol wrote, is that based on this study, he would take metformin if he became infected with COVID-19.
Jeremy Faust, MD, an emergency medicine doctor at Brigham and Women’s Hospital in Boston, also wrote about the study in his newsletter, Inside Medicine. He noted that the 42% reduction in long COVID means that 23 COVID-19 patients need to be treated with metformin to prevent one long COVID diagnosis, which is an “important reduction.”
“Bottom line: If a person who meets criteria for obesity or overweight status were to ask me if they should take metformin (for 2 weeks) starting as soon as they learn they have COVID-19, I would say yes in many if not most cases, based on this new data,” he wrote. “This is starting to look like a real win.”
A version of this article first appeared on WebMD.com.
with The Lancet on SSRN. The preprint hasn’t yet been peer-reviewed or published in a journal.
In particular, metformin led to a 42% drop in long COVID among people who had a mild to moderate COVID-19 infection.
“Long COVID affects millions of people, and preventing long COVID through a treatment like metformin could prevent significant disruptions in people’s lives,” said lead author Carolyn Bramante, MD, assistant professor of internal medicine and pediatrics at the University of Minnesota, Minneapolis.
Between January 2021 and February 2022, Dr. Bramante and colleagues tested three oral medications – metformin (typically used to treat type 2 diabetes), ivermectin (an antiparasitic), and fluvoxamine (an antidepressant) – in a clinical trial across the United States called COVID-OUT. The people being studied, investigators, care providers, and others involved in the study were blinded to the randomized treatments. The trial was decentralized, with no in-person contact with participants.
The researchers included patients who were aged 30-85 with overweight or obesity, had documentation of a confirmed COVID-19 infection, had fewer than 7 days of symptoms, had no known prior infection, and joined the study within 3 days of their positive test. The study included monthly follow-up for 300 days, and participants indicated whether they received a long COVID diagnosis from a medical doctor, which the researchers confirmed in medical records after participants gave consent.
The medications were prepackaged into pill boxes for fast delivery to participants and to ensure they took the correct number of each type of pill. The packages were sent via same-day courier or overnight shipping.
The metformin doses were doled out over 14 days, with 500 milligrams on the first day, 500 milligrams twice a day for the next 4 days, and then 500 milligrams in the morning and 1,000 milligrams in the evening for the remaining 9 days.
Among the 1,323 people studied, 1,125 agreed to do long-term follow-up for long COVID: 564 in the metformin group and 561 in the blinded placebo group. The average age was 45, and 56% were women, including 7% who were pregnant.
The average time from the start of symptoms to starting medication was 5 days, and 47% began taking the drug within 4 days or less. About 55% had received the primary COVID-19 vaccination series, including 5.1% who received an initial booster, before enrolling in the study.
Overall, 8.4% of participants reported that a medical provider diagnosed them with long COVID. Of those who took metformin, 6.3% developed long COVID, compared to 10.6% among those who took the identical-matched placebo.
The risk reduction for metformin was 42% versus the placebo, which was consistent across subgroups, including vaccination status and different COVID-19 variants.
When metformin was started less than 4 days after COVID-19 symptoms started, the effect was potentially even greater, with a 64% reduction, as compared with a 36% reduction among those who started metformin after 4 or more days after symptoms.
Neither ivermectin nor fluvoxamine showed any benefits for preventing long COVID.
At the same time, the study authors caution that more research is needed.
“The COVID-OUT trial does not indicate whether or not metformin would be effective at preventing long COVID if started at the time of emergency department visit or hospitalization for COVID-19, nor whether metformin would be effective as treatment in persons who already have long COVID,” they wrote. “With the burden of long COVID on society, confirmation is urgently needed in a trial that addresses our study’s limitations in order to translate these results into practice and policy.”
Several risk factors for long COVID emerged in the analysis. About 11.1% of the women had a long COVID diagnosis, compared with 4.9% of the men. Also, those who had received at least the primary vaccine series had a lower risk of developing long COVID, at 6.6%, as compared with 10.5% among the unvaccinated. Only 1 of the 57 people who received a booster shot developed long COVID.
Notably, pregnant and lactating people were included in this study, which is important given that pregnant people face higher risks for poor COVID-19 outcomes and are excluded from most nonobstetric clinical trials, the study authors wrote. In this study, they were randomized to metformin or placebo but not ivermectin or fluvoxamine due to limited research about the safety of those drugs during pregnancy and lactation.
The results are now under journal review but show findings consistent with those from other recent studies. Also, in August 2022, the authors published results from COVID-OUT that showed metformin led to a 42% reduction in hospital visits, emergency department visits, and deaths related to severe COVID-19.
“Given the lack of side effects and cost for a 2-week course, I think these data support use of metformin now,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief of Medscape, WebMD’s sister site for health care professionals.
Dr. Topol, who wasn’t involved with this study, has been a leading voice on COVID-19 research throughout the pandemic. He noted the need for more studies, including a factorial design trial to test metformin and Paxlovid, which has shown promise in preventing long COVID. Dr. Topol also wrote about the preprint in Ground Truths, his online newsletter.
“As I’ve written in the past, I don’t use the term ‘breakthrough’ lightly,” he wrote. “But to see such a pronounced benefit in the current randomized trial of metformin, in the context of its being so safe and low cost, I’d give it a breakthrough categorization.”
Another way to put it, Dr. Topol wrote, is that based on this study, he would take metformin if he became infected with COVID-19.
Jeremy Faust, MD, an emergency medicine doctor at Brigham and Women’s Hospital in Boston, also wrote about the study in his newsletter, Inside Medicine. He noted that the 42% reduction in long COVID means that 23 COVID-19 patients need to be treated with metformin to prevent one long COVID diagnosis, which is an “important reduction.”
“Bottom line: If a person who meets criteria for obesity or overweight status were to ask me if they should take metformin (for 2 weeks) starting as soon as they learn they have COVID-19, I would say yes in many if not most cases, based on this new data,” he wrote. “This is starting to look like a real win.”
A version of this article first appeared on WebMD.com.
with The Lancet on SSRN. The preprint hasn’t yet been peer-reviewed or published in a journal.
In particular, metformin led to a 42% drop in long COVID among people who had a mild to moderate COVID-19 infection.
“Long COVID affects millions of people, and preventing long COVID through a treatment like metformin could prevent significant disruptions in people’s lives,” said lead author Carolyn Bramante, MD, assistant professor of internal medicine and pediatrics at the University of Minnesota, Minneapolis.
Between January 2021 and February 2022, Dr. Bramante and colleagues tested three oral medications – metformin (typically used to treat type 2 diabetes), ivermectin (an antiparasitic), and fluvoxamine (an antidepressant) – in a clinical trial across the United States called COVID-OUT. The people being studied, investigators, care providers, and others involved in the study were blinded to the randomized treatments. The trial was decentralized, with no in-person contact with participants.
The researchers included patients who were aged 30-85 with overweight or obesity, had documentation of a confirmed COVID-19 infection, had fewer than 7 days of symptoms, had no known prior infection, and joined the study within 3 days of their positive test. The study included monthly follow-up for 300 days, and participants indicated whether they received a long COVID diagnosis from a medical doctor, which the researchers confirmed in medical records after participants gave consent.
The medications were prepackaged into pill boxes for fast delivery to participants and to ensure they took the correct number of each type of pill. The packages were sent via same-day courier or overnight shipping.
The metformin doses were doled out over 14 days, with 500 milligrams on the first day, 500 milligrams twice a day for the next 4 days, and then 500 milligrams in the morning and 1,000 milligrams in the evening for the remaining 9 days.
Among the 1,323 people studied, 1,125 agreed to do long-term follow-up for long COVID: 564 in the metformin group and 561 in the blinded placebo group. The average age was 45, and 56% were women, including 7% who were pregnant.
The average time from the start of symptoms to starting medication was 5 days, and 47% began taking the drug within 4 days or less. About 55% had received the primary COVID-19 vaccination series, including 5.1% who received an initial booster, before enrolling in the study.
Overall, 8.4% of participants reported that a medical provider diagnosed them with long COVID. Of those who took metformin, 6.3% developed long COVID, compared to 10.6% among those who took the identical-matched placebo.
The risk reduction for metformin was 42% versus the placebo, which was consistent across subgroups, including vaccination status and different COVID-19 variants.
When metformin was started less than 4 days after COVID-19 symptoms started, the effect was potentially even greater, with a 64% reduction, as compared with a 36% reduction among those who started metformin after 4 or more days after symptoms.
Neither ivermectin nor fluvoxamine showed any benefits for preventing long COVID.
At the same time, the study authors caution that more research is needed.
“The COVID-OUT trial does not indicate whether or not metformin would be effective at preventing long COVID if started at the time of emergency department visit or hospitalization for COVID-19, nor whether metformin would be effective as treatment in persons who already have long COVID,” they wrote. “With the burden of long COVID on society, confirmation is urgently needed in a trial that addresses our study’s limitations in order to translate these results into practice and policy.”
Several risk factors for long COVID emerged in the analysis. About 11.1% of the women had a long COVID diagnosis, compared with 4.9% of the men. Also, those who had received at least the primary vaccine series had a lower risk of developing long COVID, at 6.6%, as compared with 10.5% among the unvaccinated. Only 1 of the 57 people who received a booster shot developed long COVID.
Notably, pregnant and lactating people were included in this study, which is important given that pregnant people face higher risks for poor COVID-19 outcomes and are excluded from most nonobstetric clinical trials, the study authors wrote. In this study, they were randomized to metformin or placebo but not ivermectin or fluvoxamine due to limited research about the safety of those drugs during pregnancy and lactation.
The results are now under journal review but show findings consistent with those from other recent studies. Also, in August 2022, the authors published results from COVID-OUT that showed metformin led to a 42% reduction in hospital visits, emergency department visits, and deaths related to severe COVID-19.
“Given the lack of side effects and cost for a 2-week course, I think these data support use of metformin now,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief of Medscape, WebMD’s sister site for health care professionals.
Dr. Topol, who wasn’t involved with this study, has been a leading voice on COVID-19 research throughout the pandemic. He noted the need for more studies, including a factorial design trial to test metformin and Paxlovid, which has shown promise in preventing long COVID. Dr. Topol also wrote about the preprint in Ground Truths, his online newsletter.
“As I’ve written in the past, I don’t use the term ‘breakthrough’ lightly,” he wrote. “But to see such a pronounced benefit in the current randomized trial of metformin, in the context of its being so safe and low cost, I’d give it a breakthrough categorization.”
Another way to put it, Dr. Topol wrote, is that based on this study, he would take metformin if he became infected with COVID-19.
Jeremy Faust, MD, an emergency medicine doctor at Brigham and Women’s Hospital in Boston, also wrote about the study in his newsletter, Inside Medicine. He noted that the 42% reduction in long COVID means that 23 COVID-19 patients need to be treated with metformin to prevent one long COVID diagnosis, which is an “important reduction.”
“Bottom line: If a person who meets criteria for obesity or overweight status were to ask me if they should take metformin (for 2 weeks) starting as soon as they learn they have COVID-19, I would say yes in many if not most cases, based on this new data,” he wrote. “This is starting to look like a real win.”
A version of this article first appeared on WebMD.com.
Even mild COVID is hard on the brain
early research suggests.
“Our results suggest a severe pattern of changes in how the brain communicates as well as its structure, mainly in people with anxiety and depression with long-COVID syndrome, which affects so many people,” study investigator Clarissa Yasuda, MD, PhD, from University of Campinas, São Paulo, said in a news release.
“The magnitude of these changes suggests that they could lead to problems with memory and thinking skills, so we need to be exploring holistic treatments even for people mildly affected by COVID-19,” Dr. Yasuda added.
The findings were released March 6 ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Brain shrinkage
Some studies have shown a high prevalence of symptoms of anxiety and depression in COVID-19 survivors, but few have investigated the associated cerebral changes, Dr. Yasuda told this news organization.
The study included 254 adults (177 women, 77 men, median age 41 years) who had mild COVID-19 a median of 82 days earlier. A total of 102 had symptoms of both anxiety and depression, and 152 had no such symptoms.
On brain imaging, those with COVID-19 and anxiety and depression had atrophy in the limbic area of the brain, which plays a role in memory and emotional processing.
No shrinkage in this area was evident in people who had COVID-19 without anxiety and depression or in a healthy control group of individuals without COVID-19.
The researchers also observed a “severe” pattern of abnormal cerebral functional connectivity in those with COVID-19 and anxiety and depression.
In this functional connectivity analysis, individuals with COVID-19 and anxiety and depression had widespread functional changes in each of the 12 networks assessed, while those with COVID-19 but without symptoms of anxiety and depression showed changes in only 5 networks.
Mechanisms unclear
“Unfortunately, the underpinning mechanisms associated with brain changes and neuropsychiatric dysfunction after COVID-19 infection are unclear,” Dr. Yasuda told this news organization.
“Some studies have demonstrated an association between symptoms of anxiety and depression with inflammation. However, we hypothesize that these cerebral alterations may result from a more complex interaction of social, psychological, and systemic stressors, including inflammation. It is indeed intriguing that such alterations are present in individuals who presented mild acute infection,” Dr. Yasuda added.
“Symptoms of anxiety and depression are frequently observed after COVID-19 and are part of long-COVID syndrome for some individuals. These symptoms require adequate treatment to improve the quality of life, cognition, and work capacity,” she said.
Treating these symptoms may induce “brain plasticity, which may result in some degree of gray matter increase and eventually prevent further structural and functional damage,” Dr. Yasuda said.
A limitation of the study was that symptoms of anxiety and depression were self-reported, meaning people may have misjudged or misreported symptoms.
Commenting on the findings for this news organization, Cyrus Raji, MD, PhD, with the Mallinckrodt Institute of Radiology, Washington University, St. Louis, said the idea that COVID-19 is bad for the brain isn’t new. Dr. Raji was not involved with the study.
Early in the pandemic, Dr. Raji and colleagues published a paper detailing COVID-19’s effects on the brain, and Dr. Raji followed it up with a TED talk on the subject.
“Within the growing framework of what we already know about COVID-19 infection and its adverse effects on the brain, this work incrementally adds to this knowledge by identifying functional and structural neuroimaging abnormalities related to anxiety and depression in persons suffering from COVID-19 infection,” Dr. Raji said.
The study was supported by the São Paulo Research Foundation. The authors have no relevant disclosures. Raji is a consultant for Brainreader, Apollo Health, Pacific Neuroscience Foundation, and Neurevolution LLC.
early research suggests.
“Our results suggest a severe pattern of changes in how the brain communicates as well as its structure, mainly in people with anxiety and depression with long-COVID syndrome, which affects so many people,” study investigator Clarissa Yasuda, MD, PhD, from University of Campinas, São Paulo, said in a news release.
“The magnitude of these changes suggests that they could lead to problems with memory and thinking skills, so we need to be exploring holistic treatments even for people mildly affected by COVID-19,” Dr. Yasuda added.
The findings were released March 6 ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Brain shrinkage
Some studies have shown a high prevalence of symptoms of anxiety and depression in COVID-19 survivors, but few have investigated the associated cerebral changes, Dr. Yasuda told this news organization.
The study included 254 adults (177 women, 77 men, median age 41 years) who had mild COVID-19 a median of 82 days earlier. A total of 102 had symptoms of both anxiety and depression, and 152 had no such symptoms.
On brain imaging, those with COVID-19 and anxiety and depression had atrophy in the limbic area of the brain, which plays a role in memory and emotional processing.
No shrinkage in this area was evident in people who had COVID-19 without anxiety and depression or in a healthy control group of individuals without COVID-19.
The researchers also observed a “severe” pattern of abnormal cerebral functional connectivity in those with COVID-19 and anxiety and depression.
In this functional connectivity analysis, individuals with COVID-19 and anxiety and depression had widespread functional changes in each of the 12 networks assessed, while those with COVID-19 but without symptoms of anxiety and depression showed changes in only 5 networks.
Mechanisms unclear
“Unfortunately, the underpinning mechanisms associated with brain changes and neuropsychiatric dysfunction after COVID-19 infection are unclear,” Dr. Yasuda told this news organization.
“Some studies have demonstrated an association between symptoms of anxiety and depression with inflammation. However, we hypothesize that these cerebral alterations may result from a more complex interaction of social, psychological, and systemic stressors, including inflammation. It is indeed intriguing that such alterations are present in individuals who presented mild acute infection,” Dr. Yasuda added.
“Symptoms of anxiety and depression are frequently observed after COVID-19 and are part of long-COVID syndrome for some individuals. These symptoms require adequate treatment to improve the quality of life, cognition, and work capacity,” she said.
Treating these symptoms may induce “brain plasticity, which may result in some degree of gray matter increase and eventually prevent further structural and functional damage,” Dr. Yasuda said.
A limitation of the study was that symptoms of anxiety and depression were self-reported, meaning people may have misjudged or misreported symptoms.
Commenting on the findings for this news organization, Cyrus Raji, MD, PhD, with the Mallinckrodt Institute of Radiology, Washington University, St. Louis, said the idea that COVID-19 is bad for the brain isn’t new. Dr. Raji was not involved with the study.
Early in the pandemic, Dr. Raji and colleagues published a paper detailing COVID-19’s effects on the brain, and Dr. Raji followed it up with a TED talk on the subject.
“Within the growing framework of what we already know about COVID-19 infection and its adverse effects on the brain, this work incrementally adds to this knowledge by identifying functional and structural neuroimaging abnormalities related to anxiety and depression in persons suffering from COVID-19 infection,” Dr. Raji said.
The study was supported by the São Paulo Research Foundation. The authors have no relevant disclosures. Raji is a consultant for Brainreader, Apollo Health, Pacific Neuroscience Foundation, and Neurevolution LLC.
early research suggests.
“Our results suggest a severe pattern of changes in how the brain communicates as well as its structure, mainly in people with anxiety and depression with long-COVID syndrome, which affects so many people,” study investigator Clarissa Yasuda, MD, PhD, from University of Campinas, São Paulo, said in a news release.
“The magnitude of these changes suggests that they could lead to problems with memory and thinking skills, so we need to be exploring holistic treatments even for people mildly affected by COVID-19,” Dr. Yasuda added.
The findings were released March 6 ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Brain shrinkage
Some studies have shown a high prevalence of symptoms of anxiety and depression in COVID-19 survivors, but few have investigated the associated cerebral changes, Dr. Yasuda told this news organization.
The study included 254 adults (177 women, 77 men, median age 41 years) who had mild COVID-19 a median of 82 days earlier. A total of 102 had symptoms of both anxiety and depression, and 152 had no such symptoms.
On brain imaging, those with COVID-19 and anxiety and depression had atrophy in the limbic area of the brain, which plays a role in memory and emotional processing.
No shrinkage in this area was evident in people who had COVID-19 without anxiety and depression or in a healthy control group of individuals without COVID-19.
The researchers also observed a “severe” pattern of abnormal cerebral functional connectivity in those with COVID-19 and anxiety and depression.
In this functional connectivity analysis, individuals with COVID-19 and anxiety and depression had widespread functional changes in each of the 12 networks assessed, while those with COVID-19 but without symptoms of anxiety and depression showed changes in only 5 networks.
Mechanisms unclear
“Unfortunately, the underpinning mechanisms associated with brain changes and neuropsychiatric dysfunction after COVID-19 infection are unclear,” Dr. Yasuda told this news organization.
“Some studies have demonstrated an association between symptoms of anxiety and depression with inflammation. However, we hypothesize that these cerebral alterations may result from a more complex interaction of social, psychological, and systemic stressors, including inflammation. It is indeed intriguing that such alterations are present in individuals who presented mild acute infection,” Dr. Yasuda added.
“Symptoms of anxiety and depression are frequently observed after COVID-19 and are part of long-COVID syndrome for some individuals. These symptoms require adequate treatment to improve the quality of life, cognition, and work capacity,” she said.
Treating these symptoms may induce “brain plasticity, which may result in some degree of gray matter increase and eventually prevent further structural and functional damage,” Dr. Yasuda said.
A limitation of the study was that symptoms of anxiety and depression were self-reported, meaning people may have misjudged or misreported symptoms.
Commenting on the findings for this news organization, Cyrus Raji, MD, PhD, with the Mallinckrodt Institute of Radiology, Washington University, St. Louis, said the idea that COVID-19 is bad for the brain isn’t new. Dr. Raji was not involved with the study.
Early in the pandemic, Dr. Raji and colleagues published a paper detailing COVID-19’s effects on the brain, and Dr. Raji followed it up with a TED talk on the subject.
“Within the growing framework of what we already know about COVID-19 infection and its adverse effects on the brain, this work incrementally adds to this knowledge by identifying functional and structural neuroimaging abnormalities related to anxiety and depression in persons suffering from COVID-19 infection,” Dr. Raji said.
The study was supported by the São Paulo Research Foundation. The authors have no relevant disclosures. Raji is a consultant for Brainreader, Apollo Health, Pacific Neuroscience Foundation, and Neurevolution LLC.
Is cellular senescence related to post–COVID-19 syndrome?
Proinflammatory elements mediated through metabolic pathways related to obesity and increased cellular senescence in CD57 expression in CD8+ T cells are associated with postacute sequelae of COVID-19 (PASC), according to a Mexican study. The researchers followed a Mexican cohort of 102 patients 3 months and 6 months after acute SARS-CoV-2 infection.
The study’s principal investigator was Diana Gómez-Martín, MD, PhD, of the department of immunology and rheumatology at the Salvador Zubirán National Institute of Medical Sciences and Nutrition, Mexico City. She told this news organization that follow-up of the patients began with the objective of understanding the determinative clinical, genetic, metabolic, and immunological factors in the progression of the acute disease. However, clinical aspects associated with PASC developed in the selected cohort. As a result, the study was extended, and the clinical, metabolic, and immunologic conditions in this single-center Mexican cohort were evaluated 3 months 6 months after the onset of infection.
Dr. Gómez-Martín explained that the immune senescence in CD57 of CD8+ T cells is one of the best-known findings of the present study. If it is confirmed in future studies, it could have important implications. “Its main implication is the possibility of better understanding the physiopathology of the clinical aspects associated with postacute sequelae of COVID-19, potentially being used for early detection and to provide follow-up aimed at patients, in addition to eventually developing targeted therapeutic strategies, such as immunometabolism regulation, in certain populations.”
Patients with PASC
The study was conducted from August 2020 to August 2021. Investigators recruited 102 patients (median age, 50.5 years; 55% were women) at the Mexico City Temporary Unit with a confirmed diagnosis of SARS-CoV-2. Of the patients, 44% had mild or moderate COVID-19, 30% had severe cases, and 26% of patients had critical cases. The most frequent comorbidities were obesity (44%), hypertension (24%), and type 2 diabetes (24%). The authors used a questionnaire to assess the presence of symptoms during follow-up. They analyzed immunologic variables at the time of recruitment, as well as levels of cytokines, immunoglobulin G against SARS-CoV-2, and neutrophil extracellular traps (NETs) at 1, 3, and 6 months. At 6 months’ follow-up, 12.7% of the cohort had symptoms compatible with PASC, which was defined for the study as the presence and report of three or more symptoms at 6 months’ follow-up.
As in similar studies, the authors found that female gender, remaining in intensive care, and having had more symptoms and greater titers of anti-SARS-CoV-2 antibodies during the acute infection were associated with the development of clinical aspects associated with PASC. Patients who had the disease at 6 months had increased serum levels of interleukin-1 alpha (6.21 pg/mL vs. 2.21 pg/mL), granulocyte colony-stimulating factor (55.08 pg/mL vs. 14.68 pg/mL), and interferon gamma-induced protein 10 (2,309.40 pg/mL vs. 780 pg/mL). Also, there was a trend toward an increase in serum concentration of interleukin-1 beta, interleukin-6, and interferon-gamma.
Patients whose condition met the definition of persistent PASC had increased expression of CD57 in CD8+ T cells (42,714 arbitrary units vs. 28,506) 6 months after the acute infection. The authors reported that there was no association between the persistence of PASC and the baseline amount of NETs, TRIM63, and anticellular antibodies. Nor was there an association between PASC and the titers of anti-SARS-CoV-2 antibodies at baseline and 1 month after COVID-19 diagnosis. Nonetheless, patients with persistent PASC had higher titers of anti-SARS-CoV-2 IgGs 3 months after the onset of COVID-19.
On the basis of previous data, the researchers aimed to construct a preliminary explanatory model to address the clinical and immunologic features associated with persistent PASC 6 months after SARS-CoV-2 infection. In the univariate analysis, the variables associated with the diagnosis of persistent PASC were the serum levels of granulocyte colony-stimulating factor (odds ratio, 1.01), macrophage inflammatory protein-1 alpha (OR, 1.13), interferon gamma-induced protein 10 (OR, 1.00), interleukin-6 (OR, 1.03), the expression of CD57 in CD8+ T cells (OR, 1.00), and the titers of anti-SARS-CoV-2 IgG at 1 month (OR, 1.45).
, such as obesity, greater levels of macrophage inflammatory protein-1 alpha and interferon gamma-induced protein 10 in peripheral blood, greater expression of the senescence CD57 marker in CD8+ T lymphocytes, and persistent symptoms at 3 months.
Using these parameters to construct a predictive model after 3 months, the authors found a sensitivity of 97.7%, specificity of 53.8%, positive predictive value of 93.5%, and a negative predictive value of 77.7% for the diagnosis of clinical aspects associated with PASC at 6 months.
Interpreting CD57
One of the researchers who participated in the study was Luis Martínez-Juárez, MD, MPH, DrPH. He is on the operative solutions team at the Carlos Slim Foundation. Dr. Martínez-Juárez pointed out that one of the contributions of this study was that it specifically examined the Mexican population. He noted that “according to the findings, obesity is not only a comorbidity associated with more severe progressions during acute COVID-19 disease, but also, through inflammation parameters, such as interleukin-6, interferon gamma-induced protein 10, and macrophage inflammatory protein-1 alpha, it’s involved in the development of clinical aspects related to postacute sequelae of COVID-19.”
Dr. Gómez-Martín added that finding proinflammatory and obesity parameters in the patients could potentially support the hypothesis of the persistence of virus fragments in adipose tissue as possibly involved in clinical aspects associated with PASC, as some groups have reported in the medical literature.
Angélica Cuapio, MD, DrMed, an immunologist and senior investigator at the Karolinska Institute, Stockholm, who did not participate in the study, said in an interview that the authors’ findings on the sustained increase of the CD57 marker in CD8+ lymphocytes are of notable interest. They may be associated with senescence states or cellular aging or with a stage of chronic viral infections. Therefore, Dr. Cuapio argued, it would have been valuable to include cellular markers of the innate system, such as natural killer cells, since in various infections, an increase in CD57 in lymphocytes is accompanied by an almost proportional increase of this marker in natural killer cells.
“This information would help to determine more accurately if we are talking about a cellular senescence or more about a chronic infection in persistent COVID-19.” The finding is important, but future research is needed in this developing field.
Dr. Cuapio pointed out that the authors found an interesting elevation in interleukin-1 alpha in patients with clinical aspects associated with PASC in a clinically well-characterized population in Mexico. “It is possible that this is a specific marker either of a specific population or location, or this could be an association with a humoral response. Despite the fact that this finding is new and unclear, it is worth investigating. This study is of great value for the scientific community because it’s one more piece in the complex puzzle of clinical aspects associated with postacute sequelae of COVID-19.”
Dr. Gómez-Martín noted that the main limitations of the study consist of its single-center design and the small patient sample. Dr. Martínez-Juárez added that the study did not consider reinfections. In future studies, it would be ideal to integrate other molecular assessments associated with various hypotheses of the physiopathology of clinical aspects associated with PASC, such as microbiota alteration, coagulation anomalies, endothelial damage, and dysfunctional neurologic signaling.
The study was supported and funded by the Carlos Slim Foundation. Dr. Gómez-Martín, Dr. Martínez-Juárez, and Dr. Cuapio have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Proinflammatory elements mediated through metabolic pathways related to obesity and increased cellular senescence in CD57 expression in CD8+ T cells are associated with postacute sequelae of COVID-19 (PASC), according to a Mexican study. The researchers followed a Mexican cohort of 102 patients 3 months and 6 months after acute SARS-CoV-2 infection.
The study’s principal investigator was Diana Gómez-Martín, MD, PhD, of the department of immunology and rheumatology at the Salvador Zubirán National Institute of Medical Sciences and Nutrition, Mexico City. She told this news organization that follow-up of the patients began with the objective of understanding the determinative clinical, genetic, metabolic, and immunological factors in the progression of the acute disease. However, clinical aspects associated with PASC developed in the selected cohort. As a result, the study was extended, and the clinical, metabolic, and immunologic conditions in this single-center Mexican cohort were evaluated 3 months 6 months after the onset of infection.
Dr. Gómez-Martín explained that the immune senescence in CD57 of CD8+ T cells is one of the best-known findings of the present study. If it is confirmed in future studies, it could have important implications. “Its main implication is the possibility of better understanding the physiopathology of the clinical aspects associated with postacute sequelae of COVID-19, potentially being used for early detection and to provide follow-up aimed at patients, in addition to eventually developing targeted therapeutic strategies, such as immunometabolism regulation, in certain populations.”
Patients with PASC
The study was conducted from August 2020 to August 2021. Investigators recruited 102 patients (median age, 50.5 years; 55% were women) at the Mexico City Temporary Unit with a confirmed diagnosis of SARS-CoV-2. Of the patients, 44% had mild or moderate COVID-19, 30% had severe cases, and 26% of patients had critical cases. The most frequent comorbidities were obesity (44%), hypertension (24%), and type 2 diabetes (24%). The authors used a questionnaire to assess the presence of symptoms during follow-up. They analyzed immunologic variables at the time of recruitment, as well as levels of cytokines, immunoglobulin G against SARS-CoV-2, and neutrophil extracellular traps (NETs) at 1, 3, and 6 months. At 6 months’ follow-up, 12.7% of the cohort had symptoms compatible with PASC, which was defined for the study as the presence and report of three or more symptoms at 6 months’ follow-up.
As in similar studies, the authors found that female gender, remaining in intensive care, and having had more symptoms and greater titers of anti-SARS-CoV-2 antibodies during the acute infection were associated with the development of clinical aspects associated with PASC. Patients who had the disease at 6 months had increased serum levels of interleukin-1 alpha (6.21 pg/mL vs. 2.21 pg/mL), granulocyte colony-stimulating factor (55.08 pg/mL vs. 14.68 pg/mL), and interferon gamma-induced protein 10 (2,309.40 pg/mL vs. 780 pg/mL). Also, there was a trend toward an increase in serum concentration of interleukin-1 beta, interleukin-6, and interferon-gamma.
Patients whose condition met the definition of persistent PASC had increased expression of CD57 in CD8+ T cells (42,714 arbitrary units vs. 28,506) 6 months after the acute infection. The authors reported that there was no association between the persistence of PASC and the baseline amount of NETs, TRIM63, and anticellular antibodies. Nor was there an association between PASC and the titers of anti-SARS-CoV-2 antibodies at baseline and 1 month after COVID-19 diagnosis. Nonetheless, patients with persistent PASC had higher titers of anti-SARS-CoV-2 IgGs 3 months after the onset of COVID-19.
On the basis of previous data, the researchers aimed to construct a preliminary explanatory model to address the clinical and immunologic features associated with persistent PASC 6 months after SARS-CoV-2 infection. In the univariate analysis, the variables associated with the diagnosis of persistent PASC were the serum levels of granulocyte colony-stimulating factor (odds ratio, 1.01), macrophage inflammatory protein-1 alpha (OR, 1.13), interferon gamma-induced protein 10 (OR, 1.00), interleukin-6 (OR, 1.03), the expression of CD57 in CD8+ T cells (OR, 1.00), and the titers of anti-SARS-CoV-2 IgG at 1 month (OR, 1.45).
, such as obesity, greater levels of macrophage inflammatory protein-1 alpha and interferon gamma-induced protein 10 in peripheral blood, greater expression of the senescence CD57 marker in CD8+ T lymphocytes, and persistent symptoms at 3 months.
Using these parameters to construct a predictive model after 3 months, the authors found a sensitivity of 97.7%, specificity of 53.8%, positive predictive value of 93.5%, and a negative predictive value of 77.7% for the diagnosis of clinical aspects associated with PASC at 6 months.
Interpreting CD57
One of the researchers who participated in the study was Luis Martínez-Juárez, MD, MPH, DrPH. He is on the operative solutions team at the Carlos Slim Foundation. Dr. Martínez-Juárez pointed out that one of the contributions of this study was that it specifically examined the Mexican population. He noted that “according to the findings, obesity is not only a comorbidity associated with more severe progressions during acute COVID-19 disease, but also, through inflammation parameters, such as interleukin-6, interferon gamma-induced protein 10, and macrophage inflammatory protein-1 alpha, it’s involved in the development of clinical aspects related to postacute sequelae of COVID-19.”
Dr. Gómez-Martín added that finding proinflammatory and obesity parameters in the patients could potentially support the hypothesis of the persistence of virus fragments in adipose tissue as possibly involved in clinical aspects associated with PASC, as some groups have reported in the medical literature.
Angélica Cuapio, MD, DrMed, an immunologist and senior investigator at the Karolinska Institute, Stockholm, who did not participate in the study, said in an interview that the authors’ findings on the sustained increase of the CD57 marker in CD8+ lymphocytes are of notable interest. They may be associated with senescence states or cellular aging or with a stage of chronic viral infections. Therefore, Dr. Cuapio argued, it would have been valuable to include cellular markers of the innate system, such as natural killer cells, since in various infections, an increase in CD57 in lymphocytes is accompanied by an almost proportional increase of this marker in natural killer cells.
“This information would help to determine more accurately if we are talking about a cellular senescence or more about a chronic infection in persistent COVID-19.” The finding is important, but future research is needed in this developing field.
Dr. Cuapio pointed out that the authors found an interesting elevation in interleukin-1 alpha in patients with clinical aspects associated with PASC in a clinically well-characterized population in Mexico. “It is possible that this is a specific marker either of a specific population or location, or this could be an association with a humoral response. Despite the fact that this finding is new and unclear, it is worth investigating. This study is of great value for the scientific community because it’s one more piece in the complex puzzle of clinical aspects associated with postacute sequelae of COVID-19.”
Dr. Gómez-Martín noted that the main limitations of the study consist of its single-center design and the small patient sample. Dr. Martínez-Juárez added that the study did not consider reinfections. In future studies, it would be ideal to integrate other molecular assessments associated with various hypotheses of the physiopathology of clinical aspects associated with PASC, such as microbiota alteration, coagulation anomalies, endothelial damage, and dysfunctional neurologic signaling.
The study was supported and funded by the Carlos Slim Foundation. Dr. Gómez-Martín, Dr. Martínez-Juárez, and Dr. Cuapio have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Proinflammatory elements mediated through metabolic pathways related to obesity and increased cellular senescence in CD57 expression in CD8+ T cells are associated with postacute sequelae of COVID-19 (PASC), according to a Mexican study. The researchers followed a Mexican cohort of 102 patients 3 months and 6 months after acute SARS-CoV-2 infection.
The study’s principal investigator was Diana Gómez-Martín, MD, PhD, of the department of immunology and rheumatology at the Salvador Zubirán National Institute of Medical Sciences and Nutrition, Mexico City. She told this news organization that follow-up of the patients began with the objective of understanding the determinative clinical, genetic, metabolic, and immunological factors in the progression of the acute disease. However, clinical aspects associated with PASC developed in the selected cohort. As a result, the study was extended, and the clinical, metabolic, and immunologic conditions in this single-center Mexican cohort were evaluated 3 months 6 months after the onset of infection.
Dr. Gómez-Martín explained that the immune senescence in CD57 of CD8+ T cells is one of the best-known findings of the present study. If it is confirmed in future studies, it could have important implications. “Its main implication is the possibility of better understanding the physiopathology of the clinical aspects associated with postacute sequelae of COVID-19, potentially being used for early detection and to provide follow-up aimed at patients, in addition to eventually developing targeted therapeutic strategies, such as immunometabolism regulation, in certain populations.”
Patients with PASC
The study was conducted from August 2020 to August 2021. Investigators recruited 102 patients (median age, 50.5 years; 55% were women) at the Mexico City Temporary Unit with a confirmed diagnosis of SARS-CoV-2. Of the patients, 44% had mild or moderate COVID-19, 30% had severe cases, and 26% of patients had critical cases. The most frequent comorbidities were obesity (44%), hypertension (24%), and type 2 diabetes (24%). The authors used a questionnaire to assess the presence of symptoms during follow-up. They analyzed immunologic variables at the time of recruitment, as well as levels of cytokines, immunoglobulin G against SARS-CoV-2, and neutrophil extracellular traps (NETs) at 1, 3, and 6 months. At 6 months’ follow-up, 12.7% of the cohort had symptoms compatible with PASC, which was defined for the study as the presence and report of three or more symptoms at 6 months’ follow-up.
As in similar studies, the authors found that female gender, remaining in intensive care, and having had more symptoms and greater titers of anti-SARS-CoV-2 antibodies during the acute infection were associated with the development of clinical aspects associated with PASC. Patients who had the disease at 6 months had increased serum levels of interleukin-1 alpha (6.21 pg/mL vs. 2.21 pg/mL), granulocyte colony-stimulating factor (55.08 pg/mL vs. 14.68 pg/mL), and interferon gamma-induced protein 10 (2,309.40 pg/mL vs. 780 pg/mL). Also, there was a trend toward an increase in serum concentration of interleukin-1 beta, interleukin-6, and interferon-gamma.
Patients whose condition met the definition of persistent PASC had increased expression of CD57 in CD8+ T cells (42,714 arbitrary units vs. 28,506) 6 months after the acute infection. The authors reported that there was no association between the persistence of PASC and the baseline amount of NETs, TRIM63, and anticellular antibodies. Nor was there an association between PASC and the titers of anti-SARS-CoV-2 antibodies at baseline and 1 month after COVID-19 diagnosis. Nonetheless, patients with persistent PASC had higher titers of anti-SARS-CoV-2 IgGs 3 months after the onset of COVID-19.
On the basis of previous data, the researchers aimed to construct a preliminary explanatory model to address the clinical and immunologic features associated with persistent PASC 6 months after SARS-CoV-2 infection. In the univariate analysis, the variables associated with the diagnosis of persistent PASC were the serum levels of granulocyte colony-stimulating factor (odds ratio, 1.01), macrophage inflammatory protein-1 alpha (OR, 1.13), interferon gamma-induced protein 10 (OR, 1.00), interleukin-6 (OR, 1.03), the expression of CD57 in CD8+ T cells (OR, 1.00), and the titers of anti-SARS-CoV-2 IgG at 1 month (OR, 1.45).
, such as obesity, greater levels of macrophage inflammatory protein-1 alpha and interferon gamma-induced protein 10 in peripheral blood, greater expression of the senescence CD57 marker in CD8+ T lymphocytes, and persistent symptoms at 3 months.
Using these parameters to construct a predictive model after 3 months, the authors found a sensitivity of 97.7%, specificity of 53.8%, positive predictive value of 93.5%, and a negative predictive value of 77.7% for the diagnosis of clinical aspects associated with PASC at 6 months.
Interpreting CD57
One of the researchers who participated in the study was Luis Martínez-Juárez, MD, MPH, DrPH. He is on the operative solutions team at the Carlos Slim Foundation. Dr. Martínez-Juárez pointed out that one of the contributions of this study was that it specifically examined the Mexican population. He noted that “according to the findings, obesity is not only a comorbidity associated with more severe progressions during acute COVID-19 disease, but also, through inflammation parameters, such as interleukin-6, interferon gamma-induced protein 10, and macrophage inflammatory protein-1 alpha, it’s involved in the development of clinical aspects related to postacute sequelae of COVID-19.”
Dr. Gómez-Martín added that finding proinflammatory and obesity parameters in the patients could potentially support the hypothesis of the persistence of virus fragments in adipose tissue as possibly involved in clinical aspects associated with PASC, as some groups have reported in the medical literature.
Angélica Cuapio, MD, DrMed, an immunologist and senior investigator at the Karolinska Institute, Stockholm, who did not participate in the study, said in an interview that the authors’ findings on the sustained increase of the CD57 marker in CD8+ lymphocytes are of notable interest. They may be associated with senescence states or cellular aging or with a stage of chronic viral infections. Therefore, Dr. Cuapio argued, it would have been valuable to include cellular markers of the innate system, such as natural killer cells, since in various infections, an increase in CD57 in lymphocytes is accompanied by an almost proportional increase of this marker in natural killer cells.
“This information would help to determine more accurately if we are talking about a cellular senescence or more about a chronic infection in persistent COVID-19.” The finding is important, but future research is needed in this developing field.
Dr. Cuapio pointed out that the authors found an interesting elevation in interleukin-1 alpha in patients with clinical aspects associated with PASC in a clinically well-characterized population in Mexico. “It is possible that this is a specific marker either of a specific population or location, or this could be an association with a humoral response. Despite the fact that this finding is new and unclear, it is worth investigating. This study is of great value for the scientific community because it’s one more piece in the complex puzzle of clinical aspects associated with postacute sequelae of COVID-19.”
Dr. Gómez-Martín noted that the main limitations of the study consist of its single-center design and the small patient sample. Dr. Martínez-Juárez added that the study did not consider reinfections. In future studies, it would be ideal to integrate other molecular assessments associated with various hypotheses of the physiopathology of clinical aspects associated with PASC, such as microbiota alteration, coagulation anomalies, endothelial damage, and dysfunctional neurologic signaling.
The study was supported and funded by the Carlos Slim Foundation. Dr. Gómez-Martín, Dr. Martínez-Juárez, and Dr. Cuapio have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Metformin linked to reductions in COVID-19 viral load
These findings add to a multitude of benefits the drug has been shown to have in COVID infection.
COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.
“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.
Study details
For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.
A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.
The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.
The patients had a median age of 46 years, and all had either overweight or obesity. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.
About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.
The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.
The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; P = .003).
An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.
Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).
The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.
No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.
The findings are consistent with results of other recent observational studies, including research showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.
The authors’ previous analysis looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.
Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in influenza, and more recently, RNA assays suggesting effects against other RNA viruses, including the Zika virus.
In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.
“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.
‘Data from other studies are conflicting’
Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.
However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of HIV, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.
Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.
Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.
The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
These findings add to a multitude of benefits the drug has been shown to have in COVID infection.
COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.
“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.
Study details
For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.
A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.
The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.
The patients had a median age of 46 years, and all had either overweight or obesity. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.
About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.
The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.
The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; P = .003).
An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.
Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).
The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.
No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.
The findings are consistent with results of other recent observational studies, including research showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.
The authors’ previous analysis looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.
Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in influenza, and more recently, RNA assays suggesting effects against other RNA viruses, including the Zika virus.
In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.
“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.
‘Data from other studies are conflicting’
Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.
However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of HIV, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.
Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.
Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.
The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
These findings add to a multitude of benefits the drug has been shown to have in COVID infection.
COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.
“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.
Study details
For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.
A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.
The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.
The patients had a median age of 46 years, and all had either overweight or obesity. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.
About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.
The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.
The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; P = .003).
An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.
Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).
The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.
No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.
The findings are consistent with results of other recent observational studies, including research showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.
The authors’ previous analysis looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.
Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in influenza, and more recently, RNA assays suggesting effects against other RNA viruses, including the Zika virus.
In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.
“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.
‘Data from other studies are conflicting’
Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.
However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of HIV, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.
Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.
Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.
The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM CROI 2023
Inflammation and immunity troubles top long-COVID suspect list
“I think that it’s a much more complex picture than just inflammation, or just autoimmunity, or just immune dysregulation. And it’s probably a combination of all three causing a cascade of effects that then manifests itself as brain fog, or shortness of breath, or chronic fatigue,” says Alexander Truong, MD, a pulmonologist and assistant professor at Emory University, Atlanta, who also runs a long-COVID clinic.
Long COVID, post–COVID-19 condition, and postacute sequelae of SARS-CoV-2 (PASC) are among the terms used by the National Institutes of Health to describe the long-term health issues faced by an estimated 10%-30% of people infected with COVID-19. Symptoms – as many as 200 – can range from inconvenient to crippling, damage multiple organ systems, come and go, and relapse. Long COVID increases the risk of worsening existing health problems and triggering new ones, including cardiovascular disease and type 2 diabetes.
So far, research suggests there is no single cause, condition, or disease that explains why some people have an extensive range of symptoms long after the early COVID-19 infection has cleared up. Many experts believe some combination of biological processes – including the virus hanging around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems, and even the reactivation of dormant viruses such as the Epstein-Barr virus – could be the culprit, a theory also supported by a comprehensive and in-depth review of long-COVID studies published in the journal Nature Reviews Microbiology.
“It’s become clear over the last couple of years that there are different [symptoms] of long COVID … that cannot all be lumped together,” says Michael Peluso, MD, an assistant professor of medicine and an infectious diseases doctor at the University of California, San Francisco.
Inflammation and a virus that hangs around
Multiple studies have shown that the virus or pieces of it can remain in many parts of the body, including the kidneys, brain, heart, and gastrointestinal system, long after the early infection.
“One major question that I think is the area of most intense investigation now is whether there is viral persistence that is driving immune dysregulation and therefore symptoms,” says Dr. Peluso.
A small Harvard University study, for example, found evidence that reservoirs of the coronavirus could linger in patients up to a year after they’re first diagnosed.
An earlier German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines – small proteins that tell the body’s immune system what to do and are involved in the growth and activity of immune system cells and blood cells. Researchers said the results supported the theory that there is persistent reprogramming of certain immune cells, and that the uncontrolled “self-fueled hyperinflammation” during the early COVID-19 infection can become continued immune cell disruption that drives long-COVID symptoms.
“Long COVID is more likely due to either an inflammatory response by the body or reservoirs of virus that the body is still trying to clear … and the symptoms we’re seeing are a side effect of that,” says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.
Australian researchers found that immune system recovery appeared different, compared with those who were infected with other common coronaviruses.
These findings also support concerns that some experts express over the long-term risks of COVID-19 infections in general, but especially repeat infections.
“Anything that kind of revs up inflammation in the body can boil that pot over and make the symptoms worse. That’s very easily an infection or some other insult to the body. So that’s the generalized hypothesis as to why insults to the body may worsen the symptoms,” says Dr. Truong.
An autoimmune condition?
But inflammation alone does not fully explain post–COVID-19 problems.
Dr. Truong and his team, for example, have been documenting inflammatory markers in patients at the post-COVID clinic he cofounded more than 2 years ago at Emory Executive Park in Atlanta. When the clinic was first launched, high-dose nonsteroidal anti-inflammatory drugs – including ibuprofen – and prednisone were prescribed to long-COVID patients.
“It didn’t make a difference at all for any of these folks,” he says, adding that there are signs that autoimmunity is at play. But he cautions that it is still too early to suggest treating long-COVID patients with medications used for other autoimmune conditions.
In autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes, a person’s immune system can’t tell normal cells from foreign pathogens and attacks healthy cells. There is typically no single diagnostic test, and many share similar symptoms, making detection and diagnosis potentially difficult, according to Johns Hopkins Medicine.
A small study published in the journal Science Translational Medicine found that, among patients who failed to regain their sense of smell long after their initial infection, there was inflammation in the nose tissue where smell nerve cells are found, even though no detectable virus remained. Fewer olfactory sensory neurons were seen, as well – findings that researchers said resembled some kind of “autoimmune-like process.”
Meanwhile, scientists in Canada found signs of autoimmunity in blood samples taken from patients who still had fatigue and shortness of breath after their initial COVID-19 infection. Two specific proteins were present a year after infection in up to 30% of patients, many of whom still had shortness of breath and fatigue, the researchers reported in the Jan. 1 issue of the European Respiratory Journal. These patients had been healthy and had no autoimmune condition or other diseases before they were infected.
Immune system problems
A number of studies have suggested that a problematic immune response could also explain why symptoms persist for some people.
Researchers in France, for example, found that the immune response problems in those with severe COVID-19 infections caused exaggerated or uncontrolled formation of a type of bug-fighting defense mechanism called a neutrophil extracellular trap (NET), which in turn triggers harmful inflammation that can result in multiorgan damage. These traps are netlike structures made from fibers composed mostly of DNA strings that bind, or trap, pathogens.
Long COVID is not like an acute infectious disease, says Alexander Charney, MD, PhD, the lead principal investigator of the RECOVER adult cohort at Mount Sinai in New York, and an associate professor at Icahn School of Medicine at Mount Sinai. It is more similar to other complex chronic diseases that have taken decades to understand, such as heart disease, mental illness, and rheumatologic diseases, he says.
Biomarkers and blood clots
Scientists are homing in on biomarkers, or detectable and measurable traits – in this case, molecular indicators – that can make diagnosing long COVID easier and give better direction for treatment. These biomarkers are also key to helping sort out the complex biology of long COVID.
In one study, data from blood samples taken from hundreds of hospitalized COVID-19 patients suggests changes are happening at the molecular level during initial severe infections. These changes may be tied to the development of longer-term symptoms, according to the study by Dr. Charney and his team at Mount Sinai published in Nature Medicine
Blood clotting issues have also been detected in long COVID patients. At least one study found signs that long-COVID patients had higher levels of a type of auto-antibody linked to the abnormal formation of clots. Researchers suspect that tiny, persistent microclots – undetectable via regular pathology tests – may be cutting off oxygen flow to tissue by blocking capillaries – and could explain many of the post-COVID symptoms described by patients.
While enormous progress has been made toward understanding long COVID, the research is still considered early and faces many challenges, including varying criteria used to define the condition, the types and quality of data used, differences in how patients are defined and recruited, and the small size of many studies. Some research also appears to conflict with other studies. And while there are specialized tools for diagnosing some aspects of the condition, standard tests often don’t detect many of the signs seen in long-COVID patients. But given the urgency and global scale of the problem, experts say more funding and support should be prioritized.
“People are suffering now, and they want answers now. ... It’s not like with COVID, where the path towards a great and meaningful solution to this unbelievable problem was clear – we need a vaccine,” says Dr. Charney.
“It’s going to be a long haul to figure out what is going on.”
A version of this article originally appeared on WebMD.com.
“I think that it’s a much more complex picture than just inflammation, or just autoimmunity, or just immune dysregulation. And it’s probably a combination of all three causing a cascade of effects that then manifests itself as brain fog, or shortness of breath, or chronic fatigue,” says Alexander Truong, MD, a pulmonologist and assistant professor at Emory University, Atlanta, who also runs a long-COVID clinic.
Long COVID, post–COVID-19 condition, and postacute sequelae of SARS-CoV-2 (PASC) are among the terms used by the National Institutes of Health to describe the long-term health issues faced by an estimated 10%-30% of people infected with COVID-19. Symptoms – as many as 200 – can range from inconvenient to crippling, damage multiple organ systems, come and go, and relapse. Long COVID increases the risk of worsening existing health problems and triggering new ones, including cardiovascular disease and type 2 diabetes.
So far, research suggests there is no single cause, condition, or disease that explains why some people have an extensive range of symptoms long after the early COVID-19 infection has cleared up. Many experts believe some combination of biological processes – including the virus hanging around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems, and even the reactivation of dormant viruses such as the Epstein-Barr virus – could be the culprit, a theory also supported by a comprehensive and in-depth review of long-COVID studies published in the journal Nature Reviews Microbiology.
“It’s become clear over the last couple of years that there are different [symptoms] of long COVID … that cannot all be lumped together,” says Michael Peluso, MD, an assistant professor of medicine and an infectious diseases doctor at the University of California, San Francisco.
Inflammation and a virus that hangs around
Multiple studies have shown that the virus or pieces of it can remain in many parts of the body, including the kidneys, brain, heart, and gastrointestinal system, long after the early infection.
“One major question that I think is the area of most intense investigation now is whether there is viral persistence that is driving immune dysregulation and therefore symptoms,” says Dr. Peluso.
A small Harvard University study, for example, found evidence that reservoirs of the coronavirus could linger in patients up to a year after they’re first diagnosed.
An earlier German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines – small proteins that tell the body’s immune system what to do and are involved in the growth and activity of immune system cells and blood cells. Researchers said the results supported the theory that there is persistent reprogramming of certain immune cells, and that the uncontrolled “self-fueled hyperinflammation” during the early COVID-19 infection can become continued immune cell disruption that drives long-COVID symptoms.
“Long COVID is more likely due to either an inflammatory response by the body or reservoirs of virus that the body is still trying to clear … and the symptoms we’re seeing are a side effect of that,” says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.
Australian researchers found that immune system recovery appeared different, compared with those who were infected with other common coronaviruses.
These findings also support concerns that some experts express over the long-term risks of COVID-19 infections in general, but especially repeat infections.
“Anything that kind of revs up inflammation in the body can boil that pot over and make the symptoms worse. That’s very easily an infection or some other insult to the body. So that’s the generalized hypothesis as to why insults to the body may worsen the symptoms,” says Dr. Truong.
An autoimmune condition?
But inflammation alone does not fully explain post–COVID-19 problems.
Dr. Truong and his team, for example, have been documenting inflammatory markers in patients at the post-COVID clinic he cofounded more than 2 years ago at Emory Executive Park in Atlanta. When the clinic was first launched, high-dose nonsteroidal anti-inflammatory drugs – including ibuprofen – and prednisone were prescribed to long-COVID patients.
“It didn’t make a difference at all for any of these folks,” he says, adding that there are signs that autoimmunity is at play. But he cautions that it is still too early to suggest treating long-COVID patients with medications used for other autoimmune conditions.
In autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes, a person’s immune system can’t tell normal cells from foreign pathogens and attacks healthy cells. There is typically no single diagnostic test, and many share similar symptoms, making detection and diagnosis potentially difficult, according to Johns Hopkins Medicine.
A small study published in the journal Science Translational Medicine found that, among patients who failed to regain their sense of smell long after their initial infection, there was inflammation in the nose tissue where smell nerve cells are found, even though no detectable virus remained. Fewer olfactory sensory neurons were seen, as well – findings that researchers said resembled some kind of “autoimmune-like process.”
Meanwhile, scientists in Canada found signs of autoimmunity in blood samples taken from patients who still had fatigue and shortness of breath after their initial COVID-19 infection. Two specific proteins were present a year after infection in up to 30% of patients, many of whom still had shortness of breath and fatigue, the researchers reported in the Jan. 1 issue of the European Respiratory Journal. These patients had been healthy and had no autoimmune condition or other diseases before they were infected.
Immune system problems
A number of studies have suggested that a problematic immune response could also explain why symptoms persist for some people.
Researchers in France, for example, found that the immune response problems in those with severe COVID-19 infections caused exaggerated or uncontrolled formation of a type of bug-fighting defense mechanism called a neutrophil extracellular trap (NET), which in turn triggers harmful inflammation that can result in multiorgan damage. These traps are netlike structures made from fibers composed mostly of DNA strings that bind, or trap, pathogens.
Long COVID is not like an acute infectious disease, says Alexander Charney, MD, PhD, the lead principal investigator of the RECOVER adult cohort at Mount Sinai in New York, and an associate professor at Icahn School of Medicine at Mount Sinai. It is more similar to other complex chronic diseases that have taken decades to understand, such as heart disease, mental illness, and rheumatologic diseases, he says.
Biomarkers and blood clots
Scientists are homing in on biomarkers, or detectable and measurable traits – in this case, molecular indicators – that can make diagnosing long COVID easier and give better direction for treatment. These biomarkers are also key to helping sort out the complex biology of long COVID.
In one study, data from blood samples taken from hundreds of hospitalized COVID-19 patients suggests changes are happening at the molecular level during initial severe infections. These changes may be tied to the development of longer-term symptoms, according to the study by Dr. Charney and his team at Mount Sinai published in Nature Medicine
Blood clotting issues have also been detected in long COVID patients. At least one study found signs that long-COVID patients had higher levels of a type of auto-antibody linked to the abnormal formation of clots. Researchers suspect that tiny, persistent microclots – undetectable via regular pathology tests – may be cutting off oxygen flow to tissue by blocking capillaries – and could explain many of the post-COVID symptoms described by patients.
While enormous progress has been made toward understanding long COVID, the research is still considered early and faces many challenges, including varying criteria used to define the condition, the types and quality of data used, differences in how patients are defined and recruited, and the small size of many studies. Some research also appears to conflict with other studies. And while there are specialized tools for diagnosing some aspects of the condition, standard tests often don’t detect many of the signs seen in long-COVID patients. But given the urgency and global scale of the problem, experts say more funding and support should be prioritized.
“People are suffering now, and they want answers now. ... It’s not like with COVID, where the path towards a great and meaningful solution to this unbelievable problem was clear – we need a vaccine,” says Dr. Charney.
“It’s going to be a long haul to figure out what is going on.”
A version of this article originally appeared on WebMD.com.
“I think that it’s a much more complex picture than just inflammation, or just autoimmunity, or just immune dysregulation. And it’s probably a combination of all three causing a cascade of effects that then manifests itself as brain fog, or shortness of breath, or chronic fatigue,” says Alexander Truong, MD, a pulmonologist and assistant professor at Emory University, Atlanta, who also runs a long-COVID clinic.
Long COVID, post–COVID-19 condition, and postacute sequelae of SARS-CoV-2 (PASC) are among the terms used by the National Institutes of Health to describe the long-term health issues faced by an estimated 10%-30% of people infected with COVID-19. Symptoms – as many as 200 – can range from inconvenient to crippling, damage multiple organ systems, come and go, and relapse. Long COVID increases the risk of worsening existing health problems and triggering new ones, including cardiovascular disease and type 2 diabetes.
So far, research suggests there is no single cause, condition, or disease that explains why some people have an extensive range of symptoms long after the early COVID-19 infection has cleared up. Many experts believe some combination of biological processes – including the virus hanging around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems, and even the reactivation of dormant viruses such as the Epstein-Barr virus – could be the culprit, a theory also supported by a comprehensive and in-depth review of long-COVID studies published in the journal Nature Reviews Microbiology.
“It’s become clear over the last couple of years that there are different [symptoms] of long COVID … that cannot all be lumped together,” says Michael Peluso, MD, an assistant professor of medicine and an infectious diseases doctor at the University of California, San Francisco.
Inflammation and a virus that hangs around
Multiple studies have shown that the virus or pieces of it can remain in many parts of the body, including the kidneys, brain, heart, and gastrointestinal system, long after the early infection.
“One major question that I think is the area of most intense investigation now is whether there is viral persistence that is driving immune dysregulation and therefore symptoms,” says Dr. Peluso.
A small Harvard University study, for example, found evidence that reservoirs of the coronavirus could linger in patients up to a year after they’re first diagnosed.
An earlier German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines – small proteins that tell the body’s immune system what to do and are involved in the growth and activity of immune system cells and blood cells. Researchers said the results supported the theory that there is persistent reprogramming of certain immune cells, and that the uncontrolled “self-fueled hyperinflammation” during the early COVID-19 infection can become continued immune cell disruption that drives long-COVID symptoms.
“Long COVID is more likely due to either an inflammatory response by the body or reservoirs of virus that the body is still trying to clear … and the symptoms we’re seeing are a side effect of that,” says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.
Australian researchers found that immune system recovery appeared different, compared with those who were infected with other common coronaviruses.
These findings also support concerns that some experts express over the long-term risks of COVID-19 infections in general, but especially repeat infections.
“Anything that kind of revs up inflammation in the body can boil that pot over and make the symptoms worse. That’s very easily an infection or some other insult to the body. So that’s the generalized hypothesis as to why insults to the body may worsen the symptoms,” says Dr. Truong.
An autoimmune condition?
But inflammation alone does not fully explain post–COVID-19 problems.
Dr. Truong and his team, for example, have been documenting inflammatory markers in patients at the post-COVID clinic he cofounded more than 2 years ago at Emory Executive Park in Atlanta. When the clinic was first launched, high-dose nonsteroidal anti-inflammatory drugs – including ibuprofen – and prednisone were prescribed to long-COVID patients.
“It didn’t make a difference at all for any of these folks,” he says, adding that there are signs that autoimmunity is at play. But he cautions that it is still too early to suggest treating long-COVID patients with medications used for other autoimmune conditions.
In autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes, a person’s immune system can’t tell normal cells from foreign pathogens and attacks healthy cells. There is typically no single diagnostic test, and many share similar symptoms, making detection and diagnosis potentially difficult, according to Johns Hopkins Medicine.
A small study published in the journal Science Translational Medicine found that, among patients who failed to regain their sense of smell long after their initial infection, there was inflammation in the nose tissue where smell nerve cells are found, even though no detectable virus remained. Fewer olfactory sensory neurons were seen, as well – findings that researchers said resembled some kind of “autoimmune-like process.”
Meanwhile, scientists in Canada found signs of autoimmunity in blood samples taken from patients who still had fatigue and shortness of breath after their initial COVID-19 infection. Two specific proteins were present a year after infection in up to 30% of patients, many of whom still had shortness of breath and fatigue, the researchers reported in the Jan. 1 issue of the European Respiratory Journal. These patients had been healthy and had no autoimmune condition or other diseases before they were infected.
Immune system problems
A number of studies have suggested that a problematic immune response could also explain why symptoms persist for some people.
Researchers in France, for example, found that the immune response problems in those with severe COVID-19 infections caused exaggerated or uncontrolled formation of a type of bug-fighting defense mechanism called a neutrophil extracellular trap (NET), which in turn triggers harmful inflammation that can result in multiorgan damage. These traps are netlike structures made from fibers composed mostly of DNA strings that bind, or trap, pathogens.
Long COVID is not like an acute infectious disease, says Alexander Charney, MD, PhD, the lead principal investigator of the RECOVER adult cohort at Mount Sinai in New York, and an associate professor at Icahn School of Medicine at Mount Sinai. It is more similar to other complex chronic diseases that have taken decades to understand, such as heart disease, mental illness, and rheumatologic diseases, he says.
Biomarkers and blood clots
Scientists are homing in on biomarkers, or detectable and measurable traits – in this case, molecular indicators – that can make diagnosing long COVID easier and give better direction for treatment. These biomarkers are also key to helping sort out the complex biology of long COVID.
In one study, data from blood samples taken from hundreds of hospitalized COVID-19 patients suggests changes are happening at the molecular level during initial severe infections. These changes may be tied to the development of longer-term symptoms, according to the study by Dr. Charney and his team at Mount Sinai published in Nature Medicine
Blood clotting issues have also been detected in long COVID patients. At least one study found signs that long-COVID patients had higher levels of a type of auto-antibody linked to the abnormal formation of clots. Researchers suspect that tiny, persistent microclots – undetectable via regular pathology tests – may be cutting off oxygen flow to tissue by blocking capillaries – and could explain many of the post-COVID symptoms described by patients.
While enormous progress has been made toward understanding long COVID, the research is still considered early and faces many challenges, including varying criteria used to define the condition, the types and quality of data used, differences in how patients are defined and recruited, and the small size of many studies. Some research also appears to conflict with other studies. And while there are specialized tools for diagnosing some aspects of the condition, standard tests often don’t detect many of the signs seen in long-COVID patients. But given the urgency and global scale of the problem, experts say more funding and support should be prioritized.
“People are suffering now, and they want answers now. ... It’s not like with COVID, where the path towards a great and meaningful solution to this unbelievable problem was clear – we need a vaccine,” says Dr. Charney.
“It’s going to be a long haul to figure out what is going on.”
A version of this article originally appeared on WebMD.com.
Long COVID affecting more than one-third of college students, faculty
With a median age of 23 years, the study is unique for evaluating mostly healthy, young adults and for its rare look at long COVID in a university community.
The more symptoms during a bout with COVID, the greater the risk for long COVID, the researchers found. That lines up with previous studies. Also, the more vaccinations and booster shots against SARS-CoV-2, the virus that causes COVID, the lower the long COVID risk.
Women were more likely than men to be affected. Current or prior smoking, seeking medical care for COVID, and receiving antibody treatment also were linked to higher chances for developing long COVID.
Lead author Megan Landry, DrPH, MPH, and colleagues were already assessing students, staff, and faculty at George Washington University, Washington, who tested positive for COVID. Then they started seeing symptoms that lasted 28 days or more after their 10-day isolation period.
“We were starting to recognize that individuals ... were still having symptoms longer than the typical isolation period,” said Dr. Landry. So they developed a questionnaire to figure out the how long these symptoms last and how many people are affected by them.
The list of potential symptoms was long and included trouble thinking, fatigue, loss of smell or taste, shortness of breath, and more.
The study was published online in Emerging Infectious Diseases. Results are based on records and responses from 1,388 students, faculty, and staff from July 2021 to March 2022.
People had a median of four long COVID symptoms, about 63% were women, and 56% were non-Hispanic White. About three-quarters were students and the remainder were faculty and staff.
The finding that 36% of people with a history of COVID reported long COVID symptoms did not surprise Dr. Landry.
“Based on the literature that’s currently out there, it ranges from a 10% to an 80% prevalence of long COVID,” she said. “We kind of figured that we would fall somewhere in there.”
In contrast, that figure seemed high to Eric Topol, MD.
“That’s really high,” said Dr. Topol, founder and director of the Scripps Research Translational Institute in La Jolla, Calif. He added most studies estimate that about 10% of people with a history of acute infection develop long COVID.
Even at 10%, which could be an underestimate, that’s a lot of affected people globally.
“At least 65 million individuals around the world have long COVID, based on a conservative estimated incidence of 10% of infected people and more than 651 million documented COVID-19 cases worldwide; the number is likely much higher due to many undocumented cases,” Dr. Topol and colleagues wrote in a long COVID review article published in Nature Reviews Microbiology.
About 30% of study participants were fully vaccinated with an initial vaccine series, 42% had received a booster dose, and 29% were not fully vaccinated at the time of their first positive test for COVID. Those who were not fully vaccinated were significantly more likely to report symptoms of long COVID.
“I know a lot of people wish they could put COVID on the back burner or brush it under the rug, but COVID is still a real thing. We need to continue supporting vaccines and boosters and make sure people are up to date. Not only for COVID, but for flu as well,” Dr. Topol said
Research continues
“Long COVID is still evolving and we continue to learn more about it every day,” Landry said. “It’s just so new and there are still a lot of unknowns. That’s why it’s important to get this information out.”
People with long COVID often have a hard time with occupational, educational, social, or personal activities, compared with before COVID, with effects that can last for more than 6 months, the authors noted.
“I think across the board, universities in general need to consider the possibility of folks on their campuses are having symptoms of long COVID,” Dr. Landry said.
Moving forward, Dr. Landry and colleagues would like to continue investigating long COVID. For example, in the current study, they did not ask about severity of symptoms or how the symptoms affected daily functioning.
“I would like to continue this and dive deeper into how disruptive their symptoms of long COVID are to their everyday studying, teaching, or their activities to keeping a university running,” Dr. Landry said.
A version of this article originally appeared on WebMD.com.
With a median age of 23 years, the study is unique for evaluating mostly healthy, young adults and for its rare look at long COVID in a university community.
The more symptoms during a bout with COVID, the greater the risk for long COVID, the researchers found. That lines up with previous studies. Also, the more vaccinations and booster shots against SARS-CoV-2, the virus that causes COVID, the lower the long COVID risk.
Women were more likely than men to be affected. Current or prior smoking, seeking medical care for COVID, and receiving antibody treatment also were linked to higher chances for developing long COVID.
Lead author Megan Landry, DrPH, MPH, and colleagues were already assessing students, staff, and faculty at George Washington University, Washington, who tested positive for COVID. Then they started seeing symptoms that lasted 28 days or more after their 10-day isolation period.
“We were starting to recognize that individuals ... were still having symptoms longer than the typical isolation period,” said Dr. Landry. So they developed a questionnaire to figure out the how long these symptoms last and how many people are affected by them.
The list of potential symptoms was long and included trouble thinking, fatigue, loss of smell or taste, shortness of breath, and more.
The study was published online in Emerging Infectious Diseases. Results are based on records and responses from 1,388 students, faculty, and staff from July 2021 to March 2022.
People had a median of four long COVID symptoms, about 63% were women, and 56% were non-Hispanic White. About three-quarters were students and the remainder were faculty and staff.
The finding that 36% of people with a history of COVID reported long COVID symptoms did not surprise Dr. Landry.
“Based on the literature that’s currently out there, it ranges from a 10% to an 80% prevalence of long COVID,” she said. “We kind of figured that we would fall somewhere in there.”
In contrast, that figure seemed high to Eric Topol, MD.
“That’s really high,” said Dr. Topol, founder and director of the Scripps Research Translational Institute in La Jolla, Calif. He added most studies estimate that about 10% of people with a history of acute infection develop long COVID.
Even at 10%, which could be an underestimate, that’s a lot of affected people globally.
“At least 65 million individuals around the world have long COVID, based on a conservative estimated incidence of 10% of infected people and more than 651 million documented COVID-19 cases worldwide; the number is likely much higher due to many undocumented cases,” Dr. Topol and colleagues wrote in a long COVID review article published in Nature Reviews Microbiology.
About 30% of study participants were fully vaccinated with an initial vaccine series, 42% had received a booster dose, and 29% were not fully vaccinated at the time of their first positive test for COVID. Those who were not fully vaccinated were significantly more likely to report symptoms of long COVID.
“I know a lot of people wish they could put COVID on the back burner or brush it under the rug, but COVID is still a real thing. We need to continue supporting vaccines and boosters and make sure people are up to date. Not only for COVID, but for flu as well,” Dr. Topol said
Research continues
“Long COVID is still evolving and we continue to learn more about it every day,” Landry said. “It’s just so new and there are still a lot of unknowns. That’s why it’s important to get this information out.”
People with long COVID often have a hard time with occupational, educational, social, or personal activities, compared with before COVID, with effects that can last for more than 6 months, the authors noted.
“I think across the board, universities in general need to consider the possibility of folks on their campuses are having symptoms of long COVID,” Dr. Landry said.
Moving forward, Dr. Landry and colleagues would like to continue investigating long COVID. For example, in the current study, they did not ask about severity of symptoms or how the symptoms affected daily functioning.
“I would like to continue this and dive deeper into how disruptive their symptoms of long COVID are to their everyday studying, teaching, or their activities to keeping a university running,” Dr. Landry said.
A version of this article originally appeared on WebMD.com.
With a median age of 23 years, the study is unique for evaluating mostly healthy, young adults and for its rare look at long COVID in a university community.
The more symptoms during a bout with COVID, the greater the risk for long COVID, the researchers found. That lines up with previous studies. Also, the more vaccinations and booster shots against SARS-CoV-2, the virus that causes COVID, the lower the long COVID risk.
Women were more likely than men to be affected. Current or prior smoking, seeking medical care for COVID, and receiving antibody treatment also were linked to higher chances for developing long COVID.
Lead author Megan Landry, DrPH, MPH, and colleagues were already assessing students, staff, and faculty at George Washington University, Washington, who tested positive for COVID. Then they started seeing symptoms that lasted 28 days or more after their 10-day isolation period.
“We were starting to recognize that individuals ... were still having symptoms longer than the typical isolation period,” said Dr. Landry. So they developed a questionnaire to figure out the how long these symptoms last and how many people are affected by them.
The list of potential symptoms was long and included trouble thinking, fatigue, loss of smell or taste, shortness of breath, and more.
The study was published online in Emerging Infectious Diseases. Results are based on records and responses from 1,388 students, faculty, and staff from July 2021 to March 2022.
People had a median of four long COVID symptoms, about 63% were women, and 56% were non-Hispanic White. About three-quarters were students and the remainder were faculty and staff.
The finding that 36% of people with a history of COVID reported long COVID symptoms did not surprise Dr. Landry.
“Based on the literature that’s currently out there, it ranges from a 10% to an 80% prevalence of long COVID,” she said. “We kind of figured that we would fall somewhere in there.”
In contrast, that figure seemed high to Eric Topol, MD.
“That’s really high,” said Dr. Topol, founder and director of the Scripps Research Translational Institute in La Jolla, Calif. He added most studies estimate that about 10% of people with a history of acute infection develop long COVID.
Even at 10%, which could be an underestimate, that’s a lot of affected people globally.
“At least 65 million individuals around the world have long COVID, based on a conservative estimated incidence of 10% of infected people and more than 651 million documented COVID-19 cases worldwide; the number is likely much higher due to many undocumented cases,” Dr. Topol and colleagues wrote in a long COVID review article published in Nature Reviews Microbiology.
About 30% of study participants were fully vaccinated with an initial vaccine series, 42% had received a booster dose, and 29% were not fully vaccinated at the time of their first positive test for COVID. Those who were not fully vaccinated were significantly more likely to report symptoms of long COVID.
“I know a lot of people wish they could put COVID on the back burner or brush it under the rug, but COVID is still a real thing. We need to continue supporting vaccines and boosters and make sure people are up to date. Not only for COVID, but for flu as well,” Dr. Topol said
Research continues
“Long COVID is still evolving and we continue to learn more about it every day,” Landry said. “It’s just so new and there are still a lot of unknowns. That’s why it’s important to get this information out.”
People with long COVID often have a hard time with occupational, educational, social, or personal activities, compared with before COVID, with effects that can last for more than 6 months, the authors noted.
“I think across the board, universities in general need to consider the possibility of folks on their campuses are having symptoms of long COVID,” Dr. Landry said.
Moving forward, Dr. Landry and colleagues would like to continue investigating long COVID. For example, in the current study, they did not ask about severity of symptoms or how the symptoms affected daily functioning.
“I would like to continue this and dive deeper into how disruptive their symptoms of long COVID are to their everyday studying, teaching, or their activities to keeping a university running,” Dr. Landry said.
A version of this article originally appeared on WebMD.com.
FROM EMERGING INFECTIOUS DISEASES
Q&A with long COVID patient-researcher: Treatments lagging as cases rise
For Julia Moore Vogel, PhD, a cup of peppermint tea marked the moment her life would change forever.
One morning in early July 2020, she took a sip of her favorite strongly flavored pick-me-up and couldn’t taste it. She knew loss of taste and smell were symptoms of COVID-19, and she suspected she had contracted the virus. A doctor’s visit confirmed her fears.
“I remember trying the tea and just being so shocked and thinking: How can this be happening to me?” said Dr. Moore Vogel, a COVID-19 researcher with the Scripps Research Translational Institute in San Diego. “I’d been so incredibly careful.”
Her physician assured her that as a healthy woman in her mid-30s, she’d be “back to normal” in 2 weeks’ time and that her loss of taste and smell “very likely will be your only symptom,” she recalled.
. Now, 2½ years later, Dr. Moore Vogel is among the tens of millions of Americans with long COVID.
As a COVID-19 patient-researcher who still struggles with fatigue and migraines, she has learned to cope with her condition. She directs the Participant Center for the All of Us Research Program, a National Institutes of Health collaboration to build the largest, most diverse health database in history. She relies on a practice called pacing, which helps conserve physical, mental, and emotional energy, to avoid making her symptoms worse.
And she is a coauthor of a landmark 200-study review of long COVID published Jan. 13 in the journal Nature, with Scripps Executive Vice President and Medscape Editor-in-Chief Eric Topol, MD. Two other institute long COVID researchers and patient advocates who have the condition coauthored the review – Lisa McCorkell and Hannah E. Davis, cofounders of the Patient-Led Research Collaborative , a group of long COVID patients who study the virus.
Dr. Moore Vogel discussed the key findings of the new review and her personal experiences with this news organization.
Q: When you contracted COVID, no treatments or vaccines existed. Can you talk about what the experience was like for you?
A: “It was July 2020. The loss of taste and smell was the first symptom, and what was interesting was that was my only symptom for a little bit. Being the goal-oriented, work-oriented person that I am, I just worked the rest of the week and hoped that it wasn’t real.
“But that was a Wednesday, and by Friday, I was just getting really tired, and it was really hard to finish my workday. I ended up taking 3 weeks off to recover from the acute phase. At the time, I had read early discussions about long COVID, and it was always on my [mind] – how long was it going to take to recover?”
Q: You went to see a doctor that first week?
A: “I called them when I had the loss of taste and smell, and they said, ‘It’s very likely this will be your only symptom.’ And when I first talked to a physician, they were saying, ‘Oh, you’re young and healthy, in 2 weeks you’ll be back to normal.’ But of course that turned out not to be true.
“It’s hard to remember what it was like at that time. There were so few treatments, it was all about rationing ventilators, and it was absolutely terrifying at the time to just not know what was going to happen.”
Q: How are you managing your condition today?
A: “I have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), one of the really common diagnoses that come out of long COVID. So, that’s the biggest thing for me to manage now, and the main management is pacing.
“I also have medications for migraine management. I’ve always had some degree of migraines, like 2 a month, but now it’s like 15 a month, so it’s a totally different scale of management.”
Q: It must be frustrating, personally and professionally, that long COVID treatments remain elusive.
A: “I’m disappointed at the pace of testing things in clinical trials. There was so much progress made, so much innovation in the early stages of the pandemic to treat the acute phase, and it led to amazing things. We have all these monoclonal antibodies, the steroids are really effective, not to mention the antivirals and the vaccines, of course, on the prevention side. It’s been amazing.
“But for some reason, long COVID treatment is really lagging. What I hypothesize as part of the reason for that is that it doesn’t feel as dramatic. When you see someone on a ventilator or hear about death, it feels very dramatic, and people really worry about that.”
Q: So, let’s talk about the research. How did your personal experiences – and those of the two other coauthors with long COVID – help inform this review?
A: “I work with Eric Topol on a regular basis, and it was amazing that he invited patients to work with him on this review ... I have to say of my other long COVID patient coauthors, Hannah Davis and Lisa McCorkell, it was amazing to work with them.
“It was my first time working with people who have long COVID on a big project. The understanding that we had of each other [where] one of us might say, Oh, I’m crashing today, I can’t work on this. Can you help get us across the finish line for this deadline? That was really amazing to me in terms of how a workplace can be with real disability accommodations.
“It’s really changed my personal outlook on how important it is to have patients involved in the process.”
Q: What was the most surprising or significant finding of the review, in your view?
A: “I would say the most impactful thing to me in the process of writing this review is how much research has been done in such a short time. We started with over 250 studies that we wanted to reference in the review, and we actually had to cut out 50 in the editorial process, which was really hard!
“There’s just been so much progress that’s been made in the past couple of years. And then thinking about the progress on long COVID in general, the other things that’s important to acknowledge is all the work that’s been done on other postviral illnesses that present very similarly to long COVID in many patients, ME/CFS, and postural orthostatic tachycardia syndrome (POTS).”
Q: One thing that stood out is the review’s finding that long COVID is potentially lifelong COVID and, in some ways, is closer to HIV-AIDS than, say, influenza. Is that right?
A: “Yes. I’m really glad you took that point away from the review because that was one of the things that I felt the most strongly about incorporating. For many people, based on the treatments that we have today, this is likely to lead to lifelong disability. And that’s something, from my personal experience, for sure. I’m seeing no improvement on the horizon.
“That’s part of why I’m so passionate about there being clinical trials because I know there are millions and millions of us. So for me, that wasn’t so surprising, because I’m living it, but I can see how for the general public that was a really surprising finding.”
Q: The review breaks down long COVID’s effects on various organs/systems, and it includes the most comprehensive look to date at the effects on pregnant women. Anything you’d care to stress about that?
A: “It really underlies the importance of vaccination, given that it can affect both the pregnant person and child. There is early evidence of development delays if there’s infection while the child is still gestating. So, I think it underscores the need for vaccination to reduce that risk.
“You know, pregnancy is a stressful and terrifying time anyway. So, if there’s anything you can do to reduce the risk to yourself and your unborn child, I think it’s really worthwhile.”
Q: Why do you think this exhaustive review was needed?
A: “Because of the massive amount of literature that’s out there, it’s so hard for anybody to sift through. Eric Topol and Hannah Davis, two of the coauthors, are two people who have done it, and they keep up with all the literature, and they are always tweeting about it.
“But most people don’t have the time to be able to sift through it, so what we did was take all of that literature, organize it into sections, and summarize the key findings. Then the other thing that I think is really important for the field right now is the recommendations piece.”
Q: What impact do you think the new long COVID review in Nature will have?
A: “The response to our review is way beyond what I expected, and I think that’s in part a sign that there is growing awareness of the issue of long COVID.
“I hope that helps spiral toward more treatment trials. Because there are a lot of great candidates out there. We have a whole table in the review about the different potential treatments that should be tested.”
Q: What’s the take-home message for physicians?
A: “One of the key recommendations is about physician education. We know that it is so hard for physicians to keep up with this massive amount of literature, and we really need more physician education that’s meant for busy physicians who really don’t have time to read all of the primary literature themselves.
“So many folks are not getting the care that they need. Because these types of conditions haven’t been seen as much by primary care providers, physical therapists, etc., there’s so much more education that’s needed.
“I think the basic tenets probably could be taught in a weekend course, [including] listening to the patients, believing patients. There are so many times patient symptoms are [dismissed and not] really being taken seriously by their physicians.
“I think part of the challenge behind that is the conflating of mental health issues with these other physiological symptoms. There’s a tendency to say, ‘Oh, all this is this caused by mental health issues’ and that mental health is the root cause, when actually it’s the illness that’s the root cause.”
Q: What’s the big picture: How significant is the public health crisis that long COVID represents?
A: “I believe it’s a massive crisis, a massive emergency. A lot of people in the long COVID community are calling it a mass-disabling event. There is concern that if we let the pandemic run unmitigated for long enough – given that we expect about 10% of folks that get COVID will end up with long COVID – we could end up eventually with a majority-disabled society.
“That would be devasting – to individuals, to the economy, the medical system. So, it’s absolutely a public health emergency in my view, and that’s part of why I’ve been so surprised by the lack of trials, the lack of awareness in the public. There hasn’t been as much public education about long COVID as there has about acute COVID. I think we can do more from a public health perspective.”
Q: What are the main challenges in combating long COVID?
A: “I think the lack of treatments is the most devastating part because it’s such a hard disease to contract, and there’s no end in sight, and so that time horizon can be really difficult. That’s part of why I’m pushing the treatments so much, because I want to offer hope to the community, you know, I want there to be hope around the corner.
“My hope is that within 5 years we’ll have treatments that can really improve quality of life for the community. And I know that that may seem like a long time for those who are suffering, and I hope that there will be some clinical trials of treatments that improve symptom management within 1-2 years. But I think for really more novel things, it’s really going to take at least 5.”
Q: Any advice you’d give to someone with long COVID today?
A: “Connecting with others that are going through the experience is extremely valuable and can really help with that mental component which can be really draining.
“The other thing, in terms of what’s important for the lives of people who are living with long COVID, I would say to everyone who doesn’t have long COVID but knows someone who does, being able to offer support is crucial and can make such a difference in quality of life.
“It is really crucial, for those who don’t have long COVID, to take it into account when you’re making your risk calculations. When you’re thinking: Am I going to wear a mask here? or Am I going to go to that bar?
“Really consider the possibility that if you get COVID, you have a 10% chance of getting long COVID. And if you get long COVID, you have a 25% chance of not being able to work anymore or being so ill that you can’t work anymore and you may lose your health insurance.
“The compounding effects are absolutely devastating, and I think that’s under-factored-in to the general risk calculations of the public.”
A version of this article first appeared on Medscape.com.
For Julia Moore Vogel, PhD, a cup of peppermint tea marked the moment her life would change forever.
One morning in early July 2020, she took a sip of her favorite strongly flavored pick-me-up and couldn’t taste it. She knew loss of taste and smell were symptoms of COVID-19, and she suspected she had contracted the virus. A doctor’s visit confirmed her fears.
“I remember trying the tea and just being so shocked and thinking: How can this be happening to me?” said Dr. Moore Vogel, a COVID-19 researcher with the Scripps Research Translational Institute in San Diego. “I’d been so incredibly careful.”
Her physician assured her that as a healthy woman in her mid-30s, she’d be “back to normal” in 2 weeks’ time and that her loss of taste and smell “very likely will be your only symptom,” she recalled.
. Now, 2½ years later, Dr. Moore Vogel is among the tens of millions of Americans with long COVID.
As a COVID-19 patient-researcher who still struggles with fatigue and migraines, she has learned to cope with her condition. She directs the Participant Center for the All of Us Research Program, a National Institutes of Health collaboration to build the largest, most diverse health database in history. She relies on a practice called pacing, which helps conserve physical, mental, and emotional energy, to avoid making her symptoms worse.
And she is a coauthor of a landmark 200-study review of long COVID published Jan. 13 in the journal Nature, with Scripps Executive Vice President and Medscape Editor-in-Chief Eric Topol, MD. Two other institute long COVID researchers and patient advocates who have the condition coauthored the review – Lisa McCorkell and Hannah E. Davis, cofounders of the Patient-Led Research Collaborative , a group of long COVID patients who study the virus.
Dr. Moore Vogel discussed the key findings of the new review and her personal experiences with this news organization.
Q: When you contracted COVID, no treatments or vaccines existed. Can you talk about what the experience was like for you?
A: “It was July 2020. The loss of taste and smell was the first symptom, and what was interesting was that was my only symptom for a little bit. Being the goal-oriented, work-oriented person that I am, I just worked the rest of the week and hoped that it wasn’t real.
“But that was a Wednesday, and by Friday, I was just getting really tired, and it was really hard to finish my workday. I ended up taking 3 weeks off to recover from the acute phase. At the time, I had read early discussions about long COVID, and it was always on my [mind] – how long was it going to take to recover?”
Q: You went to see a doctor that first week?
A: “I called them when I had the loss of taste and smell, and they said, ‘It’s very likely this will be your only symptom.’ And when I first talked to a physician, they were saying, ‘Oh, you’re young and healthy, in 2 weeks you’ll be back to normal.’ But of course that turned out not to be true.
“It’s hard to remember what it was like at that time. There were so few treatments, it was all about rationing ventilators, and it was absolutely terrifying at the time to just not know what was going to happen.”
Q: How are you managing your condition today?
A: “I have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), one of the really common diagnoses that come out of long COVID. So, that’s the biggest thing for me to manage now, and the main management is pacing.
“I also have medications for migraine management. I’ve always had some degree of migraines, like 2 a month, but now it’s like 15 a month, so it’s a totally different scale of management.”
Q: It must be frustrating, personally and professionally, that long COVID treatments remain elusive.
A: “I’m disappointed at the pace of testing things in clinical trials. There was so much progress made, so much innovation in the early stages of the pandemic to treat the acute phase, and it led to amazing things. We have all these monoclonal antibodies, the steroids are really effective, not to mention the antivirals and the vaccines, of course, on the prevention side. It’s been amazing.
“But for some reason, long COVID treatment is really lagging. What I hypothesize as part of the reason for that is that it doesn’t feel as dramatic. When you see someone on a ventilator or hear about death, it feels very dramatic, and people really worry about that.”
Q: So, let’s talk about the research. How did your personal experiences – and those of the two other coauthors with long COVID – help inform this review?
A: “I work with Eric Topol on a regular basis, and it was amazing that he invited patients to work with him on this review ... I have to say of my other long COVID patient coauthors, Hannah Davis and Lisa McCorkell, it was amazing to work with them.
“It was my first time working with people who have long COVID on a big project. The understanding that we had of each other [where] one of us might say, Oh, I’m crashing today, I can’t work on this. Can you help get us across the finish line for this deadline? That was really amazing to me in terms of how a workplace can be with real disability accommodations.
“It’s really changed my personal outlook on how important it is to have patients involved in the process.”
Q: What was the most surprising or significant finding of the review, in your view?
A: “I would say the most impactful thing to me in the process of writing this review is how much research has been done in such a short time. We started with over 250 studies that we wanted to reference in the review, and we actually had to cut out 50 in the editorial process, which was really hard!
“There’s just been so much progress that’s been made in the past couple of years. And then thinking about the progress on long COVID in general, the other things that’s important to acknowledge is all the work that’s been done on other postviral illnesses that present very similarly to long COVID in many patients, ME/CFS, and postural orthostatic tachycardia syndrome (POTS).”
Q: One thing that stood out is the review’s finding that long COVID is potentially lifelong COVID and, in some ways, is closer to HIV-AIDS than, say, influenza. Is that right?
A: “Yes. I’m really glad you took that point away from the review because that was one of the things that I felt the most strongly about incorporating. For many people, based on the treatments that we have today, this is likely to lead to lifelong disability. And that’s something, from my personal experience, for sure. I’m seeing no improvement on the horizon.
“That’s part of why I’m so passionate about there being clinical trials because I know there are millions and millions of us. So for me, that wasn’t so surprising, because I’m living it, but I can see how for the general public that was a really surprising finding.”
Q: The review breaks down long COVID’s effects on various organs/systems, and it includes the most comprehensive look to date at the effects on pregnant women. Anything you’d care to stress about that?
A: “It really underlies the importance of vaccination, given that it can affect both the pregnant person and child. There is early evidence of development delays if there’s infection while the child is still gestating. So, I think it underscores the need for vaccination to reduce that risk.
“You know, pregnancy is a stressful and terrifying time anyway. So, if there’s anything you can do to reduce the risk to yourself and your unborn child, I think it’s really worthwhile.”
Q: Why do you think this exhaustive review was needed?
A: “Because of the massive amount of literature that’s out there, it’s so hard for anybody to sift through. Eric Topol and Hannah Davis, two of the coauthors, are two people who have done it, and they keep up with all the literature, and they are always tweeting about it.
“But most people don’t have the time to be able to sift through it, so what we did was take all of that literature, organize it into sections, and summarize the key findings. Then the other thing that I think is really important for the field right now is the recommendations piece.”
Q: What impact do you think the new long COVID review in Nature will have?
A: “The response to our review is way beyond what I expected, and I think that’s in part a sign that there is growing awareness of the issue of long COVID.
“I hope that helps spiral toward more treatment trials. Because there are a lot of great candidates out there. We have a whole table in the review about the different potential treatments that should be tested.”
Q: What’s the take-home message for physicians?
A: “One of the key recommendations is about physician education. We know that it is so hard for physicians to keep up with this massive amount of literature, and we really need more physician education that’s meant for busy physicians who really don’t have time to read all of the primary literature themselves.
“So many folks are not getting the care that they need. Because these types of conditions haven’t been seen as much by primary care providers, physical therapists, etc., there’s so much more education that’s needed.
“I think the basic tenets probably could be taught in a weekend course, [including] listening to the patients, believing patients. There are so many times patient symptoms are [dismissed and not] really being taken seriously by their physicians.
“I think part of the challenge behind that is the conflating of mental health issues with these other physiological symptoms. There’s a tendency to say, ‘Oh, all this is this caused by mental health issues’ and that mental health is the root cause, when actually it’s the illness that’s the root cause.”
Q: What’s the big picture: How significant is the public health crisis that long COVID represents?
A: “I believe it’s a massive crisis, a massive emergency. A lot of people in the long COVID community are calling it a mass-disabling event. There is concern that if we let the pandemic run unmitigated for long enough – given that we expect about 10% of folks that get COVID will end up with long COVID – we could end up eventually with a majority-disabled society.
“That would be devasting – to individuals, to the economy, the medical system. So, it’s absolutely a public health emergency in my view, and that’s part of why I’ve been so surprised by the lack of trials, the lack of awareness in the public. There hasn’t been as much public education about long COVID as there has about acute COVID. I think we can do more from a public health perspective.”
Q: What are the main challenges in combating long COVID?
A: “I think the lack of treatments is the most devastating part because it’s such a hard disease to contract, and there’s no end in sight, and so that time horizon can be really difficult. That’s part of why I’m pushing the treatments so much, because I want to offer hope to the community, you know, I want there to be hope around the corner.
“My hope is that within 5 years we’ll have treatments that can really improve quality of life for the community. And I know that that may seem like a long time for those who are suffering, and I hope that there will be some clinical trials of treatments that improve symptom management within 1-2 years. But I think for really more novel things, it’s really going to take at least 5.”
Q: Any advice you’d give to someone with long COVID today?
A: “Connecting with others that are going through the experience is extremely valuable and can really help with that mental component which can be really draining.
“The other thing, in terms of what’s important for the lives of people who are living with long COVID, I would say to everyone who doesn’t have long COVID but knows someone who does, being able to offer support is crucial and can make such a difference in quality of life.
“It is really crucial, for those who don’t have long COVID, to take it into account when you’re making your risk calculations. When you’re thinking: Am I going to wear a mask here? or Am I going to go to that bar?
“Really consider the possibility that if you get COVID, you have a 10% chance of getting long COVID. And if you get long COVID, you have a 25% chance of not being able to work anymore or being so ill that you can’t work anymore and you may lose your health insurance.
“The compounding effects are absolutely devastating, and I think that’s under-factored-in to the general risk calculations of the public.”
A version of this article first appeared on Medscape.com.
For Julia Moore Vogel, PhD, a cup of peppermint tea marked the moment her life would change forever.
One morning in early July 2020, she took a sip of her favorite strongly flavored pick-me-up and couldn’t taste it. She knew loss of taste and smell were symptoms of COVID-19, and she suspected she had contracted the virus. A doctor’s visit confirmed her fears.
“I remember trying the tea and just being so shocked and thinking: How can this be happening to me?” said Dr. Moore Vogel, a COVID-19 researcher with the Scripps Research Translational Institute in San Diego. “I’d been so incredibly careful.”
Her physician assured her that as a healthy woman in her mid-30s, she’d be “back to normal” in 2 weeks’ time and that her loss of taste and smell “very likely will be your only symptom,” she recalled.
. Now, 2½ years later, Dr. Moore Vogel is among the tens of millions of Americans with long COVID.
As a COVID-19 patient-researcher who still struggles with fatigue and migraines, she has learned to cope with her condition. She directs the Participant Center for the All of Us Research Program, a National Institutes of Health collaboration to build the largest, most diverse health database in history. She relies on a practice called pacing, which helps conserve physical, mental, and emotional energy, to avoid making her symptoms worse.
And she is a coauthor of a landmark 200-study review of long COVID published Jan. 13 in the journal Nature, with Scripps Executive Vice President and Medscape Editor-in-Chief Eric Topol, MD. Two other institute long COVID researchers and patient advocates who have the condition coauthored the review – Lisa McCorkell and Hannah E. Davis, cofounders of the Patient-Led Research Collaborative , a group of long COVID patients who study the virus.
Dr. Moore Vogel discussed the key findings of the new review and her personal experiences with this news organization.
Q: When you contracted COVID, no treatments or vaccines existed. Can you talk about what the experience was like for you?
A: “It was July 2020. The loss of taste and smell was the first symptom, and what was interesting was that was my only symptom for a little bit. Being the goal-oriented, work-oriented person that I am, I just worked the rest of the week and hoped that it wasn’t real.
“But that was a Wednesday, and by Friday, I was just getting really tired, and it was really hard to finish my workday. I ended up taking 3 weeks off to recover from the acute phase. At the time, I had read early discussions about long COVID, and it was always on my [mind] – how long was it going to take to recover?”
Q: You went to see a doctor that first week?
A: “I called them when I had the loss of taste and smell, and they said, ‘It’s very likely this will be your only symptom.’ And when I first talked to a physician, they were saying, ‘Oh, you’re young and healthy, in 2 weeks you’ll be back to normal.’ But of course that turned out not to be true.
“It’s hard to remember what it was like at that time. There were so few treatments, it was all about rationing ventilators, and it was absolutely terrifying at the time to just not know what was going to happen.”
Q: How are you managing your condition today?
A: “I have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), one of the really common diagnoses that come out of long COVID. So, that’s the biggest thing for me to manage now, and the main management is pacing.
“I also have medications for migraine management. I’ve always had some degree of migraines, like 2 a month, but now it’s like 15 a month, so it’s a totally different scale of management.”
Q: It must be frustrating, personally and professionally, that long COVID treatments remain elusive.
A: “I’m disappointed at the pace of testing things in clinical trials. There was so much progress made, so much innovation in the early stages of the pandemic to treat the acute phase, and it led to amazing things. We have all these monoclonal antibodies, the steroids are really effective, not to mention the antivirals and the vaccines, of course, on the prevention side. It’s been amazing.
“But for some reason, long COVID treatment is really lagging. What I hypothesize as part of the reason for that is that it doesn’t feel as dramatic. When you see someone on a ventilator or hear about death, it feels very dramatic, and people really worry about that.”
Q: So, let’s talk about the research. How did your personal experiences – and those of the two other coauthors with long COVID – help inform this review?
A: “I work with Eric Topol on a regular basis, and it was amazing that he invited patients to work with him on this review ... I have to say of my other long COVID patient coauthors, Hannah Davis and Lisa McCorkell, it was amazing to work with them.
“It was my first time working with people who have long COVID on a big project. The understanding that we had of each other [where] one of us might say, Oh, I’m crashing today, I can’t work on this. Can you help get us across the finish line for this deadline? That was really amazing to me in terms of how a workplace can be with real disability accommodations.
“It’s really changed my personal outlook on how important it is to have patients involved in the process.”
Q: What was the most surprising or significant finding of the review, in your view?
A: “I would say the most impactful thing to me in the process of writing this review is how much research has been done in such a short time. We started with over 250 studies that we wanted to reference in the review, and we actually had to cut out 50 in the editorial process, which was really hard!
“There’s just been so much progress that’s been made in the past couple of years. And then thinking about the progress on long COVID in general, the other things that’s important to acknowledge is all the work that’s been done on other postviral illnesses that present very similarly to long COVID in many patients, ME/CFS, and postural orthostatic tachycardia syndrome (POTS).”
Q: One thing that stood out is the review’s finding that long COVID is potentially lifelong COVID and, in some ways, is closer to HIV-AIDS than, say, influenza. Is that right?
A: “Yes. I’m really glad you took that point away from the review because that was one of the things that I felt the most strongly about incorporating. For many people, based on the treatments that we have today, this is likely to lead to lifelong disability. And that’s something, from my personal experience, for sure. I’m seeing no improvement on the horizon.
“That’s part of why I’m so passionate about there being clinical trials because I know there are millions and millions of us. So for me, that wasn’t so surprising, because I’m living it, but I can see how for the general public that was a really surprising finding.”
Q: The review breaks down long COVID’s effects on various organs/systems, and it includes the most comprehensive look to date at the effects on pregnant women. Anything you’d care to stress about that?
A: “It really underlies the importance of vaccination, given that it can affect both the pregnant person and child. There is early evidence of development delays if there’s infection while the child is still gestating. So, I think it underscores the need for vaccination to reduce that risk.
“You know, pregnancy is a stressful and terrifying time anyway. So, if there’s anything you can do to reduce the risk to yourself and your unborn child, I think it’s really worthwhile.”
Q: Why do you think this exhaustive review was needed?
A: “Because of the massive amount of literature that’s out there, it’s so hard for anybody to sift through. Eric Topol and Hannah Davis, two of the coauthors, are two people who have done it, and they keep up with all the literature, and they are always tweeting about it.
“But most people don’t have the time to be able to sift through it, so what we did was take all of that literature, organize it into sections, and summarize the key findings. Then the other thing that I think is really important for the field right now is the recommendations piece.”
Q: What impact do you think the new long COVID review in Nature will have?
A: “The response to our review is way beyond what I expected, and I think that’s in part a sign that there is growing awareness of the issue of long COVID.
“I hope that helps spiral toward more treatment trials. Because there are a lot of great candidates out there. We have a whole table in the review about the different potential treatments that should be tested.”
Q: What’s the take-home message for physicians?
A: “One of the key recommendations is about physician education. We know that it is so hard for physicians to keep up with this massive amount of literature, and we really need more physician education that’s meant for busy physicians who really don’t have time to read all of the primary literature themselves.
“So many folks are not getting the care that they need. Because these types of conditions haven’t been seen as much by primary care providers, physical therapists, etc., there’s so much more education that’s needed.
“I think the basic tenets probably could be taught in a weekend course, [including] listening to the patients, believing patients. There are so many times patient symptoms are [dismissed and not] really being taken seriously by their physicians.
“I think part of the challenge behind that is the conflating of mental health issues with these other physiological symptoms. There’s a tendency to say, ‘Oh, all this is this caused by mental health issues’ and that mental health is the root cause, when actually it’s the illness that’s the root cause.”
Q: What’s the big picture: How significant is the public health crisis that long COVID represents?
A: “I believe it’s a massive crisis, a massive emergency. A lot of people in the long COVID community are calling it a mass-disabling event. There is concern that if we let the pandemic run unmitigated for long enough – given that we expect about 10% of folks that get COVID will end up with long COVID – we could end up eventually with a majority-disabled society.
“That would be devasting – to individuals, to the economy, the medical system. So, it’s absolutely a public health emergency in my view, and that’s part of why I’ve been so surprised by the lack of trials, the lack of awareness in the public. There hasn’t been as much public education about long COVID as there has about acute COVID. I think we can do more from a public health perspective.”
Q: What are the main challenges in combating long COVID?
A: “I think the lack of treatments is the most devastating part because it’s such a hard disease to contract, and there’s no end in sight, and so that time horizon can be really difficult. That’s part of why I’m pushing the treatments so much, because I want to offer hope to the community, you know, I want there to be hope around the corner.
“My hope is that within 5 years we’ll have treatments that can really improve quality of life for the community. And I know that that may seem like a long time for those who are suffering, and I hope that there will be some clinical trials of treatments that improve symptom management within 1-2 years. But I think for really more novel things, it’s really going to take at least 5.”
Q: Any advice you’d give to someone with long COVID today?
A: “Connecting with others that are going through the experience is extremely valuable and can really help with that mental component which can be really draining.
“The other thing, in terms of what’s important for the lives of people who are living with long COVID, I would say to everyone who doesn’t have long COVID but knows someone who does, being able to offer support is crucial and can make such a difference in quality of life.
“It is really crucial, for those who don’t have long COVID, to take it into account when you’re making your risk calculations. When you’re thinking: Am I going to wear a mask here? or Am I going to go to that bar?
“Really consider the possibility that if you get COVID, you have a 10% chance of getting long COVID. And if you get long COVID, you have a 25% chance of not being able to work anymore or being so ill that you can’t work anymore and you may lose your health insurance.
“The compounding effects are absolutely devastating, and I think that’s under-factored-in to the general risk calculations of the public.”
A version of this article first appeared on Medscape.com.
Add this to the list of long COVID symptoms: Stigma
Most people with long COVID find they’re facing stigma due to their condition, according to a new report from researchers in the United Kingdom. In short: Relatives and friends may not believe they’re truly sick.
The U.K. team found that more than three-quarters of people studied had experienced stigma often or always.
In fact, 95% of people with long COVID faced at least one type of stigma at least sometimes, according to the study, published in November in the journal PLOS One.
Those conclusions had surprised the study’s lead researcher, Marija Pantelic, PhD, a public health lecturer at Brighton and Sussex Medical School, England.
“After years of working on HIV-related stigma, I was shocked to see how many people were turning a blind eye to and dismissing the difficulties experienced by people with long COVID,” Dr. Pantelic says. “It has also been clear to me from the start that this stigma is detrimental not just for people’s dignity, but also public health.”
Even some doctors argue that the growing attention paid to long COVID is excessive.
“It’s often normal to experience mild fatigue or weaknesses for weeks after being sick and inactive and not eating well. Calling these cases long COVID is the medicalization of modern life,” Marty Makary, MD, a surgeon and public policy researcher at Johns Hopkins University, Baltimore, wrote in a commentary in the Wall Street Journal.
Other doctors strongly disagree, including Alba Azola, MD, codirector of the Johns Hopkins Post-Acute COVID-19 Team and an expert in the stigma surrounding long COVID.
“Putting that spin on things, it’s just hurting people,” she says.
One example is people who cannot return to work.
“A lot of their family members tell me that they’re being lazy,” Dr. Azola says. “That’s part of the public stigma, that these are people just trying to get out of work.”
Some experts say the U.K. study represents a landmark.
“When you have data like this on long COVID stigma, it becomes more difficult to deny its existence or address it,” says Naomi Torres-Mackie, PhD, a clinical psychologist at Lenox Hill Hospital in New York. She also is head of research at the New York–based Mental Health Coalition, a group of experts working to end the stigma surrounding mental health.
She recalls her first patient with long COVID.
“She experienced the discomfort and pain itself, and then she had this crushing feeling that it wasn’t valid, or real. She felt very alone in it,” Dr. Torres-Mackie says.
Another one of her patients is working at her job from home but facing doubt about her condition from her employers.
“Every month, her medical doctor has to produce a letter confirming her medical condition,” Dr. Torres-Mackie says.
Taking part in the British stigma survey were 1,166 people, including 966 residents of the United Kingdom, with the average age of 48. Nearly 85% were female, and more than three-quarters were educated at the university level or higher.
Half of them said they had a clinical diagnosis of long COVID.
More than 60% of them said that at least some of the time, they were cautious about who they talked to about their condition. And fully 34% of those who did disclose their diagnosis said that they regretted having done so.
That’s a difficult experience for those with long COVID, says Leonard Jason, PhD, a professor of psychology at DePaul University in Chicago.
“It’s like they’re traumatized by the initial experience of being sick, and retraumatized by the response of others to them,” he says.
Unexplained illnesses are not well-regarded by the general public, Dr. Jason says.
He gave the example of multiple sclerosis. Before the 1980s, those with MS were considered to have a psychological illness, he says. “Then, in the 1980s, there were biomarkers that said, ‘Here’s the evidence.’ ”
The British study described three types of stigma stemming from the long COVID diagnosis of those questioned:
- Enacted stigma: People were directly treated unfairly because of their condition.
- Internalized stigma: People felt embarrassed by that condition.
- Anticipated stigma: People expected they would be treated poorly because of their diagnosis.
Dr. Azola calls the medical community a major problem when it comes to dealing with long COVID.
“What I see with my patients is medical trauma,” she says. They may have symptoms that send them to the emergency room, and then the tests come back negative. “Instead of tracking the patients’ symptoms, patients get told, ‘Everything looks good, you can go home, this is a panic attack,’ ” she says.
Some people go online to search for treatments, sometimes launching GoFundMe campaigns to raise money for unreliable treatments.
Long COVID patients may have gone through 5 to 10 doctors before they arrive for treatment with the Johns Hopkins Post-Acute COVID-19 Team. The clinic began in April 2020 remotely and in August of that year in person.
Today, the clinic staff spends an hour with a first-time long COVID patient, hearing their stories and helping relieve anxiety, Dr. Azola says.
The phenomenon of long COVID is similar to what patients have had with chronic fatigue syndrome, lupus, or fibromyalgia, where people have symptoms that are hard to explain, says Jennifer Chevinsky, MD, deputy public health officer for Riverside County, Calif.
“Stigma within medicine or health care is nothing new,” she says.
In Chicago, Dr. Jason notes that the federal government’s decision to invest hundreds of millions of dollars in long COVID research “shows the government is helping destigmatize it.”
Dr. Pantelic says she and her colleagues are continuing their research.
“We are interested in understanding the impacts of this stigma, and how to mitigate any adverse outcomes for patients and services,” she says.
A version of this article first appeared on WebMD.com.
Most people with long COVID find they’re facing stigma due to their condition, according to a new report from researchers in the United Kingdom. In short: Relatives and friends may not believe they’re truly sick.
The U.K. team found that more than three-quarters of people studied had experienced stigma often or always.
In fact, 95% of people with long COVID faced at least one type of stigma at least sometimes, according to the study, published in November in the journal PLOS One.
Those conclusions had surprised the study’s lead researcher, Marija Pantelic, PhD, a public health lecturer at Brighton and Sussex Medical School, England.
“After years of working on HIV-related stigma, I was shocked to see how many people were turning a blind eye to and dismissing the difficulties experienced by people with long COVID,” Dr. Pantelic says. “It has also been clear to me from the start that this stigma is detrimental not just for people’s dignity, but also public health.”
Even some doctors argue that the growing attention paid to long COVID is excessive.
“It’s often normal to experience mild fatigue or weaknesses for weeks after being sick and inactive and not eating well. Calling these cases long COVID is the medicalization of modern life,” Marty Makary, MD, a surgeon and public policy researcher at Johns Hopkins University, Baltimore, wrote in a commentary in the Wall Street Journal.
Other doctors strongly disagree, including Alba Azola, MD, codirector of the Johns Hopkins Post-Acute COVID-19 Team and an expert in the stigma surrounding long COVID.
“Putting that spin on things, it’s just hurting people,” she says.
One example is people who cannot return to work.
“A lot of their family members tell me that they’re being lazy,” Dr. Azola says. “That’s part of the public stigma, that these are people just trying to get out of work.”
Some experts say the U.K. study represents a landmark.
“When you have data like this on long COVID stigma, it becomes more difficult to deny its existence or address it,” says Naomi Torres-Mackie, PhD, a clinical psychologist at Lenox Hill Hospital in New York. She also is head of research at the New York–based Mental Health Coalition, a group of experts working to end the stigma surrounding mental health.
She recalls her first patient with long COVID.
“She experienced the discomfort and pain itself, and then she had this crushing feeling that it wasn’t valid, or real. She felt very alone in it,” Dr. Torres-Mackie says.
Another one of her patients is working at her job from home but facing doubt about her condition from her employers.
“Every month, her medical doctor has to produce a letter confirming her medical condition,” Dr. Torres-Mackie says.
Taking part in the British stigma survey were 1,166 people, including 966 residents of the United Kingdom, with the average age of 48. Nearly 85% were female, and more than three-quarters were educated at the university level or higher.
Half of them said they had a clinical diagnosis of long COVID.
More than 60% of them said that at least some of the time, they were cautious about who they talked to about their condition. And fully 34% of those who did disclose their diagnosis said that they regretted having done so.
That’s a difficult experience for those with long COVID, says Leonard Jason, PhD, a professor of psychology at DePaul University in Chicago.
“It’s like they’re traumatized by the initial experience of being sick, and retraumatized by the response of others to them,” he says.
Unexplained illnesses are not well-regarded by the general public, Dr. Jason says.
He gave the example of multiple sclerosis. Before the 1980s, those with MS were considered to have a psychological illness, he says. “Then, in the 1980s, there were biomarkers that said, ‘Here’s the evidence.’ ”
The British study described three types of stigma stemming from the long COVID diagnosis of those questioned:
- Enacted stigma: People were directly treated unfairly because of their condition.
- Internalized stigma: People felt embarrassed by that condition.
- Anticipated stigma: People expected they would be treated poorly because of their diagnosis.
Dr. Azola calls the medical community a major problem when it comes to dealing with long COVID.
“What I see with my patients is medical trauma,” she says. They may have symptoms that send them to the emergency room, and then the tests come back negative. “Instead of tracking the patients’ symptoms, patients get told, ‘Everything looks good, you can go home, this is a panic attack,’ ” she says.
Some people go online to search for treatments, sometimes launching GoFundMe campaigns to raise money for unreliable treatments.
Long COVID patients may have gone through 5 to 10 doctors before they arrive for treatment with the Johns Hopkins Post-Acute COVID-19 Team. The clinic began in April 2020 remotely and in August of that year in person.
Today, the clinic staff spends an hour with a first-time long COVID patient, hearing their stories and helping relieve anxiety, Dr. Azola says.
The phenomenon of long COVID is similar to what patients have had with chronic fatigue syndrome, lupus, or fibromyalgia, where people have symptoms that are hard to explain, says Jennifer Chevinsky, MD, deputy public health officer for Riverside County, Calif.
“Stigma within medicine or health care is nothing new,” she says.
In Chicago, Dr. Jason notes that the federal government’s decision to invest hundreds of millions of dollars in long COVID research “shows the government is helping destigmatize it.”
Dr. Pantelic says she and her colleagues are continuing their research.
“We are interested in understanding the impacts of this stigma, and how to mitigate any adverse outcomes for patients and services,” she says.
A version of this article first appeared on WebMD.com.
Most people with long COVID find they’re facing stigma due to their condition, according to a new report from researchers in the United Kingdom. In short: Relatives and friends may not believe they’re truly sick.
The U.K. team found that more than three-quarters of people studied had experienced stigma often or always.
In fact, 95% of people with long COVID faced at least one type of stigma at least sometimes, according to the study, published in November in the journal PLOS One.
Those conclusions had surprised the study’s lead researcher, Marija Pantelic, PhD, a public health lecturer at Brighton and Sussex Medical School, England.
“After years of working on HIV-related stigma, I was shocked to see how many people were turning a blind eye to and dismissing the difficulties experienced by people with long COVID,” Dr. Pantelic says. “It has also been clear to me from the start that this stigma is detrimental not just for people’s dignity, but also public health.”
Even some doctors argue that the growing attention paid to long COVID is excessive.
“It’s often normal to experience mild fatigue or weaknesses for weeks after being sick and inactive and not eating well. Calling these cases long COVID is the medicalization of modern life,” Marty Makary, MD, a surgeon and public policy researcher at Johns Hopkins University, Baltimore, wrote in a commentary in the Wall Street Journal.
Other doctors strongly disagree, including Alba Azola, MD, codirector of the Johns Hopkins Post-Acute COVID-19 Team and an expert in the stigma surrounding long COVID.
“Putting that spin on things, it’s just hurting people,” she says.
One example is people who cannot return to work.
“A lot of their family members tell me that they’re being lazy,” Dr. Azola says. “That’s part of the public stigma, that these are people just trying to get out of work.”
Some experts say the U.K. study represents a landmark.
“When you have data like this on long COVID stigma, it becomes more difficult to deny its existence or address it,” says Naomi Torres-Mackie, PhD, a clinical psychologist at Lenox Hill Hospital in New York. She also is head of research at the New York–based Mental Health Coalition, a group of experts working to end the stigma surrounding mental health.
She recalls her first patient with long COVID.
“She experienced the discomfort and pain itself, and then she had this crushing feeling that it wasn’t valid, or real. She felt very alone in it,” Dr. Torres-Mackie says.
Another one of her patients is working at her job from home but facing doubt about her condition from her employers.
“Every month, her medical doctor has to produce a letter confirming her medical condition,” Dr. Torres-Mackie says.
Taking part in the British stigma survey were 1,166 people, including 966 residents of the United Kingdom, with the average age of 48. Nearly 85% were female, and more than three-quarters were educated at the university level or higher.
Half of them said they had a clinical diagnosis of long COVID.
More than 60% of them said that at least some of the time, they were cautious about who they talked to about their condition. And fully 34% of those who did disclose their diagnosis said that they regretted having done so.
That’s a difficult experience for those with long COVID, says Leonard Jason, PhD, a professor of psychology at DePaul University in Chicago.
“It’s like they’re traumatized by the initial experience of being sick, and retraumatized by the response of others to them,” he says.
Unexplained illnesses are not well-regarded by the general public, Dr. Jason says.
He gave the example of multiple sclerosis. Before the 1980s, those with MS were considered to have a psychological illness, he says. “Then, in the 1980s, there were biomarkers that said, ‘Here’s the evidence.’ ”
The British study described three types of stigma stemming from the long COVID diagnosis of those questioned:
- Enacted stigma: People were directly treated unfairly because of their condition.
- Internalized stigma: People felt embarrassed by that condition.
- Anticipated stigma: People expected they would be treated poorly because of their diagnosis.
Dr. Azola calls the medical community a major problem when it comes to dealing with long COVID.
“What I see with my patients is medical trauma,” she says. They may have symptoms that send them to the emergency room, and then the tests come back negative. “Instead of tracking the patients’ symptoms, patients get told, ‘Everything looks good, you can go home, this is a panic attack,’ ” she says.
Some people go online to search for treatments, sometimes launching GoFundMe campaigns to raise money for unreliable treatments.
Long COVID patients may have gone through 5 to 10 doctors before they arrive for treatment with the Johns Hopkins Post-Acute COVID-19 Team. The clinic began in April 2020 remotely and in August of that year in person.
Today, the clinic staff spends an hour with a first-time long COVID patient, hearing their stories and helping relieve anxiety, Dr. Azola says.
The phenomenon of long COVID is similar to what patients have had with chronic fatigue syndrome, lupus, or fibromyalgia, where people have symptoms that are hard to explain, says Jennifer Chevinsky, MD, deputy public health officer for Riverside County, Calif.
“Stigma within medicine or health care is nothing new,” she says.
In Chicago, Dr. Jason notes that the federal government’s decision to invest hundreds of millions of dollars in long COVID research “shows the government is helping destigmatize it.”
Dr. Pantelic says she and her colleagues are continuing their research.
“We are interested in understanding the impacts of this stigma, and how to mitigate any adverse outcomes for patients and services,” she says.
A version of this article first appeared on WebMD.com.
PLOS ONE