Clinical

Three main reasons have been put forth for using corticosteroids in critically ill patients with COVID-19, but only one – the hope of preventing lung fibrosis in patients with unresolved acute respiratory distress syndrome – is reasonable to employ now outside of formal randomized trials, Peter Pickkers, MD, PhD, asserted at a webinar on COVID-19 sponsored by the European Society of Intensive Care Medicine.

The most commonly invoked rationale for giving steroids in patients with severe COVID-19 is to modulate the destructive inflammatory immune response that occurs with advancing disease. Another justification cited for giving steroids is to treat suspected adrenal insufficiency in those with refractory shock. Of note, both practices are endorsed in the recent Surviving Sepsis Campaign guidelines on management of critically ill patients with COVID-19 (Intensive Care Med. 2020 May;46[5]:854-87).

But those recommendations – numbers 22 and 42 out of a total of 50 recommendations included in the guidelines – should never have been made, according to Dr. Pickkers, professor of experimental intensive care medicine at Radboud University Medical Center in Nijmegen, the Netherlands.
 

Dueling guidelines

The Surviving Sepsis Campaign guidelines, which were developed by a panel comprising 36 experts in 12 countries, are quite frank in conceding that the guidance in favor of corticosteroids are weak recommendations based on low-quality evidence.

The guidelines recommend against using corticosteroids to try to modulate the immune system in mechanically ventilated COVID-19 patients without acute respiratory distress syndrome (ARDS), but do recommend steroids in those with COVID-19 and ARDS. However, the guidelines also note that, because of the very low quality of the evidence, some experts on the panel preferred not to issue a pro-steroids recommendation at all until higher-quality evidence becomes available. Dr. Pickkers said he believes that the minority view should have prevailed. Moreover, current COVID-19 guidance from the World Health Organization is at odds with the Surviving Sepsis Campaign recommendations; the WHO advises against corticosteroids unless the treatment is indicated for a reason other than immunomodulation, he noted.

The evidence in favor of steroids in an effort to blunt the immune response in COVID patients with ARDS is based largely upon a single small, retrospective, non–peer-reviewed report that 5-7 days of treatment with 1-2 mg/kg per day of methylprednisolone was associated with shortened fever duration and need for supplemental oxygen.

The evidence against steroids for immunomodulation comes mainly from earlier studies of the SARS and MERS novel coronaviruses. For example, in a multicenter study of 309 patients with the MERS (Middle East respiratory syndrome) virus, those who received corticosteroids received no benefit and experienced delayed viral clearance (Am J Respir Crit Care Med. 2018 Mar 15;197[6]:757-67).

“The thing is, virtually all COVID-19 patients in the ICU fulfill the criteria for ARDS, so following the Surviving Sepsis Campaign guidelines would have far-reaching consequences,” Dr. Pickkers said.

Those consequences include a theoretic potential for serious harm arising from dampening the immune response at a point in the course of COVID-19 when the virus is still present, which could result in slowed viral clearance and prolonged viral shedding. Moreover so far no one has been able to identify a sweet spot in the disease course where the viral load has waned and the immune response is sufficiently early that intervention with corticosteroids might have an optimal benefit/risk ratio, he continued.

“My opinion is that at this moment there is no benefit at all for corticosteroids for immunomodulation in patients with COVID-19,” Dr. Pickkers said. “My personal recommendation, in contrast to the Surviving Sepsis Campaign recommendation, is not to use this therapy outside of a study.”

He added that randomized, controlled trials of corticosteroid therapy in critically ill patients with COVID-19 are ongoing in Europe and the United States, including the large RECOVERY study of dexamethasone in the United Kingdom.

As for the Surviving Sepsis Campaign recommendation to use corticosteroids to treat refractory shock in COVID-19, Dr. Pickkers dismissed this guidance as largely irrelevant. That’s because few patients with COVID-19 who need mechanical ventilation have refractory shock as evidenced by the need for a high infusion rate of norepinephrine. Anyway, he noted, that Surviving Sepsis recommendation is based upon extrapolation from evidence of benefit in bacterial septic shock patients, which he deemed to be of questionable relevance to the COVID-19 pandemic.
 

Attacking the fibroproliferative phase of ARDS

First off, Dr. Pickkers conceded, there is no evidence that treatment with corticosteroids to prevent lung fibrosis in COVID-19 patients with nonresolving ARDS is an effective strategy; the pandemic is simply too new at this point for the appropriate studies to have been done. But this much is known: Postmortem pathologic studies show fibroplastic proliferation is present in the lungs of COVID-19 patients, as in those who die of ARDS of other causes. Also, COVID-19 patients typically aren’t admitted to the ICU until day 11 or 12 after developing their first symptoms, so by the time they display indications that their ARDS is not resolving, the virus has typically left the scene; thus, there is little risk at that point that corticosteroids will promote viral proliferation. Additionally, studies in critically ill patients with nonresolving ARDS of other causes show clinically meaningful benefits for corticosteroid therapy.

Dr. Pickkers cited as “must reading” an analysis of five randomized trials of corticosteroid therapy in a total of 518 patients with acute lung injury ARDS of non–COVID-19 origin. The analysis by investigators at the University of Tennessee, Memphis, concluded that treatment resulted in clinically meaningful reductions in duration of mechanical ventilation and ICU length of stay. Moreover, in the 400 patients whose steroid therapy commenced before day 14 of ARDS, there was a statistically significant 22% reduction in risk of death, compared with patients in whom corticosteroids were started later (Intensive Care Med. 2008 Jan;34[1]:61-9).

Session cochair Jan De Waele, MD, PhD, struck a cautious note, remarking, “It’s my perception that we’re using the evidence that we’ve gathered in other conditions and are now trying to apply it in COVID-19. But quality data on patients with COVID-19 itself is pretty scare, and it’s really hard to say whether this disease behaves similarly to bacterial septic shock or to other viral infections.”

“We need more information about the use of corticosteroids in COVID-19, although I think a lot of people are using it at this moment,” added Dr. De Waele, a surgical intensivist at Ghent (Belgium) University.

That being said, he asked Dr. Pickkers when he considers using corticosteroids to prevent pulmonary fibrosis.

Dr. Pickkers said that when he notices that a COVID-19 patient’s lung compliance is worsening, that stiff lung is a clue that fibrosis is occurring and is having clinical consequences. “We also measure blood procollagen, a not very sensitive but moderately specific marker of fibroproliferation. If we see an increase in this biomarker and the lung mechanics are changing, then we do treat these patients with corticosteroids,” Dr. Pickkers replied.

He and his colleagues try to start steroids before day 14 of ARDS, and they continue treatment for longer than 7 days in order to prevent a rebound inflammatory response upon treatment discontinuation. They also avoid using neuromuscular agents and engage in meticulous infection surveillance in order to minimize potential complications of corticosteroid therapy in the ICU.

Dr. Pickkers reported having no financial conflicts regarding his presentation.

[email protected]

Three main reasons have been put forth for using corticosteroids in critically ill patients with COVID-19, but only one – the hope of preventing lung fibrosis in patients with unresolved acute respiratory distress syndrome – is reasonable to employ now outside of formal randomized trials, Peter Pickkers, MD, PhD, asserted at a webinar on COVID-19 sponsored by the European Society of Intensive Care Medicine.

The most commonly invoked rationale for giving steroids in patients with severe COVID-19 is to modulate the destructive inflammatory immune response that occurs with advancing disease. Another justification cited for giving steroids is to treat suspected adrenal insufficiency in those with refractory shock. Of note, both practices are endorsed in the recent Surviving Sepsis Campaign guidelines on management of critically ill patients with COVID-19 (Intensive Care Med. 2020 May;46[5]:854-87).

But those recommendations – numbers 22 and 42 out of a total of 50 recommendations included in the guidelines – should never have been made, according to Dr. Pickkers, professor of experimental intensive care medicine at Radboud University Medical Center in Nijmegen, the Netherlands.
 

Dueling guidelines

The Surviving Sepsis Campaign guidelines, which were developed by a panel comprising 36 experts in 12 countries, are quite frank in conceding that the guidance in favor of corticosteroids are weak recommendations based on low-quality evidence.

The guidelines recommend against using corticosteroids to try to modulate the immune system in mechanically ventilated COVID-19 patients without acute respiratory distress syndrome (ARDS), but do recommend steroids in those with COVID-19 and ARDS. However, the guidelines also note that, because of the very low quality of the evidence, some experts on the panel preferred not to issue a pro-steroids recommendation at all until higher-quality evidence becomes available. Dr. Pickkers said he believes that the minority view should have prevailed. Moreover, current COVID-19 guidance from the World Health Organization is at odds with the Surviving Sepsis Campaign recommendations; the WHO advises against corticosteroids unless the treatment is indicated for a reason other than immunomodulation, he noted.

The evidence in favor of steroids in an effort to blunt the immune response in COVID patients with ARDS is based largely upon a single small, retrospective, non–peer-reviewed report that 5-7 days of treatment with 1-2 mg/kg per day of methylprednisolone was associated with shortened fever duration and need for supplemental oxygen.

The evidence against steroids for immunomodulation comes mainly from earlier studies of the SARS and MERS novel coronaviruses. For example, in a multicenter study of 309 patients with the MERS (Middle East respiratory syndrome) virus, those who received corticosteroids received no benefit and experienced delayed viral clearance (Am J Respir Crit Care Med. 2018 Mar 15;197[6]:757-67).

“The thing is, virtually all COVID-19 patients in the ICU fulfill the criteria for ARDS, so following the Surviving Sepsis Campaign guidelines would have far-reaching consequences,” Dr. Pickkers said.

Those consequences include a theoretic potential for serious harm arising from dampening the immune response at a point in the course of COVID-19 when the virus is still present, which could result in slowed viral clearance and prolonged viral shedding. Moreover so far no one has been able to identify a sweet spot in the disease course where the viral load has waned and the immune response is sufficiently early that intervention with corticosteroids might have an optimal benefit/risk ratio, he continued.

“My opinion is that at this moment there is no benefit at all for corticosteroids for immunomodulation in patients with COVID-19,” Dr. Pickkers said. “My personal recommendation, in contrast to the Surviving Sepsis Campaign recommendation, is not to use this therapy outside of a study.”

He added that randomized, controlled trials of corticosteroid therapy in critically ill patients with COVID-19 are ongoing in Europe and the United States, including the large RECOVERY study of dexamethasone in the United Kingdom.

As for the Surviving Sepsis Campaign recommendation to use corticosteroids to treat refractory shock in COVID-19, Dr. Pickkers dismissed this guidance as largely irrelevant. That’s because few patients with COVID-19 who need mechanical ventilation have refractory shock as evidenced by the need for a high infusion rate of norepinephrine. Anyway, he noted, that Surviving Sepsis recommendation is based upon extrapolation from evidence of benefit in bacterial septic shock patients, which he deemed to be of questionable relevance to the COVID-19 pandemic.
 

Attacking the fibroproliferative phase of ARDS

First off, Dr. Pickkers conceded, there is no evidence that treatment with corticosteroids to prevent lung fibrosis in COVID-19 patients with nonresolving ARDS is an effective strategy; the pandemic is simply too new at this point for the appropriate studies to have been done. But this much is known: Postmortem pathologic studies show fibroplastic proliferation is present in the lungs of COVID-19 patients, as in those who die of ARDS of other causes. Also, COVID-19 patients typically aren’t admitted to the ICU until day 11 or 12 after developing their first symptoms, so by the time they display indications that their ARDS is not resolving, the virus has typically left the scene; thus, there is little risk at that point that corticosteroids will promote viral proliferation. Additionally, studies in critically ill patients with nonresolving ARDS of other causes show clinically meaningful benefits for corticosteroid therapy.

Dr. Pickkers cited as “must reading” an analysis of five randomized trials of corticosteroid therapy in a total of 518 patients with acute lung injury ARDS of non–COVID-19 origin. The analysis by investigators at the University of Tennessee, Memphis, concluded that treatment resulted in clinically meaningful reductions in duration of mechanical ventilation and ICU length of stay. Moreover, in the 400 patients whose steroid therapy commenced before day 14 of ARDS, there was a statistically significant 22% reduction in risk of death, compared with patients in whom corticosteroids were started later (Intensive Care Med. 2008 Jan;34[1]:61-9).

Session cochair Jan De Waele, MD, PhD, struck a cautious note, remarking, “It’s my perception that we’re using the evidence that we’ve gathered in other conditions and are now trying to apply it in COVID-19. But quality data on patients with COVID-19 itself is pretty scare, and it’s really hard to say whether this disease behaves similarly to bacterial septic shock or to other viral infections.”

“We need more information about the use of corticosteroids in COVID-19, although I think a lot of people are using it at this moment,” added Dr. De Waele, a surgical intensivist at Ghent (Belgium) University.

That being said, he asked Dr. Pickkers when he considers using corticosteroids to prevent pulmonary fibrosis.

Dr. Pickkers said that when he notices that a COVID-19 patient’s lung compliance is worsening, that stiff lung is a clue that fibrosis is occurring and is having clinical consequences. “We also measure blood procollagen, a not very sensitive but moderately specific marker of fibroproliferation. If we see an increase in this biomarker and the lung mechanics are changing, then we do treat these patients with corticosteroids,” Dr. Pickkers replied.

He and his colleagues try to start steroids before day 14 of ARDS, and they continue treatment for longer than 7 days in order to prevent a rebound inflammatory response upon treatment discontinuation. They also avoid using neuromuscular agents and engage in meticulous infection surveillance in order to minimize potential complications of corticosteroid therapy in the ICU.

Dr. Pickkers reported having no financial conflicts regarding his presentation.

[email protected]

Three main reasons have been put forth for using corticosteroids in critically ill patients with COVID-19, but only one – the hope of preventing lung fibrosis in patients with unresolved acute respiratory distress syndrome – is reasonable to employ now outside of formal randomized trials, Peter Pickkers, MD, PhD, asserted at a webinar on COVID-19 sponsored by the European Society of Intensive Care Medicine.

The most commonly invoked rationale for giving steroids in patients with severe COVID-19 is to modulate the destructive inflammatory immune response that occurs with advancing disease. Another justification cited for giving steroids is to treat suspected adrenal insufficiency in those with refractory shock. Of note, both practices are endorsed in the recent Surviving Sepsis Campaign guidelines on management of critically ill patients with COVID-19 (Intensive Care Med. 2020 May;46[5]:854-87).

But those recommendations – numbers 22 and 42 out of a total of 50 recommendations included in the guidelines – should never have been made, according to Dr. Pickkers, professor of experimental intensive care medicine at Radboud University Medical Center in Nijmegen, the Netherlands.
 

Dueling guidelines

The Surviving Sepsis Campaign guidelines, which were developed by a panel comprising 36 experts in 12 countries, are quite frank in conceding that the guidance in favor of corticosteroids are weak recommendations based on low-quality evidence.

The guidelines recommend against using corticosteroids to try to modulate the immune system in mechanically ventilated COVID-19 patients without acute respiratory distress syndrome (ARDS), but do recommend steroids in those with COVID-19 and ARDS. However, the guidelines also note that, because of the very low quality of the evidence, some experts on the panel preferred not to issue a pro-steroids recommendation at all until higher-quality evidence becomes available. Dr. Pickkers said he believes that the minority view should have prevailed. Moreover, current COVID-19 guidance from the World Health Organization is at odds with the Surviving Sepsis Campaign recommendations; the WHO advises against corticosteroids unless the treatment is indicated for a reason other than immunomodulation, he noted.

The evidence in favor of steroids in an effort to blunt the immune response in COVID patients with ARDS is based largely upon a single small, retrospective, non–peer-reviewed report that 5-7 days of treatment with 1-2 mg/kg per day of methylprednisolone was associated with shortened fever duration and need for supplemental oxygen.

The evidence against steroids for immunomodulation comes mainly from earlier studies of the SARS and MERS novel coronaviruses. For example, in a multicenter study of 309 patients with the MERS (Middle East respiratory syndrome) virus, those who received corticosteroids received no benefit and experienced delayed viral clearance (Am J Respir Crit Care Med. 2018 Mar 15;197[6]:757-67).

“The thing is, virtually all COVID-19 patients in the ICU fulfill the criteria for ARDS, so following the Surviving Sepsis Campaign guidelines would have far-reaching consequences,” Dr. Pickkers said.

Those consequences include a theoretic potential for serious harm arising from dampening the immune response at a point in the course of COVID-19 when the virus is still present, which could result in slowed viral clearance and prolonged viral shedding. Moreover so far no one has been able to identify a sweet spot in the disease course where the viral load has waned and the immune response is sufficiently early that intervention with corticosteroids might have an optimal benefit/risk ratio, he continued.

“My opinion is that at this moment there is no benefit at all for corticosteroids for immunomodulation in patients with COVID-19,” Dr. Pickkers said. “My personal recommendation, in contrast to the Surviving Sepsis Campaign recommendation, is not to use this therapy outside of a study.”

He added that randomized, controlled trials of corticosteroid therapy in critically ill patients with COVID-19 are ongoing in Europe and the United States, including the large RECOVERY study of dexamethasone in the United Kingdom.

As for the Surviving Sepsis Campaign recommendation to use corticosteroids to treat refractory shock in COVID-19, Dr. Pickkers dismissed this guidance as largely irrelevant. That’s because few patients with COVID-19 who need mechanical ventilation have refractory shock as evidenced by the need for a high infusion rate of norepinephrine. Anyway, he noted, that Surviving Sepsis recommendation is based upon extrapolation from evidence of benefit in bacterial septic shock patients, which he deemed to be of questionable relevance to the COVID-19 pandemic.
 

Attacking the fibroproliferative phase of ARDS

First off, Dr. Pickkers conceded, there is no evidence that treatment with corticosteroids to prevent lung fibrosis in COVID-19 patients with nonresolving ARDS is an effective strategy; the pandemic is simply too new at this point for the appropriate studies to have been done. But this much is known: Postmortem pathologic studies show fibroplastic proliferation is present in the lungs of COVID-19 patients, as in those who die of ARDS of other causes. Also, COVID-19 patients typically aren’t admitted to the ICU until day 11 or 12 after developing their first symptoms, so by the time they display indications that their ARDS is not resolving, the virus has typically left the scene; thus, there is little risk at that point that corticosteroids will promote viral proliferation. Additionally, studies in critically ill patients with nonresolving ARDS of other causes show clinically meaningful benefits for corticosteroid therapy.

Dr. Pickkers cited as “must reading” an analysis of five randomized trials of corticosteroid therapy in a total of 518 patients with acute lung injury ARDS of non–COVID-19 origin. The analysis by investigators at the University of Tennessee, Memphis, concluded that treatment resulted in clinically meaningful reductions in duration of mechanical ventilation and ICU length of stay. Moreover, in the 400 patients whose steroid therapy commenced before day 14 of ARDS, there was a statistically significant 22% reduction in risk of death, compared with patients in whom corticosteroids were started later (Intensive Care Med. 2008 Jan;34[1]:61-9).

Session cochair Jan De Waele, MD, PhD, struck a cautious note, remarking, “It’s my perception that we’re using the evidence that we’ve gathered in other conditions and are now trying to apply it in COVID-19. But quality data on patients with COVID-19 itself is pretty scare, and it’s really hard to say whether this disease behaves similarly to bacterial septic shock or to other viral infections.”

“We need more information about the use of corticosteroids in COVID-19, although I think a lot of people are using it at this moment,” added Dr. De Waele, a surgical intensivist at Ghent (Belgium) University.

That being said, he asked Dr. Pickkers when he considers using corticosteroids to prevent pulmonary fibrosis.

Dr. Pickkers said that when he notices that a COVID-19 patient’s lung compliance is worsening, that stiff lung is a clue that fibrosis is occurring and is having clinical consequences. “We also measure blood procollagen, a not very sensitive but moderately specific marker of fibroproliferation. If we see an increase in this biomarker and the lung mechanics are changing, then we do treat these patients with corticosteroids,” Dr. Pickkers replied.

He and his colleagues try to start steroids before day 14 of ARDS, and they continue treatment for longer than 7 days in order to prevent a rebound inflammatory response upon treatment discontinuation. They also avoid using neuromuscular agents and engage in meticulous infection surveillance in order to minimize potential complications of corticosteroid therapy in the ICU.

Dr. Pickkers reported having no financial conflicts regarding his presentation.

[email protected]

Prescription fills for hydroxychloroquine/chloroquine spiked right after COVID-19 was declared a national emergency in March, but use of the drugs still remains well above 2019 levels, based on data from more than 58,000 U.S. pharmacies.

Hydroxychloroquine/chloroquine are also doing better than any of the prescription drugs in the top 10 based on total claims in 2019, Muthiah Vaduganathan, MD, MPH, of Brigham and Women’s Hospital, Boston, and associates reported May 28 in a research letter in JAMA.

Prescription fills for hydroxychloroquine/chloroquine have been above 2019 levels every week since the national emergency was declared on March 13, with the high occurring during the week of March 15-21, when fills were 214% higher than the corresponding week in 2019. The lowest level in that time came during the week of April 12-18, with growth of 14.6% over 2019, the investigators said.

The drugs occupying the top 10 – amlodipine, amoxicillin, atorvastatin, gabapentin, hydrocodone-acetaminophen, levothyroxine, lisinopril, losartan, omeprazole, and sertraline – have not done as well. Losartan, the only one that hasn’t lost ground in any week since March 13, rose by almost 49% during March 15-21, but was down to a 1.7% rise by the end of the study period, they reported.

Meanwhile, the other drug touted as a treatment for COVID-19, azithromycin, has fallen farther than most of the top 10. By April 19-25, the last week of the study period, fills for the antibiotic were down 62.7%, compared with last year, the analysis showed. Only amoxicillin had dropped more (64.4%).

“The modest decline for most common long-term therapies after peak could represent reduced contact with prescribing clinicians, restricted access to pharmacies, pharmacist rationing, loss of insurance from unemployment, or replete supplies from early stockpiling,” Dr. Vaduganathan and associates wrote.

The investigators “used all-payer U.S. pharmacy data from 58,332 chain, independent, and mail-order pharmacies across 14,421 zip codes in 50 states, reflecting approximately 17 million deidentified claims,” to estimate national prescription fills, they explained.

[email protected]

SOURCE: Vaduganathan M et al. JAMA 2020 May 28. doi: 10.1001/jama.2020.9184.

Prescription fills for hydroxychloroquine/chloroquine spiked right after COVID-19 was declared a national emergency in March, but use of the drugs still remains well above 2019 levels, based on data from more than 58,000 U.S. pharmacies.

Hydroxychloroquine/chloroquine are also doing better than any of the prescription drugs in the top 10 based on total claims in 2019, Muthiah Vaduganathan, MD, MPH, of Brigham and Women’s Hospital, Boston, and associates reported May 28 in a research letter in JAMA.

Prescription fills for hydroxychloroquine/chloroquine have been above 2019 levels every week since the national emergency was declared on March 13, with the high occurring during the week of March 15-21, when fills were 214% higher than the corresponding week in 2019. The lowest level in that time came during the week of April 12-18, with growth of 14.6% over 2019, the investigators said.

The drugs occupying the top 10 – amlodipine, amoxicillin, atorvastatin, gabapentin, hydrocodone-acetaminophen, levothyroxine, lisinopril, losartan, omeprazole, and sertraline – have not done as well. Losartan, the only one that hasn’t lost ground in any week since March 13, rose by almost 49% during March 15-21, but was down to a 1.7% rise by the end of the study period, they reported.

Meanwhile, the other drug touted as a treatment for COVID-19, azithromycin, has fallen farther than most of the top 10. By April 19-25, the last week of the study period, fills for the antibiotic were down 62.7%, compared with last year, the analysis showed. Only amoxicillin had dropped more (64.4%).

“The modest decline for most common long-term therapies after peak could represent reduced contact with prescribing clinicians, restricted access to pharmacies, pharmacist rationing, loss of insurance from unemployment, or replete supplies from early stockpiling,” Dr. Vaduganathan and associates wrote.

The investigators “used all-payer U.S. pharmacy data from 58,332 chain, independent, and mail-order pharmacies across 14,421 zip codes in 50 states, reflecting approximately 17 million deidentified claims,” to estimate national prescription fills, they explained.

[email protected]

SOURCE: Vaduganathan M et al. JAMA 2020 May 28. doi: 10.1001/jama.2020.9184.

Prescription fills for hydroxychloroquine/chloroquine spiked right after COVID-19 was declared a national emergency in March, but use of the drugs still remains well above 2019 levels, based on data from more than 58,000 U.S. pharmacies.

Hydroxychloroquine/chloroquine are also doing better than any of the prescription drugs in the top 10 based on total claims in 2019, Muthiah Vaduganathan, MD, MPH, of Brigham and Women’s Hospital, Boston, and associates reported May 28 in a research letter in JAMA.

Prescription fills for hydroxychloroquine/chloroquine have been above 2019 levels every week since the national emergency was declared on March 13, with the high occurring during the week of March 15-21, when fills were 214% higher than the corresponding week in 2019. The lowest level in that time came during the week of April 12-18, with growth of 14.6% over 2019, the investigators said.

The drugs occupying the top 10 – amlodipine, amoxicillin, atorvastatin, gabapentin, hydrocodone-acetaminophen, levothyroxine, lisinopril, losartan, omeprazole, and sertraline – have not done as well. Losartan, the only one that hasn’t lost ground in any week since March 13, rose by almost 49% during March 15-21, but was down to a 1.7% rise by the end of the study period, they reported.

Meanwhile, the other drug touted as a treatment for COVID-19, azithromycin, has fallen farther than most of the top 10. By April 19-25, the last week of the study period, fills for the antibiotic were down 62.7%, compared with last year, the analysis showed. Only amoxicillin had dropped more (64.4%).

“The modest decline for most common long-term therapies after peak could represent reduced contact with prescribing clinicians, restricted access to pharmacies, pharmacist rationing, loss of insurance from unemployment, or replete supplies from early stockpiling,” Dr. Vaduganathan and associates wrote.

The investigators “used all-payer U.S. pharmacy data from 58,332 chain, independent, and mail-order pharmacies across 14,421 zip codes in 50 states, reflecting approximately 17 million deidentified claims,” to estimate national prescription fills, they explained.

[email protected]

SOURCE: Vaduganathan M et al. JAMA 2020 May 28. doi: 10.1001/jama.2020.9184.

The hospitalist team at Overlake Medical Center and Clinics in Bellevue, Wash., has been a major partner of our Clinical Documentation Integrity Department in achieving its goal of accurately capturing the quality care patients receive on their records.

For many years, we have been witnesses of our hospitalists’ hard work, and the unique challenges of this pandemic further showed their tenacity and resilience. I thought that the best way to tell this story is through the poster accompanying this article.

Gerardo Valentin, BSN, RN, CCDS

The hospitalist team at Overlake Medical Center and Clinics in Bellevue, Wash., has been a major partner of our Clinical Documentation Integrity Department in achieving its goal of accurately capturing the quality care patients receive on their records.

For many years, we have been witnesses of our hospitalists’ hard work, and the unique challenges of this pandemic further showed their tenacity and resilience. I thought that the best way to tell this story is through the poster accompanying this article.

Gerardo Valentin, BSN, RN, CCDS

The hospitalist team at Overlake Medical Center and Clinics in Bellevue, Wash., has been a major partner of our Clinical Documentation Integrity Department in achieving its goal of accurately capturing the quality care patients receive on their records.

For many years, we have been witnesses of our hospitalists’ hard work, and the unique challenges of this pandemic further showed their tenacity and resilience. I thought that the best way to tell this story is through the poster accompanying this article.

Gerardo Valentin, BSN, RN, CCDS

Hospitalized pregnant women with COVID-19 may be at increased risk for preterm birth and cesarean delivery, data from northern Italy suggest.

Herjua/Thinkstock

Among 57 hospitalized patients with SARS-CoV-2 infection who underwent vaginal or cesarean delivery, 7 had spontaneous preterm or respiratory-indicated preterm delivery, a rate of 12%, according to a study published in Obstetrics & Gynecology. For comparison, 7% of patients had preterm delivery in 2019, researchers reported “We also noted a high cesarean delivery rate in the study population (39% vs. 27% in the same area in 2019), mainly as a result of maternal respiratory-indicated urgent delivery,” wrote Valeria M. Savasi, MD, PhD, of the University of Milan and Luigi Sacco Hospital, also in Milan, and colleagues.

Data do not indicate that pregnant women are more susceptible to severe COVID-19 infection, nor have studies suggested an increased risk of miscarriage, congenital anomalies, or early pregnancy loss in pregnant patients with COVID-19, the authors wrote. Studies have described an increased risk of preterm birth, however.

To study clinical features of maternal SARS-CoV-2 infection and potential factors associated with severe disease and iatrogenic delivery, Dr. Savasi and colleagues conducted a prospective study of 77 women with laboratory-confirmed SARS-CoV-2 infection who were admitted during pregnancy or the immediate postpartum period in 12 maternity hospitals in northern Italy between Feb. 23 and March 28, 2020.

The investigators classified patients as having severe disease if they underwent urgent delivery based on maternal respiratory function or if they were admitted to an ICU or subintensive care department. In all, 14 patients (18%) were classified as having severe disease.

“Three patients were intubated after emergency cesarean delivery performed for maternal deterioration, and one patient underwent extracorporeal membrane oxygenation,” Dr. Savasi and colleagues reported. The results are consistent with epidemiologic data in the nonpregnant population with COVID-19 disease.

Of 11 patients with severe disease who underwent urgent delivery for respiratory compromise, 6 had significant postpartum improvement in clinical conditions. No maternal deaths occurred.

“Increased BMI [body mass index] was a significant risk factor for severe disease,” Dr. Savasi and colleagues wrote. “Fever and dyspnea on admission were symptoms significantly associated with subsequent severe maternal respiratory deterioration.”

Most patients (65%) were admitted during the third trimester, and 20 patients were still pregnant at discharge.

“Nine newborns were admitted to the neonatal intensive care unit,” the authors wrote. “Interestingly, besides prematurity, fetal oxygenation and well-being at delivery were not apparently affected by the maternal acute conditions.” Three newborns with vaginal delivery and one with cesarean delivery tested positive for SARS-CoV-2. The newborns may have been infected after delivery, Dr. Savasi and colleagues added. For all newborns, rooming-in and breastfeeding were performed, and none developed respiratory symptoms.

Criteria for hospital admission and therapeutic protocols may have varied between hospitals, the authors noted. In addition, the study included 12 patients who were asymptomatic and admitted for obstetric indications. These patients were tested for SARS-CoV-2 because of contact with an infected individual. Most patients were symptomatic, however, which explains the high rate of maternal severe outcomes. Hospitals have since adopted a universal SARS-CoV-2 screening policy for hospitalized pregnant patients.

Kristina Adams Waldorf, MD, professor of obstetrics and gynecology at the University of Washington, Seattle, commented in an interview that Savasi et al. describe one of the larger COVID-19 in pregnancy cohorts to date with rates of severe disease and delivery for respiratory compromise, which is remarkably similar to Washington state (severe disease, 18% vs. nearly 15%; delivery for respiratory compromise, 16% vs. 20%). As in Washington state, Italian women with a higher prepregnancy BMI were overrepresented in the severe disease group.

“Data are beginning to emerge that identify women who were overweight or obese prior to pregnancy as a high risk group for developing severe COVID-19. These data are similar to known associations between obesity and critical illness in pregnancy during the 2009 ‘swine flu’ (influenza A virus, H₁N₁) pandemic,” she said.

“This study and others indicate that the late second and third trimesters may be a time when women are more likely to be symptomatic from COVID-19. It remains unclear if women in the first trimester are protected from severe COVID-19 outcomes or have outcomes similar to nonpregnant women,” concluded Dr. Waldorf.

One study author disclosed receiving funds from Lo Li Pharma and Zambongroup. The other authors did not report any potential conflicts of interest. Dr. Waldorf said she had no relevant financial disclosures.

[email protected]

SOURCE: Savasi VM et al. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003979.
 

Hospitalized pregnant women with COVID-19 may be at increased risk for preterm birth and cesarean delivery, data from northern Italy suggest.

Herjua/Thinkstock

Among 57 hospitalized patients with SARS-CoV-2 infection who underwent vaginal or cesarean delivery, 7 had spontaneous preterm or respiratory-indicated preterm delivery, a rate of 12%, according to a study published in Obstetrics & Gynecology. For comparison, 7% of patients had preterm delivery in 2019, researchers reported “We also noted a high cesarean delivery rate in the study population (39% vs. 27% in the same area in 2019), mainly as a result of maternal respiratory-indicated urgent delivery,” wrote Valeria M. Savasi, MD, PhD, of the University of Milan and Luigi Sacco Hospital, also in Milan, and colleagues.

Data do not indicate that pregnant women are more susceptible to severe COVID-19 infection, nor have studies suggested an increased risk of miscarriage, congenital anomalies, or early pregnancy loss in pregnant patients with COVID-19, the authors wrote. Studies have described an increased risk of preterm birth, however.

To study clinical features of maternal SARS-CoV-2 infection and potential factors associated with severe disease and iatrogenic delivery, Dr. Savasi and colleagues conducted a prospective study of 77 women with laboratory-confirmed SARS-CoV-2 infection who were admitted during pregnancy or the immediate postpartum period in 12 maternity hospitals in northern Italy between Feb. 23 and March 28, 2020.

The investigators classified patients as having severe disease if they underwent urgent delivery based on maternal respiratory function or if they were admitted to an ICU or subintensive care department. In all, 14 patients (18%) were classified as having severe disease.

“Three patients were intubated after emergency cesarean delivery performed for maternal deterioration, and one patient underwent extracorporeal membrane oxygenation,” Dr. Savasi and colleagues reported. The results are consistent with epidemiologic data in the nonpregnant population with COVID-19 disease.

Of 11 patients with severe disease who underwent urgent delivery for respiratory compromise, 6 had significant postpartum improvement in clinical conditions. No maternal deaths occurred.

“Increased BMI [body mass index] was a significant risk factor for severe disease,” Dr. Savasi and colleagues wrote. “Fever and dyspnea on admission were symptoms significantly associated with subsequent severe maternal respiratory deterioration.”

Most patients (65%) were admitted during the third trimester, and 20 patients were still pregnant at discharge.

“Nine newborns were admitted to the neonatal intensive care unit,” the authors wrote. “Interestingly, besides prematurity, fetal oxygenation and well-being at delivery were not apparently affected by the maternal acute conditions.” Three newborns with vaginal delivery and one with cesarean delivery tested positive for SARS-CoV-2. The newborns may have been infected after delivery, Dr. Savasi and colleagues added. For all newborns, rooming-in and breastfeeding were performed, and none developed respiratory symptoms.

Criteria for hospital admission and therapeutic protocols may have varied between hospitals, the authors noted. In addition, the study included 12 patients who were asymptomatic and admitted for obstetric indications. These patients were tested for SARS-CoV-2 because of contact with an infected individual. Most patients were symptomatic, however, which explains the high rate of maternal severe outcomes. Hospitals have since adopted a universal SARS-CoV-2 screening policy for hospitalized pregnant patients.

Kristina Adams Waldorf, MD, professor of obstetrics and gynecology at the University of Washington, Seattle, commented in an interview that Savasi et al. describe one of the larger COVID-19 in pregnancy cohorts to date with rates of severe disease and delivery for respiratory compromise, which is remarkably similar to Washington state (severe disease, 18% vs. nearly 15%; delivery for respiratory compromise, 16% vs. 20%). As in Washington state, Italian women with a higher prepregnancy BMI were overrepresented in the severe disease group.

“Data are beginning to emerge that identify women who were overweight or obese prior to pregnancy as a high risk group for developing severe COVID-19. These data are similar to known associations between obesity and critical illness in pregnancy during the 2009 ‘swine flu’ (influenza A virus, H₁N₁) pandemic,” she said.

“This study and others indicate that the late second and third trimesters may be a time when women are more likely to be symptomatic from COVID-19. It remains unclear if women in the first trimester are protected from severe COVID-19 outcomes or have outcomes similar to nonpregnant women,” concluded Dr. Waldorf.

One study author disclosed receiving funds from Lo Li Pharma and Zambongroup. The other authors did not report any potential conflicts of interest. Dr. Waldorf said she had no relevant financial disclosures.

[email protected]

SOURCE: Savasi VM et al. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003979.
 

Hospitalized pregnant women with COVID-19 may be at increased risk for preterm birth and cesarean delivery, data from northern Italy suggest.

Herjua/Thinkstock

Among 57 hospitalized patients with SARS-CoV-2 infection who underwent vaginal or cesarean delivery, 7 had spontaneous preterm or respiratory-indicated preterm delivery, a rate of 12%, according to a study published in Obstetrics & Gynecology. For comparison, 7% of patients had preterm delivery in 2019, researchers reported “We also noted a high cesarean delivery rate in the study population (39% vs. 27% in the same area in 2019), mainly as a result of maternal respiratory-indicated urgent delivery,” wrote Valeria M. Savasi, MD, PhD, of the University of Milan and Luigi Sacco Hospital, also in Milan, and colleagues.

Data do not indicate that pregnant women are more susceptible to severe COVID-19 infection, nor have studies suggested an increased risk of miscarriage, congenital anomalies, or early pregnancy loss in pregnant patients with COVID-19, the authors wrote. Studies have described an increased risk of preterm birth, however.

To study clinical features of maternal SARS-CoV-2 infection and potential factors associated with severe disease and iatrogenic delivery, Dr. Savasi and colleagues conducted a prospective study of 77 women with laboratory-confirmed SARS-CoV-2 infection who were admitted during pregnancy or the immediate postpartum period in 12 maternity hospitals in northern Italy between Feb. 23 and March 28, 2020.

The investigators classified patients as having severe disease if they underwent urgent delivery based on maternal respiratory function or if they were admitted to an ICU or subintensive care department. In all, 14 patients (18%) were classified as having severe disease.

“Three patients were intubated after emergency cesarean delivery performed for maternal deterioration, and one patient underwent extracorporeal membrane oxygenation,” Dr. Savasi and colleagues reported. The results are consistent with epidemiologic data in the nonpregnant population with COVID-19 disease.

Of 11 patients with severe disease who underwent urgent delivery for respiratory compromise, 6 had significant postpartum improvement in clinical conditions. No maternal deaths occurred.

“Increased BMI [body mass index] was a significant risk factor for severe disease,” Dr. Savasi and colleagues wrote. “Fever and dyspnea on admission were symptoms significantly associated with subsequent severe maternal respiratory deterioration.”

Most patients (65%) were admitted during the third trimester, and 20 patients were still pregnant at discharge.

“Nine newborns were admitted to the neonatal intensive care unit,” the authors wrote. “Interestingly, besides prematurity, fetal oxygenation and well-being at delivery were not apparently affected by the maternal acute conditions.” Three newborns with vaginal delivery and one with cesarean delivery tested positive for SARS-CoV-2. The newborns may have been infected after delivery, Dr. Savasi and colleagues added. For all newborns, rooming-in and breastfeeding were performed, and none developed respiratory symptoms.

Criteria for hospital admission and therapeutic protocols may have varied between hospitals, the authors noted. In addition, the study included 12 patients who were asymptomatic and admitted for obstetric indications. These patients were tested for SARS-CoV-2 because of contact with an infected individual. Most patients were symptomatic, however, which explains the high rate of maternal severe outcomes. Hospitals have since adopted a universal SARS-CoV-2 screening policy for hospitalized pregnant patients.

Kristina Adams Waldorf, MD, professor of obstetrics and gynecology at the University of Washington, Seattle, commented in an interview that Savasi et al. describe one of the larger COVID-19 in pregnancy cohorts to date with rates of severe disease and delivery for respiratory compromise, which is remarkably similar to Washington state (severe disease, 18% vs. nearly 15%; delivery for respiratory compromise, 16% vs. 20%). As in Washington state, Italian women with a higher prepregnancy BMI were overrepresented in the severe disease group.

“Data are beginning to emerge that identify women who were overweight or obese prior to pregnancy as a high risk group for developing severe COVID-19. These data are similar to known associations between obesity and critical illness in pregnancy during the 2009 ‘swine flu’ (influenza A virus, H₁N₁) pandemic,” she said.

“This study and others indicate that the late second and third trimesters may be a time when women are more likely to be symptomatic from COVID-19. It remains unclear if women in the first trimester are protected from severe COVID-19 outcomes or have outcomes similar to nonpregnant women,” concluded Dr. Waldorf.

One study author disclosed receiving funds from Lo Li Pharma and Zambongroup. The other authors did not report any potential conflicts of interest. Dr. Waldorf said she had no relevant financial disclosures.

[email protected]

SOURCE: Savasi VM et al. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003979.
 

US government and industry projections that a COVID-19 vaccine will be ready by this fall or even January would take compressing what usually takes at least a decade into months, with little room for error or safety surprises.

“If all the cards fall into the right place and all the stars are aligned, you definitely could get a vaccine by December or January,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said last week.

But Fauci said a more realistic timeline is still 12 to 18 months, and experts interviewed by Medscape Medical News agree. They say that although recent developments are encouraging, history and scientific reason say the day when a COVID-19 vaccine is widely available will not come this year and may not come by the end of 2021.

The encouraging signals come primarily from two recent announcements: the $1.2 billion United States backing last week of one vaccine platform and the announcement on May 18 that the first human trials of another have produced some positive phase 1 results.
 

Recent developments

On May 21, the US Department of Health and Human Services (HHS) under “Operation Warp Speed” announced that the US will give AstraZeneca $1.2 billion “to make available at least 300 million doses of a coronavirus vaccine called AZD1222, with the first doses delivered as early as October 2020.”

On May 18, the Massachusetts-based biotechnology company Moderna announced that phase 1 clinical results showed that its vaccine candidate, which uses a new messenger RNA (mRNA) technology, appeared safe. Eight participants in the human trials were able to produce neutralizing antibodies that researchers believe are important in developing protection from the virus.

Moderna Chief Medical Officer Tal Zaks, MD, PhD told CNN that if the vaccine candidate does well in phase 2, “it could be ready by January 2021.”

The two candidates are among 10 in clinical trials for the SARS-CoV-2 virus, according to the World Health Organization (WHO). The AstraZeneca/ AZD1222 candidate (also called ChAdOx1 nCoV-19, in collaboration with the University of Oxford) has entered phase 2/3.

Moderna’s candidate and another being developed in Beijing, China, are in phase 2, WHO reports. As of yesterday, 115 other candidates are in preclinical evaluation.

Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, Texas, told Medscape Medical News it’s important to realize that, in the case of the $1.2 billion US investment, “what they’re talking about is manufacturing.”

The idea, she said, is to pay AstraZeneca up front so that manufacturing can start before it is known whether the vaccine candidate is safe or effective, the reverse of how the clinical trial process usually works.

That way, if the candidate is deemed safe and effective, time is not lost by then deciding how to make it and distribute it.

By the end of this year, she said, “Maybe we will have many vaccines made and stored in a refrigerator somewhere. But between now and December, there’s absolutely no way you can show efficacy of the vaccine at the same time you confirm that it’s safe.”
 

“Take these things with a grain of salt”

Animal testing for the AstraZeneca candidate, made in partnership with the University of Oxford in the United Kingdom, has yielded lackluster results, according to results on the preprint server BioRxiv, which have not been peer-reviewed.

“The results were not bad, but they were not gangbusters,” Bottazzi said. The results show the vaccine offered only partial protection.

“Partial protection is better than no protection,” she noted. “You have to take these things with a grain of salt. We don’t know what’s going to happen in humans.”

As for the Moderna candidate, Bottazzi said, “the good news is they found an appropriate safety profile. But from an eight-person group to make the extrapolation that they have efficacy — it’s unrealistic.”

Nicole Lurie, MD, MSPH, is senior adviser to the CEO for the Coalition for Epidemic Preparedness Innovation (CEPI), a nongovernmental organization funded by the Wellcome Trust, the Bill and Melinda Gates Foundation, the European Commission, and eight countries (Australia, Belgium, Canada, Ethiopia, Germany, Japan, Norway, and the United Kingdom) charged with supporting development of vaccines for pathogens on WHO’s priority list.

She and her colleagues write in a paper published online in the New England Journal of Medicine on March 30 that “it typically takes multiple candidates and many years to produce a licensed vaccine.”

The fastest time for developing a vaccine to date is 4 years, for the mumps vaccine, licensed in 1967.

As to whether she would expect a rollout of any vaccine by the end of the year, Lurie told Medscape Medical News, “If everything goes according to plan in every way, shape or form, well then maybe you can get there. But I wouldn’t hold my breath.”

Lurie and her colleagues write that “it’s far from certain that these new platforms will be scalable or that existing capacity can provide sufficient quantities of vaccine fast enough.”

On a call with reporters today, leaders of some of the words largest pharmaceutical companies said that one of the key bottlenecks is the sheer number of vials needed in order to distribute billions of doses of a successful vaccine.

Pfizer CEO Albert Bourla, DVM, PhD, said, “Typically we are producing vaccines in single-dose vials. We are exploring with governments right now if it would be more convenient if there were 5-dose vials or 10-dose vials. I think we can resolve a significant part of the bottleneck.”

Despite the challenges, experts interviewed for this article agree that it will be possible to make a vaccine for COVID-19. They don’t expect attempts to meet the same complications that HIV researchers have seen over decades as the virus continues to confound with mutations.

Fred Ledley, MD, director of the Center for Integration of Science and Industry at Bentley University in Waltham, Massachusetts, told Medscape Medical News, “There doesn’t appear to be anything terribly diabolical about this virus. The mutation rate doesn’t appear to be anything like HIV. It appears to have some big, ugly proteins on the surface, which is good for vaccines — proteins with a lot of physical features look distinguishable from healthy cells. Signs all point to that it should be possible to make a vaccine.”
 

History raises safety concerns

However, Ledley said, “The idea of doing it in 6 months is largely unrealistic.”

He says 18 months is more realistic, primarily because of the sheer number of people that would have to be enrolled in a phase 3 study to truly test whether the endpoints are being met.

Vaccines are given to healthy volunteers. If safety signals arise, they may not be apparent until massive numbers of people are tested in phase 3.

“You’re never going to see the rates cut to 0%, but to see the difference between 10 people getting sick and seven people getting sick, takes very, very large numbers,” Ledley said. “There’s no way that can be done in 6 months. You’re talking about tens of thousands of people enrolled.”

He notes at this point it’s unclear what the endpoints will be and what the safety thresholds will be after consideration of risks and benefit.

Another big question for Ledley: “We don’t know what type of immunity we need to protect us against the virus. Do you just need the antibodies in your blood or do you need cells that are primed to attack the virus? Is it more of a chemical clearance or do the cells need to physically go in and digest the virus?”

History also points to the need for rigorous safety precautions that scientists fear could be compromised as trial phases overlap and processes are run in parallel instead of one step at a time.

An early batch of the Salk vaccine for polio in 1955, for example, turned out to be contaminated and caused paralysis in some children and 10 deaths, he points out.

CEPI’s Lurie adds that early candidates for another coronavirus, severe acute respiratory syndrome (SARS), “caused a reaction in the lungs that was very dangerous” before development was halted.

She also pointed to previous findings that a vaccine for dengue fever could worsen the disease in some people through a phenomenon called antibody-dependent enhancement.

Lurie and colleagues write in their paper that “it’s critical that vaccines also be developed using the tried-and-true methods, even if they may take longer to enter clinical trials or to result in large numbers of doses.”
 

Live attenuated vaccine

Raul Andino, PhD, a virologist at the University of California San Francisco, is among the scientists working with a tried-and-true method ­— a live attenuated vaccine — and he told Medscape Medical News he’s predicting it will take 2 years to develop.

He said it is cheaper to produce because scientists just have to learn how to grow the virus. Because the technology is already proven, a live attenuated vaccine could be rapidly produced on a worldwide scale.

The hope is also that a live attenuated vaccine would be given once in a lifetime and therefore be more affordable, especially in poorer countries.

“While a Moderna vaccine might be good for Europe and the United States,” he said, “It’s not going to be good for Africa, India, Brazil.”

Andino said, “I would bet money” that the front-runner vaccines so far will not be one-time vaccines.

He points out that most of the vaccine candidates are trying to protect people from disease. While there’s nothing wrong with that, he said, “In my opinion that is the lower-hanging fruit.”

“In my mind we need something that interrupts the chain of transmission and induces protection,” Andino said, important for developing herd immunity.

The reason this type of approach takes longer is because you are introducing a weakened form of the virus to the body and you have to make sure it doesn’t cause disease, not just in a small test population, but in populations who may be more susceptible to the disease, Andino said.
 

A call for unified strategies

Universities, countries, international consortiums, and public-private partnerships are all racing to find several safe and effective vaccines as no one entity will likely be able to provide the global solution.

Some of the efforts involve overlap of entities but with different focuses.

Along with “Operation Warp Speed” and CEPI, other collaborations include Gavi the Vaccine Alliance, whose core partners include WHO, UNICEF, the World Bank, and the Gates Foundation; and “Accelerating Therapeutic Interventions and Vaccines (ACTIV) partnership,” led by the National Institutes of Health.

Industry partners in ACTIV (18 biopharmaceutical companies), according to a May 18 article published online in the Journal of the American Medical Association, have said they will contribute their respective clinical trial capacities, regardless of which agent is studied.

Some, however, have called for more streamlining of efforts.

“Ideally we’d be working together,” Lurie told Medscape Medical News.

“I’m hopeful we will find ways to collaborate scientifically,” she said. “The US government’s responsibility is to make doses for the US. CEPI’s responsibility is to make doses for the world. A big focus of CEPI is to make sure we have manufacturing capacity outside of the US so those doses can be available to the world and they don’t get seized by wealthy countries.”

Bottazzi, Ledley, Lurie, and Andino report no relevant financial relationships.

This article first appeared on Medscape.com.

US government and industry projections that a COVID-19 vaccine will be ready by this fall or even January would take compressing what usually takes at least a decade into months, with little room for error or safety surprises.

“If all the cards fall into the right place and all the stars are aligned, you definitely could get a vaccine by December or January,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said last week.

But Fauci said a more realistic timeline is still 12 to 18 months, and experts interviewed by Medscape Medical News agree. They say that although recent developments are encouraging, history and scientific reason say the day when a COVID-19 vaccine is widely available will not come this year and may not come by the end of 2021.

The encouraging signals come primarily from two recent announcements: the $1.2 billion United States backing last week of one vaccine platform and the announcement on May 18 that the first human trials of another have produced some positive phase 1 results.
 

Recent developments

On May 21, the US Department of Health and Human Services (HHS) under “Operation Warp Speed” announced that the US will give AstraZeneca $1.2 billion “to make available at least 300 million doses of a coronavirus vaccine called AZD1222, with the first doses delivered as early as October 2020.”

On May 18, the Massachusetts-based biotechnology company Moderna announced that phase 1 clinical results showed that its vaccine candidate, which uses a new messenger RNA (mRNA) technology, appeared safe. Eight participants in the human trials were able to produce neutralizing antibodies that researchers believe are important in developing protection from the virus.

Moderna Chief Medical Officer Tal Zaks, MD, PhD told CNN that if the vaccine candidate does well in phase 2, “it could be ready by January 2021.”

The two candidates are among 10 in clinical trials for the SARS-CoV-2 virus, according to the World Health Organization (WHO). The AstraZeneca/ AZD1222 candidate (also called ChAdOx1 nCoV-19, in collaboration with the University of Oxford) has entered phase 2/3.

Moderna’s candidate and another being developed in Beijing, China, are in phase 2, WHO reports. As of yesterday, 115 other candidates are in preclinical evaluation.

Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, Texas, told Medscape Medical News it’s important to realize that, in the case of the $1.2 billion US investment, “what they’re talking about is manufacturing.”

The idea, she said, is to pay AstraZeneca up front so that manufacturing can start before it is known whether the vaccine candidate is safe or effective, the reverse of how the clinical trial process usually works.

That way, if the candidate is deemed safe and effective, time is not lost by then deciding how to make it and distribute it.

By the end of this year, she said, “Maybe we will have many vaccines made and stored in a refrigerator somewhere. But between now and December, there’s absolutely no way you can show efficacy of the vaccine at the same time you confirm that it’s safe.”
 

“Take these things with a grain of salt”

Animal testing for the AstraZeneca candidate, made in partnership with the University of Oxford in the United Kingdom, has yielded lackluster results, according to results on the preprint server BioRxiv, which have not been peer-reviewed.

“The results were not bad, but they were not gangbusters,” Bottazzi said. The results show the vaccine offered only partial protection.

“Partial protection is better than no protection,” she noted. “You have to take these things with a grain of salt. We don’t know what’s going to happen in humans.”

As for the Moderna candidate, Bottazzi said, “the good news is they found an appropriate safety profile. But from an eight-person group to make the extrapolation that they have efficacy — it’s unrealistic.”

Nicole Lurie, MD, MSPH, is senior adviser to the CEO for the Coalition for Epidemic Preparedness Innovation (CEPI), a nongovernmental organization funded by the Wellcome Trust, the Bill and Melinda Gates Foundation, the European Commission, and eight countries (Australia, Belgium, Canada, Ethiopia, Germany, Japan, Norway, and the United Kingdom) charged with supporting development of vaccines for pathogens on WHO’s priority list.

She and her colleagues write in a paper published online in the New England Journal of Medicine on March 30 that “it typically takes multiple candidates and many years to produce a licensed vaccine.”

The fastest time for developing a vaccine to date is 4 years, for the mumps vaccine, licensed in 1967.

As to whether she would expect a rollout of any vaccine by the end of the year, Lurie told Medscape Medical News, “If everything goes according to plan in every way, shape or form, well then maybe you can get there. But I wouldn’t hold my breath.”

Lurie and her colleagues write that “it’s far from certain that these new platforms will be scalable or that existing capacity can provide sufficient quantities of vaccine fast enough.”

On a call with reporters today, leaders of some of the words largest pharmaceutical companies said that one of the key bottlenecks is the sheer number of vials needed in order to distribute billions of doses of a successful vaccine.

Pfizer CEO Albert Bourla, DVM, PhD, said, “Typically we are producing vaccines in single-dose vials. We are exploring with governments right now if it would be more convenient if there were 5-dose vials or 10-dose vials. I think we can resolve a significant part of the bottleneck.”

Despite the challenges, experts interviewed for this article agree that it will be possible to make a vaccine for COVID-19. They don’t expect attempts to meet the same complications that HIV researchers have seen over decades as the virus continues to confound with mutations.

Fred Ledley, MD, director of the Center for Integration of Science and Industry at Bentley University in Waltham, Massachusetts, told Medscape Medical News, “There doesn’t appear to be anything terribly diabolical about this virus. The mutation rate doesn’t appear to be anything like HIV. It appears to have some big, ugly proteins on the surface, which is good for vaccines — proteins with a lot of physical features look distinguishable from healthy cells. Signs all point to that it should be possible to make a vaccine.”
 

History raises safety concerns

However, Ledley said, “The idea of doing it in 6 months is largely unrealistic.”

He says 18 months is more realistic, primarily because of the sheer number of people that would have to be enrolled in a phase 3 study to truly test whether the endpoints are being met.

Vaccines are given to healthy volunteers. If safety signals arise, they may not be apparent until massive numbers of people are tested in phase 3.

“You’re never going to see the rates cut to 0%, but to see the difference between 10 people getting sick and seven people getting sick, takes very, very large numbers,” Ledley said. “There’s no way that can be done in 6 months. You’re talking about tens of thousands of people enrolled.”

He notes at this point it’s unclear what the endpoints will be and what the safety thresholds will be after consideration of risks and benefit.

Another big question for Ledley: “We don’t know what type of immunity we need to protect us against the virus. Do you just need the antibodies in your blood or do you need cells that are primed to attack the virus? Is it more of a chemical clearance or do the cells need to physically go in and digest the virus?”

History also points to the need for rigorous safety precautions that scientists fear could be compromised as trial phases overlap and processes are run in parallel instead of one step at a time.

An early batch of the Salk vaccine for polio in 1955, for example, turned out to be contaminated and caused paralysis in some children and 10 deaths, he points out.

CEPI’s Lurie adds that early candidates for another coronavirus, severe acute respiratory syndrome (SARS), “caused a reaction in the lungs that was very dangerous” before development was halted.

She also pointed to previous findings that a vaccine for dengue fever could worsen the disease in some people through a phenomenon called antibody-dependent enhancement.

Lurie and colleagues write in their paper that “it’s critical that vaccines also be developed using the tried-and-true methods, even if they may take longer to enter clinical trials or to result in large numbers of doses.”
 

Live attenuated vaccine

Raul Andino, PhD, a virologist at the University of California San Francisco, is among the scientists working with a tried-and-true method ­— a live attenuated vaccine — and he told Medscape Medical News he’s predicting it will take 2 years to develop.

He said it is cheaper to produce because scientists just have to learn how to grow the virus. Because the technology is already proven, a live attenuated vaccine could be rapidly produced on a worldwide scale.

The hope is also that a live attenuated vaccine would be given once in a lifetime and therefore be more affordable, especially in poorer countries.

“While a Moderna vaccine might be good for Europe and the United States,” he said, “It’s not going to be good for Africa, India, Brazil.”

Andino said, “I would bet money” that the front-runner vaccines so far will not be one-time vaccines.

He points out that most of the vaccine candidates are trying to protect people from disease. While there’s nothing wrong with that, he said, “In my opinion that is the lower-hanging fruit.”

“In my mind we need something that interrupts the chain of transmission and induces protection,” Andino said, important for developing herd immunity.

The reason this type of approach takes longer is because you are introducing a weakened form of the virus to the body and you have to make sure it doesn’t cause disease, not just in a small test population, but in populations who may be more susceptible to the disease, Andino said.
 

A call for unified strategies

Universities, countries, international consortiums, and public-private partnerships are all racing to find several safe and effective vaccines as no one entity will likely be able to provide the global solution.

Some of the efforts involve overlap of entities but with different focuses.

Along with “Operation Warp Speed” and CEPI, other collaborations include Gavi the Vaccine Alliance, whose core partners include WHO, UNICEF, the World Bank, and the Gates Foundation; and “Accelerating Therapeutic Interventions and Vaccines (ACTIV) partnership,” led by the National Institutes of Health.

Industry partners in ACTIV (18 biopharmaceutical companies), according to a May 18 article published online in the Journal of the American Medical Association, have said they will contribute their respective clinical trial capacities, regardless of which agent is studied.

Some, however, have called for more streamlining of efforts.

“Ideally we’d be working together,” Lurie told Medscape Medical News.

“I’m hopeful we will find ways to collaborate scientifically,” she said. “The US government’s responsibility is to make doses for the US. CEPI’s responsibility is to make doses for the world. A big focus of CEPI is to make sure we have manufacturing capacity outside of the US so those doses can be available to the world and they don’t get seized by wealthy countries.”

Bottazzi, Ledley, Lurie, and Andino report no relevant financial relationships.

This article first appeared on Medscape.com.

US government and industry projections that a COVID-19 vaccine will be ready by this fall or even January would take compressing what usually takes at least a decade into months, with little room for error or safety surprises.

“If all the cards fall into the right place and all the stars are aligned, you definitely could get a vaccine by December or January,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said last week.

But Fauci said a more realistic timeline is still 12 to 18 months, and experts interviewed by Medscape Medical News agree. They say that although recent developments are encouraging, history and scientific reason say the day when a COVID-19 vaccine is widely available will not come this year and may not come by the end of 2021.

The encouraging signals come primarily from two recent announcements: the $1.2 billion United States backing last week of one vaccine platform and the announcement on May 18 that the first human trials of another have produced some positive phase 1 results.
 

Recent developments

On May 21, the US Department of Health and Human Services (HHS) under “Operation Warp Speed” announced that the US will give AstraZeneca $1.2 billion “to make available at least 300 million doses of a coronavirus vaccine called AZD1222, with the first doses delivered as early as October 2020.”

On May 18, the Massachusetts-based biotechnology company Moderna announced that phase 1 clinical results showed that its vaccine candidate, which uses a new messenger RNA (mRNA) technology, appeared safe. Eight participants in the human trials were able to produce neutralizing antibodies that researchers believe are important in developing protection from the virus.

Moderna Chief Medical Officer Tal Zaks, MD, PhD told CNN that if the vaccine candidate does well in phase 2, “it could be ready by January 2021.”

The two candidates are among 10 in clinical trials for the SARS-CoV-2 virus, according to the World Health Organization (WHO). The AstraZeneca/ AZD1222 candidate (also called ChAdOx1 nCoV-19, in collaboration with the University of Oxford) has entered phase 2/3.

Moderna’s candidate and another being developed in Beijing, China, are in phase 2, WHO reports. As of yesterday, 115 other candidates are in preclinical evaluation.

Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, Texas, told Medscape Medical News it’s important to realize that, in the case of the $1.2 billion US investment, “what they’re talking about is manufacturing.”

The idea, she said, is to pay AstraZeneca up front so that manufacturing can start before it is known whether the vaccine candidate is safe or effective, the reverse of how the clinical trial process usually works.

That way, if the candidate is deemed safe and effective, time is not lost by then deciding how to make it and distribute it.

By the end of this year, she said, “Maybe we will have many vaccines made and stored in a refrigerator somewhere. But between now and December, there’s absolutely no way you can show efficacy of the vaccine at the same time you confirm that it’s safe.”
 

“Take these things with a grain of salt”

Animal testing for the AstraZeneca candidate, made in partnership with the University of Oxford in the United Kingdom, has yielded lackluster results, according to results on the preprint server BioRxiv, which have not been peer-reviewed.

“The results were not bad, but they were not gangbusters,” Bottazzi said. The results show the vaccine offered only partial protection.

“Partial protection is better than no protection,” she noted. “You have to take these things with a grain of salt. We don’t know what’s going to happen in humans.”

As for the Moderna candidate, Bottazzi said, “the good news is they found an appropriate safety profile. But from an eight-person group to make the extrapolation that they have efficacy — it’s unrealistic.”

Nicole Lurie, MD, MSPH, is senior adviser to the CEO for the Coalition for Epidemic Preparedness Innovation (CEPI), a nongovernmental organization funded by the Wellcome Trust, the Bill and Melinda Gates Foundation, the European Commission, and eight countries (Australia, Belgium, Canada, Ethiopia, Germany, Japan, Norway, and the United Kingdom) charged with supporting development of vaccines for pathogens on WHO’s priority list.

She and her colleagues write in a paper published online in the New England Journal of Medicine on March 30 that “it typically takes multiple candidates and many years to produce a licensed vaccine.”

The fastest time for developing a vaccine to date is 4 years, for the mumps vaccine, licensed in 1967.

As to whether she would expect a rollout of any vaccine by the end of the year, Lurie told Medscape Medical News, “If everything goes according to plan in every way, shape or form, well then maybe you can get there. But I wouldn’t hold my breath.”

Lurie and her colleagues write that “it’s far from certain that these new platforms will be scalable or that existing capacity can provide sufficient quantities of vaccine fast enough.”

On a call with reporters today, leaders of some of the words largest pharmaceutical companies said that one of the key bottlenecks is the sheer number of vials needed in order to distribute billions of doses of a successful vaccine.

Pfizer CEO Albert Bourla, DVM, PhD, said, “Typically we are producing vaccines in single-dose vials. We are exploring with governments right now if it would be more convenient if there were 5-dose vials or 10-dose vials. I think we can resolve a significant part of the bottleneck.”

Despite the challenges, experts interviewed for this article agree that it will be possible to make a vaccine for COVID-19. They don’t expect attempts to meet the same complications that HIV researchers have seen over decades as the virus continues to confound with mutations.

Fred Ledley, MD, director of the Center for Integration of Science and Industry at Bentley University in Waltham, Massachusetts, told Medscape Medical News, “There doesn’t appear to be anything terribly diabolical about this virus. The mutation rate doesn’t appear to be anything like HIV. It appears to have some big, ugly proteins on the surface, which is good for vaccines — proteins with a lot of physical features look distinguishable from healthy cells. Signs all point to that it should be possible to make a vaccine.”
 

History raises safety concerns

However, Ledley said, “The idea of doing it in 6 months is largely unrealistic.”

He says 18 months is more realistic, primarily because of the sheer number of people that would have to be enrolled in a phase 3 study to truly test whether the endpoints are being met.

Vaccines are given to healthy volunteers. If safety signals arise, they may not be apparent until massive numbers of people are tested in phase 3.

“You’re never going to see the rates cut to 0%, but to see the difference between 10 people getting sick and seven people getting sick, takes very, very large numbers,” Ledley said. “There’s no way that can be done in 6 months. You’re talking about tens of thousands of people enrolled.”

He notes at this point it’s unclear what the endpoints will be and what the safety thresholds will be after consideration of risks and benefit.

Another big question for Ledley: “We don’t know what type of immunity we need to protect us against the virus. Do you just need the antibodies in your blood or do you need cells that are primed to attack the virus? Is it more of a chemical clearance or do the cells need to physically go in and digest the virus?”

History also points to the need for rigorous safety precautions that scientists fear could be compromised as trial phases overlap and processes are run in parallel instead of one step at a time.

An early batch of the Salk vaccine for polio in 1955, for example, turned out to be contaminated and caused paralysis in some children and 10 deaths, he points out.

CEPI’s Lurie adds that early candidates for another coronavirus, severe acute respiratory syndrome (SARS), “caused a reaction in the lungs that was very dangerous” before development was halted.

She also pointed to previous findings that a vaccine for dengue fever could worsen the disease in some people through a phenomenon called antibody-dependent enhancement.

Lurie and colleagues write in their paper that “it’s critical that vaccines also be developed using the tried-and-true methods, even if they may take longer to enter clinical trials or to result in large numbers of doses.”
 

Live attenuated vaccine

Raul Andino, PhD, a virologist at the University of California San Francisco, is among the scientists working with a tried-and-true method ­— a live attenuated vaccine — and he told Medscape Medical News he’s predicting it will take 2 years to develop.

He said it is cheaper to produce because scientists just have to learn how to grow the virus. Because the technology is already proven, a live attenuated vaccine could be rapidly produced on a worldwide scale.

The hope is also that a live attenuated vaccine would be given once in a lifetime and therefore be more affordable, especially in poorer countries.

“While a Moderna vaccine might be good for Europe and the United States,” he said, “It’s not going to be good for Africa, India, Brazil.”

Andino said, “I would bet money” that the front-runner vaccines so far will not be one-time vaccines.

He points out that most of the vaccine candidates are trying to protect people from disease. While there’s nothing wrong with that, he said, “In my opinion that is the lower-hanging fruit.”

“In my mind we need something that interrupts the chain of transmission and induces protection,” Andino said, important for developing herd immunity.

The reason this type of approach takes longer is because you are introducing a weakened form of the virus to the body and you have to make sure it doesn’t cause disease, not just in a small test population, but in populations who may be more susceptible to the disease, Andino said.
 

A call for unified strategies

Universities, countries, international consortiums, and public-private partnerships are all racing to find several safe and effective vaccines as no one entity will likely be able to provide the global solution.

Some of the efforts involve overlap of entities but with different focuses.

Along with “Operation Warp Speed” and CEPI, other collaborations include Gavi the Vaccine Alliance, whose core partners include WHO, UNICEF, the World Bank, and the Gates Foundation; and “Accelerating Therapeutic Interventions and Vaccines (ACTIV) partnership,” led by the National Institutes of Health.

Industry partners in ACTIV (18 biopharmaceutical companies), according to a May 18 article published online in the Journal of the American Medical Association, have said they will contribute their respective clinical trial capacities, regardless of which agent is studied.

Some, however, have called for more streamlining of efforts.

“Ideally we’d be working together,” Lurie told Medscape Medical News.

“I’m hopeful we will find ways to collaborate scientifically,” she said. “The US government’s responsibility is to make doses for the US. CEPI’s responsibility is to make doses for the world. A big focus of CEPI is to make sure we have manufacturing capacity outside of the US so those doses can be available to the world and they don’t get seized by wealthy countries.”

Bottazzi, Ledley, Lurie, and Andino report no relevant financial relationships.

This article first appeared on Medscape.com.

Background: Often atrial fibrillation terminates spontaneously and occasionally recurs; therefore, the advantage of immediate electric or pharmacologic cardioversion over watchful waiting and subsequent delayed cardioversion is not clear.

This was a noninferiority, open-label study that was not powered enough to study harm between the two strategies. It showed a 30% incidence of recurrence of AFib regardless of study assignment. Hospitalists should not feel pressured to initiate early cardioversion for new-onset AFib. Rate control, anticoagulation (if applicable), prompt follow-up, and early discharge (even from the ED) seem to be a safe and practical approach.

Bottom line: In patients presenting with symptomatic recent-onset AFib, delayed cardioversion in a wait-and-see approach was noninferior to early cardioversion in achieving sinus rhythm at 4 weeks’ follow-up.

Citation: Pluymaekers NA et al. Early or delayed cardioversion in recent-onset atrial fibrillation. N Engl J Med.

2019 Apr 18;380(16):1499-508.

Dr. Abdo is a hospitalist at Duke University Health System.

Background: Often atrial fibrillation terminates spontaneously and occasionally recurs; therefore, the advantage of immediate electric or pharmacologic cardioversion over watchful waiting and subsequent delayed cardioversion is not clear.

This was a noninferiority, open-label study that was not powered enough to study harm between the two strategies. It showed a 30% incidence of recurrence of AFib regardless of study assignment. Hospitalists should not feel pressured to initiate early cardioversion for new-onset AFib. Rate control, anticoagulation (if applicable), prompt follow-up, and early discharge (even from the ED) seem to be a safe and practical approach.

Bottom line: In patients presenting with symptomatic recent-onset AFib, delayed cardioversion in a wait-and-see approach was noninferior to early cardioversion in achieving sinus rhythm at 4 weeks’ follow-up.

Citation: Pluymaekers NA et al. Early or delayed cardioversion in recent-onset atrial fibrillation. N Engl J Med.

2019 Apr 18;380(16):1499-508.

Dr. Abdo is a hospitalist at Duke University Health System.

Background: Often atrial fibrillation terminates spontaneously and occasionally recurs; therefore, the advantage of immediate electric or pharmacologic cardioversion over watchful waiting and subsequent delayed cardioversion is not clear.

This was a noninferiority, open-label study that was not powered enough to study harm between the two strategies. It showed a 30% incidence of recurrence of AFib regardless of study assignment. Hospitalists should not feel pressured to initiate early cardioversion for new-onset AFib. Rate control, anticoagulation (if applicable), prompt follow-up, and early discharge (even from the ED) seem to be a safe and practical approach.

Bottom line: In patients presenting with symptomatic recent-onset AFib, delayed cardioversion in a wait-and-see approach was noninferior to early cardioversion in achieving sinus rhythm at 4 weeks’ follow-up.

Citation: Pluymaekers NA et al. Early or delayed cardioversion in recent-onset atrial fibrillation. N Engl J Med.

2019 Apr 18;380(16):1499-508.

Dr. Abdo is a hospitalist at Duke University Health System.

When it comes to COVID-19, studies show that social distancing flattened the curve.

Cumulative hospitalizations in four states with stay-at-home orders were well short of the projected exponential growth curves, Soumya Sen, PhD, of the University of Minnesota, Minneapolis, and associates reported May 27 in a research letter in JAMA. All states were observed through April 28.

The deviations between observed cases and worst-case projections in the four states – Colorado, Minnesota, Ohio, and Virginia – all began within 8-10 days of the stay-at-home orders. In Minnesota, 17 days after the order, there were 361 cumulative hospitalizations, compared with a projection of 988 had no such action been taken. In Virginia, the corresponding numbers were 1,048 observed and 2,335 projected, they reported.

“Observed hospitalizations consistently fell outside of the 95% prediction bands of the projected exponential growth curve,” Dr. Sen and associates noted.

In a separate Canadian study measuring COVID-19 patients occupying ICU beds in Ontario and deaths among those cases, hospitals “would have rapidly exceeded ICU capacity and observed substantially higher mortality” without any physical distancing intervention, Ashleigh R. Tuite, PhD, MPH, of the University of Toronto and associates wrote May 27 in a letter in Annals of Internal Medicine.

Their model, based on a 70% reduction in physical contacts for March 19–May 3, projected 2.0 cases per 100,000 population with physical distancing and 37.4 per 100,000 without. Deaths among those ICU patients were projected at 2.5 per 100,000 with distancing and 12.7 per 100,000 without intervention, they reported.

“Our modeling also shows the challenges associated with relaxation of physical distancing measures without a concomitant increase in other public health measures. Specifically, when the number of contacts between persons returns to more than 50% of normal, we expect disease activity to resurge rapidly and ICUs to quickly reach capacity,” they wrote.

The study published in JAMA used publicly available data from the University of Minnesota COVID-19 Hospitalization Project, which is partially funded by the University of Minnesota Office of Academic Clinical Affairs and United Health Foundation.
 

[email protected]

SOURCES: Sen S et al. JAMA. 2020 May 27. doi: 10.1001/jama.2020.9176; Tuite AR et al. Ann Intern Med. 2020 May 27. doi: 10.7326/M20-2945.

When it comes to COVID-19, studies show that social distancing flattened the curve.

Cumulative hospitalizations in four states with stay-at-home orders were well short of the projected exponential growth curves, Soumya Sen, PhD, of the University of Minnesota, Minneapolis, and associates reported May 27 in a research letter in JAMA. All states were observed through April 28.

The deviations between observed cases and worst-case projections in the four states – Colorado, Minnesota, Ohio, and Virginia – all began within 8-10 days of the stay-at-home orders. In Minnesota, 17 days after the order, there were 361 cumulative hospitalizations, compared with a projection of 988 had no such action been taken. In Virginia, the corresponding numbers were 1,048 observed and 2,335 projected, they reported.

“Observed hospitalizations consistently fell outside of the 95% prediction bands of the projected exponential growth curve,” Dr. Sen and associates noted.

In a separate Canadian study measuring COVID-19 patients occupying ICU beds in Ontario and deaths among those cases, hospitals “would have rapidly exceeded ICU capacity and observed substantially higher mortality” without any physical distancing intervention, Ashleigh R. Tuite, PhD, MPH, of the University of Toronto and associates wrote May 27 in a letter in Annals of Internal Medicine.

Their model, based on a 70% reduction in physical contacts for March 19–May 3, projected 2.0 cases per 100,000 population with physical distancing and 37.4 per 100,000 without. Deaths among those ICU patients were projected at 2.5 per 100,000 with distancing and 12.7 per 100,000 without intervention, they reported.

“Our modeling also shows the challenges associated with relaxation of physical distancing measures without a concomitant increase in other public health measures. Specifically, when the number of contacts between persons returns to more than 50% of normal, we expect disease activity to resurge rapidly and ICUs to quickly reach capacity,” they wrote.

The study published in JAMA used publicly available data from the University of Minnesota COVID-19 Hospitalization Project, which is partially funded by the University of Minnesota Office of Academic Clinical Affairs and United Health Foundation.
 

[email protected]

SOURCES: Sen S et al. JAMA. 2020 May 27. doi: 10.1001/jama.2020.9176; Tuite AR et al. Ann Intern Med. 2020 May 27. doi: 10.7326/M20-2945.

When it comes to COVID-19, studies show that social distancing flattened the curve.

Cumulative hospitalizations in four states with stay-at-home orders were well short of the projected exponential growth curves, Soumya Sen, PhD, of the University of Minnesota, Minneapolis, and associates reported May 27 in a research letter in JAMA. All states were observed through April 28.

The deviations between observed cases and worst-case projections in the four states – Colorado, Minnesota, Ohio, and Virginia – all began within 8-10 days of the stay-at-home orders. In Minnesota, 17 days after the order, there were 361 cumulative hospitalizations, compared with a projection of 988 had no such action been taken. In Virginia, the corresponding numbers were 1,048 observed and 2,335 projected, they reported.

“Observed hospitalizations consistently fell outside of the 95% prediction bands of the projected exponential growth curve,” Dr. Sen and associates noted.

In a separate Canadian study measuring COVID-19 patients occupying ICU beds in Ontario and deaths among those cases, hospitals “would have rapidly exceeded ICU capacity and observed substantially higher mortality” without any physical distancing intervention, Ashleigh R. Tuite, PhD, MPH, of the University of Toronto and associates wrote May 27 in a letter in Annals of Internal Medicine.

Their model, based on a 70% reduction in physical contacts for March 19–May 3, projected 2.0 cases per 100,000 population with physical distancing and 37.4 per 100,000 without. Deaths among those ICU patients were projected at 2.5 per 100,000 with distancing and 12.7 per 100,000 without intervention, they reported.

“Our modeling also shows the challenges associated with relaxation of physical distancing measures without a concomitant increase in other public health measures. Specifically, when the number of contacts between persons returns to more than 50% of normal, we expect disease activity to resurge rapidly and ICUs to quickly reach capacity,” they wrote.

The study published in JAMA used publicly available data from the University of Minnesota COVID-19 Hospitalization Project, which is partially funded by the University of Minnesota Office of Academic Clinical Affairs and United Health Foundation.
 

[email protected]

SOURCES: Sen S et al. JAMA. 2020 May 27. doi: 10.1001/jama.2020.9176; Tuite AR et al. Ann Intern Med. 2020 May 27. doi: 10.7326/M20-2945.

Maternal vascular malperfusion and intervillous thrombi were more common in the placentas of women infected with SARS-CoV-2, compared with historic controls, report researchers who conducted the first-of-its-kind case series in the English literature. Nevertheless, the neonates in the report appear to be healthy so far and all tested negative for the virus.

Although the series examining placentas from 16 women is small, it carries a larger implication – that increased antenatal surveillance for pregnant women infected with SARS-CoV-2 may be indicated, the researchers noted.

Furthermore, the results could align with other reports of coagulation and vascular abnormalities among people with COVID-19. “I would say that our findings fit into that larger picture of vascular injury. This is developing, and there are some significant ways that these feeder vessels to the placenta are different, but if this is the emerging paradigm, our findings can fit into it,” Jeffrey A. Goldstein, MD, PhD, assistant professor of pathology at Northwestern University, Chicago, said in an interview.

The research was published in the American Journal of Clinical Pathology.

Prior case series reported in Wuhan, China, do not currently suggest that pregnant women are more likely to experience severe COVID-19, in contrast to observations during severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks. “However,” the researchers noted, “adverse perinatal outcomes have been reported, including increased risks of miscarriage, preeclampsia, preterm birth, and stillbirth.”

To learn more, Dr. Goldstein, lead author Elisheva D. Shanes, MD, and colleagues examined the histology of placentas from women with COVID-19 giving birth between March 18 and May 5, 2020. They compared these placentas with over 17,000 historic controls and 215 women who had their placentas evaluated as part of a melanoma history study.

A total of 10 women were diagnosed with COVID-19 upon presentation to labor and delivery, 4 others were diagnosed approximately 1 month before delivery and the remaining 2 within 1 week of delivery. Ten of the patients were symptomatic and two required oxygen. None of the patients received intubation or died. A total of 14 patients delivered at term, 1 delivered at 34 weeks, and the remaining case experienced a 16-week intrauterine fetal demise (IUFD). The IUFD was excluded from subsequent statistical analysis.

The neonates each had a 5-minute Apgar score of 9. Most infants were discharged on the first or second day of life, and there were no neonatal deaths.
 

Key findings

Of the 15 placentas, 12 featured maternal vascular malperfusion. This rate was significantly higher than historic controls (P = .046) and melanoma study controls (P = .001).

Specific features varied between groups, with decidual arteriopathy, atherosis and fibrinoid necrosis of maternal vessels, and mural hypertrophy of membrane arterioles observed more often in COVID-19 cases than in all historical controls. In addition, peripheral infarctions, decidual arteriopathy, atherosis, and fibrinoid necrosis, and mural hypertrophy being more common in COVID-19 cases than in placentas of women with a history of melanoma.

In contrast, features of fetal vascular malperfusion were observed in 12 of 15 cases, but not at rates significantly different from the control groups. Chorangiosis, villous edema, and intervillous thrombi also were more common in the COVID-19 cohort.

Dr. Goldstein was surprised they did not observe much acute or chronic inflammation. “We see chronic inflammation in the placenta in response to many viruses, such as cytomegalovirus, so you might expect similar findings, but we didn’t see any increase above the controls.”

There are a couple of case reports of histiocytic intervillositis – a particularly severe form of chronic inflammation – associated with COVID-19, “but we didn’t see that in our study,” he added.
 

Clinical implications

The healthy neonatal outcomes reported in the study occurred despite the placental injury, which may be caused by the redundancy built into placentas for delivering oxygen and nutrients and for removing waste.

The negative COVID-19 test results in all infants also supports existing evidence that vertical transmission of the virus is uncommon. The finding also suggests that any damage to the placenta is likely related to maternal infection.

Only one mother in the COVID-19 cohort was hypertensive, which surprised the researchers because intervillous thrombi have been associated with maternal high blood pressure. “In the context of research suggesting an increase of thrombotic and thromboembolic disorders in COVID-19,” the researchers noted, “these may represent placental formation or deposition of thrombi in response to the virus.”

One of the priorities for the researchers going forward is to monitor the longer-term outcomes of the infants, Dr. Goldstein said. “We know the people in utero during the 1918-1919 flu pandemic had higher rates of heart disease and other long-term problems, so we want to be on the lookout for something similar.”
 

Valuable insight

“This is a comprehensive case series of this topic, with findings worth noting and sharing in a timely fashion,” Karen Mestan, MD, associate professor of pediatrics within the division of neonatology at Northwestern University, said when asked to comment on the study.

“The information is valuable to neonatologists as the short- and long-term effects of COVID-19 exposure on newborn infants are still largely unknown,” she added. “Details of placental pathology provide emerging insight and may help us understand mother-baby vertical transmission during the current pandemic.”

Dr. Goldstein and Dr. Mestan had no relevant financial disclosures.

SOURCE: Shanes ED et al. Am J Clin Pathol. 2020 May 22. doi: 10.1093/ajcp/aqaa089.

Maternal vascular malperfusion and intervillous thrombi were more common in the placentas of women infected with SARS-CoV-2, compared with historic controls, report researchers who conducted the first-of-its-kind case series in the English literature. Nevertheless, the neonates in the report appear to be healthy so far and all tested negative for the virus.

Although the series examining placentas from 16 women is small, it carries a larger implication – that increased antenatal surveillance for pregnant women infected with SARS-CoV-2 may be indicated, the researchers noted.

Furthermore, the results could align with other reports of coagulation and vascular abnormalities among people with COVID-19. “I would say that our findings fit into that larger picture of vascular injury. This is developing, and there are some significant ways that these feeder vessels to the placenta are different, but if this is the emerging paradigm, our findings can fit into it,” Jeffrey A. Goldstein, MD, PhD, assistant professor of pathology at Northwestern University, Chicago, said in an interview.

The research was published in the American Journal of Clinical Pathology.

Prior case series reported in Wuhan, China, do not currently suggest that pregnant women are more likely to experience severe COVID-19, in contrast to observations during severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks. “However,” the researchers noted, “adverse perinatal outcomes have been reported, including increased risks of miscarriage, preeclampsia, preterm birth, and stillbirth.”

To learn more, Dr. Goldstein, lead author Elisheva D. Shanes, MD, and colleagues examined the histology of placentas from women with COVID-19 giving birth between March 18 and May 5, 2020. They compared these placentas with over 17,000 historic controls and 215 women who had their placentas evaluated as part of a melanoma history study.

A total of 10 women were diagnosed with COVID-19 upon presentation to labor and delivery, 4 others were diagnosed approximately 1 month before delivery and the remaining 2 within 1 week of delivery. Ten of the patients were symptomatic and two required oxygen. None of the patients received intubation or died. A total of 14 patients delivered at term, 1 delivered at 34 weeks, and the remaining case experienced a 16-week intrauterine fetal demise (IUFD). The IUFD was excluded from subsequent statistical analysis.

The neonates each had a 5-minute Apgar score of 9. Most infants were discharged on the first or second day of life, and there were no neonatal deaths.
 

Key findings

Of the 15 placentas, 12 featured maternal vascular malperfusion. This rate was significantly higher than historic controls (P = .046) and melanoma study controls (P = .001).

Specific features varied between groups, with decidual arteriopathy, atherosis and fibrinoid necrosis of maternal vessels, and mural hypertrophy of membrane arterioles observed more often in COVID-19 cases than in all historical controls. In addition, peripheral infarctions, decidual arteriopathy, atherosis, and fibrinoid necrosis, and mural hypertrophy being more common in COVID-19 cases than in placentas of women with a history of melanoma.

In contrast, features of fetal vascular malperfusion were observed in 12 of 15 cases, but not at rates significantly different from the control groups. Chorangiosis, villous edema, and intervillous thrombi also were more common in the COVID-19 cohort.

Dr. Goldstein was surprised they did not observe much acute or chronic inflammation. “We see chronic inflammation in the placenta in response to many viruses, such as cytomegalovirus, so you might expect similar findings, but we didn’t see any increase above the controls.”

There are a couple of case reports of histiocytic intervillositis – a particularly severe form of chronic inflammation – associated with COVID-19, “but we didn’t see that in our study,” he added.
 

Clinical implications

The healthy neonatal outcomes reported in the study occurred despite the placental injury, which may be caused by the redundancy built into placentas for delivering oxygen and nutrients and for removing waste.

The negative COVID-19 test results in all infants also supports existing evidence that vertical transmission of the virus is uncommon. The finding also suggests that any damage to the placenta is likely related to maternal infection.

Only one mother in the COVID-19 cohort was hypertensive, which surprised the researchers because intervillous thrombi have been associated with maternal high blood pressure. “In the context of research suggesting an increase of thrombotic and thromboembolic disorders in COVID-19,” the researchers noted, “these may represent placental formation or deposition of thrombi in response to the virus.”

One of the priorities for the researchers going forward is to monitor the longer-term outcomes of the infants, Dr. Goldstein said. “We know the people in utero during the 1918-1919 flu pandemic had higher rates of heart disease and other long-term problems, so we want to be on the lookout for something similar.”
 

Valuable insight

“This is a comprehensive case series of this topic, with findings worth noting and sharing in a timely fashion,” Karen Mestan, MD, associate professor of pediatrics within the division of neonatology at Northwestern University, said when asked to comment on the study.

“The information is valuable to neonatologists as the short- and long-term effects of COVID-19 exposure on newborn infants are still largely unknown,” she added. “Details of placental pathology provide emerging insight and may help us understand mother-baby vertical transmission during the current pandemic.”

Dr. Goldstein and Dr. Mestan had no relevant financial disclosures.

SOURCE: Shanes ED et al. Am J Clin Pathol. 2020 May 22. doi: 10.1093/ajcp/aqaa089.

Maternal vascular malperfusion and intervillous thrombi were more common in the placentas of women infected with SARS-CoV-2, compared with historic controls, report researchers who conducted the first-of-its-kind case series in the English literature. Nevertheless, the neonates in the report appear to be healthy so far and all tested negative for the virus.

Although the series examining placentas from 16 women is small, it carries a larger implication – that increased antenatal surveillance for pregnant women infected with SARS-CoV-2 may be indicated, the researchers noted.

Furthermore, the results could align with other reports of coagulation and vascular abnormalities among people with COVID-19. “I would say that our findings fit into that larger picture of vascular injury. This is developing, and there are some significant ways that these feeder vessels to the placenta are different, but if this is the emerging paradigm, our findings can fit into it,” Jeffrey A. Goldstein, MD, PhD, assistant professor of pathology at Northwestern University, Chicago, said in an interview.

The research was published in the American Journal of Clinical Pathology.

Prior case series reported in Wuhan, China, do not currently suggest that pregnant women are more likely to experience severe COVID-19, in contrast to observations during severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks. “However,” the researchers noted, “adverse perinatal outcomes have been reported, including increased risks of miscarriage, preeclampsia, preterm birth, and stillbirth.”

To learn more, Dr. Goldstein, lead author Elisheva D. Shanes, MD, and colleagues examined the histology of placentas from women with COVID-19 giving birth between March 18 and May 5, 2020. They compared these placentas with over 17,000 historic controls and 215 women who had their placentas evaluated as part of a melanoma history study.

A total of 10 women were diagnosed with COVID-19 upon presentation to labor and delivery, 4 others were diagnosed approximately 1 month before delivery and the remaining 2 within 1 week of delivery. Ten of the patients were symptomatic and two required oxygen. None of the patients received intubation or died. A total of 14 patients delivered at term, 1 delivered at 34 weeks, and the remaining case experienced a 16-week intrauterine fetal demise (IUFD). The IUFD was excluded from subsequent statistical analysis.

The neonates each had a 5-minute Apgar score of 9. Most infants were discharged on the first or second day of life, and there were no neonatal deaths.
 

Key findings

Of the 15 placentas, 12 featured maternal vascular malperfusion. This rate was significantly higher than historic controls (P = .046) and melanoma study controls (P = .001).

Specific features varied between groups, with decidual arteriopathy, atherosis and fibrinoid necrosis of maternal vessels, and mural hypertrophy of membrane arterioles observed more often in COVID-19 cases than in all historical controls. In addition, peripheral infarctions, decidual arteriopathy, atherosis, and fibrinoid necrosis, and mural hypertrophy being more common in COVID-19 cases than in placentas of women with a history of melanoma.

In contrast, features of fetal vascular malperfusion were observed in 12 of 15 cases, but not at rates significantly different from the control groups. Chorangiosis, villous edema, and intervillous thrombi also were more common in the COVID-19 cohort.

Dr. Goldstein was surprised they did not observe much acute or chronic inflammation. “We see chronic inflammation in the placenta in response to many viruses, such as cytomegalovirus, so you might expect similar findings, but we didn’t see any increase above the controls.”

There are a couple of case reports of histiocytic intervillositis – a particularly severe form of chronic inflammation – associated with COVID-19, “but we didn’t see that in our study,” he added.
 

Clinical implications

The healthy neonatal outcomes reported in the study occurred despite the placental injury, which may be caused by the redundancy built into placentas for delivering oxygen and nutrients and for removing waste.

The negative COVID-19 test results in all infants also supports existing evidence that vertical transmission of the virus is uncommon. The finding also suggests that any damage to the placenta is likely related to maternal infection.

Only one mother in the COVID-19 cohort was hypertensive, which surprised the researchers because intervillous thrombi have been associated with maternal high blood pressure. “In the context of research suggesting an increase of thrombotic and thromboembolic disorders in COVID-19,” the researchers noted, “these may represent placental formation or deposition of thrombi in response to the virus.”

One of the priorities for the researchers going forward is to monitor the longer-term outcomes of the infants, Dr. Goldstein said. “We know the people in utero during the 1918-1919 flu pandemic had higher rates of heart disease and other long-term problems, so we want to be on the lookout for something similar.”
 

Valuable insight

“This is a comprehensive case series of this topic, with findings worth noting and sharing in a timely fashion,” Karen Mestan, MD, associate professor of pediatrics within the division of neonatology at Northwestern University, said when asked to comment on the study.

“The information is valuable to neonatologists as the short- and long-term effects of COVID-19 exposure on newborn infants are still largely unknown,” she added. “Details of placental pathology provide emerging insight and may help us understand mother-baby vertical transmission during the current pandemic.”

Dr. Goldstein and Dr. Mestan had no relevant financial disclosures.

SOURCE: Shanes ED et al. Am J Clin Pathol. 2020 May 22. doi: 10.1093/ajcp/aqaa089.

Among women with a planned delivery in a New York City health system during the first half of April, the rate of asymptomatic SARS-CoV-2 infection was 16%, according to a study published in Obstetrics & Gynecology. Among the patients’ designated support persons, the asymptomatic carrier rate was 10%.

“If universal testing of pregnant patients in a high prevalence area is not performed, health care workers will be inadvertently exposed to COVID-19, unless universal precautions with personal protective equipment are taken,” wrote the researchers affiliated with the department of obstetrics, gynecology, and reproductive medicine at Icahn School of Medicine at Mount Sinai, New York.

Angela Bianco, MD, and colleagues conducted an observational study of women who were scheduled for a planned delivery within the Mount Sinai Health System between April 4 and April 15, 2020. Patients and their designated support person completed a telephone screen and underwent COVID-19 testing the day before a scheduled delivery. If support persons screened positive during the telephone interview about COVID-19 symptoms, they could not attend the birth, and patients could contact a different support person to be screened and tested. “All patients and their support persons were informed of their SARS-CoV-2 test results before admission,” the investigators wrote. “Those who tested positive were counseled regarding symptomatology that should prompt medical attention.”

In all, researchers screened 158 patients with a planned delivery, and 155 agreed to undergo COVID-19 testing. Of the 155 women tested, 24 (16%) tested positive for SARS CoV-2 infection. Among 146 support persons who had a negative interview screen and underwent SARS-CoV-2 testing, 14 (10%) tested positive for SARS-CoV-2 infection.

Test results were substantially concordant among patient and support person pairs. “Among patients who tested positive for COVID-19 infection and had a support person present, 11 of 19 (58%) support persons also tested positive for COVID-19 infection,” the authors reported. “Among patients who tested negative for COVID-19 infection and had a support person present, only 3 of 127 (2.4%) support persons tested positive for COVID-19 infection.”

Telephone screening did not identify any of the COVID-19–positive cases. Of the 24 patients with SARS-CoV-2 infection, none of their newborns tested positive at birth.

“Universal testing ... provides a mechanism for more accurate counseling of patients regarding issues such as newborn skin-to-skin contact and breastfeeding,” noted Dr. Bianco and colleagues. At their institution, parents with COVID-19 are instructed to wear a mask and practice proper hand hygiene when caring for their newborns.

Kristina Adams Waldorf, MD, said in an interview that the study by Bianco et al. underscores the high rate of asymptomatic or mildly symptomatic COVID-19 infections detected with universal screening in a hospital at the U.S. epicenter of the pandemic. “Each state and hospital will need to evaluate their own data to determine the value of universal screening for their patient population. In rural parts of America that have yet to see cases, universal screening may not make sense, but these areas are likely to be few and far between. The rest of America will need to quickly get on board with universal screening to protect their labor and delivery staff.”

Testing the partner was a strength of the study. “It is reassuring that when a pregnant woman tested negative for SARS-CoV-2, the rate was very, very low (2.4%) that her partner would test positive. However, it was disconcerting that telephone screening for common symptoms associated with COVID-19 was not very helpful in identifying cases,” said Dr. Waldorf, a professor of obstetrics and gynecology at the University of Washington, Seattle. She was not involved in the study by Bianco et al.

One study author receives payment from the American Board of Obstetrics and Gynecology for serving as a board examiner, receives payment from UpToDate, and serves as an expert witness in malpractice and products liability cases. The other authors did not report any potential conflicts of interest. Dr. Waldorf said she had no relevant financial disclosures.

[email protected]

SOURCE: Bianco A et al. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003985.

Among women with a planned delivery in a New York City health system during the first half of April, the rate of asymptomatic SARS-CoV-2 infection was 16%, according to a study published in Obstetrics & Gynecology. Among the patients’ designated support persons, the asymptomatic carrier rate was 10%.

“If universal testing of pregnant patients in a high prevalence area is not performed, health care workers will be inadvertently exposed to COVID-19, unless universal precautions with personal protective equipment are taken,” wrote the researchers affiliated with the department of obstetrics, gynecology, and reproductive medicine at Icahn School of Medicine at Mount Sinai, New York.

Angela Bianco, MD, and colleagues conducted an observational study of women who were scheduled for a planned delivery within the Mount Sinai Health System between April 4 and April 15, 2020. Patients and their designated support person completed a telephone screen and underwent COVID-19 testing the day before a scheduled delivery. If support persons screened positive during the telephone interview about COVID-19 symptoms, they could not attend the birth, and patients could contact a different support person to be screened and tested. “All patients and their support persons were informed of their SARS-CoV-2 test results before admission,” the investigators wrote. “Those who tested positive were counseled regarding symptomatology that should prompt medical attention.”

In all, researchers screened 158 patients with a planned delivery, and 155 agreed to undergo COVID-19 testing. Of the 155 women tested, 24 (16%) tested positive for SARS CoV-2 infection. Among 146 support persons who had a negative interview screen and underwent SARS-CoV-2 testing, 14 (10%) tested positive for SARS-CoV-2 infection.

Test results were substantially concordant among patient and support person pairs. “Among patients who tested positive for COVID-19 infection and had a support person present, 11 of 19 (58%) support persons also tested positive for COVID-19 infection,” the authors reported. “Among patients who tested negative for COVID-19 infection and had a support person present, only 3 of 127 (2.4%) support persons tested positive for COVID-19 infection.”

Telephone screening did not identify any of the COVID-19–positive cases. Of the 24 patients with SARS-CoV-2 infection, none of their newborns tested positive at birth.

“Universal testing ... provides a mechanism for more accurate counseling of patients regarding issues such as newborn skin-to-skin contact and breastfeeding,” noted Dr. Bianco and colleagues. At their institution, parents with COVID-19 are instructed to wear a mask and practice proper hand hygiene when caring for their newborns.

Kristina Adams Waldorf, MD, said in an interview that the study by Bianco et al. underscores the high rate of asymptomatic or mildly symptomatic COVID-19 infections detected with universal screening in a hospital at the U.S. epicenter of the pandemic. “Each state and hospital will need to evaluate their own data to determine the value of universal screening for their patient population. In rural parts of America that have yet to see cases, universal screening may not make sense, but these areas are likely to be few and far between. The rest of America will need to quickly get on board with universal screening to protect their labor and delivery staff.”

Testing the partner was a strength of the study. “It is reassuring that when a pregnant woman tested negative for SARS-CoV-2, the rate was very, very low (2.4%) that her partner would test positive. However, it was disconcerting that telephone screening for common symptoms associated with COVID-19 was not very helpful in identifying cases,” said Dr. Waldorf, a professor of obstetrics and gynecology at the University of Washington, Seattle. She was not involved in the study by Bianco et al.

One study author receives payment from the American Board of Obstetrics and Gynecology for serving as a board examiner, receives payment from UpToDate, and serves as an expert witness in malpractice and products liability cases. The other authors did not report any potential conflicts of interest. Dr. Waldorf said she had no relevant financial disclosures.

[email protected]

SOURCE: Bianco A et al. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003985.

Among women with a planned delivery in a New York City health system during the first half of April, the rate of asymptomatic SARS-CoV-2 infection was 16%, according to a study published in Obstetrics & Gynecology. Among the patients’ designated support persons, the asymptomatic carrier rate was 10%.

“If universal testing of pregnant patients in a high prevalence area is not performed, health care workers will be inadvertently exposed to COVID-19, unless universal precautions with personal protective equipment are taken,” wrote the researchers affiliated with the department of obstetrics, gynecology, and reproductive medicine at Icahn School of Medicine at Mount Sinai, New York.

Angela Bianco, MD, and colleagues conducted an observational study of women who were scheduled for a planned delivery within the Mount Sinai Health System between April 4 and April 15, 2020. Patients and their designated support person completed a telephone screen and underwent COVID-19 testing the day before a scheduled delivery. If support persons screened positive during the telephone interview about COVID-19 symptoms, they could not attend the birth, and patients could contact a different support person to be screened and tested. “All patients and their support persons were informed of their SARS-CoV-2 test results before admission,” the investigators wrote. “Those who tested positive were counseled regarding symptomatology that should prompt medical attention.”

In all, researchers screened 158 patients with a planned delivery, and 155 agreed to undergo COVID-19 testing. Of the 155 women tested, 24 (16%) tested positive for SARS CoV-2 infection. Among 146 support persons who had a negative interview screen and underwent SARS-CoV-2 testing, 14 (10%) tested positive for SARS-CoV-2 infection.

Test results were substantially concordant among patient and support person pairs. “Among patients who tested positive for COVID-19 infection and had a support person present, 11 of 19 (58%) support persons also tested positive for COVID-19 infection,” the authors reported. “Among patients who tested negative for COVID-19 infection and had a support person present, only 3 of 127 (2.4%) support persons tested positive for COVID-19 infection.”

Telephone screening did not identify any of the COVID-19–positive cases. Of the 24 patients with SARS-CoV-2 infection, none of their newborns tested positive at birth.

“Universal testing ... provides a mechanism for more accurate counseling of patients regarding issues such as newborn skin-to-skin contact and breastfeeding,” noted Dr. Bianco and colleagues. At their institution, parents with COVID-19 are instructed to wear a mask and practice proper hand hygiene when caring for their newborns.

Kristina Adams Waldorf, MD, said in an interview that the study by Bianco et al. underscores the high rate of asymptomatic or mildly symptomatic COVID-19 infections detected with universal screening in a hospital at the U.S. epicenter of the pandemic. “Each state and hospital will need to evaluate their own data to determine the value of universal screening for their patient population. In rural parts of America that have yet to see cases, universal screening may not make sense, but these areas are likely to be few and far between. The rest of America will need to quickly get on board with universal screening to protect their labor and delivery staff.”

Testing the partner was a strength of the study. “It is reassuring that when a pregnant woman tested negative for SARS-CoV-2, the rate was very, very low (2.4%) that her partner would test positive. However, it was disconcerting that telephone screening for common symptoms associated with COVID-19 was not very helpful in identifying cases,” said Dr. Waldorf, a professor of obstetrics and gynecology at the University of Washington, Seattle. She was not involved in the study by Bianco et al.

One study author receives payment from the American Board of Obstetrics and Gynecology for serving as a board examiner, receives payment from UpToDate, and serves as an expert witness in malpractice and products liability cases. The other authors did not report any potential conflicts of interest. Dr. Waldorf said she had no relevant financial disclosures.

[email protected]

SOURCE: Bianco A et al. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003985.

Labor & delivery units may need to consider regional prevalence of COVID-19 when deciding whether to test asymptomatic pregnant women for SARS-CoV-2 infection at the time of admission, research published online in Obstetrics & Gynecology suggests.

In Los Angeles, researchers stopped universal testing after none of the first 80 asymptomatic women had positive results. Researchers in Chicago, on the other hand, found a positive rate of approximately 1.6% among 614 asymptomatic patients and continue to test all patients.

“Decisions regarding universal testing need to be made in the context of regional prevalence of COVID-19 infection, with recognition that a ‘one-size-fits-all’ approach is unlikely to be justifiable,” Torri D. Metz, MD,of University of Utah Health in Salt Lake City said in an editorial accompanying research letters that described the experience in Los Angeles and Chicago. “In the setting of low population prevalence of COVID-19 infection or in locations with limited testing availability, deferring universal testing may represent the better part of valor when weighing risks, benefits, economic burden, and unintended consequences of testing for SARS-CoV-2 infection. In high-prevalence regions, universal testing may be a valuable addition to obstetric care that will prevent infections in health care workers and neonates.”

Testing all patients also may provide valuable population-level surveillance, added Dr. Metz, who is an associate professor of obstetrics and gynecology, a maternal-fetal medicine subspecialist, and vice-chair of research in obstetrics and gynecology.

One week of data

After New York hospitals reported an approximately 13% prevalence of SARS-CoV-2 infection among asymptomatic laboring women, Cedars-Sinai Medical Center in Los Angeles changed its policy from testing only women with COVID-19 symptoms to testing all women beginning April 4, 2020. “Data from New York made us very concerned about the possibility of asymptomatic infections among our own pregnant patients,” Mariam Naqvi, MD, a maternal-fetal medicine specialist at Cedars-Sinai Medical Center, said in a news release. “This would have implications for them, their babies, their households, and for the health of our staff caring for them.”

In 1 week, 82 pregnant women admitted to the obstetric unit were tested for SARS-CoV-2 infection. Of two women who reported COVID-19 symptoms, one tested positive for SARS-CoV-2. “Of the remaining 80 asymptomatic women, none tested positive for SARS-CoV-2 infection, and all remained symptom free throughout their hospitalizations,” Dr. Naqvi and colleagues reported. “One asymptomatic patient had an inadequate nasopharyngeal specimen and declined repeat testing.”

Precautions taken during universal testing meant that all members of the treatment team used valuable personal protective equipment. In some cases, mothers and newborns were separated until test results were available.

“We discontinued universal testing after a 7-day period, because we could not justify continued testing of asymptomatic women in the absence of positive test results for SARS-CoV-2 infection,” they noted. “Though universal testing did not yield enough positive results on our obstetric unit to warrant continued testing at this time, our approach may change if local rates of infection increase.”

20 days of testing

In a prospective case series of pregnant women admitted to Northwestern Memorial Hospital in Chicago from April 8 to April 27, 2020, universal testing did detect asymptomatic infections. Women with scheduled admissions were tested 12-36 hours before admission in a drive-through testing center, and women with unscheduled admissions received a test that has a 2- to 3-hour turnaround time. In addition, patients were screened for symptoms such as fever, shortness of breath, cough, sore throat, body aches, chills, new-onset vomiting, diarrhea, loss of taste or smell, and red or painful eyes.

“Asymptomatic women with pending tests were managed on the routine labor floor, but health care workers used personal protective equipment that included a respirator during the second stage of labor and delivery until the test result became available,” wrote Emily S. Miller, MD, MPH, of Northwestern University, Chicago, and colleagues.

During the first 20 days of universal testing, 635 pregnant women were admitted, and 23 (3.6%) tested positive for SARS-CoV-2 infection. Of 21 women with COVID-19 symptoms, 13 (62%) tested positive for SARS-CoV-2 infection. Of 614 women who were asymptomatic, 10 (1.6%) tested positive for SARS-CoV-2. “Our data corroborate the observation that pregnant women with SARS-CoV-2 infection on admission do not seem to be reliably identified using symptom screening alone,” the researchers wrote.
 

Unintended consequences

Despite a lack of effective treatments for mild to moderate COVID-19, “knowledge of the disease state allows ... health care workers to wear appropriate personal protective equipment to avoid exposure,” Dr. Metz wrote. It also allows “women to be counseled about ways to decrease transmission to neonates” and enables close monitoring of patients with infection.

At the same time, universal testing may have unintended consequences for infected patients, such as stigmatization, separation from the newborn, and delays in care related to health care providers spending more time donning personal protective equipment or changes in medical decision-making regarding cesarean delivery, she emphasized.

“Obstetricians should remain aware of disease prevalence in their communities and consider universal screening of asymptomatic women on an ongoing basis as new ‘hot spots’ for COVID-19 infection are identified,” Dr. Metz concluded.

One of Dr. Naqvi’s coauthors disclosed receiving funds from Contemporary OB/GYN, Keneka, and the American College of Obstetricians and Gynecologists and serving as a board examiner for the American Board of Obstetrics and Gynecology; her coauthors did not report any relevant financial disclosures. Dr. Metz disclosed that money was paid to her institution from Pfizer and GestVision for work related to an RSV vaccination trial and a preeclampsia test, respectively. Dr. Miller and colleagues did not report any potential conflicts of interest.

[email protected]

SOURCES: Naqvi M et al. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003987; Miller ES et al. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003983; Metz TD. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003972.


 

Labor & delivery units may need to consider regional prevalence of COVID-19 when deciding whether to test asymptomatic pregnant women for SARS-CoV-2 infection at the time of admission, research published online in Obstetrics & Gynecology suggests.

In Los Angeles, researchers stopped universal testing after none of the first 80 asymptomatic women had positive results. Researchers in Chicago, on the other hand, found a positive rate of approximately 1.6% among 614 asymptomatic patients and continue to test all patients.

“Decisions regarding universal testing need to be made in the context of regional prevalence of COVID-19 infection, with recognition that a ‘one-size-fits-all’ approach is unlikely to be justifiable,” Torri D. Metz, MD,of University of Utah Health in Salt Lake City said in an editorial accompanying research letters that described the experience in Los Angeles and Chicago. “In the setting of low population prevalence of COVID-19 infection or in locations with limited testing availability, deferring universal testing may represent the better part of valor when weighing risks, benefits, economic burden, and unintended consequences of testing for SARS-CoV-2 infection. In high-prevalence regions, universal testing may be a valuable addition to obstetric care that will prevent infections in health care workers and neonates.”

Testing all patients also may provide valuable population-level surveillance, added Dr. Metz, who is an associate professor of obstetrics and gynecology, a maternal-fetal medicine subspecialist, and vice-chair of research in obstetrics and gynecology.

One week of data

After New York hospitals reported an approximately 13% prevalence of SARS-CoV-2 infection among asymptomatic laboring women, Cedars-Sinai Medical Center in Los Angeles changed its policy from testing only women with COVID-19 symptoms to testing all women beginning April 4, 2020. “Data from New York made us very concerned about the possibility of asymptomatic infections among our own pregnant patients,” Mariam Naqvi, MD, a maternal-fetal medicine specialist at Cedars-Sinai Medical Center, said in a news release. “This would have implications for them, their babies, their households, and for the health of our staff caring for them.”

In 1 week, 82 pregnant women admitted to the obstetric unit were tested for SARS-CoV-2 infection. Of two women who reported COVID-19 symptoms, one tested positive for SARS-CoV-2. “Of the remaining 80 asymptomatic women, none tested positive for SARS-CoV-2 infection, and all remained symptom free throughout their hospitalizations,” Dr. Naqvi and colleagues reported. “One asymptomatic patient had an inadequate nasopharyngeal specimen and declined repeat testing.”

Precautions taken during universal testing meant that all members of the treatment team used valuable personal protective equipment. In some cases, mothers and newborns were separated until test results were available.

“We discontinued universal testing after a 7-day period, because we could not justify continued testing of asymptomatic women in the absence of positive test results for SARS-CoV-2 infection,” they noted. “Though universal testing did not yield enough positive results on our obstetric unit to warrant continued testing at this time, our approach may change if local rates of infection increase.”

20 days of testing

In a prospective case series of pregnant women admitted to Northwestern Memorial Hospital in Chicago from April 8 to April 27, 2020, universal testing did detect asymptomatic infections. Women with scheduled admissions were tested 12-36 hours before admission in a drive-through testing center, and women with unscheduled admissions received a test that has a 2- to 3-hour turnaround time. In addition, patients were screened for symptoms such as fever, shortness of breath, cough, sore throat, body aches, chills, new-onset vomiting, diarrhea, loss of taste or smell, and red or painful eyes.

“Asymptomatic women with pending tests were managed on the routine labor floor, but health care workers used personal protective equipment that included a respirator during the second stage of labor and delivery until the test result became available,” wrote Emily S. Miller, MD, MPH, of Northwestern University, Chicago, and colleagues.

During the first 20 days of universal testing, 635 pregnant women were admitted, and 23 (3.6%) tested positive for SARS-CoV-2 infection. Of 21 women with COVID-19 symptoms, 13 (62%) tested positive for SARS-CoV-2 infection. Of 614 women who were asymptomatic, 10 (1.6%) tested positive for SARS-CoV-2. “Our data corroborate the observation that pregnant women with SARS-CoV-2 infection on admission do not seem to be reliably identified using symptom screening alone,” the researchers wrote.
 

Unintended consequences

Despite a lack of effective treatments for mild to moderate COVID-19, “knowledge of the disease state allows ... health care workers to wear appropriate personal protective equipment to avoid exposure,” Dr. Metz wrote. It also allows “women to be counseled about ways to decrease transmission to neonates” and enables close monitoring of patients with infection.

At the same time, universal testing may have unintended consequences for infected patients, such as stigmatization, separation from the newborn, and delays in care related to health care providers spending more time donning personal protective equipment or changes in medical decision-making regarding cesarean delivery, she emphasized.

“Obstetricians should remain aware of disease prevalence in their communities and consider universal screening of asymptomatic women on an ongoing basis as new ‘hot spots’ for COVID-19 infection are identified,” Dr. Metz concluded.

One of Dr. Naqvi’s coauthors disclosed receiving funds from Contemporary OB/GYN, Keneka, and the American College of Obstetricians and Gynecologists and serving as a board examiner for the American Board of Obstetrics and Gynecology; her coauthors did not report any relevant financial disclosures. Dr. Metz disclosed that money was paid to her institution from Pfizer and GestVision for work related to an RSV vaccination trial and a preeclampsia test, respectively. Dr. Miller and colleagues did not report any potential conflicts of interest.

[email protected]

SOURCES: Naqvi M et al. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003987; Miller ES et al. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003983; Metz TD. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003972.


 

Labor & delivery units may need to consider regional prevalence of COVID-19 when deciding whether to test asymptomatic pregnant women for SARS-CoV-2 infection at the time of admission, research published online in Obstetrics & Gynecology suggests.

In Los Angeles, researchers stopped universal testing after none of the first 80 asymptomatic women had positive results. Researchers in Chicago, on the other hand, found a positive rate of approximately 1.6% among 614 asymptomatic patients and continue to test all patients.

“Decisions regarding universal testing need to be made in the context of regional prevalence of COVID-19 infection, with recognition that a ‘one-size-fits-all’ approach is unlikely to be justifiable,” Torri D. Metz, MD,of University of Utah Health in Salt Lake City said in an editorial accompanying research letters that described the experience in Los Angeles and Chicago. “In the setting of low population prevalence of COVID-19 infection or in locations with limited testing availability, deferring universal testing may represent the better part of valor when weighing risks, benefits, economic burden, and unintended consequences of testing for SARS-CoV-2 infection. In high-prevalence regions, universal testing may be a valuable addition to obstetric care that will prevent infections in health care workers and neonates.”

Testing all patients also may provide valuable population-level surveillance, added Dr. Metz, who is an associate professor of obstetrics and gynecology, a maternal-fetal medicine subspecialist, and vice-chair of research in obstetrics and gynecology.

One week of data

After New York hospitals reported an approximately 13% prevalence of SARS-CoV-2 infection among asymptomatic laboring women, Cedars-Sinai Medical Center in Los Angeles changed its policy from testing only women with COVID-19 symptoms to testing all women beginning April 4, 2020. “Data from New York made us very concerned about the possibility of asymptomatic infections among our own pregnant patients,” Mariam Naqvi, MD, a maternal-fetal medicine specialist at Cedars-Sinai Medical Center, said in a news release. “This would have implications for them, their babies, their households, and for the health of our staff caring for them.”

In 1 week, 82 pregnant women admitted to the obstetric unit were tested for SARS-CoV-2 infection. Of two women who reported COVID-19 symptoms, one tested positive for SARS-CoV-2. “Of the remaining 80 asymptomatic women, none tested positive for SARS-CoV-2 infection, and all remained symptom free throughout their hospitalizations,” Dr. Naqvi and colleagues reported. “One asymptomatic patient had an inadequate nasopharyngeal specimen and declined repeat testing.”

Precautions taken during universal testing meant that all members of the treatment team used valuable personal protective equipment. In some cases, mothers and newborns were separated until test results were available.

“We discontinued universal testing after a 7-day period, because we could not justify continued testing of asymptomatic women in the absence of positive test results for SARS-CoV-2 infection,” they noted. “Though universal testing did not yield enough positive results on our obstetric unit to warrant continued testing at this time, our approach may change if local rates of infection increase.”

20 days of testing

In a prospective case series of pregnant women admitted to Northwestern Memorial Hospital in Chicago from April 8 to April 27, 2020, universal testing did detect asymptomatic infections. Women with scheduled admissions were tested 12-36 hours before admission in a drive-through testing center, and women with unscheduled admissions received a test that has a 2- to 3-hour turnaround time. In addition, patients were screened for symptoms such as fever, shortness of breath, cough, sore throat, body aches, chills, new-onset vomiting, diarrhea, loss of taste or smell, and red or painful eyes.

“Asymptomatic women with pending tests were managed on the routine labor floor, but health care workers used personal protective equipment that included a respirator during the second stage of labor and delivery until the test result became available,” wrote Emily S. Miller, MD, MPH, of Northwestern University, Chicago, and colleagues.

During the first 20 days of universal testing, 635 pregnant women were admitted, and 23 (3.6%) tested positive for SARS-CoV-2 infection. Of 21 women with COVID-19 symptoms, 13 (62%) tested positive for SARS-CoV-2 infection. Of 614 women who were asymptomatic, 10 (1.6%) tested positive for SARS-CoV-2. “Our data corroborate the observation that pregnant women with SARS-CoV-2 infection on admission do not seem to be reliably identified using symptom screening alone,” the researchers wrote.
 

Unintended consequences

Despite a lack of effective treatments for mild to moderate COVID-19, “knowledge of the disease state allows ... health care workers to wear appropriate personal protective equipment to avoid exposure,” Dr. Metz wrote. It also allows “women to be counseled about ways to decrease transmission to neonates” and enables close monitoring of patients with infection.

At the same time, universal testing may have unintended consequences for infected patients, such as stigmatization, separation from the newborn, and delays in care related to health care providers spending more time donning personal protective equipment or changes in medical decision-making regarding cesarean delivery, she emphasized.

“Obstetricians should remain aware of disease prevalence in their communities and consider universal screening of asymptomatic women on an ongoing basis as new ‘hot spots’ for COVID-19 infection are identified,” Dr. Metz concluded.

One of Dr. Naqvi’s coauthors disclosed receiving funds from Contemporary OB/GYN, Keneka, and the American College of Obstetricians and Gynecologists and serving as a board examiner for the American Board of Obstetrics and Gynecology; her coauthors did not report any relevant financial disclosures. Dr. Metz disclosed that money was paid to her institution from Pfizer and GestVision for work related to an RSV vaccination trial and a preeclampsia test, respectively. Dr. Miller and colleagues did not report any potential conflicts of interest.

[email protected]

SOURCES: Naqvi M et al. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003987; Miller ES et al. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003983; Metz TD. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003972.