Journal of Clinical Outcomes Management

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.
 

On March 9 my team was given a directive by the chief medical officer of our health system. We were charged with opening a drive-through COVID-19 testing center for our community in just 2 days’ time. It seemed like an impossible task, involving the mobilization of people, processes, and technology at a scale and speed we had never before achieved. It turned out getting this done was impossible. In spite of our best efforts, we failed to meet the deadline – it actually took us 3 days. Still, by March 12, we had opened the doors on the first community testing site in our area and gained the attention of local and national news outlets for our accomplishment.

Now more than 2 months later, I’m quite proud of what our team was able to achieve for the health system, but I’m still quite frustrated at the state of COVID-19 testing nationwide – there’s simply not enough available, and there is tremendous variability in the reliability of the tests. In this column, we’d like to highlight some of the challenges we’ve faced and reflect on how the shortcomings of modern technology have once again proven that medicine is both a science and an art.
 

Our dangerous lack of preparation

Prior to the coronavirus pandemic, I had never considered surgical masks, face shields, and nasal swabs to be critical components of medical technology. My opinion quickly changed after opening our drive-through COVID-19 site. I now have a much greater appreciation for the importance of personal protective equipment and basic testing supplies.

I was shocked by how difficult obtaining it has been during the past few months. It seems that no one anticipated the possibility of a pandemic on this grand a scale, so stockpiles of equipment were depleted quickly and couldn’t be replenished. Also, most manufacturing occurs outside the United States, which creates additional barriers to controlling the supply chain. One need not look far to find stories of widespread price-gouging, black market racketeering, and even hijackings that have stood in the way of accessing the necessary supplies. Sadly, the lack of equipment is far from the only challenge we’ve faced. In some cases, it has been a mistrust of results that has prevented widespread testing and mitigation.
 

The risks of flying blind

When President Trump touted the introduction of a rapid COVID-19 test at the end of March, many people were excited. Promising positive results in as few as 5 minutes, the assay was granted an Emergency Use Authorization (EUA) by the Food and Drug Administration in order to expedite its availability in the market. According to the FDA’s website, an EUA allows “unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions.” This rapid (though untested) approval was all that many health care providers needed to hear – immediately hospitals and physicians scrambled to get their hands on the testing devices. Unfortunately, on May 14th, the FDA issued a press release that raised concerns about that same test because it seemed to be reporting a high number of false-negative results. Just as quickly as the devices had been adopted, health care providers began backing away from them in favor of other assays, and a serious truth about COVID-19 testing was revealed: In many ways, we’re flying blind.

Laboratory manufacturers have been working overtime to create assays for SARS-CoV-2 (the coronavirus that causes COVID-19) and have used different technologies for detection. The most commonly used are polymerase chain reaction (PCR) tests. In these assays, viral RNA is converted to DNA by reverse transcriptase, then amplified through the addition of primers that enable detection. PCR technology has been available for years and is a reliable method for identifying DNA and RNA, but the required heating and cooling process takes time and results can take several hours to return. To address this and expedite testing, other methods of detection have been tried, such as the loop-mediated isothermal amplification (LAMP) technique employed by the rapid assay mentioned above. Regardless of methodology, all laboratory tests have one thing in common: None of them is perfect.

Every assay has a different level of reliability. When screening for a disease such as COVID-19, we are particularly interested in a test’s sensitivity (that is, it’s ability to detect disease); we’d love such a screening test to be 100% sensitive and thereby not miss a single case. In truth, no test’s sensitivity is 100%, and in this particular case even the best assays only score around 98%. This means that out of every 100 patients with COVID-19 who are evaluated, two might test negative for the virus. In a pandemic this can have dire consequences, so health care providers – unable to fully trust their instruments – must employ clinical acumen and years of experience to navigate these cloudy skies. We are hopeful that additional tools will complement our current methods, but with new assays also come new questions.
 

Is anyone safe?

We receive regular questions from physicians about the value of antibody testing, but it’s not yet clear how best to respond. While the assays seem to be reliable, the utility of the results are still ill defined. Antibodies to SARS-CoV-2 (both IgG and IgM) appear to peak about 2-3 weeks after symptom onset, but we don’t yet know if the presence of those antibodies confers long-term immunity. Therefore, patients should not use the information to change their masking or social-distancing practices, nor should they presume that they are safe from becoming reinfected with COVID-19. While new research looks promising, there are still too many unknowns to be able to confidently reassure providers or patients of the true value of antibody testing. This underscores our final point: Medicine remains an art.

As we are regularly reminded, we’ll never fully anticipate the challenges or barriers to success, and technology will never replace the value of clinical judgment and human experience. While the situation is unsettling in many ways, we are reassured and encouraged by the role we still get to play in keeping our patients healthy in this health care crisis, and we’ll continue to do so through whatever the future holds.
 

Dr. Notte is a family physician and chief medical officer of Abington Lansdale (Pa.) Hospital - Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
 

On March 9 my team was given a directive by the chief medical officer of our health system. We were charged with opening a drive-through COVID-19 testing center for our community in just 2 days’ time. It seemed like an impossible task, involving the mobilization of people, processes, and technology at a scale and speed we had never before achieved. It turned out getting this done was impossible. In spite of our best efforts, we failed to meet the deadline – it actually took us 3 days. Still, by March 12, we had opened the doors on the first community testing site in our area and gained the attention of local and national news outlets for our accomplishment.

Now more than 2 months later, I’m quite proud of what our team was able to achieve for the health system, but I’m still quite frustrated at the state of COVID-19 testing nationwide – there’s simply not enough available, and there is tremendous variability in the reliability of the tests. In this column, we’d like to highlight some of the challenges we’ve faced and reflect on how the shortcomings of modern technology have once again proven that medicine is both a science and an art.
 

Our dangerous lack of preparation

Prior to the coronavirus pandemic, I had never considered surgical masks, face shields, and nasal swabs to be critical components of medical technology. My opinion quickly changed after opening our drive-through COVID-19 site. I now have a much greater appreciation for the importance of personal protective equipment and basic testing supplies.

I was shocked by how difficult obtaining it has been during the past few months. It seems that no one anticipated the possibility of a pandemic on this grand a scale, so stockpiles of equipment were depleted quickly and couldn’t be replenished. Also, most manufacturing occurs outside the United States, which creates additional barriers to controlling the supply chain. One need not look far to find stories of widespread price-gouging, black market racketeering, and even hijackings that have stood in the way of accessing the necessary supplies. Sadly, the lack of equipment is far from the only challenge we’ve faced. In some cases, it has been a mistrust of results that has prevented widespread testing and mitigation.
 

The risks of flying blind

When President Trump touted the introduction of a rapid COVID-19 test at the end of March, many people were excited. Promising positive results in as few as 5 minutes, the assay was granted an Emergency Use Authorization (EUA) by the Food and Drug Administration in order to expedite its availability in the market. According to the FDA’s website, an EUA allows “unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions.” This rapid (though untested) approval was all that many health care providers needed to hear – immediately hospitals and physicians scrambled to get their hands on the testing devices. Unfortunately, on May 14th, the FDA issued a press release that raised concerns about that same test because it seemed to be reporting a high number of false-negative results. Just as quickly as the devices had been adopted, health care providers began backing away from them in favor of other assays, and a serious truth about COVID-19 testing was revealed: In many ways, we’re flying blind.

Laboratory manufacturers have been working overtime to create assays for SARS-CoV-2 (the coronavirus that causes COVID-19) and have used different technologies for detection. The most commonly used are polymerase chain reaction (PCR) tests. In these assays, viral RNA is converted to DNA by reverse transcriptase, then amplified through the addition of primers that enable detection. PCR technology has been available for years and is a reliable method for identifying DNA and RNA, but the required heating and cooling process takes time and results can take several hours to return. To address this and expedite testing, other methods of detection have been tried, such as the loop-mediated isothermal amplification (LAMP) technique employed by the rapid assay mentioned above. Regardless of methodology, all laboratory tests have one thing in common: None of them is perfect.

Every assay has a different level of reliability. When screening for a disease such as COVID-19, we are particularly interested in a test’s sensitivity (that is, it’s ability to detect disease); we’d love such a screening test to be 100% sensitive and thereby not miss a single case. In truth, no test’s sensitivity is 100%, and in this particular case even the best assays only score around 98%. This means that out of every 100 patients with COVID-19 who are evaluated, two might test negative for the virus. In a pandemic this can have dire consequences, so health care providers – unable to fully trust their instruments – must employ clinical acumen and years of experience to navigate these cloudy skies. We are hopeful that additional tools will complement our current methods, but with new assays also come new questions.
 

Is anyone safe?

We receive regular questions from physicians about the value of antibody testing, but it’s not yet clear how best to respond. While the assays seem to be reliable, the utility of the results are still ill defined. Antibodies to SARS-CoV-2 (both IgG and IgM) appear to peak about 2-3 weeks after symptom onset, but we don’t yet know if the presence of those antibodies confers long-term immunity. Therefore, patients should not use the information to change their masking or social-distancing practices, nor should they presume that they are safe from becoming reinfected with COVID-19. While new research looks promising, there are still too many unknowns to be able to confidently reassure providers or patients of the true value of antibody testing. This underscores our final point: Medicine remains an art.

As we are regularly reminded, we’ll never fully anticipate the challenges or barriers to success, and technology will never replace the value of clinical judgment and human experience. While the situation is unsettling in many ways, we are reassured and encouraged by the role we still get to play in keeping our patients healthy in this health care crisis, and we’ll continue to do so through whatever the future holds.
 

Dr. Notte is a family physician and chief medical officer of Abington Lansdale (Pa.) Hospital - Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
 

On March 9 my team was given a directive by the chief medical officer of our health system. We were charged with opening a drive-through COVID-19 testing center for our community in just 2 days’ time. It seemed like an impossible task, involving the mobilization of people, processes, and technology at a scale and speed we had never before achieved. It turned out getting this done was impossible. In spite of our best efforts, we failed to meet the deadline – it actually took us 3 days. Still, by March 12, we had opened the doors on the first community testing site in our area and gained the attention of local and national news outlets for our accomplishment.

Now more than 2 months later, I’m quite proud of what our team was able to achieve for the health system, but I’m still quite frustrated at the state of COVID-19 testing nationwide – there’s simply not enough available, and there is tremendous variability in the reliability of the tests. In this column, we’d like to highlight some of the challenges we’ve faced and reflect on how the shortcomings of modern technology have once again proven that medicine is both a science and an art.
 

Our dangerous lack of preparation

Prior to the coronavirus pandemic, I had never considered surgical masks, face shields, and nasal swabs to be critical components of medical technology. My opinion quickly changed after opening our drive-through COVID-19 site. I now have a much greater appreciation for the importance of personal protective equipment and basic testing supplies.

I was shocked by how difficult obtaining it has been during the past few months. It seems that no one anticipated the possibility of a pandemic on this grand a scale, so stockpiles of equipment were depleted quickly and couldn’t be replenished. Also, most manufacturing occurs outside the United States, which creates additional barriers to controlling the supply chain. One need not look far to find stories of widespread price-gouging, black market racketeering, and even hijackings that have stood in the way of accessing the necessary supplies. Sadly, the lack of equipment is far from the only challenge we’ve faced. In some cases, it has been a mistrust of results that has prevented widespread testing and mitigation.
 

The risks of flying blind

When President Trump touted the introduction of a rapid COVID-19 test at the end of March, many people were excited. Promising positive results in as few as 5 minutes, the assay was granted an Emergency Use Authorization (EUA) by the Food and Drug Administration in order to expedite its availability in the market. According to the FDA’s website, an EUA allows “unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions.” This rapid (though untested) approval was all that many health care providers needed to hear – immediately hospitals and physicians scrambled to get their hands on the testing devices. Unfortunately, on May 14th, the FDA issued a press release that raised concerns about that same test because it seemed to be reporting a high number of false-negative results. Just as quickly as the devices had been adopted, health care providers began backing away from them in favor of other assays, and a serious truth about COVID-19 testing was revealed: In many ways, we’re flying blind.

Laboratory manufacturers have been working overtime to create assays for SARS-CoV-2 (the coronavirus that causes COVID-19) and have used different technologies for detection. The most commonly used are polymerase chain reaction (PCR) tests. In these assays, viral RNA is converted to DNA by reverse transcriptase, then amplified through the addition of primers that enable detection. PCR technology has been available for years and is a reliable method for identifying DNA and RNA, but the required heating and cooling process takes time and results can take several hours to return. To address this and expedite testing, other methods of detection have been tried, such as the loop-mediated isothermal amplification (LAMP) technique employed by the rapid assay mentioned above. Regardless of methodology, all laboratory tests have one thing in common: None of them is perfect.

Every assay has a different level of reliability. When screening for a disease such as COVID-19, we are particularly interested in a test’s sensitivity (that is, it’s ability to detect disease); we’d love such a screening test to be 100% sensitive and thereby not miss a single case. In truth, no test’s sensitivity is 100%, and in this particular case even the best assays only score around 98%. This means that out of every 100 patients with COVID-19 who are evaluated, two might test negative for the virus. In a pandemic this can have dire consequences, so health care providers – unable to fully trust their instruments – must employ clinical acumen and years of experience to navigate these cloudy skies. We are hopeful that additional tools will complement our current methods, but with new assays also come new questions.
 

Is anyone safe?

We receive regular questions from physicians about the value of antibody testing, but it’s not yet clear how best to respond. While the assays seem to be reliable, the utility of the results are still ill defined. Antibodies to SARS-CoV-2 (both IgG and IgM) appear to peak about 2-3 weeks after symptom onset, but we don’t yet know if the presence of those antibodies confers long-term immunity. Therefore, patients should not use the information to change their masking or social-distancing practices, nor should they presume that they are safe from becoming reinfected with COVID-19. While new research looks promising, there are still too many unknowns to be able to confidently reassure providers or patients of the true value of antibody testing. This underscores our final point: Medicine remains an art.

As we are regularly reminded, we’ll never fully anticipate the challenges or barriers to success, and technology will never replace the value of clinical judgment and human experience. While the situation is unsettling in many ways, we are reassured and encouraged by the role we still get to play in keeping our patients healthy in this health care crisis, and we’ll continue to do so through whatever the future holds.
 

Dr. Notte is a family physician and chief medical officer of Abington Lansdale (Pa.) Hospital - Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
 

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.

Is maintenance therapy with an immune checkpoint inhibitor a good idea for patients with advanced bladder cancer who do not progress after initial chemotherapy?

Yes, and furthermore this approach offers “a new first-line standard of care for advanced urothelial cancer,” said Thomas Powles, MD, professor of genitourinary oncology and director of the Barts Cancer Centre in London.

Dr. Powles was discussing “first-line maintenance therapy” with avelumab (Bavencio, EMD Serono and Pfizer) from the JAVELIN Bladder 100 trial.

Results from this trial will be presented at the plenary session of the 2020 annual meeting of the American Society of Clinical Oncology, held virtually because the coronavirus pandemic. ASCO chief medical officer Richard Schilsky, MD, PhD, highlighted this abstract as one of three from the plenary session that were “practice changing.”

Dr. Powles provided a glimpse of the results at a premeeting press briefing.

The trial involved 700 patients who had not progressed after at least four cycles of first-line, platinum-based chemotherapy. Maintenance therapy with avelumab improved overall survival by 7.1 months when compared with best supportive care (BSC) alone.

The median OS was 21.4 months for avelumab plus BSC versus 14.3 months for BSC alone (hazard ratio, 0.69; P = .0005).

An expert not involved with the study was impressed with the outcome.

“The data are encouraging and we look forward to FDA review, and hopefully approval [in this setting],” said Padmanee Sharma, MD, PhD, a genitourinary medical oncologist at the University of Texas MD Anderson Cancer Center, Houston.

Avelumab is already approved for use in advanced urothelial cancer, but in a second-line setting, like a number of other immune checkpoint inhibitors.
 

“Instead of waiting for cancer to return”

Dr. Powles commented that about 65%-75% of patients with advanced urothelial cancer have disease control with first-line chemotherapy, but that progression-free survival (PFS) and OS are “short” because of chemoresistance.

Many patients do not receive second-line treatment with immunotherapy and only a “minority” achieve durable clinical benefit, he added.

“Instead of waiting for the cancer to return,” which it will do “quickly,” Dr. Powles suggested that maintenance with immunotherapy should become the standard of care.

“Our findings should give hope to many patients with advanced urothelial cancer who face a very challenging and difficult condition,” coauthor Petros Grivas, MD, PhD, clinical director of the Genitourinary Cancers Program at the Seattle Cancer Care Alliance, said in a statement. He was the global coprincipal investigator of the JAVELIN Bladder 100 trial.

“People with advanced urothelial cancer generally have a poor prognosis, and most experience cancer progression (growth) within 8 months after initiation of first-line chemotherapy,” he said.

“We are very excited with these results, which indicate that immunotherapy with avelumab first-line maintenance could offer a new treatment option that helps patients live longer. Even if this is likely not a complete cure and may cause potential side effects in some patients, the significant prolongation of overall survival is clearly a remarkable improvement, while many treated patients may not experience significant side effects from this approach,” he added.

The safety profile was “manageable” and consistent with other studies of avelumab, Dr. Powles reported.

All-causality adverse events (AEs) were reported at any grade in 98% versus 77.7% in the avelumab plus BSC versus BSC-alone groups; AEs of grade 3 or higher were 47.4% vs 25.2%. The most frequent grade ≥3 AEs were urinary tract infection (4.4% vs. 2.6%), anemia (3.8% vs. 2.9%), hematuria (1.7% vs. 1.4%), fatigue (1.7% vs. 0.6%), and back pain (1.2% vs. 2.3%).

The results from JAVELIN with avelumab show the “largest survival benefit” seen so far in advanced urothelial cancer in the maintenance setting, according to ASCO press materials.

Has there ever been a survival benefit found with maintenance therapy?

No, according to a 2019 review in Future Oncology. Three prospective, randomized, controlled trials (of vinflunine, sunitinib, and lapatinib, respectively) did not reveal any significant oncologic benefit vs placebo.

But in a phase 2, randomized, controlled trial involving 107 patients, maintenance pembrolizumab provided longer PFS, compared with placebo (5.4 vs 3.2 months, HR, 0.64; 95% confidence interval, 0.41-0.98).

This pembrolizumab trial showed a “similar PFS hazard ratio” to that seen with avelumab in JAVELIN, Dr. Powles commented, noting however that the pembrolizumab trial was not designed to look at survival.
 

Even better response among PD-L1-positive patients

JAVELIN patients had unresectable locally advanced or metastatic urothelial carcinoma and were treated with gemcitabine with either cisplatin or carboplatin.

Just over half (51%) of these patients had tumors that were PD-L1 positive.

The maintenance therapy strategy was even more effective in these patients. Avelumab plus BSC significantly prolonged OS versus BSC alone in patients with PD-L1-positive tumors (HR, 0.56; 1-sided P = .0003). Median OS was not reached versus 17.1 months, respectively.

An OS benefit was also observed across all prespecified subgroups, including those patients with visceral metastases.

Commenting on the study, Dr. Sharma said she would like to see more detailed outcome data related to the number of chemotherapy cycles administered (the range was 4 to 6) and information on the amount of time between the end of chemo to the start of avelumab. Dr. Powles commented that his international team has not looked at number of cycles and outcome, nor the time from completion of chemotherapy and randomization. “They are both valid questions for the future,” he said.

The study was funded by Pfizer. Dr. Powles and many of the coauthors have financial relationships with Pfizer and other pharmaceuticals. Dr. Sharma has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Is maintenance therapy with an immune checkpoint inhibitor a good idea for patients with advanced bladder cancer who do not progress after initial chemotherapy?

Yes, and furthermore this approach offers “a new first-line standard of care for advanced urothelial cancer,” said Thomas Powles, MD, professor of genitourinary oncology and director of the Barts Cancer Centre in London.

Dr. Powles was discussing “first-line maintenance therapy” with avelumab (Bavencio, EMD Serono and Pfizer) from the JAVELIN Bladder 100 trial.

Results from this trial will be presented at the plenary session of the 2020 annual meeting of the American Society of Clinical Oncology, held virtually because the coronavirus pandemic. ASCO chief medical officer Richard Schilsky, MD, PhD, highlighted this abstract as one of three from the plenary session that were “practice changing.”

Dr. Powles provided a glimpse of the results at a premeeting press briefing.

The trial involved 700 patients who had not progressed after at least four cycles of first-line, platinum-based chemotherapy. Maintenance therapy with avelumab improved overall survival by 7.1 months when compared with best supportive care (BSC) alone.

The median OS was 21.4 months for avelumab plus BSC versus 14.3 months for BSC alone (hazard ratio, 0.69; P = .0005).

An expert not involved with the study was impressed with the outcome.

“The data are encouraging and we look forward to FDA review, and hopefully approval [in this setting],” said Padmanee Sharma, MD, PhD, a genitourinary medical oncologist at the University of Texas MD Anderson Cancer Center, Houston.

Avelumab is already approved for use in advanced urothelial cancer, but in a second-line setting, like a number of other immune checkpoint inhibitors.
 

“Instead of waiting for cancer to return”

Dr. Powles commented that about 65%-75% of patients with advanced urothelial cancer have disease control with first-line chemotherapy, but that progression-free survival (PFS) and OS are “short” because of chemoresistance.

Many patients do not receive second-line treatment with immunotherapy and only a “minority” achieve durable clinical benefit, he added.

“Instead of waiting for the cancer to return,” which it will do “quickly,” Dr. Powles suggested that maintenance with immunotherapy should become the standard of care.

“Our findings should give hope to many patients with advanced urothelial cancer who face a very challenging and difficult condition,” coauthor Petros Grivas, MD, PhD, clinical director of the Genitourinary Cancers Program at the Seattle Cancer Care Alliance, said in a statement. He was the global coprincipal investigator of the JAVELIN Bladder 100 trial.

“People with advanced urothelial cancer generally have a poor prognosis, and most experience cancer progression (growth) within 8 months after initiation of first-line chemotherapy,” he said.

“We are very excited with these results, which indicate that immunotherapy with avelumab first-line maintenance could offer a new treatment option that helps patients live longer. Even if this is likely not a complete cure and may cause potential side effects in some patients, the significant prolongation of overall survival is clearly a remarkable improvement, while many treated patients may not experience significant side effects from this approach,” he added.

The safety profile was “manageable” and consistent with other studies of avelumab, Dr. Powles reported.

All-causality adverse events (AEs) were reported at any grade in 98% versus 77.7% in the avelumab plus BSC versus BSC-alone groups; AEs of grade 3 or higher were 47.4% vs 25.2%. The most frequent grade ≥3 AEs were urinary tract infection (4.4% vs. 2.6%), anemia (3.8% vs. 2.9%), hematuria (1.7% vs. 1.4%), fatigue (1.7% vs. 0.6%), and back pain (1.2% vs. 2.3%).

The results from JAVELIN with avelumab show the “largest survival benefit” seen so far in advanced urothelial cancer in the maintenance setting, according to ASCO press materials.

Has there ever been a survival benefit found with maintenance therapy?

No, according to a 2019 review in Future Oncology. Three prospective, randomized, controlled trials (of vinflunine, sunitinib, and lapatinib, respectively) did not reveal any significant oncologic benefit vs placebo.

But in a phase 2, randomized, controlled trial involving 107 patients, maintenance pembrolizumab provided longer PFS, compared with placebo (5.4 vs 3.2 months, HR, 0.64; 95% confidence interval, 0.41-0.98).

This pembrolizumab trial showed a “similar PFS hazard ratio” to that seen with avelumab in JAVELIN, Dr. Powles commented, noting however that the pembrolizumab trial was not designed to look at survival.
 

Even better response among PD-L1-positive patients

JAVELIN patients had unresectable locally advanced or metastatic urothelial carcinoma and were treated with gemcitabine with either cisplatin or carboplatin.

Just over half (51%) of these patients had tumors that were PD-L1 positive.

The maintenance therapy strategy was even more effective in these patients. Avelumab plus BSC significantly prolonged OS versus BSC alone in patients with PD-L1-positive tumors (HR, 0.56; 1-sided P = .0003). Median OS was not reached versus 17.1 months, respectively.

An OS benefit was also observed across all prespecified subgroups, including those patients with visceral metastases.

Commenting on the study, Dr. Sharma said she would like to see more detailed outcome data related to the number of chemotherapy cycles administered (the range was 4 to 6) and information on the amount of time between the end of chemo to the start of avelumab. Dr. Powles commented that his international team has not looked at number of cycles and outcome, nor the time from completion of chemotherapy and randomization. “They are both valid questions for the future,” he said.

The study was funded by Pfizer. Dr. Powles and many of the coauthors have financial relationships with Pfizer and other pharmaceuticals. Dr. Sharma has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Is maintenance therapy with an immune checkpoint inhibitor a good idea for patients with advanced bladder cancer who do not progress after initial chemotherapy?

Yes, and furthermore this approach offers “a new first-line standard of care for advanced urothelial cancer,” said Thomas Powles, MD, professor of genitourinary oncology and director of the Barts Cancer Centre in London.

Dr. Powles was discussing “first-line maintenance therapy” with avelumab (Bavencio, EMD Serono and Pfizer) from the JAVELIN Bladder 100 trial.

Results from this trial will be presented at the plenary session of the 2020 annual meeting of the American Society of Clinical Oncology, held virtually because the coronavirus pandemic. ASCO chief medical officer Richard Schilsky, MD, PhD, highlighted this abstract as one of three from the plenary session that were “practice changing.”

Dr. Powles provided a glimpse of the results at a premeeting press briefing.

The trial involved 700 patients who had not progressed after at least four cycles of first-line, platinum-based chemotherapy. Maintenance therapy with avelumab improved overall survival by 7.1 months when compared with best supportive care (BSC) alone.

The median OS was 21.4 months for avelumab plus BSC versus 14.3 months for BSC alone (hazard ratio, 0.69; P = .0005).

An expert not involved with the study was impressed with the outcome.

“The data are encouraging and we look forward to FDA review, and hopefully approval [in this setting],” said Padmanee Sharma, MD, PhD, a genitourinary medical oncologist at the University of Texas MD Anderson Cancer Center, Houston.

Avelumab is already approved for use in advanced urothelial cancer, but in a second-line setting, like a number of other immune checkpoint inhibitors.
 

“Instead of waiting for cancer to return”

Dr. Powles commented that about 65%-75% of patients with advanced urothelial cancer have disease control with first-line chemotherapy, but that progression-free survival (PFS) and OS are “short” because of chemoresistance.

Many patients do not receive second-line treatment with immunotherapy and only a “minority” achieve durable clinical benefit, he added.

“Instead of waiting for the cancer to return,” which it will do “quickly,” Dr. Powles suggested that maintenance with immunotherapy should become the standard of care.

“Our findings should give hope to many patients with advanced urothelial cancer who face a very challenging and difficult condition,” coauthor Petros Grivas, MD, PhD, clinical director of the Genitourinary Cancers Program at the Seattle Cancer Care Alliance, said in a statement. He was the global coprincipal investigator of the JAVELIN Bladder 100 trial.

“People with advanced urothelial cancer generally have a poor prognosis, and most experience cancer progression (growth) within 8 months after initiation of first-line chemotherapy,” he said.

“We are very excited with these results, which indicate that immunotherapy with avelumab first-line maintenance could offer a new treatment option that helps patients live longer. Even if this is likely not a complete cure and may cause potential side effects in some patients, the significant prolongation of overall survival is clearly a remarkable improvement, while many treated patients may not experience significant side effects from this approach,” he added.

The safety profile was “manageable” and consistent with other studies of avelumab, Dr. Powles reported.

All-causality adverse events (AEs) were reported at any grade in 98% versus 77.7% in the avelumab plus BSC versus BSC-alone groups; AEs of grade 3 or higher were 47.4% vs 25.2%. The most frequent grade ≥3 AEs were urinary tract infection (4.4% vs. 2.6%), anemia (3.8% vs. 2.9%), hematuria (1.7% vs. 1.4%), fatigue (1.7% vs. 0.6%), and back pain (1.2% vs. 2.3%).

The results from JAVELIN with avelumab show the “largest survival benefit” seen so far in advanced urothelial cancer in the maintenance setting, according to ASCO press materials.

Has there ever been a survival benefit found with maintenance therapy?

No, according to a 2019 review in Future Oncology. Three prospective, randomized, controlled trials (of vinflunine, sunitinib, and lapatinib, respectively) did not reveal any significant oncologic benefit vs placebo.

But in a phase 2, randomized, controlled trial involving 107 patients, maintenance pembrolizumab provided longer PFS, compared with placebo (5.4 vs 3.2 months, HR, 0.64; 95% confidence interval, 0.41-0.98).

This pembrolizumab trial showed a “similar PFS hazard ratio” to that seen with avelumab in JAVELIN, Dr. Powles commented, noting however that the pembrolizumab trial was not designed to look at survival.
 

Even better response among PD-L1-positive patients

JAVELIN patients had unresectable locally advanced or metastatic urothelial carcinoma and were treated with gemcitabine with either cisplatin or carboplatin.

Just over half (51%) of these patients had tumors that were PD-L1 positive.

The maintenance therapy strategy was even more effective in these patients. Avelumab plus BSC significantly prolonged OS versus BSC alone in patients with PD-L1-positive tumors (HR, 0.56; 1-sided P = .0003). Median OS was not reached versus 17.1 months, respectively.

An OS benefit was also observed across all prespecified subgroups, including those patients with visceral metastases.

Commenting on the study, Dr. Sharma said she would like to see more detailed outcome data related to the number of chemotherapy cycles administered (the range was 4 to 6) and information on the amount of time between the end of chemo to the start of avelumab. Dr. Powles commented that his international team has not looked at number of cycles and outcome, nor the time from completion of chemotherapy and randomization. “They are both valid questions for the future,” he said.

The study was funded by Pfizer. Dr. Powles and many of the coauthors have financial relationships with Pfizer and other pharmaceuticals. Dr. Sharma has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

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.

Patients with COVID-19 and progressing cancer had a fivefold increase in the risk of 30-day mortality, compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer, according to data from the COVID-19 and Cancer Consortium (CCC19) registry.

Mongkolchon Akesin/Shutterstock

Other independent risk factors for death in patients with COVID-19 and cancer were older age, male sex, former smoking, number of comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status of 2 or greater, and treatment with hydroxychloroquine plus azithromycin.

In fact, patients who received hydroxychloroquine and azithromycin had a nearly threefold higher risk of death than did patients who had not received the combination. However, this finding was of “uncertain validity due to a high risk of residual confounding; for example, patients receiving this combination were more likely to have severe disease or more likely to be hospitalized,” said Jeremy L. Warner, MD, of Vanderbilt University Medical Center in Nashville, Tennessee.

Dr. Warner presented these findings in an online press briefing. Additional findings from the CCC19 registry are set to be presented as part of the American Society of Clinical Oncology (ASCO) virtual scientific program. The findings were also published in The Lancet.

‘Severe impact’ in cancer patients

“For people with cancer, the impact of COVID-19 is especially severe, whether they have been exposed to the virus or not. Patients with cancer are typically older adults, often with other underlying conditions, and their immune systems may be suppressed by the cancer, or due to chemotherapy, radiation, or other treatment,” commented ASCO President Howard A. Burris III, MD, who moderated the press briefing but was not involved in the study of CCC19 registry data.

“ASCO members tell us that they have had to delay or modify treatment plans to reduce patients’ risk of infection, and we’re unclear what the impact of these changes will be. Delays in cancer screening and diagnosis are also a major concern,” Dr. Burris continued.

“This does confirm reports that have come out from other centers, including other parts of the world, where they have found that people who have cancer and COVID-19 have a worse outcome,” said Andrew T. Chan, MD, MPH, of Massachusetts General Hospital in Boston, who was not involved in the research.

Dr. Chan’s group has developed a COVID-19 symptom study app with the aim of defining whether people living with cancer are at increased risk for infections, in addition to whether cancer is an independent risk factor for COVID-19 severity or mortality.

“Using data from our app, we were able to show that people who reported living with cancer did have a higher risk of developing COVID and were more likely to be hospitalized related to COVID,” Dr. Chan said in an interview.
 

Study details

The CCC19 registry collects information from 104 participating institutions in the United States and Canada, as well as anonymous data from individuals in the United States, Argentina, Canada, the European Union, and the United Kingdom.

The sample of 928 patients Dr. Warner presented was evenly balanced by sex. The median age was 66 years, and 30% of patients were aged 75 years or older.

In all, 39% of patients were on active anticancer therapy, and 43% had measurable disease. Breast cancer was the most common diagnosis, followed by prostate cancer, gastrointestinal cancers, lymphomas, and thoracic cancers.

Two-thirds of the patients (68%) had an ECOG performance status of 0 or 1, 8% had a performance status of 2, and 5% a status of 3 or 4. The remaining patients had unknown performance status.

Slightly more than half of patients (52%) were never smokers, 37% were former smokers, and 5% were current smokers. The remaining 6% of patients had unknown smoking status.

At a median follow-up of 21 days, 121 patients (13%) had died. All deaths occurred within 30 days of COVID-19 diagnosis. Among patients who died, 78 were male, 64 were former smokers, 70 were aged 75 years or older, 41 had active stable or responding cancer, 25 had progressing cancer, and 42 had an ECOG performance status of 2 or higher.

In all, 466 patients were hospitalized, and 106 in this group (23%) died. Among the 132 patients admitted to an ICU, 50 (38%) died, including 27 patients aged 75 years or older, and 15 with an ECOG performance status of 2 or greater. Of the 116 patients who required intubation, 50 (43%) died, including 26 who were 75 years or older, and 11 who had a performance status of 2 or greater.

It’s early days yet, and a larger sample size with longer follow-up will be needed to get a more complete picture of how COVID-19 affects specific patient subsets over time, Dr. Warner said.

ASCO has established its own COVID-19 registry to collect both near-term and longitudinal data during the pandemic.

“We’ll be able to learn about both how the pandemic has impacted delivery of cancer care, as well as the longer-term effects of COVID-19 on cancer patients and understand what care approaches are working best,” said Richard L. Schilsky, MD, chief medical officer and executive vice president of ASCO, during the briefing.

The study of CCC19 registry data was supported in part by the National Institutes of Health and the American Cancer Society. Dr. Warner disclosed stock/ownership in HemOnc.org, consulting for IBM and Westat, and travel expenses from IBM. Dr. Burris, Dr. Schilsky, and Dr. Chan reported no disclosures relevant to the study.
 

SOURCE: Warner J L et al. ASCO 2020, Abstract LBA110.

Patients with COVID-19 and progressing cancer had a fivefold increase in the risk of 30-day mortality, compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer, according to data from the COVID-19 and Cancer Consortium (CCC19) registry.

Mongkolchon Akesin/Shutterstock

Other independent risk factors for death in patients with COVID-19 and cancer were older age, male sex, former smoking, number of comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status of 2 or greater, and treatment with hydroxychloroquine plus azithromycin.

In fact, patients who received hydroxychloroquine and azithromycin had a nearly threefold higher risk of death than did patients who had not received the combination. However, this finding was of “uncertain validity due to a high risk of residual confounding; for example, patients receiving this combination were more likely to have severe disease or more likely to be hospitalized,” said Jeremy L. Warner, MD, of Vanderbilt University Medical Center in Nashville, Tennessee.

Dr. Warner presented these findings in an online press briefing. Additional findings from the CCC19 registry are set to be presented as part of the American Society of Clinical Oncology (ASCO) virtual scientific program. The findings were also published in The Lancet.

‘Severe impact’ in cancer patients

“For people with cancer, the impact of COVID-19 is especially severe, whether they have been exposed to the virus or not. Patients with cancer are typically older adults, often with other underlying conditions, and their immune systems may be suppressed by the cancer, or due to chemotherapy, radiation, or other treatment,” commented ASCO President Howard A. Burris III, MD, who moderated the press briefing but was not involved in the study of CCC19 registry data.

“ASCO members tell us that they have had to delay or modify treatment plans to reduce patients’ risk of infection, and we’re unclear what the impact of these changes will be. Delays in cancer screening and diagnosis are also a major concern,” Dr. Burris continued.

“This does confirm reports that have come out from other centers, including other parts of the world, where they have found that people who have cancer and COVID-19 have a worse outcome,” said Andrew T. Chan, MD, MPH, of Massachusetts General Hospital in Boston, who was not involved in the research.

Dr. Chan’s group has developed a COVID-19 symptom study app with the aim of defining whether people living with cancer are at increased risk for infections, in addition to whether cancer is an independent risk factor for COVID-19 severity or mortality.

“Using data from our app, we were able to show that people who reported living with cancer did have a higher risk of developing COVID and were more likely to be hospitalized related to COVID,” Dr. Chan said in an interview.
 

Study details

The CCC19 registry collects information from 104 participating institutions in the United States and Canada, as well as anonymous data from individuals in the United States, Argentina, Canada, the European Union, and the United Kingdom.

The sample of 928 patients Dr. Warner presented was evenly balanced by sex. The median age was 66 years, and 30% of patients were aged 75 years or older.

In all, 39% of patients were on active anticancer therapy, and 43% had measurable disease. Breast cancer was the most common diagnosis, followed by prostate cancer, gastrointestinal cancers, lymphomas, and thoracic cancers.

Two-thirds of the patients (68%) had an ECOG performance status of 0 or 1, 8% had a performance status of 2, and 5% a status of 3 or 4. The remaining patients had unknown performance status.

Slightly more than half of patients (52%) were never smokers, 37% were former smokers, and 5% were current smokers. The remaining 6% of patients had unknown smoking status.

At a median follow-up of 21 days, 121 patients (13%) had died. All deaths occurred within 30 days of COVID-19 diagnosis. Among patients who died, 78 were male, 64 were former smokers, 70 were aged 75 years or older, 41 had active stable or responding cancer, 25 had progressing cancer, and 42 had an ECOG performance status of 2 or higher.

In all, 466 patients were hospitalized, and 106 in this group (23%) died. Among the 132 patients admitted to an ICU, 50 (38%) died, including 27 patients aged 75 years or older, and 15 with an ECOG performance status of 2 or greater. Of the 116 patients who required intubation, 50 (43%) died, including 26 who were 75 years or older, and 11 who had a performance status of 2 or greater.

It’s early days yet, and a larger sample size with longer follow-up will be needed to get a more complete picture of how COVID-19 affects specific patient subsets over time, Dr. Warner said.

ASCO has established its own COVID-19 registry to collect both near-term and longitudinal data during the pandemic.

“We’ll be able to learn about both how the pandemic has impacted delivery of cancer care, as well as the longer-term effects of COVID-19 on cancer patients and understand what care approaches are working best,” said Richard L. Schilsky, MD, chief medical officer and executive vice president of ASCO, during the briefing.

The study of CCC19 registry data was supported in part by the National Institutes of Health and the American Cancer Society. Dr. Warner disclosed stock/ownership in HemOnc.org, consulting for IBM and Westat, and travel expenses from IBM. Dr. Burris, Dr. Schilsky, and Dr. Chan reported no disclosures relevant to the study.
 

SOURCE: Warner J L et al. ASCO 2020, Abstract LBA110.

Patients with COVID-19 and progressing cancer had a fivefold increase in the risk of 30-day mortality, compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer, according to data from the COVID-19 and Cancer Consortium (CCC19) registry.

Mongkolchon Akesin/Shutterstock

Other independent risk factors for death in patients with COVID-19 and cancer were older age, male sex, former smoking, number of comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status of 2 or greater, and treatment with hydroxychloroquine plus azithromycin.

In fact, patients who received hydroxychloroquine and azithromycin had a nearly threefold higher risk of death than did patients who had not received the combination. However, this finding was of “uncertain validity due to a high risk of residual confounding; for example, patients receiving this combination were more likely to have severe disease or more likely to be hospitalized,” said Jeremy L. Warner, MD, of Vanderbilt University Medical Center in Nashville, Tennessee.

Dr. Warner presented these findings in an online press briefing. Additional findings from the CCC19 registry are set to be presented as part of the American Society of Clinical Oncology (ASCO) virtual scientific program. The findings were also published in The Lancet.

‘Severe impact’ in cancer patients

“For people with cancer, the impact of COVID-19 is especially severe, whether they have been exposed to the virus or not. Patients with cancer are typically older adults, often with other underlying conditions, and their immune systems may be suppressed by the cancer, or due to chemotherapy, radiation, or other treatment,” commented ASCO President Howard A. Burris III, MD, who moderated the press briefing but was not involved in the study of CCC19 registry data.

“ASCO members tell us that they have had to delay or modify treatment plans to reduce patients’ risk of infection, and we’re unclear what the impact of these changes will be. Delays in cancer screening and diagnosis are also a major concern,” Dr. Burris continued.

“This does confirm reports that have come out from other centers, including other parts of the world, where they have found that people who have cancer and COVID-19 have a worse outcome,” said Andrew T. Chan, MD, MPH, of Massachusetts General Hospital in Boston, who was not involved in the research.

Dr. Chan’s group has developed a COVID-19 symptom study app with the aim of defining whether people living with cancer are at increased risk for infections, in addition to whether cancer is an independent risk factor for COVID-19 severity or mortality.

“Using data from our app, we were able to show that people who reported living with cancer did have a higher risk of developing COVID and were more likely to be hospitalized related to COVID,” Dr. Chan said in an interview.
 

Study details

The CCC19 registry collects information from 104 participating institutions in the United States and Canada, as well as anonymous data from individuals in the United States, Argentina, Canada, the European Union, and the United Kingdom.

The sample of 928 patients Dr. Warner presented was evenly balanced by sex. The median age was 66 years, and 30% of patients were aged 75 years or older.

In all, 39% of patients were on active anticancer therapy, and 43% had measurable disease. Breast cancer was the most common diagnosis, followed by prostate cancer, gastrointestinal cancers, lymphomas, and thoracic cancers.

Two-thirds of the patients (68%) had an ECOG performance status of 0 or 1, 8% had a performance status of 2, and 5% a status of 3 or 4. The remaining patients had unknown performance status.

Slightly more than half of patients (52%) were never smokers, 37% were former smokers, and 5% were current smokers. The remaining 6% of patients had unknown smoking status.

At a median follow-up of 21 days, 121 patients (13%) had died. All deaths occurred within 30 days of COVID-19 diagnosis. Among patients who died, 78 were male, 64 were former smokers, 70 were aged 75 years or older, 41 had active stable or responding cancer, 25 had progressing cancer, and 42 had an ECOG performance status of 2 or higher.

In all, 466 patients were hospitalized, and 106 in this group (23%) died. Among the 132 patients admitted to an ICU, 50 (38%) died, including 27 patients aged 75 years or older, and 15 with an ECOG performance status of 2 or greater. Of the 116 patients who required intubation, 50 (43%) died, including 26 who were 75 years or older, and 11 who had a performance status of 2 or greater.

It’s early days yet, and a larger sample size with longer follow-up will be needed to get a more complete picture of how COVID-19 affects specific patient subsets over time, Dr. Warner said.

ASCO has established its own COVID-19 registry to collect both near-term and longitudinal data during the pandemic.

“We’ll be able to learn about both how the pandemic has impacted delivery of cancer care, as well as the longer-term effects of COVID-19 on cancer patients and understand what care approaches are working best,” said Richard L. Schilsky, MD, chief medical officer and executive vice president of ASCO, during the briefing.

The study of CCC19 registry data was supported in part by the National Institutes of Health and the American Cancer Society. Dr. Warner disclosed stock/ownership in HemOnc.org, consulting for IBM and Westat, and travel expenses from IBM. Dr. Burris, Dr. Schilsky, and Dr. Chan reported no disclosures relevant to the study.
 

SOURCE: Warner J L et al. ASCO 2020, Abstract LBA110.

Adjuvant therapy with osimertinib was associated with a nearly 80% reduction in the risk of disease recurrence or death in patients with stage IB-IIIA non–small cell lung cancer (NSCLC) bearing EGFR mutations, results of the ADAURA trial showed.

The randomized, phase 3 trial was a comparison of osimertinib treatment with placebo following complete resection of localized or locally advanced NSCLC with negative margins. The trial was unblinded early and halted on the recommendation of the independent data-monitoring committee, due to the efficacy of osimertinib.

“If I were on the committee, I would have done the same thing. These are extraordinary results,” said study investigator Roy S. Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center and Smilow Cancer Center at Yale University in New Haven, Conn.

Dr. Herbst is scheduled to present results from ADAURA as part of the American Society of Clinical Oncology virtual scientific program.

In an online briefing prior to the meeting, Dr. Herbst said the impressive results reminded him of a lesson imparted by his mentor, the late Isaiah Fidler, DVM, PhD.

“He taught me, he taught all of us, that metastasis is a spread of tumor that kills patients,” Dr. Herbst said. “Drugs such as this, based on biology, given to patients at the earliest possible time, prevent those metastases and allow patients to live longer and with a better quality of life.”

Results from the ADAURA trial provide compelling evidence of the benefit of adjuvant osimertinib for a select group of patients, according to Tina Cascone, MD, PhD, assistant professor in the department of thoracic head and neck medical oncology at The University of Texas MD Anderson Cancer Center in Houston. She was not involved in the study.

“These are unprecedented results for a potentially curable, resected population of patients,” Dr. Cascone said in an interview. “This definitely has the potential to shift the paradigm in the treatments that we have available for patients with resected disease. It’s very important to emphasize how much we’ve learned from the metastatic setting and how we’re bringing what we’ve learned into early stage disease.”

 

High recurrence rates

An estimated 30% of patients with NSCLC present with resectable disease at diagnosis, but 5-year recurrence rates following surgery and cisplatin-based adjuvant chemotherapy remain high, ranging from 45% among patients with stage IB disease to 62% for patients with stage II NSCLC and 76% for patients with stage III disease, Dr. Herbst noted.

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) targeted to EGFR. It has been shown to offer improvements in both progression-free survival and overall survival compared with the EGFR-TKIs erlotinib and gefitinib for patients with advanced EGFR-mutated NSCLC, as well as in patients with central nervous system metastases.

Osimertinib’s efficacy and safety profile against advanced disease suggests it may also be effective against early stage disease, a hypothesis the ADAURA trial was designed to test.
 

Study details

The phase 3, randomized, double-blind trial was conducted at centers in the United States, Europe, Asia, and Australia. A total of 682 patients with completely resected stage IB, II, or IIIA NSCLC, with or without planned adjuvant chemotherapy, were enrolled.

After stratification by stage, EGFR mutation, and race (Asian vs. non-Asian), patients were randomized on a 1:1 basis to receive either osimertinib at 80 mg once daily or placebo. The planned treatment duration was a maximum of 3 years.

Members of the independent data-monitoring committee held a meeting in April 2020. Although they had not planned an efficacy analysis at that time, they decided the results were clearly in favor of osimertinib. So they recommended unblinding and halting of the trial.

At the time of unblinding, the study had completed enrollment, and all patients had been followed for at least 1 year.
 

Efficacy and safety

For the primary endpoint of disease-free survival (DFS) in patients with stage II to IIIA disease, the median DFS was not reached for patients assigned to osimertinib, but it was 20.4 months for patients assigned to placebo (hazard ratio, 0.17; P < .0001).

The numbers were similar for the secondary endpoint of DFS in the overall population, including patients with stage IB disease. The median DFS was not reached for patients on osimertinib but was 28.1 months for patients on placebo (HR, 0.21; P < .0001).

DFS was significantly superior with osimertinib across all subgroups in the overall population, including sex, age, smoking status, race, stage, EGFR mutation, and adjuvant chemotherapy (yes or no).

Dr. Herbst said patients tolerated osimertinib well, and the drug’s safety profile was consistent with that already known. There were no adverse events leading to death in the osimertinib arm, and the incidence of grade 3 or 4 adverse events of any kind was low.

In all, 10 patients (3%) in the osimertinib arm were reported to have interstitial lung disease. Prolongation of the QT interval was reported in 22 patients (7%) on osimertinib and 4 patients (1%) in the placebo arm.

The results show that “adjuvant osimertinib provides a highly effective, practice-changing treatment for patients with stage IB, II, IIIA, EGFR mutation-positive non–small cell lung cancer after complete tumor resection,” Dr. Herbst said.

Dr. Herbst disclosed relationships with AstraZeneca, which funded the study, as well as Jun Shi Pharmaceuticals and other companies. Dr. Cascone is the international principal investigator of the NeoCOAST trial evaluating durvalumab, an AstraZeneca product.

SOURCE: Herbst RS et al. ASCO 2020, Abstract LBA5.

Adjuvant therapy with osimertinib was associated with a nearly 80% reduction in the risk of disease recurrence or death in patients with stage IB-IIIA non–small cell lung cancer (NSCLC) bearing EGFR mutations, results of the ADAURA trial showed.

The randomized, phase 3 trial was a comparison of osimertinib treatment with placebo following complete resection of localized or locally advanced NSCLC with negative margins. The trial was unblinded early and halted on the recommendation of the independent data-monitoring committee, due to the efficacy of osimertinib.

“If I were on the committee, I would have done the same thing. These are extraordinary results,” said study investigator Roy S. Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center and Smilow Cancer Center at Yale University in New Haven, Conn.

Dr. Herbst is scheduled to present results from ADAURA as part of the American Society of Clinical Oncology virtual scientific program.

In an online briefing prior to the meeting, Dr. Herbst said the impressive results reminded him of a lesson imparted by his mentor, the late Isaiah Fidler, DVM, PhD.

“He taught me, he taught all of us, that metastasis is a spread of tumor that kills patients,” Dr. Herbst said. “Drugs such as this, based on biology, given to patients at the earliest possible time, prevent those metastases and allow patients to live longer and with a better quality of life.”

Results from the ADAURA trial provide compelling evidence of the benefit of adjuvant osimertinib for a select group of patients, according to Tina Cascone, MD, PhD, assistant professor in the department of thoracic head and neck medical oncology at The University of Texas MD Anderson Cancer Center in Houston. She was not involved in the study.

“These are unprecedented results for a potentially curable, resected population of patients,” Dr. Cascone said in an interview. “This definitely has the potential to shift the paradigm in the treatments that we have available for patients with resected disease. It’s very important to emphasize how much we’ve learned from the metastatic setting and how we’re bringing what we’ve learned into early stage disease.”

 

High recurrence rates

An estimated 30% of patients with NSCLC present with resectable disease at diagnosis, but 5-year recurrence rates following surgery and cisplatin-based adjuvant chemotherapy remain high, ranging from 45% among patients with stage IB disease to 62% for patients with stage II NSCLC and 76% for patients with stage III disease, Dr. Herbst noted.

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) targeted to EGFR. It has been shown to offer improvements in both progression-free survival and overall survival compared with the EGFR-TKIs erlotinib and gefitinib for patients with advanced EGFR-mutated NSCLC, as well as in patients with central nervous system metastases.

Osimertinib’s efficacy and safety profile against advanced disease suggests it may also be effective against early stage disease, a hypothesis the ADAURA trial was designed to test.
 

Study details

The phase 3, randomized, double-blind trial was conducted at centers in the United States, Europe, Asia, and Australia. A total of 682 patients with completely resected stage IB, II, or IIIA NSCLC, with or without planned adjuvant chemotherapy, were enrolled.

After stratification by stage, EGFR mutation, and race (Asian vs. non-Asian), patients were randomized on a 1:1 basis to receive either osimertinib at 80 mg once daily or placebo. The planned treatment duration was a maximum of 3 years.

Members of the independent data-monitoring committee held a meeting in April 2020. Although they had not planned an efficacy analysis at that time, they decided the results were clearly in favor of osimertinib. So they recommended unblinding and halting of the trial.

At the time of unblinding, the study had completed enrollment, and all patients had been followed for at least 1 year.
 

Efficacy and safety

For the primary endpoint of disease-free survival (DFS) in patients with stage II to IIIA disease, the median DFS was not reached for patients assigned to osimertinib, but it was 20.4 months for patients assigned to placebo (hazard ratio, 0.17; P < .0001).

The numbers were similar for the secondary endpoint of DFS in the overall population, including patients with stage IB disease. The median DFS was not reached for patients on osimertinib but was 28.1 months for patients on placebo (HR, 0.21; P < .0001).

DFS was significantly superior with osimertinib across all subgroups in the overall population, including sex, age, smoking status, race, stage, EGFR mutation, and adjuvant chemotherapy (yes or no).

Dr. Herbst said patients tolerated osimertinib well, and the drug’s safety profile was consistent with that already known. There were no adverse events leading to death in the osimertinib arm, and the incidence of grade 3 or 4 adverse events of any kind was low.

In all, 10 patients (3%) in the osimertinib arm were reported to have interstitial lung disease. Prolongation of the QT interval was reported in 22 patients (7%) on osimertinib and 4 patients (1%) in the placebo arm.

The results show that “adjuvant osimertinib provides a highly effective, practice-changing treatment for patients with stage IB, II, IIIA, EGFR mutation-positive non–small cell lung cancer after complete tumor resection,” Dr. Herbst said.

Dr. Herbst disclosed relationships with AstraZeneca, which funded the study, as well as Jun Shi Pharmaceuticals and other companies. Dr. Cascone is the international principal investigator of the NeoCOAST trial evaluating durvalumab, an AstraZeneca product.

SOURCE: Herbst RS et al. ASCO 2020, Abstract LBA5.

Adjuvant therapy with osimertinib was associated with a nearly 80% reduction in the risk of disease recurrence or death in patients with stage IB-IIIA non–small cell lung cancer (NSCLC) bearing EGFR mutations, results of the ADAURA trial showed.

The randomized, phase 3 trial was a comparison of osimertinib treatment with placebo following complete resection of localized or locally advanced NSCLC with negative margins. The trial was unblinded early and halted on the recommendation of the independent data-monitoring committee, due to the efficacy of osimertinib.

“If I were on the committee, I would have done the same thing. These are extraordinary results,” said study investigator Roy S. Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center and Smilow Cancer Center at Yale University in New Haven, Conn.

Dr. Herbst is scheduled to present results from ADAURA as part of the American Society of Clinical Oncology virtual scientific program.

In an online briefing prior to the meeting, Dr. Herbst said the impressive results reminded him of a lesson imparted by his mentor, the late Isaiah Fidler, DVM, PhD.

“He taught me, he taught all of us, that metastasis is a spread of tumor that kills patients,” Dr. Herbst said. “Drugs such as this, based on biology, given to patients at the earliest possible time, prevent those metastases and allow patients to live longer and with a better quality of life.”

Results from the ADAURA trial provide compelling evidence of the benefit of adjuvant osimertinib for a select group of patients, according to Tina Cascone, MD, PhD, assistant professor in the department of thoracic head and neck medical oncology at The University of Texas MD Anderson Cancer Center in Houston. She was not involved in the study.

“These are unprecedented results for a potentially curable, resected population of patients,” Dr. Cascone said in an interview. “This definitely has the potential to shift the paradigm in the treatments that we have available for patients with resected disease. It’s very important to emphasize how much we’ve learned from the metastatic setting and how we’re bringing what we’ve learned into early stage disease.”

 

High recurrence rates

An estimated 30% of patients with NSCLC present with resectable disease at diagnosis, but 5-year recurrence rates following surgery and cisplatin-based adjuvant chemotherapy remain high, ranging from 45% among patients with stage IB disease to 62% for patients with stage II NSCLC and 76% for patients with stage III disease, Dr. Herbst noted.

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) targeted to EGFR. It has been shown to offer improvements in both progression-free survival and overall survival compared with the EGFR-TKIs erlotinib and gefitinib for patients with advanced EGFR-mutated NSCLC, as well as in patients with central nervous system metastases.

Osimertinib’s efficacy and safety profile against advanced disease suggests it may also be effective against early stage disease, a hypothesis the ADAURA trial was designed to test.
 

Study details

The phase 3, randomized, double-blind trial was conducted at centers in the United States, Europe, Asia, and Australia. A total of 682 patients with completely resected stage IB, II, or IIIA NSCLC, with or without planned adjuvant chemotherapy, were enrolled.

After stratification by stage, EGFR mutation, and race (Asian vs. non-Asian), patients were randomized on a 1:1 basis to receive either osimertinib at 80 mg once daily or placebo. The planned treatment duration was a maximum of 3 years.

Members of the independent data-monitoring committee held a meeting in April 2020. Although they had not planned an efficacy analysis at that time, they decided the results were clearly in favor of osimertinib. So they recommended unblinding and halting of the trial.

At the time of unblinding, the study had completed enrollment, and all patients had been followed for at least 1 year.
 

Efficacy and safety

For the primary endpoint of disease-free survival (DFS) in patients with stage II to IIIA disease, the median DFS was not reached for patients assigned to osimertinib, but it was 20.4 months for patients assigned to placebo (hazard ratio, 0.17; P < .0001).

The numbers were similar for the secondary endpoint of DFS in the overall population, including patients with stage IB disease. The median DFS was not reached for patients on osimertinib but was 28.1 months for patients on placebo (HR, 0.21; P < .0001).

DFS was significantly superior with osimertinib across all subgroups in the overall population, including sex, age, smoking status, race, stage, EGFR mutation, and adjuvant chemotherapy (yes or no).

Dr. Herbst said patients tolerated osimertinib well, and the drug’s safety profile was consistent with that already known. There were no adverse events leading to death in the osimertinib arm, and the incidence of grade 3 or 4 adverse events of any kind was low.

In all, 10 patients (3%) in the osimertinib arm were reported to have interstitial lung disease. Prolongation of the QT interval was reported in 22 patients (7%) on osimertinib and 4 patients (1%) in the placebo arm.

The results show that “adjuvant osimertinib provides a highly effective, practice-changing treatment for patients with stage IB, II, IIIA, EGFR mutation-positive non–small cell lung cancer after complete tumor resection,” Dr. Herbst said.

Dr. Herbst disclosed relationships with AstraZeneca, which funded the study, as well as Jun Shi Pharmaceuticals and other companies. Dr. Cascone is the international principal investigator of the NeoCOAST trial evaluating durvalumab, an AstraZeneca product.

SOURCE: Herbst RS et al. ASCO 2020, Abstract LBA5.

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.