Rheumatology News

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.

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.

Here are the stories our MDedge editors across specialties think you need to know about today:

Long road to recovery includes lung rehab

For seriously ill COVID-19 patients, there may a long recovery period even after leaving the intensive care unit. Eladio (“Lad”) Braganza, age 77, is one of those patients. For 28 days, he was on a ventilator in a Seattle ICU. Now – after a 46-day hospitalization for SARS-CoV-2 infection – he’s making progress in inpatient rehab. “The vast majority of COVID patients in the ICU have lung disease that is quite severe, much more severe than I have seen in my 20 years of doing this,” said critical care specialist Anna Nolan, MD, of the department of medicine at New York University. READ MORE.

Detox unit keeps running during COVID-19

Substance use disorder doesn’t take a break for a pandemic. In fact, the stressors from the current COVID-19 situation have increased substance use. In a commentary published on MDedge, Keji Fagbemi, MD, a hospitalist at the BronxCare Health System, shared how his hospital kept its inpatient detoxification unit running, despite the challenges presented by COVID-19. “At a time when many inpatient detoxification units within the city were temporarily closed due to fear of inpatient spread of the virus or to provide extra COVID beds in anticipation for the peak surge, we have been able to provide a needed service,” he wrote. “In fact, several other inpatient detoxification programs within the city have been able to refer their patients to our facility.” READ MORE.

Air pollution linked to MS risk

Air pollution may be another environmental risk factor for developing multiple sclerosis, suggests new research released as part of the Congress of the European Academy of Neurology (EAN) 2020. The findings, which are based on a large cohort study of nearly 550,000 individuals in Italy, appear to confirm the relationship between exposure to air pollutants and risk for MS that has been shown in prior studies. “Countermeasures that cut air pollution can be important for public health, not only to reduce deaths related to cardiac and pulmonary diseases but also the risk of chronic autoimmune diseases such as MS,” said Roberto Bergamaschi, MD, PhD, director of the Multiple Sclerosis Center, IRCCS Mondino Foundation, Pavia, Italy. READ MORE.
 

Trials produce conflicting results in Alzheimer’s disease

High-dose aducanumab, a human monoclonal antibody in development for the treatment of Alzheimer’s disease, significantly reduced clinical decline in people with early disease in one randomized, placebo-controlled phase 3 study. But there was no statistically significant change in outcomes in an identical study. “We believe that the difference between the results was largely due to patients’ greater exposure to the high dose of aducanumab,” said Samantha Budd Haeberlein, PhD, one of the study investigators and senior vice president and head of the neurodegeneration development unit at Biogen, which is developing the drug. READ MORE.

Pregnant patients have asymptomatic SARS-CoV-2 infection

The rate of asymptomatic SARS-CoV-2 infection was 16% among women with a planned delivery in a New York City health system during the first half of April, according to recent study results. “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,” researchers wrote in Obstetrics & Gynecology. READ MORE.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Long road to recovery includes lung rehab

For seriously ill COVID-19 patients, there may a long recovery period even after leaving the intensive care unit. Eladio (“Lad”) Braganza, age 77, is one of those patients. For 28 days, he was on a ventilator in a Seattle ICU. Now – after a 46-day hospitalization for SARS-CoV-2 infection – he’s making progress in inpatient rehab. “The vast majority of COVID patients in the ICU have lung disease that is quite severe, much more severe than I have seen in my 20 years of doing this,” said critical care specialist Anna Nolan, MD, of the department of medicine at New York University. READ MORE.

Detox unit keeps running during COVID-19

Substance use disorder doesn’t take a break for a pandemic. In fact, the stressors from the current COVID-19 situation have increased substance use. In a commentary published on MDedge, Keji Fagbemi, MD, a hospitalist at the BronxCare Health System, shared how his hospital kept its inpatient detoxification unit running, despite the challenges presented by COVID-19. “At a time when many inpatient detoxification units within the city were temporarily closed due to fear of inpatient spread of the virus or to provide extra COVID beds in anticipation for the peak surge, we have been able to provide a needed service,” he wrote. “In fact, several other inpatient detoxification programs within the city have been able to refer their patients to our facility.” READ MORE.

Air pollution linked to MS risk

Air pollution may be another environmental risk factor for developing multiple sclerosis, suggests new research released as part of the Congress of the European Academy of Neurology (EAN) 2020. The findings, which are based on a large cohort study of nearly 550,000 individuals in Italy, appear to confirm the relationship between exposure to air pollutants and risk for MS that has been shown in prior studies. “Countermeasures that cut air pollution can be important for public health, not only to reduce deaths related to cardiac and pulmonary diseases but also the risk of chronic autoimmune diseases such as MS,” said Roberto Bergamaschi, MD, PhD, director of the Multiple Sclerosis Center, IRCCS Mondino Foundation, Pavia, Italy. READ MORE.
 

Trials produce conflicting results in Alzheimer’s disease

High-dose aducanumab, a human monoclonal antibody in development for the treatment of Alzheimer’s disease, significantly reduced clinical decline in people with early disease in one randomized, placebo-controlled phase 3 study. But there was no statistically significant change in outcomes in an identical study. “We believe that the difference between the results was largely due to patients’ greater exposure to the high dose of aducanumab,” said Samantha Budd Haeberlein, PhD, one of the study investigators and senior vice president and head of the neurodegeneration development unit at Biogen, which is developing the drug. READ MORE.

Pregnant patients have asymptomatic SARS-CoV-2 infection

The rate of asymptomatic SARS-CoV-2 infection was 16% among women with a planned delivery in a New York City health system during the first half of April, according to recent study results. “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,” researchers wrote in Obstetrics & Gynecology. READ MORE.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Long road to recovery includes lung rehab

For seriously ill COVID-19 patients, there may a long recovery period even after leaving the intensive care unit. Eladio (“Lad”) Braganza, age 77, is one of those patients. For 28 days, he was on a ventilator in a Seattle ICU. Now – after a 46-day hospitalization for SARS-CoV-2 infection – he’s making progress in inpatient rehab. “The vast majority of COVID patients in the ICU have lung disease that is quite severe, much more severe than I have seen in my 20 years of doing this,” said critical care specialist Anna Nolan, MD, of the department of medicine at New York University. READ MORE.

Detox unit keeps running during COVID-19

Substance use disorder doesn’t take a break for a pandemic. In fact, the stressors from the current COVID-19 situation have increased substance use. In a commentary published on MDedge, Keji Fagbemi, MD, a hospitalist at the BronxCare Health System, shared how his hospital kept its inpatient detoxification unit running, despite the challenges presented by COVID-19. “At a time when many inpatient detoxification units within the city were temporarily closed due to fear of inpatient spread of the virus or to provide extra COVID beds in anticipation for the peak surge, we have been able to provide a needed service,” he wrote. “In fact, several other inpatient detoxification programs within the city have been able to refer their patients to our facility.” READ MORE.

Air pollution linked to MS risk

Air pollution may be another environmental risk factor for developing multiple sclerosis, suggests new research released as part of the Congress of the European Academy of Neurology (EAN) 2020. The findings, which are based on a large cohort study of nearly 550,000 individuals in Italy, appear to confirm the relationship between exposure to air pollutants and risk for MS that has been shown in prior studies. “Countermeasures that cut air pollution can be important for public health, not only to reduce deaths related to cardiac and pulmonary diseases but also the risk of chronic autoimmune diseases such as MS,” said Roberto Bergamaschi, MD, PhD, director of the Multiple Sclerosis Center, IRCCS Mondino Foundation, Pavia, Italy. READ MORE.
 

Trials produce conflicting results in Alzheimer’s disease

High-dose aducanumab, a human monoclonal antibody in development for the treatment of Alzheimer’s disease, significantly reduced clinical decline in people with early disease in one randomized, placebo-controlled phase 3 study. But there was no statistically significant change in outcomes in an identical study. “We believe that the difference between the results was largely due to patients’ greater exposure to the high dose of aducanumab,” said Samantha Budd Haeberlein, PhD, one of the study investigators and senior vice president and head of the neurodegeneration development unit at Biogen, which is developing the drug. READ MORE.

Pregnant patients have asymptomatic SARS-CoV-2 infection

The rate of asymptomatic SARS-CoV-2 infection was 16% among women with a planned delivery in a New York City health system during the first half of April, according to recent study results. “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,” researchers wrote in Obstetrics & Gynecology. READ MORE.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Nonpharmacologic recommendations for ankylosing spondylitis aren’t often followed by rheumatologists in the Boston-based Partners Healthcare system, and probably elsewhere, according to a review presented at the virtual annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

The American College of Rheumatology, Spondylitis Association of America, and SPARTAN released joint guidelines for ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis in 2016. Nonpharmacologic recommendations for AS included regular disease activity monitoring using a validated measure and C-reactive protein or erythrocyte sedimentation rate; physical therapy (PT) or home back exercises; and screening for osteoporosis with dual x-ray absorptiometry (DXA) scanning.

However, “the extent to which these recommendations are followed in clinical practice is unknown,” said lead investigator Akash Patel, of the Brigham and Women’s Hospital Division of Rheumatology, Immunology, and Allergy, in Boston.

To find out, the team reviewed electronic records for 304 AS patients who had 564 rheumatology clinic visits with Brigham and Women’s and other Partners Healthcare physicians from July 1, 2016, to June 30, 2019.

Records documented DXA scans in less than 20% of visits. PT was documented in only 9% of visits, and home back exercise in just 7%. Inflammatory marker measurement was documented in about half of visits, and disease activity was measured in only 17%.

Comparing the first year of the study – right after the recommendations came out – to the third year, the team found just an 8% increase in disease activity documentation, and about a 3% increase in documentation of PT and back exercises.

In short, the recommendations “were performed at low frequencies in this study population,” Mr. Patel said at the meeting, which was held online this year because of the COVID-19 pandemic.

It’s unclear what’s going on. Perhaps some physicians disagree with the 2016 advice – the regular monitoring of disease activity, after all, was a conditional recommendation based on low-quality evidence. Other times, physicians might not have had enough time to talk about exercise or draw blood for AS biomarkers. Maybe they didn’t bring up PT when they knew their patients couldn’t afford the out-of-pocket cost.

Whatever the case, future iterations of the guidelines should include advice on how to implement them. “We believe that including some sort of strategy for rheumatologists may help increase compliance,” Mr. Patel said.

A member of the online viewing audience suggested that the problem may be widespread in rheumatology. "I think if we did this at my institution,” for example, “it would also look abysmal. I think we all just suck at this,” the attendee said.*

Mr. Patel and his team presented the results to Brigham and Women’s rheumatologists in February 2020, but it’s too early to tell if it made a difference.

It was a typical AS cohort. Almost three-quarters of the subjects were men; the average age was 50 years old; and the diagnosis was made by imaging. The majority of patients were HLA-B27 positive, and over one-third had a history of uveitis.

The study’s funding source and disclosures – if any – weren’t reported.

*Correction, 6/3/2020: A previous version of this story misattributed this quote.

[email protected]

SOURCE: Patel A et al. SPARTAN 2020 abstract session May 15.

Nonpharmacologic recommendations for ankylosing spondylitis aren’t often followed by rheumatologists in the Boston-based Partners Healthcare system, and probably elsewhere, according to a review presented at the virtual annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

The American College of Rheumatology, Spondylitis Association of America, and SPARTAN released joint guidelines for ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis in 2016. Nonpharmacologic recommendations for AS included regular disease activity monitoring using a validated measure and C-reactive protein or erythrocyte sedimentation rate; physical therapy (PT) or home back exercises; and screening for osteoporosis with dual x-ray absorptiometry (DXA) scanning.

However, “the extent to which these recommendations are followed in clinical practice is unknown,” said lead investigator Akash Patel, of the Brigham and Women’s Hospital Division of Rheumatology, Immunology, and Allergy, in Boston.

To find out, the team reviewed electronic records for 304 AS patients who had 564 rheumatology clinic visits with Brigham and Women’s and other Partners Healthcare physicians from July 1, 2016, to June 30, 2019.

Records documented DXA scans in less than 20% of visits. PT was documented in only 9% of visits, and home back exercise in just 7%. Inflammatory marker measurement was documented in about half of visits, and disease activity was measured in only 17%.

Comparing the first year of the study – right after the recommendations came out – to the third year, the team found just an 8% increase in disease activity documentation, and about a 3% increase in documentation of PT and back exercises.

In short, the recommendations “were performed at low frequencies in this study population,” Mr. Patel said at the meeting, which was held online this year because of the COVID-19 pandemic.

It’s unclear what’s going on. Perhaps some physicians disagree with the 2016 advice – the regular monitoring of disease activity, after all, was a conditional recommendation based on low-quality evidence. Other times, physicians might not have had enough time to talk about exercise or draw blood for AS biomarkers. Maybe they didn’t bring up PT when they knew their patients couldn’t afford the out-of-pocket cost.

Whatever the case, future iterations of the guidelines should include advice on how to implement them. “We believe that including some sort of strategy for rheumatologists may help increase compliance,” Mr. Patel said.

A member of the online viewing audience suggested that the problem may be widespread in rheumatology. "I think if we did this at my institution,” for example, “it would also look abysmal. I think we all just suck at this,” the attendee said.*

Mr. Patel and his team presented the results to Brigham and Women’s rheumatologists in February 2020, but it’s too early to tell if it made a difference.

It was a typical AS cohort. Almost three-quarters of the subjects were men; the average age was 50 years old; and the diagnosis was made by imaging. The majority of patients were HLA-B27 positive, and over one-third had a history of uveitis.

The study’s funding source and disclosures – if any – weren’t reported.

*Correction, 6/3/2020: A previous version of this story misattributed this quote.

[email protected]

SOURCE: Patel A et al. SPARTAN 2020 abstract session May 15.

Nonpharmacologic recommendations for ankylosing spondylitis aren’t often followed by rheumatologists in the Boston-based Partners Healthcare system, and probably elsewhere, according to a review presented at the virtual annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

The American College of Rheumatology, Spondylitis Association of America, and SPARTAN released joint guidelines for ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis in 2016. Nonpharmacologic recommendations for AS included regular disease activity monitoring using a validated measure and C-reactive protein or erythrocyte sedimentation rate; physical therapy (PT) or home back exercises; and screening for osteoporosis with dual x-ray absorptiometry (DXA) scanning.

However, “the extent to which these recommendations are followed in clinical practice is unknown,” said lead investigator Akash Patel, of the Brigham and Women’s Hospital Division of Rheumatology, Immunology, and Allergy, in Boston.

To find out, the team reviewed electronic records for 304 AS patients who had 564 rheumatology clinic visits with Brigham and Women’s and other Partners Healthcare physicians from July 1, 2016, to June 30, 2019.

Records documented DXA scans in less than 20% of visits. PT was documented in only 9% of visits, and home back exercise in just 7%. Inflammatory marker measurement was documented in about half of visits, and disease activity was measured in only 17%.

Comparing the first year of the study – right after the recommendations came out – to the third year, the team found just an 8% increase in disease activity documentation, and about a 3% increase in documentation of PT and back exercises.

In short, the recommendations “were performed at low frequencies in this study population,” Mr. Patel said at the meeting, which was held online this year because of the COVID-19 pandemic.

It’s unclear what’s going on. Perhaps some physicians disagree with the 2016 advice – the regular monitoring of disease activity, after all, was a conditional recommendation based on low-quality evidence. Other times, physicians might not have had enough time to talk about exercise or draw blood for AS biomarkers. Maybe they didn’t bring up PT when they knew their patients couldn’t afford the out-of-pocket cost.

Whatever the case, future iterations of the guidelines should include advice on how to implement them. “We believe that including some sort of strategy for rheumatologists may help increase compliance,” Mr. Patel said.

A member of the online viewing audience suggested that the problem may be widespread in rheumatology. "I think if we did this at my institution,” for example, “it would also look abysmal. I think we all just suck at this,” the attendee said.*

Mr. Patel and his team presented the results to Brigham and Women’s rheumatologists in February 2020, but it’s too early to tell if it made a difference.

It was a typical AS cohort. Almost three-quarters of the subjects were men; the average age was 50 years old; and the diagnosis was made by imaging. The majority of patients were HLA-B27 positive, and over one-third had a history of uveitis.

The study’s funding source and disclosures – if any – weren’t reported.

*Correction, 6/3/2020: A previous version of this story misattributed this quote.

[email protected]

SOURCE: Patel A et al. SPARTAN 2020 abstract session May 15.

Substance use disorder and its daily consequences take no breaks even during a pandemic. The stressors created by COVID-19, including deaths of loved ones and the disruptions to normal life from policies aimed at flattening the curve, seem to have increased substance use.

Courtesy Dr. Keji Fagbemi

I practice as a hospitalist with an internal medicine background and specialty in addiction medicine at BronxCare Health System’s inpatient detoxification unit, a 24/7, 20-bed medically-supervised unit in South Bronx in New York City. It is one of the comprehensive services provided by the BronxCare’s life recovery center and addiction services, which also includes an outpatient clinic, opioid treatment program, inpatient rehab, and a half-way house. Inpatient detoxification units like ours are designed to treat serious addictions and chemical dependency and prevent and treat life-threatening withdrawal symptoms and signs or complications. Our patients come from all over the city and its adjoining suburbs, including from emergency room referrals, referral clinics, courts and the justice system, walk-ins, and self-referrals.

At a time when many inpatient detoxification units within the city were temporarily closed due to fear of inpatient spread of the virus or to provide extra COVID beds in anticipation for the peak surge, we have been able to provide a needed service. In fact, several other inpatient detoxification programs within the city have been able to refer their patients to our facility.

Individuals with substance use disorder have historically been a vulnerable and underserved population and possess high risk for multiple health problems as well as preexisting conditions. Many have limited life options financially, educationally, and with housing, and encounter barriers to accessing primary health care services, including preventive services. The introduction of the COVID-19 pandemic into these patients’ precarious health situations only made things worse as many of the limited resources for patients with substance use disorder were diverted to battling the pandemic. Numerous inpatient and outpatient addiction services, for example, were temporarily shut down. This has led to an increase in domestic violence, and psychiatric decompensation, including psychosis, suicidal attempts, and worsening of medical comorbidities in these patients.

Our wake-up call came when the first case of COVID-19 was confirmed in New York in early March. Within a short period of time the state became the epicenter for COVID-19. With the projection of millions of cases being positive and the number of new cases doubling every third day at the onset in New York City, we knew we had a battle brewing and needed to radically transform our mode of operation fast.

Our first task was to ensure the safety of our patients and the dedicated health workers attending to them. Instead of shutting down we decided to focus on education, screening, mask usage, social distancing, and intensifying hygiene. We streamlined the patient point of entry through one screening site, while also brushing up on our history-taking to intently screen for COVID-19. This included not just focusing on travels from China, but from Europe and other parts of the world.

Yes, we did ask patients about cough, fever, shortness of breath or difficulty breathing, feeling fatigued, severe body ache, and possible contact with someone who is sick or has traveled overseas. But we were also attuned to the increased rate of community spread and the presentation of other symptoms, such as loss of taste and smell, early in the process. Hence we were able to triage patients with suspected cases to the appropriate sections of the hospital for further screening, testing, and evaluation, instead of having those patients admitted to the detox unit.

Courtesy Dr. Keji Fagbemi

Dr. Fagbemi is a hospitalist at BronxCare Health System, a not-for-profit health and teaching hospital system serving South and Central Bronx in New York. He has no conflicts of interest to disclose.

Substance use disorder and its daily consequences take no breaks even during a pandemic. The stressors created by COVID-19, including deaths of loved ones and the disruptions to normal life from policies aimed at flattening the curve, seem to have increased substance use.

Courtesy Dr. Keji Fagbemi

I practice as a hospitalist with an internal medicine background and specialty in addiction medicine at BronxCare Health System’s inpatient detoxification unit, a 24/7, 20-bed medically-supervised unit in South Bronx in New York City. It is one of the comprehensive services provided by the BronxCare’s life recovery center and addiction services, which also includes an outpatient clinic, opioid treatment program, inpatient rehab, and a half-way house. Inpatient detoxification units like ours are designed to treat serious addictions and chemical dependency and prevent and treat life-threatening withdrawal symptoms and signs or complications. Our patients come from all over the city and its adjoining suburbs, including from emergency room referrals, referral clinics, courts and the justice system, walk-ins, and self-referrals.

At a time when many inpatient detoxification units within the city were temporarily closed due to fear of inpatient spread of the virus or to provide extra COVID beds in anticipation for the peak surge, we have been able to provide a needed service. In fact, several other inpatient detoxification programs within the city have been able to refer their patients to our facility.

Individuals with substance use disorder have historically been a vulnerable and underserved population and possess high risk for multiple health problems as well as preexisting conditions. Many have limited life options financially, educationally, and with housing, and encounter barriers to accessing primary health care services, including preventive services. The introduction of the COVID-19 pandemic into these patients’ precarious health situations only made things worse as many of the limited resources for patients with substance use disorder were diverted to battling the pandemic. Numerous inpatient and outpatient addiction services, for example, were temporarily shut down. This has led to an increase in domestic violence, and psychiatric decompensation, including psychosis, suicidal attempts, and worsening of medical comorbidities in these patients.

Our wake-up call came when the first case of COVID-19 was confirmed in New York in early March. Within a short period of time the state became the epicenter for COVID-19. With the projection of millions of cases being positive and the number of new cases doubling every third day at the onset in New York City, we knew we had a battle brewing and needed to radically transform our mode of operation fast.

Our first task was to ensure the safety of our patients and the dedicated health workers attending to them. Instead of shutting down we decided to focus on education, screening, mask usage, social distancing, and intensifying hygiene. We streamlined the patient point of entry through one screening site, while also brushing up on our history-taking to intently screen for COVID-19. This included not just focusing on travels from China, but from Europe and other parts of the world.

Yes, we did ask patients about cough, fever, shortness of breath or difficulty breathing, feeling fatigued, severe body ache, and possible contact with someone who is sick or has traveled overseas. But we were also attuned to the increased rate of community spread and the presentation of other symptoms, such as loss of taste and smell, early in the process. Hence we were able to triage patients with suspected cases to the appropriate sections of the hospital for further screening, testing, and evaluation, instead of having those patients admitted to the detox unit.

Courtesy Dr. Keji Fagbemi

Dr. Fagbemi is a hospitalist at BronxCare Health System, a not-for-profit health and teaching hospital system serving South and Central Bronx in New York. He has no conflicts of interest to disclose.

Substance use disorder and its daily consequences take no breaks even during a pandemic. The stressors created by COVID-19, including deaths of loved ones and the disruptions to normal life from policies aimed at flattening the curve, seem to have increased substance use.

Courtesy Dr. Keji Fagbemi

I practice as a hospitalist with an internal medicine background and specialty in addiction medicine at BronxCare Health System’s inpatient detoxification unit, a 24/7, 20-bed medically-supervised unit in South Bronx in New York City. It is one of the comprehensive services provided by the BronxCare’s life recovery center and addiction services, which also includes an outpatient clinic, opioid treatment program, inpatient rehab, and a half-way house. Inpatient detoxification units like ours are designed to treat serious addictions and chemical dependency and prevent and treat life-threatening withdrawal symptoms and signs or complications. Our patients come from all over the city and its adjoining suburbs, including from emergency room referrals, referral clinics, courts and the justice system, walk-ins, and self-referrals.

At a time when many inpatient detoxification units within the city were temporarily closed due to fear of inpatient spread of the virus or to provide extra COVID beds in anticipation for the peak surge, we have been able to provide a needed service. In fact, several other inpatient detoxification programs within the city have been able to refer their patients to our facility.

Individuals with substance use disorder have historically been a vulnerable and underserved population and possess high risk for multiple health problems as well as preexisting conditions. Many have limited life options financially, educationally, and with housing, and encounter barriers to accessing primary health care services, including preventive services. The introduction of the COVID-19 pandemic into these patients’ precarious health situations only made things worse as many of the limited resources for patients with substance use disorder were diverted to battling the pandemic. Numerous inpatient and outpatient addiction services, for example, were temporarily shut down. This has led to an increase in domestic violence, and psychiatric decompensation, including psychosis, suicidal attempts, and worsening of medical comorbidities in these patients.

Our wake-up call came when the first case of COVID-19 was confirmed in New York in early March. Within a short period of time the state became the epicenter for COVID-19. With the projection of millions of cases being positive and the number of new cases doubling every third day at the onset in New York City, we knew we had a battle brewing and needed to radically transform our mode of operation fast.

Our first task was to ensure the safety of our patients and the dedicated health workers attending to them. Instead of shutting down we decided to focus on education, screening, mask usage, social distancing, and intensifying hygiene. We streamlined the patient point of entry through one screening site, while also brushing up on our history-taking to intently screen for COVID-19. This included not just focusing on travels from China, but from Europe and other parts of the world.

Yes, we did ask patients about cough, fever, shortness of breath or difficulty breathing, feeling fatigued, severe body ache, and possible contact with someone who is sick or has traveled overseas. But we were also attuned to the increased rate of community spread and the presentation of other symptoms, such as loss of taste and smell, early in the process. Hence we were able to triage patients with suspected cases to the appropriate sections of the hospital for further screening, testing, and evaluation, instead of having those patients admitted to the detox unit.

Courtesy Dr. Keji Fagbemi

Dr. Fagbemi is a hospitalist at BronxCare Health System, a not-for-profit health and teaching hospital system serving South and Central Bronx in New York. He has no conflicts of interest to disclose.

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.