Journal of Clinical Outcomes Management

More than 780,000 doses of the JYNNEOS monkeypox vaccine will be available in the United States beginning July 29, the Department of Health & Human Services announced on July 28 in a press call.

HHS Secretary Xavier Becerra urged local and state public health departments to use these doses for preventive vaccination efforts to stay ahead of the virus and end the outbreak, noting that the HHS and Centers for Disease Control and Prevention do not control how vaccines are distributed at state and local levels. “We don’t have the authority to tell them what to do,” he said during the call. “We need them to work with us.”

As of July 28, there were 4,907 reported cases of monkeypox in the United States and officials expect cases will continue to rise in the coming weeks.

HHS already has distributed more 338,000 doses to states and jurisdictions, but the vaccine remains in high demand. The vaccine is manufactured by the small Danish company Bavarian Nordic. These additional 786,000 doses were previously stored at a plant in Denmark, awaiting the completion of an inspection and authorization of the vaccine plant by the Food and Drug Administration. The agency announced on July 27 that both the vaccine doses and the manufacturing plant met standards.

With the announcement of these additional doses, the vaccine allocation plan is also being updated to take into account two important factors: the number of people at high risk in a jurisdiction and the number of new cases reported since the last vaccine allocation.

“This update gives greater weight to prioritizing vaccines to areas with the greatest number of people at risk, which includes men who have sex with men who have HIV or who are eligible for HIV pre-exposure prophylaxis, while still considering where we are seeing cases increase,” said Capt. Jennifer McQuiston, DVM, deputy director of the division of high consequence pathogens and pathology at the CDC.

Capt.McQuiston also provided additional demographic information on the U.S. outbreak. The median age of people with confirmed cases is 35 years old, with a range from 17 to 76. (This does not include the two cases in children reported on July 22.) Of the cases where sex at birth was provided, 99% were individuals assigned male sex at birth. In cases with reported ethnicity and race, 37% were non-Hispanic White people, 31% were Hispanic/Latino, 27% were Black or African American, and 4% were of Asian descent. The most common symptoms were rash – present in 99% of cases – malaise, fever, and swollen lymph nodes.

HHS and CDC did not have data on how many people have received at least one dose of the monkeypox vaccine. When asked how many people need to be fully vaccinated against monkeypox to contain the outbreak, Mr. Becerra did not provide an estimate but implied that preventive vaccination could help limit the number of vaccines needed and expressed optimism about quelling the outbreak in the United States. “We believe that we have done everything we can at the federal level to work with our state and local partners and communities affected to make sure we can stay ahead of this and end this outbreak,” he said, “but everybody’s got to do their part.”

A version of this article first appeared on Medscape.com.

More than 780,000 doses of the JYNNEOS monkeypox vaccine will be available in the United States beginning July 29, the Department of Health & Human Services announced on July 28 in a press call.

HHS Secretary Xavier Becerra urged local and state public health departments to use these doses for preventive vaccination efforts to stay ahead of the virus and end the outbreak, noting that the HHS and Centers for Disease Control and Prevention do not control how vaccines are distributed at state and local levels. “We don’t have the authority to tell them what to do,” he said during the call. “We need them to work with us.”

As of July 28, there were 4,907 reported cases of monkeypox in the United States and officials expect cases will continue to rise in the coming weeks.

HHS already has distributed more 338,000 doses to states and jurisdictions, but the vaccine remains in high demand. The vaccine is manufactured by the small Danish company Bavarian Nordic. These additional 786,000 doses were previously stored at a plant in Denmark, awaiting the completion of an inspection and authorization of the vaccine plant by the Food and Drug Administration. The agency announced on July 27 that both the vaccine doses and the manufacturing plant met standards.

With the announcement of these additional doses, the vaccine allocation plan is also being updated to take into account two important factors: the number of people at high risk in a jurisdiction and the number of new cases reported since the last vaccine allocation.

“This update gives greater weight to prioritizing vaccines to areas with the greatest number of people at risk, which includes men who have sex with men who have HIV or who are eligible for HIV pre-exposure prophylaxis, while still considering where we are seeing cases increase,” said Capt. Jennifer McQuiston, DVM, deputy director of the division of high consequence pathogens and pathology at the CDC.

Capt.McQuiston also provided additional demographic information on the U.S. outbreak. The median age of people with confirmed cases is 35 years old, with a range from 17 to 76. (This does not include the two cases in children reported on July 22.) Of the cases where sex at birth was provided, 99% were individuals assigned male sex at birth. In cases with reported ethnicity and race, 37% were non-Hispanic White people, 31% were Hispanic/Latino, 27% were Black or African American, and 4% were of Asian descent. The most common symptoms were rash – present in 99% of cases – malaise, fever, and swollen lymph nodes.

HHS and CDC did not have data on how many people have received at least one dose of the monkeypox vaccine. When asked how many people need to be fully vaccinated against monkeypox to contain the outbreak, Mr. Becerra did not provide an estimate but implied that preventive vaccination could help limit the number of vaccines needed and expressed optimism about quelling the outbreak in the United States. “We believe that we have done everything we can at the federal level to work with our state and local partners and communities affected to make sure we can stay ahead of this and end this outbreak,” he said, “but everybody’s got to do their part.”

A version of this article first appeared on Medscape.com.

More than 780,000 doses of the JYNNEOS monkeypox vaccine will be available in the United States beginning July 29, the Department of Health & Human Services announced on July 28 in a press call.

HHS Secretary Xavier Becerra urged local and state public health departments to use these doses for preventive vaccination efforts to stay ahead of the virus and end the outbreak, noting that the HHS and Centers for Disease Control and Prevention do not control how vaccines are distributed at state and local levels. “We don’t have the authority to tell them what to do,” he said during the call. “We need them to work with us.”

As of July 28, there were 4,907 reported cases of monkeypox in the United States and officials expect cases will continue to rise in the coming weeks.

HHS already has distributed more 338,000 doses to states and jurisdictions, but the vaccine remains in high demand. The vaccine is manufactured by the small Danish company Bavarian Nordic. These additional 786,000 doses were previously stored at a plant in Denmark, awaiting the completion of an inspection and authorization of the vaccine plant by the Food and Drug Administration. The agency announced on July 27 that both the vaccine doses and the manufacturing plant met standards.

With the announcement of these additional doses, the vaccine allocation plan is also being updated to take into account two important factors: the number of people at high risk in a jurisdiction and the number of new cases reported since the last vaccine allocation.

“This update gives greater weight to prioritizing vaccines to areas with the greatest number of people at risk, which includes men who have sex with men who have HIV or who are eligible for HIV pre-exposure prophylaxis, while still considering where we are seeing cases increase,” said Capt. Jennifer McQuiston, DVM, deputy director of the division of high consequence pathogens and pathology at the CDC.

Capt.McQuiston also provided additional demographic information on the U.S. outbreak. The median age of people with confirmed cases is 35 years old, with a range from 17 to 76. (This does not include the two cases in children reported on July 22.) Of the cases where sex at birth was provided, 99% were individuals assigned male sex at birth. In cases with reported ethnicity and race, 37% were non-Hispanic White people, 31% were Hispanic/Latino, 27% were Black or African American, and 4% were of Asian descent. The most common symptoms were rash – present in 99% of cases – malaise, fever, and swollen lymph nodes.

HHS and CDC did not have data on how many people have received at least one dose of the monkeypox vaccine. When asked how many people need to be fully vaccinated against monkeypox to contain the outbreak, Mr. Becerra did not provide an estimate but implied that preventive vaccination could help limit the number of vaccines needed and expressed optimism about quelling the outbreak in the United States. “We believe that we have done everything we can at the federal level to work with our state and local partners and communities affected to make sure we can stay ahead of this and end this outbreak,” he said, “but everybody’s got to do their part.”

A version of this article first appeared on Medscape.com.

MONTREAL – The case of a patient in an HIV study whose viral load dropped to undetectable levels and whose immune cells soared has captured the attention of organizers at a meeting of the International AIDS Society.

Although the 59-year-old woman is one of many who are known as posttreatment controllers (PTCs) – having been in remission for more than 15 years after stopping antiretroviral therapy (ART) – it is an immune-based therapy study in which she took part in 2005, and her unusually high levels of memory-like NK cells and gamma-delta T cells since then, that are raising some eyebrows.

“This case opens new avenues in the HIV functional-cure field,” lead investigator Núria Climent, PhD, of the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

“As far as we know, this is the first time that the gamma-delta T cells have been identified in a PTC, and concerning the memory-like NK cells, there are very few published data and only sparse information presented in several congresses,” she said, explaining that these cells “have a high capacity to inhibit the replication of the virus in vitro. For that reason, we think that this PTC has cells able to dramatically reduce the virus amount. We think that the potential capacity to increase these cells in this PTC woman could be not only mediated by especial genetic factors ... but also mediated by early ART treatment and might be by the immunomediated treatment.”

The findings suggest the potential for “increasing the amount of those memory-like NK cells and gamma-delta T cells in order to translate this potent antiviral activity in new therapies to achieve an HIV functional cure,” she said, adding: “As far as we know, aiming to increase these specific cells has never been done before in people living with HIV.”

In a press conference during the meeting, Dr. Climent explained that the patient was enrolled in a study in which she received a combination of ART and immunomodulatory therapy. This involved a combination of cyclosporine A, low-dose interleukin 2, granulocyte macrophage colony-stimulating factor, and pegylated interferon alfa-2b.

“None of the other 19 patients included in the trial controlled viral replication,” senior investigator Jose Miro, MD, PhD, also from the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the conference, said in an interview that although the significance of the case is unclear, the IAS selected it as a highlight for the meeting. “It is important for clinicians to understand the complexities in interpreting these case reports. Their patients are probably likely to ask them about the report, and it’s important [that] they can explain it to them.”

Dr. Lewin, who is professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity in Melbourne, added that it is impossible to determine the mechanism of action from a single case report. “We don’t know if the intervention played a role or if this person is a ‘posttreatment controller,’ which has been previously described many times,” she said in an interview. “In this patient, the virus is at very low, but controlled, levels, and virus could be grown out. While it’s still exciting and important, this is really what we would consider a remission. The intense study of a single case such as this is certainly worthwhile and important but can only provide new ideas for research. So, I don’t think we can draw any conclusion on the role of NK cells, et cetera. We need much larger case series or controlled trials to reach any conclusion on the reasons for her remission.”

Dr. Climent disclosed no relevant financial conflicts of interest. Dr. Lewin has disclosed investigator-initiated industry-funded research (Gilead, ViiV, Merck), scientific advisory board honoraria paid to her personally (Gilead, Merck, ViiV, Esfam, Immunocore, Vaxxinity), and nonfunded collaborative research (AbbVie, Genentech, Bristol-Myers Squibb).

A version of this article first appeared on Medscape.com.

MONTREAL – The case of a patient in an HIV study whose viral load dropped to undetectable levels and whose immune cells soared has captured the attention of organizers at a meeting of the International AIDS Society.

Although the 59-year-old woman is one of many who are known as posttreatment controllers (PTCs) – having been in remission for more than 15 years after stopping antiretroviral therapy (ART) – it is an immune-based therapy study in which she took part in 2005, and her unusually high levels of memory-like NK cells and gamma-delta T cells since then, that are raising some eyebrows.

“This case opens new avenues in the HIV functional-cure field,” lead investigator Núria Climent, PhD, of the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

“As far as we know, this is the first time that the gamma-delta T cells have been identified in a PTC, and concerning the memory-like NK cells, there are very few published data and only sparse information presented in several congresses,” she said, explaining that these cells “have a high capacity to inhibit the replication of the virus in vitro. For that reason, we think that this PTC has cells able to dramatically reduce the virus amount. We think that the potential capacity to increase these cells in this PTC woman could be not only mediated by especial genetic factors ... but also mediated by early ART treatment and might be by the immunomediated treatment.”

The findings suggest the potential for “increasing the amount of those memory-like NK cells and gamma-delta T cells in order to translate this potent antiviral activity in new therapies to achieve an HIV functional cure,” she said, adding: “As far as we know, aiming to increase these specific cells has never been done before in people living with HIV.”

In a press conference during the meeting, Dr. Climent explained that the patient was enrolled in a study in which she received a combination of ART and immunomodulatory therapy. This involved a combination of cyclosporine A, low-dose interleukin 2, granulocyte macrophage colony-stimulating factor, and pegylated interferon alfa-2b.

“None of the other 19 patients included in the trial controlled viral replication,” senior investigator Jose Miro, MD, PhD, also from the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the conference, said in an interview that although the significance of the case is unclear, the IAS selected it as a highlight for the meeting. “It is important for clinicians to understand the complexities in interpreting these case reports. Their patients are probably likely to ask them about the report, and it’s important [that] they can explain it to them.”

Dr. Lewin, who is professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity in Melbourne, added that it is impossible to determine the mechanism of action from a single case report. “We don’t know if the intervention played a role or if this person is a ‘posttreatment controller,’ which has been previously described many times,” she said in an interview. “In this patient, the virus is at very low, but controlled, levels, and virus could be grown out. While it’s still exciting and important, this is really what we would consider a remission. The intense study of a single case such as this is certainly worthwhile and important but can only provide new ideas for research. So, I don’t think we can draw any conclusion on the role of NK cells, et cetera. We need much larger case series or controlled trials to reach any conclusion on the reasons for her remission.”

Dr. Climent disclosed no relevant financial conflicts of interest. Dr. Lewin has disclosed investigator-initiated industry-funded research (Gilead, ViiV, Merck), scientific advisory board honoraria paid to her personally (Gilead, Merck, ViiV, Esfam, Immunocore, Vaxxinity), and nonfunded collaborative research (AbbVie, Genentech, Bristol-Myers Squibb).

A version of this article first appeared on Medscape.com.

MONTREAL – The case of a patient in an HIV study whose viral load dropped to undetectable levels and whose immune cells soared has captured the attention of organizers at a meeting of the International AIDS Society.

Although the 59-year-old woman is one of many who are known as posttreatment controllers (PTCs) – having been in remission for more than 15 years after stopping antiretroviral therapy (ART) – it is an immune-based therapy study in which she took part in 2005, and her unusually high levels of memory-like NK cells and gamma-delta T cells since then, that are raising some eyebrows.

“This case opens new avenues in the HIV functional-cure field,” lead investigator Núria Climent, PhD, of the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

“As far as we know, this is the first time that the gamma-delta T cells have been identified in a PTC, and concerning the memory-like NK cells, there are very few published data and only sparse information presented in several congresses,” she said, explaining that these cells “have a high capacity to inhibit the replication of the virus in vitro. For that reason, we think that this PTC has cells able to dramatically reduce the virus amount. We think that the potential capacity to increase these cells in this PTC woman could be not only mediated by especial genetic factors ... but also mediated by early ART treatment and might be by the immunomediated treatment.”

The findings suggest the potential for “increasing the amount of those memory-like NK cells and gamma-delta T cells in order to translate this potent antiviral activity in new therapies to achieve an HIV functional cure,” she said, adding: “As far as we know, aiming to increase these specific cells has never been done before in people living with HIV.”

In a press conference during the meeting, Dr. Climent explained that the patient was enrolled in a study in which she received a combination of ART and immunomodulatory therapy. This involved a combination of cyclosporine A, low-dose interleukin 2, granulocyte macrophage colony-stimulating factor, and pegylated interferon alfa-2b.

“None of the other 19 patients included in the trial controlled viral replication,” senior investigator Jose Miro, MD, PhD, also from the HIV unit at Hospital Clinic-IDIBAPS/University of Barcelona, told this news organization.

Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the conference, said in an interview that although the significance of the case is unclear, the IAS selected it as a highlight for the meeting. “It is important for clinicians to understand the complexities in interpreting these case reports. Their patients are probably likely to ask them about the report, and it’s important [that] they can explain it to them.”

Dr. Lewin, who is professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity in Melbourne, added that it is impossible to determine the mechanism of action from a single case report. “We don’t know if the intervention played a role or if this person is a ‘posttreatment controller,’ which has been previously described many times,” she said in an interview. “In this patient, the virus is at very low, but controlled, levels, and virus could be grown out. While it’s still exciting and important, this is really what we would consider a remission. The intense study of a single case such as this is certainly worthwhile and important but can only provide new ideas for research. So, I don’t think we can draw any conclusion on the role of NK cells, et cetera. We need much larger case series or controlled trials to reach any conclusion on the reasons for her remission.”

Dr. Climent disclosed no relevant financial conflicts of interest. Dr. Lewin has disclosed investigator-initiated industry-funded research (Gilead, ViiV, Merck), scientific advisory board honoraria paid to her personally (Gilead, Merck, ViiV, Esfam, Immunocore, Vaxxinity), and nonfunded collaborative research (AbbVie, Genentech, Bristol-Myers Squibb).

A version of this article first appeared on Medscape.com.

Many scientists and public health experts have long said the coronavirus that has caused a global pandemic originated in a marketplace in Wuhan, China. Now, two new studies strengthen that argument.

The original spread of the virus was a one-two punch, the studies found. Twice, the virus jumped from animals to humans. Virus genetics and outbreak modeling in one study revealed two strains released a few weeks apart in November and December 2019.

“Now I realize it sounds like I just said that a once-in-a-generation event happened twice in short succession, and pandemics are indeed rare,” Joel O. Wertheim, PhD, said at a briefing sponsored by the American Association for the Advancement of Science.

A unique storm of factors had to be present for the outbreak to blow up into a pandemic: Animals carrying a virus that could spread to humans, close human contact with these animals, and a city large enough for the infection to take off before it could be contained are examples.

Unluckily for us humans, this coronavirus – SARS-CoV-2 – is a “generalist virus” capable of infecting many animals, including humans.

“Once all the conditions are in place ... the barriers to spillover have been lowered,” said Dr. Wertheim, a researcher in genetic and molecular networks at the University of California, San Diego. In fact, beyond the two strains of the virus that took hold, there were likely up to two dozen more times where people got the virus but did not spread it far and wide, and it died out.

Overall, the odds were against the virus – 78% of the time, the “introduction” to humans was likely to go extinct, the study showed.

The research revealed the COVID-19 pandemic started small.

“Our model shows that there were likely only a few dozen infections, and only several hospitalizations due to COVID-19, by early December,” said Jonathan Pekar, a graduate student working with Dr. Wertheim.

In Wuhan in late 2019, Mr. Pekar said, there was not a single positive coronavirus sample from thousands of samples from healthy blood donors tested between September and December. Likewise, not one blood sample from patients hospitalized with flu-like illness from October to December 2019 tested positive for SARS-CoV-2.
 

Mapping the outbreak

A second study published in the journal Science mapped out the earliest COVID-19 cases. This effort showed a tight cluster around the wholesale seafood market inside Wuhan, a city of 11 million residents.

When researchers tried other scenarios – modeling outbreaks in other parts of the city – the pattern did not hold. Again, the Wuhan market appeared to be ground zero for the start of the pandemic.

Michael Worobey, PhD, and colleagues used data from Chinese scientists and the World Health Organization for the study.

“There was this extraordinary pattern where the highest density of cases was both extremely near to and very centered on this market,” said Dr. Worobey, head of ecology and evolutionary biology at the University of Arizona, Tucson.

The highest density of cases, in a city of 8,000 square kilometers, was a “very, very small area of about a third of a kilometer square,” he said.

The outbreak pattern showed the Wuhan market “smack dab in the middle.”

So if it started with infected workers at the market, how did it spread from there? It’s likely the virus got into the community as the vendors at the market went to local shops, infecting people in those stores. Then local community members not linked to the market started getting the virus, Dr. Worobey said.

The investigators also identified which stalls in the market were most likely involved, a sort of internal clustering. “That clustering is very, very specifically in the parts of the market where ... they were selling wildlife, including, for example, raccoon dogs and other animals that we know are susceptible to infection with SARS-CoV-2,” said Kristian Andersen, PhD, director of infectious disease genomics at the Scripps Research Institute in La Jolla, Calif.

What remains unknown is which animal or animals carried the virus, although the raccoon dog – an animal similar to a fox that is native to parts of Asia – remains central to most theories. In addition, many of the farms supplying animals to the market have since been closed, making it challenging for researchers to figure out exactly where infected animals came from.

“We don’t know necessarily, but raccoon dogs were sold at this market all the way up to the beginning of the pandemic,” Dr. Andersen said.
 

Not ruling out other theories

People who believe SARS-CoV-2 was released from a laboratory in China at first included Dr. Worobey himself. “I’ve in the past been much more open to the lab leak idea,” he said. “And published that in a letter in Science” in November 2021.

The letter was “much more influential than I thought it would be in ways that I think it turned out to be quite damaging,” he said. As more evidence emerged since then, Dr. Worobey said he came around to the Wuhan market source theory.

Dr. Andersen agreed he was more open to the lab-leak theory at first. “I was quite convinced of the lab leak myself until we dove into this very carefully and looked at it much closer,” he said. Newer evidence convinced him “that actually, the data points to this particular market.”

“Have we disproved the lab-leak theory? No,” Dr. Anderson said. “Will we ever be able to? No.” But the Wuhan market origin scenario is more plausible. “I would say these two papers combined present the strongest evidence of that to date.”

Identifying the source of the outbreak that led to the COVID-19 pandemic is based in science, Dr. Andersen said. “What we’re trying to understand is the origin of the pandemic. We’re not trying to place blame.”
 

Future directions

“With pandemics being pandemics, they affect all of us,” Dr. Andersen said. “We can’t prevent these kinds of events that led to the COVID-19 pandemic. But what we can hope to do is to prevent outbreaks from becoming pandemics.”

Rapid reporting of data and cooperation are needed going forward, Dr. Andersen said. Very strong surveillance systems, including wastewater surveillance, could help monitor for SARS-CoV-2, and other pathogens of potential concern in the future as well.

It should be standard practice for medical professionals to be on alert for unusual respiratory infections too, the researchers said.

“It’s a bloody lucky thing that the doctors at the Shinwa hospital were so on the ball, that they noticed that these cases were something unusual at the end of December,” Dr. Worobey said. “It didn’t have to work out that way.”

A version of this article first appeared on WebMD.com.

Many scientists and public health experts have long said the coronavirus that has caused a global pandemic originated in a marketplace in Wuhan, China. Now, two new studies strengthen that argument.

The original spread of the virus was a one-two punch, the studies found. Twice, the virus jumped from animals to humans. Virus genetics and outbreak modeling in one study revealed two strains released a few weeks apart in November and December 2019.

“Now I realize it sounds like I just said that a once-in-a-generation event happened twice in short succession, and pandemics are indeed rare,” Joel O. Wertheim, PhD, said at a briefing sponsored by the American Association for the Advancement of Science.

A unique storm of factors had to be present for the outbreak to blow up into a pandemic: Animals carrying a virus that could spread to humans, close human contact with these animals, and a city large enough for the infection to take off before it could be contained are examples.

Unluckily for us humans, this coronavirus – SARS-CoV-2 – is a “generalist virus” capable of infecting many animals, including humans.

“Once all the conditions are in place ... the barriers to spillover have been lowered,” said Dr. Wertheim, a researcher in genetic and molecular networks at the University of California, San Diego. In fact, beyond the two strains of the virus that took hold, there were likely up to two dozen more times where people got the virus but did not spread it far and wide, and it died out.

Overall, the odds were against the virus – 78% of the time, the “introduction” to humans was likely to go extinct, the study showed.

The research revealed the COVID-19 pandemic started small.

“Our model shows that there were likely only a few dozen infections, and only several hospitalizations due to COVID-19, by early December,” said Jonathan Pekar, a graduate student working with Dr. Wertheim.

In Wuhan in late 2019, Mr. Pekar said, there was not a single positive coronavirus sample from thousands of samples from healthy blood donors tested between September and December. Likewise, not one blood sample from patients hospitalized with flu-like illness from October to December 2019 tested positive for SARS-CoV-2.
 

Mapping the outbreak

A second study published in the journal Science mapped out the earliest COVID-19 cases. This effort showed a tight cluster around the wholesale seafood market inside Wuhan, a city of 11 million residents.

When researchers tried other scenarios – modeling outbreaks in other parts of the city – the pattern did not hold. Again, the Wuhan market appeared to be ground zero for the start of the pandemic.

Michael Worobey, PhD, and colleagues used data from Chinese scientists and the World Health Organization for the study.

“There was this extraordinary pattern where the highest density of cases was both extremely near to and very centered on this market,” said Dr. Worobey, head of ecology and evolutionary biology at the University of Arizona, Tucson.

The highest density of cases, in a city of 8,000 square kilometers, was a “very, very small area of about a third of a kilometer square,” he said.

The outbreak pattern showed the Wuhan market “smack dab in the middle.”

So if it started with infected workers at the market, how did it spread from there? It’s likely the virus got into the community as the vendors at the market went to local shops, infecting people in those stores. Then local community members not linked to the market started getting the virus, Dr. Worobey said.

The investigators also identified which stalls in the market were most likely involved, a sort of internal clustering. “That clustering is very, very specifically in the parts of the market where ... they were selling wildlife, including, for example, raccoon dogs and other animals that we know are susceptible to infection with SARS-CoV-2,” said Kristian Andersen, PhD, director of infectious disease genomics at the Scripps Research Institute in La Jolla, Calif.

What remains unknown is which animal or animals carried the virus, although the raccoon dog – an animal similar to a fox that is native to parts of Asia – remains central to most theories. In addition, many of the farms supplying animals to the market have since been closed, making it challenging for researchers to figure out exactly where infected animals came from.

“We don’t know necessarily, but raccoon dogs were sold at this market all the way up to the beginning of the pandemic,” Dr. Andersen said.
 

Not ruling out other theories

People who believe SARS-CoV-2 was released from a laboratory in China at first included Dr. Worobey himself. “I’ve in the past been much more open to the lab leak idea,” he said. “And published that in a letter in Science” in November 2021.

The letter was “much more influential than I thought it would be in ways that I think it turned out to be quite damaging,” he said. As more evidence emerged since then, Dr. Worobey said he came around to the Wuhan market source theory.

Dr. Andersen agreed he was more open to the lab-leak theory at first. “I was quite convinced of the lab leak myself until we dove into this very carefully and looked at it much closer,” he said. Newer evidence convinced him “that actually, the data points to this particular market.”

“Have we disproved the lab-leak theory? No,” Dr. Anderson said. “Will we ever be able to? No.” But the Wuhan market origin scenario is more plausible. “I would say these two papers combined present the strongest evidence of that to date.”

Identifying the source of the outbreak that led to the COVID-19 pandemic is based in science, Dr. Andersen said. “What we’re trying to understand is the origin of the pandemic. We’re not trying to place blame.”
 

Future directions

“With pandemics being pandemics, they affect all of us,” Dr. Andersen said. “We can’t prevent these kinds of events that led to the COVID-19 pandemic. But what we can hope to do is to prevent outbreaks from becoming pandemics.”

Rapid reporting of data and cooperation are needed going forward, Dr. Andersen said. Very strong surveillance systems, including wastewater surveillance, could help monitor for SARS-CoV-2, and other pathogens of potential concern in the future as well.

It should be standard practice for medical professionals to be on alert for unusual respiratory infections too, the researchers said.

“It’s a bloody lucky thing that the doctors at the Shinwa hospital were so on the ball, that they noticed that these cases were something unusual at the end of December,” Dr. Worobey said. “It didn’t have to work out that way.”

A version of this article first appeared on WebMD.com.

Many scientists and public health experts have long said the coronavirus that has caused a global pandemic originated in a marketplace in Wuhan, China. Now, two new studies strengthen that argument.

The original spread of the virus was a one-two punch, the studies found. Twice, the virus jumped from animals to humans. Virus genetics and outbreak modeling in one study revealed two strains released a few weeks apart in November and December 2019.

“Now I realize it sounds like I just said that a once-in-a-generation event happened twice in short succession, and pandemics are indeed rare,” Joel O. Wertheim, PhD, said at a briefing sponsored by the American Association for the Advancement of Science.

A unique storm of factors had to be present for the outbreak to blow up into a pandemic: Animals carrying a virus that could spread to humans, close human contact with these animals, and a city large enough for the infection to take off before it could be contained are examples.

Unluckily for us humans, this coronavirus – SARS-CoV-2 – is a “generalist virus” capable of infecting many animals, including humans.

“Once all the conditions are in place ... the barriers to spillover have been lowered,” said Dr. Wertheim, a researcher in genetic and molecular networks at the University of California, San Diego. In fact, beyond the two strains of the virus that took hold, there were likely up to two dozen more times where people got the virus but did not spread it far and wide, and it died out.

Overall, the odds were against the virus – 78% of the time, the “introduction” to humans was likely to go extinct, the study showed.

The research revealed the COVID-19 pandemic started small.

“Our model shows that there were likely only a few dozen infections, and only several hospitalizations due to COVID-19, by early December,” said Jonathan Pekar, a graduate student working with Dr. Wertheim.

In Wuhan in late 2019, Mr. Pekar said, there was not a single positive coronavirus sample from thousands of samples from healthy blood donors tested between September and December. Likewise, not one blood sample from patients hospitalized with flu-like illness from October to December 2019 tested positive for SARS-CoV-2.
 

Mapping the outbreak

A second study published in the journal Science mapped out the earliest COVID-19 cases. This effort showed a tight cluster around the wholesale seafood market inside Wuhan, a city of 11 million residents.

When researchers tried other scenarios – modeling outbreaks in other parts of the city – the pattern did not hold. Again, the Wuhan market appeared to be ground zero for the start of the pandemic.

Michael Worobey, PhD, and colleagues used data from Chinese scientists and the World Health Organization for the study.

“There was this extraordinary pattern where the highest density of cases was both extremely near to and very centered on this market,” said Dr. Worobey, head of ecology and evolutionary biology at the University of Arizona, Tucson.

The highest density of cases, in a city of 8,000 square kilometers, was a “very, very small area of about a third of a kilometer square,” he said.

The outbreak pattern showed the Wuhan market “smack dab in the middle.”

So if it started with infected workers at the market, how did it spread from there? It’s likely the virus got into the community as the vendors at the market went to local shops, infecting people in those stores. Then local community members not linked to the market started getting the virus, Dr. Worobey said.

The investigators also identified which stalls in the market were most likely involved, a sort of internal clustering. “That clustering is very, very specifically in the parts of the market where ... they were selling wildlife, including, for example, raccoon dogs and other animals that we know are susceptible to infection with SARS-CoV-2,” said Kristian Andersen, PhD, director of infectious disease genomics at the Scripps Research Institute in La Jolla, Calif.

What remains unknown is which animal or animals carried the virus, although the raccoon dog – an animal similar to a fox that is native to parts of Asia – remains central to most theories. In addition, many of the farms supplying animals to the market have since been closed, making it challenging for researchers to figure out exactly where infected animals came from.

“We don’t know necessarily, but raccoon dogs were sold at this market all the way up to the beginning of the pandemic,” Dr. Andersen said.
 

Not ruling out other theories

People who believe SARS-CoV-2 was released from a laboratory in China at first included Dr. Worobey himself. “I’ve in the past been much more open to the lab leak idea,” he said. “And published that in a letter in Science” in November 2021.

The letter was “much more influential than I thought it would be in ways that I think it turned out to be quite damaging,” he said. As more evidence emerged since then, Dr. Worobey said he came around to the Wuhan market source theory.

Dr. Andersen agreed he was more open to the lab-leak theory at first. “I was quite convinced of the lab leak myself until we dove into this very carefully and looked at it much closer,” he said. Newer evidence convinced him “that actually, the data points to this particular market.”

“Have we disproved the lab-leak theory? No,” Dr. Anderson said. “Will we ever be able to? No.” But the Wuhan market origin scenario is more plausible. “I would say these two papers combined present the strongest evidence of that to date.”

Identifying the source of the outbreak that led to the COVID-19 pandemic is based in science, Dr. Andersen said. “What we’re trying to understand is the origin of the pandemic. We’re not trying to place blame.”
 

Future directions

“With pandemics being pandemics, they affect all of us,” Dr. Andersen said. “We can’t prevent these kinds of events that led to the COVID-19 pandemic. But what we can hope to do is to prevent outbreaks from becoming pandemics.”

Rapid reporting of data and cooperation are needed going forward, Dr. Andersen said. Very strong surveillance systems, including wastewater surveillance, could help monitor for SARS-CoV-2, and other pathogens of potential concern in the future as well.

It should be standard practice for medical professionals to be on alert for unusual respiratory infections too, the researchers said.

“It’s a bloody lucky thing that the doctors at the Shinwa hospital were so on the ball, that they noticed that these cases were something unusual at the end of December,” Dr. Worobey said. “It didn’t have to work out that way.”

A version of this article first appeared on WebMD.com.

A procalcitonin-based algorithm could safely reduce unnecessary usage of antibiotics in patients with acute pancreatitis, based on results of a randomized controlled trial.

Physicians should consider incorporating the decision-making process into their daily practice, suggested lead author Ajith K. Siriwardena, MD, of Manchester (England) University and colleagues, who also recommended that the algorithm be added to future guidelines.

“Overuse of antibiotics and the resultant emergence of multidrug resistant microorganisms is a potent threat to the welfare of humanity in the 21st century,” the investigators wrote in The Lancet Gastroenterology & Hepatology.

Antibiotic overuse is common in cases of acute pancreatitis, they noted, because clinical features are typically insufficient to distinguish between inflammation and infection. While measuring procalcitonin can help can detect infection, “indiscriminate measurement” of the biomarker is not cost effective, according to the investigators, leading previous reviews and analyses to conclude that further research is needed before widespread usage can be recommended.

Dr. Siriwardena and colleagues aimed to meet this need by conducting a randomized controlled trial involving 260 patients hospitalized for acute pancreatitis at Manchester Royal Infirmary. Patients were randomized in a near 1:1 ratio. Both the intervention group (n = 132) and the control group (n = 128) received guideline-based care; however, in addition to standard of care, procalcitonin was measured in the intervention group at days 0, 4, and 7 then weekly. Among these patients, antibiotics were stopped or not started when procalcitonin was below 1.0 ng/mL, but antibiotics were started or continued when procalcitonin was 1.0 ng/mL or more.

The primary outcome was presence or absence of antibiotic use during hospital stay. A range of secondary outcomes were also reported, included all-cause mortality, days of antibiotic use, rates of infection, and endoscopic, radiological, or surgical intervention.

Significantly fewer patients in the procalcitonin group received antibiotics during their stay, compared with the usual-care group (45% vs. 63%), which translated to an adjusted risk difference of –15.6% (P = .0071). Patients in the procalcitonin group who did receive antibiotics received about 1 day less of antibiotic treatment.

Despite the reduced antibiotic usage, length of hospital stay was similar between groups, as were rates of clinical infection, hospital-acquired infection, death, and adverse events, which suggests that the algorithm safely reduced antibiotic usage without negatively impacting clinical outcomes, according to investigators.

“Procalcitonin-based algorithms to guide antibiotic use should be considered in the care of this group of patients and be incorporated into future guidelines on the management of acute pancreatitis,” the investigators concluded.

Aaron Sasson, MD, director of the pancreatic cancer center and codirector of the gastrointestinal oncology team at Stony Brook (N.Y.) Medicine, said the study is noteworthy because it addresses an important topic with a large prospective randomized trial; however, he pointed out some limitations.

“There are several issues with this trial,” Dr. Sasson said in a written comment. “First, it included a large percentage of patients with mild acute pancreatitis, a group of patients for whom the use of antibiotics is not controversial. Secondly, the rate of infected pancreatic necrosis was 5% in both arms of the study, indicating the lack of severity of the cohort of patients.”

Dr. Sasson said that the algorithm “could be useful” to differentiate between inflammation and infection in patients with acute pancreatitis, “but only as an adjunct with other clinical parameters.”

He suggested that the algorithm would offer more utility if it could distinguish between pancreatic necrosis and infected pancreatic necrosis. “Unfortunately, this trial did not answer this question,” he said, noting that a similar trial involving “only patients with severe pancreatitis” would be needed.

The investigators and Dr. Sasson disclosed no competing interests.

A procalcitonin-based algorithm could safely reduce unnecessary usage of antibiotics in patients with acute pancreatitis, based on results of a randomized controlled trial.

Physicians should consider incorporating the decision-making process into their daily practice, suggested lead author Ajith K. Siriwardena, MD, of Manchester (England) University and colleagues, who also recommended that the algorithm be added to future guidelines.

“Overuse of antibiotics and the resultant emergence of multidrug resistant microorganisms is a potent threat to the welfare of humanity in the 21st century,” the investigators wrote in The Lancet Gastroenterology & Hepatology.

Antibiotic overuse is common in cases of acute pancreatitis, they noted, because clinical features are typically insufficient to distinguish between inflammation and infection. While measuring procalcitonin can help can detect infection, “indiscriminate measurement” of the biomarker is not cost effective, according to the investigators, leading previous reviews and analyses to conclude that further research is needed before widespread usage can be recommended.

Dr. Siriwardena and colleagues aimed to meet this need by conducting a randomized controlled trial involving 260 patients hospitalized for acute pancreatitis at Manchester Royal Infirmary. Patients were randomized in a near 1:1 ratio. Both the intervention group (n = 132) and the control group (n = 128) received guideline-based care; however, in addition to standard of care, procalcitonin was measured in the intervention group at days 0, 4, and 7 then weekly. Among these patients, antibiotics were stopped or not started when procalcitonin was below 1.0 ng/mL, but antibiotics were started or continued when procalcitonin was 1.0 ng/mL or more.

The primary outcome was presence or absence of antibiotic use during hospital stay. A range of secondary outcomes were also reported, included all-cause mortality, days of antibiotic use, rates of infection, and endoscopic, radiological, or surgical intervention.

Significantly fewer patients in the procalcitonin group received antibiotics during their stay, compared with the usual-care group (45% vs. 63%), which translated to an adjusted risk difference of –15.6% (P = .0071). Patients in the procalcitonin group who did receive antibiotics received about 1 day less of antibiotic treatment.

Despite the reduced antibiotic usage, length of hospital stay was similar between groups, as were rates of clinical infection, hospital-acquired infection, death, and adverse events, which suggests that the algorithm safely reduced antibiotic usage without negatively impacting clinical outcomes, according to investigators.

“Procalcitonin-based algorithms to guide antibiotic use should be considered in the care of this group of patients and be incorporated into future guidelines on the management of acute pancreatitis,” the investigators concluded.

Aaron Sasson, MD, director of the pancreatic cancer center and codirector of the gastrointestinal oncology team at Stony Brook (N.Y.) Medicine, said the study is noteworthy because it addresses an important topic with a large prospective randomized trial; however, he pointed out some limitations.

“There are several issues with this trial,” Dr. Sasson said in a written comment. “First, it included a large percentage of patients with mild acute pancreatitis, a group of patients for whom the use of antibiotics is not controversial. Secondly, the rate of infected pancreatic necrosis was 5% in both arms of the study, indicating the lack of severity of the cohort of patients.”

Dr. Sasson said that the algorithm “could be useful” to differentiate between inflammation and infection in patients with acute pancreatitis, “but only as an adjunct with other clinical parameters.”

He suggested that the algorithm would offer more utility if it could distinguish between pancreatic necrosis and infected pancreatic necrosis. “Unfortunately, this trial did not answer this question,” he said, noting that a similar trial involving “only patients with severe pancreatitis” would be needed.

The investigators and Dr. Sasson disclosed no competing interests.

A procalcitonin-based algorithm could safely reduce unnecessary usage of antibiotics in patients with acute pancreatitis, based on results of a randomized controlled trial.

Physicians should consider incorporating the decision-making process into their daily practice, suggested lead author Ajith K. Siriwardena, MD, of Manchester (England) University and colleagues, who also recommended that the algorithm be added to future guidelines.

“Overuse of antibiotics and the resultant emergence of multidrug resistant microorganisms is a potent threat to the welfare of humanity in the 21st century,” the investigators wrote in The Lancet Gastroenterology & Hepatology.

Antibiotic overuse is common in cases of acute pancreatitis, they noted, because clinical features are typically insufficient to distinguish between inflammation and infection. While measuring procalcitonin can help can detect infection, “indiscriminate measurement” of the biomarker is not cost effective, according to the investigators, leading previous reviews and analyses to conclude that further research is needed before widespread usage can be recommended.

Dr. Siriwardena and colleagues aimed to meet this need by conducting a randomized controlled trial involving 260 patients hospitalized for acute pancreatitis at Manchester Royal Infirmary. Patients were randomized in a near 1:1 ratio. Both the intervention group (n = 132) and the control group (n = 128) received guideline-based care; however, in addition to standard of care, procalcitonin was measured in the intervention group at days 0, 4, and 7 then weekly. Among these patients, antibiotics were stopped or not started when procalcitonin was below 1.0 ng/mL, but antibiotics were started or continued when procalcitonin was 1.0 ng/mL or more.

The primary outcome was presence or absence of antibiotic use during hospital stay. A range of secondary outcomes were also reported, included all-cause mortality, days of antibiotic use, rates of infection, and endoscopic, radiological, or surgical intervention.

Significantly fewer patients in the procalcitonin group received antibiotics during their stay, compared with the usual-care group (45% vs. 63%), which translated to an adjusted risk difference of –15.6% (P = .0071). Patients in the procalcitonin group who did receive antibiotics received about 1 day less of antibiotic treatment.

Despite the reduced antibiotic usage, length of hospital stay was similar between groups, as were rates of clinical infection, hospital-acquired infection, death, and adverse events, which suggests that the algorithm safely reduced antibiotic usage without negatively impacting clinical outcomes, according to investigators.

“Procalcitonin-based algorithms to guide antibiotic use should be considered in the care of this group of patients and be incorporated into future guidelines on the management of acute pancreatitis,” the investigators concluded.

Aaron Sasson, MD, director of the pancreatic cancer center and codirector of the gastrointestinal oncology team at Stony Brook (N.Y.) Medicine, said the study is noteworthy because it addresses an important topic with a large prospective randomized trial; however, he pointed out some limitations.

“There are several issues with this trial,” Dr. Sasson said in a written comment. “First, it included a large percentage of patients with mild acute pancreatitis, a group of patients for whom the use of antibiotics is not controversial. Secondly, the rate of infected pancreatic necrosis was 5% in both arms of the study, indicating the lack of severity of the cohort of patients.”

Dr. Sasson said that the algorithm “could be useful” to differentiate between inflammation and infection in patients with acute pancreatitis, “but only as an adjunct with other clinical parameters.”

He suggested that the algorithm would offer more utility if it could distinguish between pancreatic necrosis and infected pancreatic necrosis. “Unfortunately, this trial did not answer this question,” he said, noting that a similar trial involving “only patients with severe pancreatitis” would be needed.

The investigators and Dr. Sasson disclosed no competing interests.

Approximately 80% of patients in intensive care showed clinical improvement in gram-positive bacterial infections after treatment with linezolid, based on data from more than 300 individuals.

Bacterial infections remain a challenge in the management of critically ill patients, as many gram-positive pathogens have become resistant to multiple drug options, Aijia Ma, MD, of West China Hospital of Sichuan University, and colleagues wrote.

Linezolid has demonstrated effectiveness against MRSA and skin and soft-tissue infections (SSTIs), but its use in critically ill patients with gram-positive infections in the ICU has not been characterized, they said.

In a multicenter, real-world study published in the Journal of Intensive Medicine, the researchers reviewed data from 52 hospitals between June 2018 and December 2019. The study population included 366 patients admitted to the ICU with a clinical or laboratory diagnosis of a gram-positive bacterial infection. Patients were treated with linezolid injections (200 mg/100 mL) and followed up once a day until 48 hours after discontinuing therapy, transferring out of the ICU, or death. Most of the patients (243) were older than 65 years; 90 were aged 18-65 years, and 30 were younger than 18 years. Approximately two-thirds (67%) were men. The primary outcome of clinical efficacy was success (cured or improved).

Linezolid was used as second-line and first-line treatment in 232 (63.4%) and 134 (36.6%) patients, respectively. The most common isolated strain was Staphylococcus aureus (31% MRSA; 12.6% methicillin-susceptible S. aureus [MSSA]) followed by Enterococci (6.7% vancomycin resistant, 9.2% vancomycin susceptible) and Streptococcus pneumoniae (3.4% multidrug resistant, 1.7% non–multidrug resistant).

Overall, 82.2% of patients met the criteria for clinical success; 34 (9.3%) were cured and 267 (73%) improved. Clinical success rates for first-line and second-line linezolid therapy were 79.9% and 83.6%, respectively. Failure rates for linezolid were higher for second-line versus first-line treatment (9.5% vs. 5.2%).

The clinical success rate was highest against MSSA (93.3%), followed by MRSA (83.8%). The average daily linezolid dose was 1,109 mg, and the mean treatment time was 5.1 days.

A total of eight patients (2.2%) reported linezolid-related adverse events, and four patients discontinued the medication because of them; none reported treatment-related serious adverse events. The low incidence of thrombocytopenia in the current study (two patients), compared with previous studies may have been related to avoidance of linezolid for at-risk patients as determined by clinicians, and the relatively short duration of linezolid use, the researchers wrote.

The study findings were limited by several factors, including the observational design and inability to compare the efficacy of different drugs; the small sample size; and the lack of data on drugs used prior to ICU admission, the researchers noted. Other limitations included the low detection rate of gram-positive bacteria and potential underreporting of adverse events.

However, the results suggest that linezolid is a safe and effective treatment for gram-positive bacterial infections, although clinicians will need to pay close attention to possible side effects and evaluate patient conditions on an individual basis before using linezolid in the clinic, they concluded.

The study was supported by grants from West China Hospital of Sichuan University. The researchers reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Approximately 80% of patients in intensive care showed clinical improvement in gram-positive bacterial infections after treatment with linezolid, based on data from more than 300 individuals.

Bacterial infections remain a challenge in the management of critically ill patients, as many gram-positive pathogens have become resistant to multiple drug options, Aijia Ma, MD, of West China Hospital of Sichuan University, and colleagues wrote.

Linezolid has demonstrated effectiveness against MRSA and skin and soft-tissue infections (SSTIs), but its use in critically ill patients with gram-positive infections in the ICU has not been characterized, they said.

In a multicenter, real-world study published in the Journal of Intensive Medicine, the researchers reviewed data from 52 hospitals between June 2018 and December 2019. The study population included 366 patients admitted to the ICU with a clinical or laboratory diagnosis of a gram-positive bacterial infection. Patients were treated with linezolid injections (200 mg/100 mL) and followed up once a day until 48 hours after discontinuing therapy, transferring out of the ICU, or death. Most of the patients (243) were older than 65 years; 90 were aged 18-65 years, and 30 were younger than 18 years. Approximately two-thirds (67%) were men. The primary outcome of clinical efficacy was success (cured or improved).

Linezolid was used as second-line and first-line treatment in 232 (63.4%) and 134 (36.6%) patients, respectively. The most common isolated strain was Staphylococcus aureus (31% MRSA; 12.6% methicillin-susceptible S. aureus [MSSA]) followed by Enterococci (6.7% vancomycin resistant, 9.2% vancomycin susceptible) and Streptococcus pneumoniae (3.4% multidrug resistant, 1.7% non–multidrug resistant).

Overall, 82.2% of patients met the criteria for clinical success; 34 (9.3%) were cured and 267 (73%) improved. Clinical success rates for first-line and second-line linezolid therapy were 79.9% and 83.6%, respectively. Failure rates for linezolid were higher for second-line versus first-line treatment (9.5% vs. 5.2%).

The clinical success rate was highest against MSSA (93.3%), followed by MRSA (83.8%). The average daily linezolid dose was 1,109 mg, and the mean treatment time was 5.1 days.

A total of eight patients (2.2%) reported linezolid-related adverse events, and four patients discontinued the medication because of them; none reported treatment-related serious adverse events. The low incidence of thrombocytopenia in the current study (two patients), compared with previous studies may have been related to avoidance of linezolid for at-risk patients as determined by clinicians, and the relatively short duration of linezolid use, the researchers wrote.

The study findings were limited by several factors, including the observational design and inability to compare the efficacy of different drugs; the small sample size; and the lack of data on drugs used prior to ICU admission, the researchers noted. Other limitations included the low detection rate of gram-positive bacteria and potential underreporting of adverse events.

However, the results suggest that linezolid is a safe and effective treatment for gram-positive bacterial infections, although clinicians will need to pay close attention to possible side effects and evaluate patient conditions on an individual basis before using linezolid in the clinic, they concluded.

The study was supported by grants from West China Hospital of Sichuan University. The researchers reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Approximately 80% of patients in intensive care showed clinical improvement in gram-positive bacterial infections after treatment with linezolid, based on data from more than 300 individuals.

Bacterial infections remain a challenge in the management of critically ill patients, as many gram-positive pathogens have become resistant to multiple drug options, Aijia Ma, MD, of West China Hospital of Sichuan University, and colleagues wrote.

Linezolid has demonstrated effectiveness against MRSA and skin and soft-tissue infections (SSTIs), but its use in critically ill patients with gram-positive infections in the ICU has not been characterized, they said.

In a multicenter, real-world study published in the Journal of Intensive Medicine, the researchers reviewed data from 52 hospitals between June 2018 and December 2019. The study population included 366 patients admitted to the ICU with a clinical or laboratory diagnosis of a gram-positive bacterial infection. Patients were treated with linezolid injections (200 mg/100 mL) and followed up once a day until 48 hours after discontinuing therapy, transferring out of the ICU, or death. Most of the patients (243) were older than 65 years; 90 were aged 18-65 years, and 30 were younger than 18 years. Approximately two-thirds (67%) were men. The primary outcome of clinical efficacy was success (cured or improved).

Linezolid was used as second-line and first-line treatment in 232 (63.4%) and 134 (36.6%) patients, respectively. The most common isolated strain was Staphylococcus aureus (31% MRSA; 12.6% methicillin-susceptible S. aureus [MSSA]) followed by Enterococci (6.7% vancomycin resistant, 9.2% vancomycin susceptible) and Streptococcus pneumoniae (3.4% multidrug resistant, 1.7% non–multidrug resistant).

Overall, 82.2% of patients met the criteria for clinical success; 34 (9.3%) were cured and 267 (73%) improved. Clinical success rates for first-line and second-line linezolid therapy were 79.9% and 83.6%, respectively. Failure rates for linezolid were higher for second-line versus first-line treatment (9.5% vs. 5.2%).

The clinical success rate was highest against MSSA (93.3%), followed by MRSA (83.8%). The average daily linezolid dose was 1,109 mg, and the mean treatment time was 5.1 days.

A total of eight patients (2.2%) reported linezolid-related adverse events, and four patients discontinued the medication because of them; none reported treatment-related serious adverse events. The low incidence of thrombocytopenia in the current study (two patients), compared with previous studies may have been related to avoidance of linezolid for at-risk patients as determined by clinicians, and the relatively short duration of linezolid use, the researchers wrote.

The study findings were limited by several factors, including the observational design and inability to compare the efficacy of different drugs; the small sample size; and the lack of data on drugs used prior to ICU admission, the researchers noted. Other limitations included the low detection rate of gram-positive bacteria and potential underreporting of adverse events.

However, the results suggest that linezolid is a safe and effective treatment for gram-positive bacterial infections, although clinicians will need to pay close attention to possible side effects and evaluate patient conditions on an individual basis before using linezolid in the clinic, they concluded.

The study was supported by grants from West China Hospital of Sichuan University. The researchers reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

As cases of monkeypox continue to mount in the United States and abroad, infectious disease experts are closely monitoring one group of people in particular: women.

So far, the overwhelming majority of cases of the viral disease have been reported in men who have sex with men. But in recent days, officials have learned of a handful of cases in women – possibly indicating that the outbreak may be widening.

Researchers are keeping close tabs on the proportion of cases in women to “assess whether the outbreak is moving away” from networks of men who have sex with men, where most of the initial cases have been identified, according to a briefing from the UK Health Security Agency (UKHSA).

“There is insufficient evidence to support a change in the transmission dynamics,” the agency said. “However, over the last few weeks the proportion of female cases has been increasing, so this trend needs to be monitored closely.”

A global collaboration of researchers and clinicians recently described 528 cases of monkeypox in 16 countries – but none were in women.

Since data collection for that study ended in June, the research group has confirmed cases in women, said study coauthor John P. Thornhill, MD, PhD, consultant physician in sexual health and HIV and clinical senior lecturer at Barts Health NHS Trust and Queen Mary University of London.

“Cases in women have certainly been reported but are currently far less common,” Dr. Thornhill told this news organization.

Although infections in women have been outliers during the current outbreak, they can be severe when they do occur. Several women in England have been hospitalized with severe symptoms.

A similar pattern has been seen in New York City, where just one woman is among the 639 total cases, according to a July 21 report from the city’s health agency.

Researchers have recently published guidance on monkeypox for ob.gyns., maternal-fetal medicine subspecialists, and people who are pregnant or breastfeeding in anticipation of the possibility of more cases in women.

The Centers for Disease Control and Prevention advises that “pregnant, recently pregnant, and breastfeeding people should be prioritized for medical treatment” of monkeypox if needed. 

One monkeypox vaccine, Jynneos, can be offered to people who are pregnant or breastfeeding and are otherwise eligible for vaccination on the basis of confirmed or likely contact with cases, ideally within 4 days of exposure. Some people at high risk for exposure, such as laboratory workers, may receive the vaccine preemptively.

Another vaccine, ACAM2000, is contraindicated in people who are pregnant or breastfeeding, according to the CDC.
 

Transmission dynamics

Investigators have not yet identified substantial spread of monkeypox beyond men who have sex with men, although transmission among household contacts, including women and children, has been reported.

Most initial infections during the current outbreak occurred during sexual activity. But monkeypox can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC. It also may spread from mother to child in utero.

Infected pets have been known to spread the disease as well. A multistate monkeypox outbreak in the United States in 2003 was linked to pet prairie dogs, including in childcare and school settings. That year, 55% of the 71 cases occurred in female patients.
 

More testing, higher positivity rates in men

Since May, more men than women in the United Kingdom have undergone testing for monkeypox, with 3,467 tests in men versus 447 tests in women. Among those tested, the positivity rate has been far higher in men than in women, 54% versus 2.2%, respectively.

As of July 20, about 0.65% of U.K. cases with known gender were in women. Two weeks prior, about 0.4% were in women.

In all, 13 monkeypox cases in England have been in women, and four had severe manifestations that required hospitalization, according to the UKHSA.

Globally, more than 16,000 monkeypox cases have been reported, according to the World Health Organization. The agency said that it plans to rename the disease to reduce stigma.
 

Monkeypox and pregnancy

Ob.gyns. are often on the “front line in terms of identifying people with infectious diseases,” said Denise J. Jamieson, MD, MPH, Emory University, Atlanta. Dr. Jamieson coauthored “A Primer on Monkeypox Virus for Obstetrician-Gynecologists,” published in Obstetrics & Gynecology.

“Obstetricians need to be aware of what infectious diseases are circulating and be aware of what is going on in the community,” she said.

With monkeypox, “it is anybody’s guess as to how widespread this is going to be,” Dr. Jamieson said.

“The initial monkeypox cases in the current outbreak have been predominately but not exclusively among men who have sex with men; enhanced transmission in this group may be facilitated by sexual activity and spread through complex sexual networks,” Dr. Thornhill said. “As the outbreak continues, we will likely see more monkeypox infections” outside that group.

“Those working in sexual health should have a high index of suspicion in all individuals presenting with genital and oral ulcers and those with proctitis,” he added.

During previous monkeypox outbreaks, the chain of household transmissions has been short, typically two or three people, said Chloe M. Orkin, MD, professor of HIV medicine at Queen Mary University of London. Dr. Orkin directs the Sexual Health and HIV All East Research (SHARE) Collaborative, which has worked to compile the international case series.

Though monkeypox has mainly been transmitted among men who have sex with men, not all identify as gay and some may also have female and nonbinary partners, Dr. Orkin said.

“Clinicians should bear this in mind when examining any person,” she said.

A version of this article first appeared on Medscape.com.

As cases of monkeypox continue to mount in the United States and abroad, infectious disease experts are closely monitoring one group of people in particular: women.

So far, the overwhelming majority of cases of the viral disease have been reported in men who have sex with men. But in recent days, officials have learned of a handful of cases in women – possibly indicating that the outbreak may be widening.

Researchers are keeping close tabs on the proportion of cases in women to “assess whether the outbreak is moving away” from networks of men who have sex with men, where most of the initial cases have been identified, according to a briefing from the UK Health Security Agency (UKHSA).

“There is insufficient evidence to support a change in the transmission dynamics,” the agency said. “However, over the last few weeks the proportion of female cases has been increasing, so this trend needs to be monitored closely.”

A global collaboration of researchers and clinicians recently described 528 cases of monkeypox in 16 countries – but none were in women.

Since data collection for that study ended in June, the research group has confirmed cases in women, said study coauthor John P. Thornhill, MD, PhD, consultant physician in sexual health and HIV and clinical senior lecturer at Barts Health NHS Trust and Queen Mary University of London.

“Cases in women have certainly been reported but are currently far less common,” Dr. Thornhill told this news organization.

Although infections in women have been outliers during the current outbreak, they can be severe when they do occur. Several women in England have been hospitalized with severe symptoms.

A similar pattern has been seen in New York City, where just one woman is among the 639 total cases, according to a July 21 report from the city’s health agency.

Researchers have recently published guidance on monkeypox for ob.gyns., maternal-fetal medicine subspecialists, and people who are pregnant or breastfeeding in anticipation of the possibility of more cases in women.

The Centers for Disease Control and Prevention advises that “pregnant, recently pregnant, and breastfeeding people should be prioritized for medical treatment” of monkeypox if needed. 

One monkeypox vaccine, Jynneos, can be offered to people who are pregnant or breastfeeding and are otherwise eligible for vaccination on the basis of confirmed or likely contact with cases, ideally within 4 days of exposure. Some people at high risk for exposure, such as laboratory workers, may receive the vaccine preemptively.

Another vaccine, ACAM2000, is contraindicated in people who are pregnant or breastfeeding, according to the CDC.
 

Transmission dynamics

Investigators have not yet identified substantial spread of monkeypox beyond men who have sex with men, although transmission among household contacts, including women and children, has been reported.

Most initial infections during the current outbreak occurred during sexual activity. But monkeypox can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC. It also may spread from mother to child in utero.

Infected pets have been known to spread the disease as well. A multistate monkeypox outbreak in the United States in 2003 was linked to pet prairie dogs, including in childcare and school settings. That year, 55% of the 71 cases occurred in female patients.
 

More testing, higher positivity rates in men

Since May, more men than women in the United Kingdom have undergone testing for monkeypox, with 3,467 tests in men versus 447 tests in women. Among those tested, the positivity rate has been far higher in men than in women, 54% versus 2.2%, respectively.

As of July 20, about 0.65% of U.K. cases with known gender were in women. Two weeks prior, about 0.4% were in women.

In all, 13 monkeypox cases in England have been in women, and four had severe manifestations that required hospitalization, according to the UKHSA.

Globally, more than 16,000 monkeypox cases have been reported, according to the World Health Organization. The agency said that it plans to rename the disease to reduce stigma.
 

Monkeypox and pregnancy

Ob.gyns. are often on the “front line in terms of identifying people with infectious diseases,” said Denise J. Jamieson, MD, MPH, Emory University, Atlanta. Dr. Jamieson coauthored “A Primer on Monkeypox Virus for Obstetrician-Gynecologists,” published in Obstetrics & Gynecology.

“Obstetricians need to be aware of what infectious diseases are circulating and be aware of what is going on in the community,” she said.

With monkeypox, “it is anybody’s guess as to how widespread this is going to be,” Dr. Jamieson said.

“The initial monkeypox cases in the current outbreak have been predominately but not exclusively among men who have sex with men; enhanced transmission in this group may be facilitated by sexual activity and spread through complex sexual networks,” Dr. Thornhill said. “As the outbreak continues, we will likely see more monkeypox infections” outside that group.

“Those working in sexual health should have a high index of suspicion in all individuals presenting with genital and oral ulcers and those with proctitis,” he added.

During previous monkeypox outbreaks, the chain of household transmissions has been short, typically two or three people, said Chloe M. Orkin, MD, professor of HIV medicine at Queen Mary University of London. Dr. Orkin directs the Sexual Health and HIV All East Research (SHARE) Collaborative, which has worked to compile the international case series.

Though monkeypox has mainly been transmitted among men who have sex with men, not all identify as gay and some may also have female and nonbinary partners, Dr. Orkin said.

“Clinicians should bear this in mind when examining any person,” she said.

A version of this article first appeared on Medscape.com.

As cases of monkeypox continue to mount in the United States and abroad, infectious disease experts are closely monitoring one group of people in particular: women.

So far, the overwhelming majority of cases of the viral disease have been reported in men who have sex with men. But in recent days, officials have learned of a handful of cases in women – possibly indicating that the outbreak may be widening.

Researchers are keeping close tabs on the proportion of cases in women to “assess whether the outbreak is moving away” from networks of men who have sex with men, where most of the initial cases have been identified, according to a briefing from the UK Health Security Agency (UKHSA).

“There is insufficient evidence to support a change in the transmission dynamics,” the agency said. “However, over the last few weeks the proportion of female cases has been increasing, so this trend needs to be monitored closely.”

A global collaboration of researchers and clinicians recently described 528 cases of monkeypox in 16 countries – but none were in women.

Since data collection for that study ended in June, the research group has confirmed cases in women, said study coauthor John P. Thornhill, MD, PhD, consultant physician in sexual health and HIV and clinical senior lecturer at Barts Health NHS Trust and Queen Mary University of London.

“Cases in women have certainly been reported but are currently far less common,” Dr. Thornhill told this news organization.

Although infections in women have been outliers during the current outbreak, they can be severe when they do occur. Several women in England have been hospitalized with severe symptoms.

A similar pattern has been seen in New York City, where just one woman is among the 639 total cases, according to a July 21 report from the city’s health agency.

Researchers have recently published guidance on monkeypox for ob.gyns., maternal-fetal medicine subspecialists, and people who are pregnant or breastfeeding in anticipation of the possibility of more cases in women.

The Centers for Disease Control and Prevention advises that “pregnant, recently pregnant, and breastfeeding people should be prioritized for medical treatment” of monkeypox if needed. 

One monkeypox vaccine, Jynneos, can be offered to people who are pregnant or breastfeeding and are otherwise eligible for vaccination on the basis of confirmed or likely contact with cases, ideally within 4 days of exposure. Some people at high risk for exposure, such as laboratory workers, may receive the vaccine preemptively.

Another vaccine, ACAM2000, is contraindicated in people who are pregnant or breastfeeding, according to the CDC.
 

Transmission dynamics

Investigators have not yet identified substantial spread of monkeypox beyond men who have sex with men, although transmission among household contacts, including women and children, has been reported.

Most initial infections during the current outbreak occurred during sexual activity. But monkeypox can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC. It also may spread from mother to child in utero.

Infected pets have been known to spread the disease as well. A multistate monkeypox outbreak in the United States in 2003 was linked to pet prairie dogs, including in childcare and school settings. That year, 55% of the 71 cases occurred in female patients.
 

More testing, higher positivity rates in men

Since May, more men than women in the United Kingdom have undergone testing for monkeypox, with 3,467 tests in men versus 447 tests in women. Among those tested, the positivity rate has been far higher in men than in women, 54% versus 2.2%, respectively.

As of July 20, about 0.65% of U.K. cases with known gender were in women. Two weeks prior, about 0.4% were in women.

In all, 13 monkeypox cases in England have been in women, and four had severe manifestations that required hospitalization, according to the UKHSA.

Globally, more than 16,000 monkeypox cases have been reported, according to the World Health Organization. The agency said that it plans to rename the disease to reduce stigma.
 

Monkeypox and pregnancy

Ob.gyns. are often on the “front line in terms of identifying people with infectious diseases,” said Denise J. Jamieson, MD, MPH, Emory University, Atlanta. Dr. Jamieson coauthored “A Primer on Monkeypox Virus for Obstetrician-Gynecologists,” published in Obstetrics & Gynecology.

“Obstetricians need to be aware of what infectious diseases are circulating and be aware of what is going on in the community,” she said.

With monkeypox, “it is anybody’s guess as to how widespread this is going to be,” Dr. Jamieson said.

“The initial monkeypox cases in the current outbreak have been predominately but not exclusively among men who have sex with men; enhanced transmission in this group may be facilitated by sexual activity and spread through complex sexual networks,” Dr. Thornhill said. “As the outbreak continues, we will likely see more monkeypox infections” outside that group.

“Those working in sexual health should have a high index of suspicion in all individuals presenting with genital and oral ulcers and those with proctitis,” he added.

During previous monkeypox outbreaks, the chain of household transmissions has been short, typically two or three people, said Chloe M. Orkin, MD, professor of HIV medicine at Queen Mary University of London. Dr. Orkin directs the Sexual Health and HIV All East Research (SHARE) Collaborative, which has worked to compile the international case series.

Though monkeypox has mainly been transmitted among men who have sex with men, not all identify as gay and some may also have female and nonbinary partners, Dr. Orkin said.

“Clinicians should bear this in mind when examining any person,” she said.

A version of this article first appeared on Medscape.com.

Taking vitamin D supplements did not significantly reduce the risk of fractures among adults in midlife and older adults, compared with placebo, according to results from an ancillary study of the Vitamin D and Omega-3 Trial (VITAL).

The data showed that taking 2,000 IU of supplemental vitamin D each day without coadministered calcium did not have a significant effect on nonvertebral fractures (hazard ratio, 0.97; P = .50), hip fractures (HR, 1.01; P = .96), or total fractures (HR, 0.98; P = .70), compared with taking placebo, among individuals who did not have osteoporosis, vitamin D deficiency, or low bone mass, report Meryl S. LeBoff, MD, a professor of medicine at Harvard Medical School and chief of the calcium and bone section at Brigham and Women’s Hospital, both in Boston, and colleagues.

iStock/thinkstock

The findings were published online in the New England Journal of Medicine.

Prior randomized, controlled trials have presented conflicting findings. Some have shown that there is some benefit to supplemental vitamin D, whereas others have shown no effect or even harm with regard to risk of fractures, Dr. LeBoff noted.

“Because of the conflicting data at the time, we tested this hypothesis in an effort to advance science and understanding of the effects of vitamin D on bone. In a previous study, we did not see an effect of supplemental vitamin D on bone density in a subcohort from the VITAL trial,” Dr. LeBoff said in an interview.

“We previously reported that vitamin D, about 2,000 units per day, did not increase bone density, nor did it affect bone structure, according to PQCT [peripheral quantitative CT]. So that was an indicator that since bone density is a surrogate marker of fractures, there may not be an effect on fractures,” she added.

These results should dispel any idea that vitamin D alone could significantly reduce fracture rates in the general population, noted Steven R. Cummings, MD, of the University of California, San Francisco, and Clifford Rosen, MD, of Maine Medical Center Research Institute, Scarborough, in an accompanying editorial.

“Adding those findings to previous reports from VITAL and other trials showing the lack of an effect for preventing numerous conditions suggests that providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements, and people should stop taking vitamin D supplements to prevent major diseases or extend life,” the editorialists wrote.

The researchers assessed 25,871 participants from all 50 states during a median follow-up time of 5.3 years. Participants were randomly assigned in a 1:1 ratio to receive placebo or vitamin D.

The mean age of the participants was 67.1 years; 50.6% of the study cohort were women, and 20.2% of the cohort were Black. Participants did not have low bone mass, vitamin D deficiency, or osteoporosis.

Participants agreed not to supplement their dietary intake with more than 1,200 mg of calcium each day and no more than 800 IU of vitamin D each day.

Participants filled out detailed surveys to evaluate baseline prescription drug use, demographic factors, medical history, and the consumption of supplements, such as fish oil, calcium, and vitamin D, during the run-in stage. Yearly surveys were used to assess side effects, adherence to the investigation protocol, falls, fractures, physical activity, osteoporosis and associated risk factors, onset of major illness, and the use of nontrial prescription drugs and supplements, such as vitamin D and calcium.

The researchers adjudicated incident fracture data using a centralized medical record review. To approximate the therapeutic effect in intention-to-treat analyses, they used proportional-hazard models.

Notably, outcomes were similar for the placebo and vitamin D groups with regard to incident kidney stones and hypercalcemia.

The effect of vitamin D supplementation was not modified by baseline parameters such as race or ethnicity, sex, body mass index, age, or blood 25-hydroxyvitamin D levels.

Dr. Cummings and Dr. Rosen pointed out that these findings, along with other VITAL trial data, show that no subgroups classified on the basis of baseline 25-hydroxyvitamin D levels, including those with levels less than 20 ng/mL, benefited from vitamin supplementation.

“There is no justification for measuring 25-hydroxyvitamin D in the general population or treating to a target serum level. A 25-hydroxyvitamin D level might be a useful diagnostic test for some patients with conditions that may be due to or that may cause severe deficiency,” the editorialists noted.

Except with regard to select patients, such as individuals living in nursing homes who have limited sun exposure, the use of the terms “vitamin D deficiency” and “vitamin D “insufficiency” should now be reevaluated, Dr. Rosen and Dr. Cummings wrote.

The study’s limitations include its assessment of only one dosage of vitamin D supplementation and a lack of adjustment for multiplicity, exploratory, parent trial, or secondary endpoints, the researchers noted.

The number of participants who had vitamin D deficiency was limited, owing to ethical and feasibility concerns regarding these patients. The data are not generalizable to individuals who are older and institutionalized or those who have osteomalacia or osteoporosis, the researchers wrote.
 

Expert commentary

“The interpretation of this [study] to me is that vitamin D is not for everybody,” said Baha Arafah, MD, professor of medicine at Case Western Reserve University and chief of the division of endocrinology at University Hospital, both in Cleveland, who was not involved in the study.

“This is not the final word; I would suggest that you don’t throw vitamin D at everybody. I would use markers of bone formation as a better measure to determine whether they need vitamin D or not, specifically looking at parathyroid hormone,” Dr. Arafah said in an interview.

Dr. Arafah pointed out that these data do not mean that clinicians should stop thinking about vitamin D altogether. “I think that would be the wrong message to read. If you read through the article, you will find that there are people who do need vitamin D; people who are deficient do need vitamin D. There’s no question that excessive or extreme vitamin D deficiency can lead to other things, specifically, osteomalacia, weak bones, [and] poor mineralization, so we are not totally out of the woods at this time.”

The ancillary study of the VITAL trial was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Pharmavite donated the vitamin D 3 supplements used in the trial. Dr. LeBoff reported that she holds stock in Amgen. Cummings reported receiving personal fees and nonfinancial support from Amgen outside the submitted work. Dr. Rosen is associate editor of the New England Journal of Medicine. Dr. Arafah reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Taking vitamin D supplements did not significantly reduce the risk of fractures among adults in midlife and older adults, compared with placebo, according to results from an ancillary study of the Vitamin D and Omega-3 Trial (VITAL).

The data showed that taking 2,000 IU of supplemental vitamin D each day without coadministered calcium did not have a significant effect on nonvertebral fractures (hazard ratio, 0.97; P = .50), hip fractures (HR, 1.01; P = .96), or total fractures (HR, 0.98; P = .70), compared with taking placebo, among individuals who did not have osteoporosis, vitamin D deficiency, or low bone mass, report Meryl S. LeBoff, MD, a professor of medicine at Harvard Medical School and chief of the calcium and bone section at Brigham and Women’s Hospital, both in Boston, and colleagues.

iStock/thinkstock

The findings were published online in the New England Journal of Medicine.

Prior randomized, controlled trials have presented conflicting findings. Some have shown that there is some benefit to supplemental vitamin D, whereas others have shown no effect or even harm with regard to risk of fractures, Dr. LeBoff noted.

“Because of the conflicting data at the time, we tested this hypothesis in an effort to advance science and understanding of the effects of vitamin D on bone. In a previous study, we did not see an effect of supplemental vitamin D on bone density in a subcohort from the VITAL trial,” Dr. LeBoff said in an interview.

“We previously reported that vitamin D, about 2,000 units per day, did not increase bone density, nor did it affect bone structure, according to PQCT [peripheral quantitative CT]. So that was an indicator that since bone density is a surrogate marker of fractures, there may not be an effect on fractures,” she added.

These results should dispel any idea that vitamin D alone could significantly reduce fracture rates in the general population, noted Steven R. Cummings, MD, of the University of California, San Francisco, and Clifford Rosen, MD, of Maine Medical Center Research Institute, Scarborough, in an accompanying editorial.

“Adding those findings to previous reports from VITAL and other trials showing the lack of an effect for preventing numerous conditions suggests that providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements, and people should stop taking vitamin D supplements to prevent major diseases or extend life,” the editorialists wrote.

The researchers assessed 25,871 participants from all 50 states during a median follow-up time of 5.3 years. Participants were randomly assigned in a 1:1 ratio to receive placebo or vitamin D.

The mean age of the participants was 67.1 years; 50.6% of the study cohort were women, and 20.2% of the cohort were Black. Participants did not have low bone mass, vitamin D deficiency, or osteoporosis.

Participants agreed not to supplement their dietary intake with more than 1,200 mg of calcium each day and no more than 800 IU of vitamin D each day.

Participants filled out detailed surveys to evaluate baseline prescription drug use, demographic factors, medical history, and the consumption of supplements, such as fish oil, calcium, and vitamin D, during the run-in stage. Yearly surveys were used to assess side effects, adherence to the investigation protocol, falls, fractures, physical activity, osteoporosis and associated risk factors, onset of major illness, and the use of nontrial prescription drugs and supplements, such as vitamin D and calcium.

The researchers adjudicated incident fracture data using a centralized medical record review. To approximate the therapeutic effect in intention-to-treat analyses, they used proportional-hazard models.

Notably, outcomes were similar for the placebo and vitamin D groups with regard to incident kidney stones and hypercalcemia.

The effect of vitamin D supplementation was not modified by baseline parameters such as race or ethnicity, sex, body mass index, age, or blood 25-hydroxyvitamin D levels.

Dr. Cummings and Dr. Rosen pointed out that these findings, along with other VITAL trial data, show that no subgroups classified on the basis of baseline 25-hydroxyvitamin D levels, including those with levels less than 20 ng/mL, benefited from vitamin supplementation.

“There is no justification for measuring 25-hydroxyvitamin D in the general population or treating to a target serum level. A 25-hydroxyvitamin D level might be a useful diagnostic test for some patients with conditions that may be due to or that may cause severe deficiency,” the editorialists noted.

Except with regard to select patients, such as individuals living in nursing homes who have limited sun exposure, the use of the terms “vitamin D deficiency” and “vitamin D “insufficiency” should now be reevaluated, Dr. Rosen and Dr. Cummings wrote.

The study’s limitations include its assessment of only one dosage of vitamin D supplementation and a lack of adjustment for multiplicity, exploratory, parent trial, or secondary endpoints, the researchers noted.

The number of participants who had vitamin D deficiency was limited, owing to ethical and feasibility concerns regarding these patients. The data are not generalizable to individuals who are older and institutionalized or those who have osteomalacia or osteoporosis, the researchers wrote.
 

Expert commentary

“The interpretation of this [study] to me is that vitamin D is not for everybody,” said Baha Arafah, MD, professor of medicine at Case Western Reserve University and chief of the division of endocrinology at University Hospital, both in Cleveland, who was not involved in the study.

“This is not the final word; I would suggest that you don’t throw vitamin D at everybody. I would use markers of bone formation as a better measure to determine whether they need vitamin D or not, specifically looking at parathyroid hormone,” Dr. Arafah said in an interview.

Dr. Arafah pointed out that these data do not mean that clinicians should stop thinking about vitamin D altogether. “I think that would be the wrong message to read. If you read through the article, you will find that there are people who do need vitamin D; people who are deficient do need vitamin D. There’s no question that excessive or extreme vitamin D deficiency can lead to other things, specifically, osteomalacia, weak bones, [and] poor mineralization, so we are not totally out of the woods at this time.”

The ancillary study of the VITAL trial was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Pharmavite donated the vitamin D 3 supplements used in the trial. Dr. LeBoff reported that she holds stock in Amgen. Cummings reported receiving personal fees and nonfinancial support from Amgen outside the submitted work. Dr. Rosen is associate editor of the New England Journal of Medicine. Dr. Arafah reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Taking vitamin D supplements did not significantly reduce the risk of fractures among adults in midlife and older adults, compared with placebo, according to results from an ancillary study of the Vitamin D and Omega-3 Trial (VITAL).

The data showed that taking 2,000 IU of supplemental vitamin D each day without coadministered calcium did not have a significant effect on nonvertebral fractures (hazard ratio, 0.97; P = .50), hip fractures (HR, 1.01; P = .96), or total fractures (HR, 0.98; P = .70), compared with taking placebo, among individuals who did not have osteoporosis, vitamin D deficiency, or low bone mass, report Meryl S. LeBoff, MD, a professor of medicine at Harvard Medical School and chief of the calcium and bone section at Brigham and Women’s Hospital, both in Boston, and colleagues.

iStock/thinkstock

The findings were published online in the New England Journal of Medicine.

Prior randomized, controlled trials have presented conflicting findings. Some have shown that there is some benefit to supplemental vitamin D, whereas others have shown no effect or even harm with regard to risk of fractures, Dr. LeBoff noted.

“Because of the conflicting data at the time, we tested this hypothesis in an effort to advance science and understanding of the effects of vitamin D on bone. In a previous study, we did not see an effect of supplemental vitamin D on bone density in a subcohort from the VITAL trial,” Dr. LeBoff said in an interview.

“We previously reported that vitamin D, about 2,000 units per day, did not increase bone density, nor did it affect bone structure, according to PQCT [peripheral quantitative CT]. So that was an indicator that since bone density is a surrogate marker of fractures, there may not be an effect on fractures,” she added.

These results should dispel any idea that vitamin D alone could significantly reduce fracture rates in the general population, noted Steven R. Cummings, MD, of the University of California, San Francisco, and Clifford Rosen, MD, of Maine Medical Center Research Institute, Scarborough, in an accompanying editorial.

“Adding those findings to previous reports from VITAL and other trials showing the lack of an effect for preventing numerous conditions suggests that providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements, and people should stop taking vitamin D supplements to prevent major diseases or extend life,” the editorialists wrote.

The researchers assessed 25,871 participants from all 50 states during a median follow-up time of 5.3 years. Participants were randomly assigned in a 1:1 ratio to receive placebo or vitamin D.

The mean age of the participants was 67.1 years; 50.6% of the study cohort were women, and 20.2% of the cohort were Black. Participants did not have low bone mass, vitamin D deficiency, or osteoporosis.

Participants agreed not to supplement their dietary intake with more than 1,200 mg of calcium each day and no more than 800 IU of vitamin D each day.

Participants filled out detailed surveys to evaluate baseline prescription drug use, demographic factors, medical history, and the consumption of supplements, such as fish oil, calcium, and vitamin D, during the run-in stage. Yearly surveys were used to assess side effects, adherence to the investigation protocol, falls, fractures, physical activity, osteoporosis and associated risk factors, onset of major illness, and the use of nontrial prescription drugs and supplements, such as vitamin D and calcium.

The researchers adjudicated incident fracture data using a centralized medical record review. To approximate the therapeutic effect in intention-to-treat analyses, they used proportional-hazard models.

Notably, outcomes were similar for the placebo and vitamin D groups with regard to incident kidney stones and hypercalcemia.

The effect of vitamin D supplementation was not modified by baseline parameters such as race or ethnicity, sex, body mass index, age, or blood 25-hydroxyvitamin D levels.

Dr. Cummings and Dr. Rosen pointed out that these findings, along with other VITAL trial data, show that no subgroups classified on the basis of baseline 25-hydroxyvitamin D levels, including those with levels less than 20 ng/mL, benefited from vitamin supplementation.

“There is no justification for measuring 25-hydroxyvitamin D in the general population or treating to a target serum level. A 25-hydroxyvitamin D level might be a useful diagnostic test for some patients with conditions that may be due to or that may cause severe deficiency,” the editorialists noted.

Except with regard to select patients, such as individuals living in nursing homes who have limited sun exposure, the use of the terms “vitamin D deficiency” and “vitamin D “insufficiency” should now be reevaluated, Dr. Rosen and Dr. Cummings wrote.

The study’s limitations include its assessment of only one dosage of vitamin D supplementation and a lack of adjustment for multiplicity, exploratory, parent trial, or secondary endpoints, the researchers noted.

The number of participants who had vitamin D deficiency was limited, owing to ethical and feasibility concerns regarding these patients. The data are not generalizable to individuals who are older and institutionalized or those who have osteomalacia or osteoporosis, the researchers wrote.
 

Expert commentary

“The interpretation of this [study] to me is that vitamin D is not for everybody,” said Baha Arafah, MD, professor of medicine at Case Western Reserve University and chief of the division of endocrinology at University Hospital, both in Cleveland, who was not involved in the study.

“This is not the final word; I would suggest that you don’t throw vitamin D at everybody. I would use markers of bone formation as a better measure to determine whether they need vitamin D or not, specifically looking at parathyroid hormone,” Dr. Arafah said in an interview.

Dr. Arafah pointed out that these data do not mean that clinicians should stop thinking about vitamin D altogether. “I think that would be the wrong message to read. If you read through the article, you will find that there are people who do need vitamin D; people who are deficient do need vitamin D. There’s no question that excessive or extreme vitamin D deficiency can lead to other things, specifically, osteomalacia, weak bones, [and] poor mineralization, so we are not totally out of the woods at this time.”

The ancillary study of the VITAL trial was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Pharmavite donated the vitamin D 3 supplements used in the trial. Dr. LeBoff reported that she holds stock in Amgen. Cummings reported receiving personal fees and nonfinancial support from Amgen outside the submitted work. Dr. Rosen is associate editor of the New England Journal of Medicine. Dr. Arafah reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

U.S. Medicare beneficiaries with type 2 diabetes who had health coverage through a Medicare Advantage (MA) plan received treatment with an sodium-glucose cotransporter 2 inhibitor or glucagonlike peptide–1 receptor agonist significantly less often than patients with traditional fee-for-service (FFS) Medicare coverage in 2014-2019, according to a study of more than 411,000 patients.

“MA beneficiaries had modestly but significantly poorer intermediate health outcomes and were less likely to be treated with newer evidence-based antihyperglycemic therapies, compared with Medicare FFS beneficiaries,” concluded Utibe R. Essien, MD, and coauthors in a study published in Diabetes Care.

The report comes as the U.S. Congress is looking closely at the MA program and evidence that insurance companies that provide these policies sometimes impose inappropriate barriers on enrolled beneficiaries by denying or limiting access to treatments and interventions in ways that run counter to Medicare’s coverage policies.

According to Representative Diana DeGette (D-Colo.), who chaired a hearing on MA plans on June 28 by the House of Representatives’ Energy and Commerce Subcommittee on Oversight and Investigations, beneficiaries who are covered through an MA plan “do not always get the care that they are entitled to.”

The study by Dr. Essien and colleagues also documents some positives of care delivered through MA plans for patients with type 2 diabetes, compared with what FFS Medicare beneficiaries generally receive, such as significantly higher rates of screening for nephropathy and ophthalmologic disorders, and foot examinations.

But the apparently dampened use of SGLT2 inhibitors and GLP-1 receptor agonists among MA beneficiaries stand out as notable shortcomings, Dr. Essien maintained.
 

Cost containment may limit use

“The differences in health outcomes and in treatments in MA plans are important to highlight,” Dr. Essien said in an interview. “We worry that the cost-containment challenges [associated with MA plans] may be limiting use of these newer treatments.”

The study was based on 2014-2019 data from the Diabetes Collaborative Registry, which collects information from more than 5,000 U.S. clinicians whose practices include patients with diabetes, as well as claims data recorded by the Centers for Medicare and Medicaid Services during 2014-2017.

The main analysis focused on 345,911 Medicare beneficiaries with diabetes, which included 34% with MA coverage and 66% with FFS coverage. The two subgroups had similar ages, about 75 years old, and roughly half were women in both subgroups. The rate at which both subgroups received statin treatment was nearly the same: 72% for those with MA coverage and 71% for those with FFS Medicare.

But MA beneficiaries differed from those with FFS coverage in several other ways. MA beneficiaries had a higher prevalence of Medicaid eligibility than the FFS group (20% vs 12%) and lower rates of consultations with cardiologists (41% vs. 45%) or endocrinologists (7% vs. 10%).

Some of the positive differences in the care received by MA beneficiaries, compared with FFS beneficiaries, after adjustment for potential clinical and sociodemographic confounders, included:

• Screening for nephropathy, at a significant 14% higher relative rate.
• Screening for ophthalmologic disorders, at a significant 8% higher relative rate.
• Undergoing a diabetic foot examination, at a significant 13% higher relative rate.
• Receiving smoking-cessation counseling, at a significant 5% higher relative rate.
• Receiving treatment with an ACE inhibitor or angiotensin-receptor blocker (87% vs. 81%).
• More consistently receiving treatment with metformin, with rates of 72% versus 69% in 2017.

However, these positive differences were accompanied by these relative shortcomings for those with MA, compared with FFS coverage:

• Lower rates of treatment with an SGLT2 inhibitor (5.4% vs. 6.7%), a significant 9% relative difference after adjustment.
• Lower rates of treatment with a GLP-1 agonist (6.9% vs. 9.0%), a significant 20% relative difference after adjustment.
• Higher average levels of LDL cholesterol (81.5 vs. 78.9 mg/dL), a significantly higher average hemoglobin A1c level (7.1% vs. 7.0%), and a trend toward a lower prevalence of blood pressure control (70.3% vs. 71.5%).

Researchers also highlight that the lower rate at which people with MA coverage received SGLT2 inhibitors or GLP-1 agonists was consistent in patients with established cardiovascular or kidney disease, for whom these agents are particularly recommended.

In addition, a secondary analysis of data for another 65,000 Medicare beneficiaries in 2018 and 2019 showed the disparity in use of agents from these two drug classes continued.
 

Low systemic use of SGLT2 inhibitors, GLP-1 agonists

Dr. Essien acknowledged that, even in people with FFS Medicare coverage, use of SGLT2 inhibitors and GLP-1 agonists was low, but the difference between those with MA coverage is “important.”

Researchers offered four factors that might drive reduced prescribing of agents from these two classes for patients with type 2 diabetes with MA coverage: cost-containment strategies put in place by MA plans; the lower rate of consultations with specialists (cardiologists and endocrinologists); possible exclusion of clinicians from MA provider networks who tend to prescribe these higher-price agents; and lower household incomes of people with MA plans, which may lead to cost-related nonadherence.

Most SGLT2 inhibitors have an average retail cost of about $6,000/year, and some GLP-1 agonists cost more than $10,000/year.

In general, MA coverage includes more oversight of care and its cost than occurs with FFS coverage, noted Dr. Essien, an internal medicine physician at the University of Pittsburgh and a researcher at the Center for Health Equity Research and Promotion of the VA Pittsburgh Healthcare System.

“Incentives for using these more expensive treatments may not be there in MA plans,” he explained. Overcoming cost-related barriers is a challenge that will require “bold policy changes,” as well as better education of clinicians so they make correct treatment decisions, and of patients to resolve possible concerns about treatment safety.

Rep. DeGette hinted during her remarks at the June hearing that policy changes may be coming from Congress.

“Our seniors and their doctors should not be required to jump through numerous hoops to get coverage for straightforward and medically necessary procedures,” she said.

The study received no commercial funding. Dr. Essien reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

U.S. Medicare beneficiaries with type 2 diabetes who had health coverage through a Medicare Advantage (MA) plan received treatment with an sodium-glucose cotransporter 2 inhibitor or glucagonlike peptide–1 receptor agonist significantly less often than patients with traditional fee-for-service (FFS) Medicare coverage in 2014-2019, according to a study of more than 411,000 patients.

“MA beneficiaries had modestly but significantly poorer intermediate health outcomes and were less likely to be treated with newer evidence-based antihyperglycemic therapies, compared with Medicare FFS beneficiaries,” concluded Utibe R. Essien, MD, and coauthors in a study published in Diabetes Care.

The report comes as the U.S. Congress is looking closely at the MA program and evidence that insurance companies that provide these policies sometimes impose inappropriate barriers on enrolled beneficiaries by denying or limiting access to treatments and interventions in ways that run counter to Medicare’s coverage policies.

According to Representative Diana DeGette (D-Colo.), who chaired a hearing on MA plans on June 28 by the House of Representatives’ Energy and Commerce Subcommittee on Oversight and Investigations, beneficiaries who are covered through an MA plan “do not always get the care that they are entitled to.”

The study by Dr. Essien and colleagues also documents some positives of care delivered through MA plans for patients with type 2 diabetes, compared with what FFS Medicare beneficiaries generally receive, such as significantly higher rates of screening for nephropathy and ophthalmologic disorders, and foot examinations.

But the apparently dampened use of SGLT2 inhibitors and GLP-1 receptor agonists among MA beneficiaries stand out as notable shortcomings, Dr. Essien maintained.
 

Cost containment may limit use

“The differences in health outcomes and in treatments in MA plans are important to highlight,” Dr. Essien said in an interview. “We worry that the cost-containment challenges [associated with MA plans] may be limiting use of these newer treatments.”

The study was based on 2014-2019 data from the Diabetes Collaborative Registry, which collects information from more than 5,000 U.S. clinicians whose practices include patients with diabetes, as well as claims data recorded by the Centers for Medicare and Medicaid Services during 2014-2017.

The main analysis focused on 345,911 Medicare beneficiaries with diabetes, which included 34% with MA coverage and 66% with FFS coverage. The two subgroups had similar ages, about 75 years old, and roughly half were women in both subgroups. The rate at which both subgroups received statin treatment was nearly the same: 72% for those with MA coverage and 71% for those with FFS Medicare.

But MA beneficiaries differed from those with FFS coverage in several other ways. MA beneficiaries had a higher prevalence of Medicaid eligibility than the FFS group (20% vs 12%) and lower rates of consultations with cardiologists (41% vs. 45%) or endocrinologists (7% vs. 10%).

Some of the positive differences in the care received by MA beneficiaries, compared with FFS beneficiaries, after adjustment for potential clinical and sociodemographic confounders, included:

• Screening for nephropathy, at a significant 14% higher relative rate.
• Screening for ophthalmologic disorders, at a significant 8% higher relative rate.
• Undergoing a diabetic foot examination, at a significant 13% higher relative rate.
• Receiving smoking-cessation counseling, at a significant 5% higher relative rate.
• Receiving treatment with an ACE inhibitor or angiotensin-receptor blocker (87% vs. 81%).
• More consistently receiving treatment with metformin, with rates of 72% versus 69% in 2017.

However, these positive differences were accompanied by these relative shortcomings for those with MA, compared with FFS coverage:

• Lower rates of treatment with an SGLT2 inhibitor (5.4% vs. 6.7%), a significant 9% relative difference after adjustment.
• Lower rates of treatment with a GLP-1 agonist (6.9% vs. 9.0%), a significant 20% relative difference after adjustment.
• Higher average levels of LDL cholesterol (81.5 vs. 78.9 mg/dL), a significantly higher average hemoglobin A1c level (7.1% vs. 7.0%), and a trend toward a lower prevalence of blood pressure control (70.3% vs. 71.5%).

Researchers also highlight that the lower rate at which people with MA coverage received SGLT2 inhibitors or GLP-1 agonists was consistent in patients with established cardiovascular or kidney disease, for whom these agents are particularly recommended.

In addition, a secondary analysis of data for another 65,000 Medicare beneficiaries in 2018 and 2019 showed the disparity in use of agents from these two drug classes continued.
 

Low systemic use of SGLT2 inhibitors, GLP-1 agonists

Dr. Essien acknowledged that, even in people with FFS Medicare coverage, use of SGLT2 inhibitors and GLP-1 agonists was low, but the difference between those with MA coverage is “important.”

Researchers offered four factors that might drive reduced prescribing of agents from these two classes for patients with type 2 diabetes with MA coverage: cost-containment strategies put in place by MA plans; the lower rate of consultations with specialists (cardiologists and endocrinologists); possible exclusion of clinicians from MA provider networks who tend to prescribe these higher-price agents; and lower household incomes of people with MA plans, which may lead to cost-related nonadherence.

Most SGLT2 inhibitors have an average retail cost of about $6,000/year, and some GLP-1 agonists cost more than $10,000/year.

In general, MA coverage includes more oversight of care and its cost than occurs with FFS coverage, noted Dr. Essien, an internal medicine physician at the University of Pittsburgh and a researcher at the Center for Health Equity Research and Promotion of the VA Pittsburgh Healthcare System.

“Incentives for using these more expensive treatments may not be there in MA plans,” he explained. Overcoming cost-related barriers is a challenge that will require “bold policy changes,” as well as better education of clinicians so they make correct treatment decisions, and of patients to resolve possible concerns about treatment safety.

Rep. DeGette hinted during her remarks at the June hearing that policy changes may be coming from Congress.

“Our seniors and their doctors should not be required to jump through numerous hoops to get coverage for straightforward and medically necessary procedures,” she said.

The study received no commercial funding. Dr. Essien reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

U.S. Medicare beneficiaries with type 2 diabetes who had health coverage through a Medicare Advantage (MA) plan received treatment with an sodium-glucose cotransporter 2 inhibitor or glucagonlike peptide–1 receptor agonist significantly less often than patients with traditional fee-for-service (FFS) Medicare coverage in 2014-2019, according to a study of more than 411,000 patients.

“MA beneficiaries had modestly but significantly poorer intermediate health outcomes and were less likely to be treated with newer evidence-based antihyperglycemic therapies, compared with Medicare FFS beneficiaries,” concluded Utibe R. Essien, MD, and coauthors in a study published in Diabetes Care.

The report comes as the U.S. Congress is looking closely at the MA program and evidence that insurance companies that provide these policies sometimes impose inappropriate barriers on enrolled beneficiaries by denying or limiting access to treatments and interventions in ways that run counter to Medicare’s coverage policies.

According to Representative Diana DeGette (D-Colo.), who chaired a hearing on MA plans on June 28 by the House of Representatives’ Energy and Commerce Subcommittee on Oversight and Investigations, beneficiaries who are covered through an MA plan “do not always get the care that they are entitled to.”

The study by Dr. Essien and colleagues also documents some positives of care delivered through MA plans for patients with type 2 diabetes, compared with what FFS Medicare beneficiaries generally receive, such as significantly higher rates of screening for nephropathy and ophthalmologic disorders, and foot examinations.

But the apparently dampened use of SGLT2 inhibitors and GLP-1 receptor agonists among MA beneficiaries stand out as notable shortcomings, Dr. Essien maintained.
 

Cost containment may limit use

“The differences in health outcomes and in treatments in MA plans are important to highlight,” Dr. Essien said in an interview. “We worry that the cost-containment challenges [associated with MA plans] may be limiting use of these newer treatments.”

The study was based on 2014-2019 data from the Diabetes Collaborative Registry, which collects information from more than 5,000 U.S. clinicians whose practices include patients with diabetes, as well as claims data recorded by the Centers for Medicare and Medicaid Services during 2014-2017.

The main analysis focused on 345,911 Medicare beneficiaries with diabetes, which included 34% with MA coverage and 66% with FFS coverage. The two subgroups had similar ages, about 75 years old, and roughly half were women in both subgroups. The rate at which both subgroups received statin treatment was nearly the same: 72% for those with MA coverage and 71% for those with FFS Medicare.

But MA beneficiaries differed from those with FFS coverage in several other ways. MA beneficiaries had a higher prevalence of Medicaid eligibility than the FFS group (20% vs 12%) and lower rates of consultations with cardiologists (41% vs. 45%) or endocrinologists (7% vs. 10%).

Some of the positive differences in the care received by MA beneficiaries, compared with FFS beneficiaries, after adjustment for potential clinical and sociodemographic confounders, included:

• Screening for nephropathy, at a significant 14% higher relative rate.
• Screening for ophthalmologic disorders, at a significant 8% higher relative rate.
• Undergoing a diabetic foot examination, at a significant 13% higher relative rate.
• Receiving smoking-cessation counseling, at a significant 5% higher relative rate.
• Receiving treatment with an ACE inhibitor or angiotensin-receptor blocker (87% vs. 81%).
• More consistently receiving treatment with metformin, with rates of 72% versus 69% in 2017.

However, these positive differences were accompanied by these relative shortcomings for those with MA, compared with FFS coverage:

• Lower rates of treatment with an SGLT2 inhibitor (5.4% vs. 6.7%), a significant 9% relative difference after adjustment.
• Lower rates of treatment with a GLP-1 agonist (6.9% vs. 9.0%), a significant 20% relative difference after adjustment.
• Higher average levels of LDL cholesterol (81.5 vs. 78.9 mg/dL), a significantly higher average hemoglobin A1c level (7.1% vs. 7.0%), and a trend toward a lower prevalence of blood pressure control (70.3% vs. 71.5%).

Researchers also highlight that the lower rate at which people with MA coverage received SGLT2 inhibitors or GLP-1 agonists was consistent in patients with established cardiovascular or kidney disease, for whom these agents are particularly recommended.

In addition, a secondary analysis of data for another 65,000 Medicare beneficiaries in 2018 and 2019 showed the disparity in use of agents from these two drug classes continued.
 

Low systemic use of SGLT2 inhibitors, GLP-1 agonists

Dr. Essien acknowledged that, even in people with FFS Medicare coverage, use of SGLT2 inhibitors and GLP-1 agonists was low, but the difference between those with MA coverage is “important.”

Researchers offered four factors that might drive reduced prescribing of agents from these two classes for patients with type 2 diabetes with MA coverage: cost-containment strategies put in place by MA plans; the lower rate of consultations with specialists (cardiologists and endocrinologists); possible exclusion of clinicians from MA provider networks who tend to prescribe these higher-price agents; and lower household incomes of people with MA plans, which may lead to cost-related nonadherence.

Most SGLT2 inhibitors have an average retail cost of about $6,000/year, and some GLP-1 agonists cost more than $10,000/year.

In general, MA coverage includes more oversight of care and its cost than occurs with FFS coverage, noted Dr. Essien, an internal medicine physician at the University of Pittsburgh and a researcher at the Center for Health Equity Research and Promotion of the VA Pittsburgh Healthcare System.

“Incentives for using these more expensive treatments may not be there in MA plans,” he explained. Overcoming cost-related barriers is a challenge that will require “bold policy changes,” as well as better education of clinicians so they make correct treatment decisions, and of patients to resolve possible concerns about treatment safety.

Rep. DeGette hinted during her remarks at the June hearing that policy changes may be coming from Congress.

“Our seniors and their doctors should not be required to jump through numerous hoops to get coverage for straightforward and medically necessary procedures,” she said.

The study received no commercial funding. Dr. Essien reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

MONTREAL – A 66-year-old U.S. man has become the world’s fourth known HIV patient to show complete clearance of the virus after being treated for acute myelogenous leukemia with an allogeneic hematopoietic stem cell transplantation from a naturally HIV-resistant donor, U.S. researchers announced at a meeting of the International AIDS Society.

The man received the transplant nearly 3.5 years ago. Since discontinuation of antiretroviral therapy (ART) more than 17 months ago, he has shown no evidence of HIV-1 RNA rebound and no detectable HIV-1 DNA, reported lead investigator Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope, a Duarte, Calif.–based stem cell transplantation center for patients with blood cancers and patients with HIV/blood cancer.

Known as the City of Hope (COH) patient, he is different from the three previously reported patients in that “he was the oldest person to successfully undergo a stem cell transplant with HIV and leukemia and then achieve remission from both conditions,” Dr. Dickter said during a press briefing for the meeting. “He has been living with HIV the longest of any of the patients to date – more than 31 years prior to transplant – and he had also received the least immunosuppressive preparative regimen prior to transplant,” she added.

She said that, like the three previous patients, known as the Berlin, London, and New York patients, the COH patient received a transplant from a donor with natural resistance to HIV because of a rare CCR5-delta 32 mutation.

Dr. Dickter and her coinvestigators used the term “remission” but went further, suggesting that an “HIV cure is feasible” after transplant, given this and the previous cases.

“It’s a bit early to say the patient is cured, but they are clearly in remission,” said Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the meeting. Nevertheless, Dr. Lewin, professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity, in Melbourne, acknowledged that cure is “very likely.”

“Two of the previously reported patients have been off ART for long periods of time – Berlin, 12 years (until Timothy’s death in 2020); London, 4 years – and both had far more extensive investigations to try and find intact virus, including very large blood draws, tissue biopsies, etc. For the New York and now this COH patient, the duration off ART has been much shorter. ... But given the prior cases, it is very likely that the New York and COH patients are indeed cured. But I think it’s too early to make that call, hence my preference to use the word, ‘remission,’ “ she told this news organization.

“Although a transplant is not an option for most people with HIV, these cases are still interesting, still inspiring, and help illuminate the search for a cure,” she added.

Dr. Dickter acknowledged that the complexity of stem cell transplant procedures and their potential for significant side effects make them unsuitable as treatment options for most people with HIV, although she said the COH case is evidence that some HIV patients with blood cancers may not need such intensive pretransplant conditioning regimens.

The COH patient received a reduced-intensity fludarabine and melphalan regimen that had been designed at Dr. Dickter’s center “for older and less fit patients to make transplantation more tolerable,” she said. In addition, the graft-vs.-host disease prophylaxis that the COH patient received included only tacrolimus and sirolimus, whereas the previous patients received additional immunosuppressive therapies, and some also had undergone total body irradiation.

Dr. Dickter has disclosed no relevant financial relationships. Dr. Lewin has relationships with AbbVie, BMS, Esfam, Genentech, Gilead, Immunocore, Merck, Vaxxinity, and Viiv.

A version of this article first appeared on Medscape.com.

MONTREAL – A 66-year-old U.S. man has become the world’s fourth known HIV patient to show complete clearance of the virus after being treated for acute myelogenous leukemia with an allogeneic hematopoietic stem cell transplantation from a naturally HIV-resistant donor, U.S. researchers announced at a meeting of the International AIDS Society.

The man received the transplant nearly 3.5 years ago. Since discontinuation of antiretroviral therapy (ART) more than 17 months ago, he has shown no evidence of HIV-1 RNA rebound and no detectable HIV-1 DNA, reported lead investigator Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope, a Duarte, Calif.–based stem cell transplantation center for patients with blood cancers and patients with HIV/blood cancer.

Known as the City of Hope (COH) patient, he is different from the three previously reported patients in that “he was the oldest person to successfully undergo a stem cell transplant with HIV and leukemia and then achieve remission from both conditions,” Dr. Dickter said during a press briefing for the meeting. “He has been living with HIV the longest of any of the patients to date – more than 31 years prior to transplant – and he had also received the least immunosuppressive preparative regimen prior to transplant,” she added.

She said that, like the three previous patients, known as the Berlin, London, and New York patients, the COH patient received a transplant from a donor with natural resistance to HIV because of a rare CCR5-delta 32 mutation.

Dr. Dickter and her coinvestigators used the term “remission” but went further, suggesting that an “HIV cure is feasible” after transplant, given this and the previous cases.

“It’s a bit early to say the patient is cured, but they are clearly in remission,” said Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the meeting. Nevertheless, Dr. Lewin, professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity, in Melbourne, acknowledged that cure is “very likely.”

“Two of the previously reported patients have been off ART for long periods of time – Berlin, 12 years (until Timothy’s death in 2020); London, 4 years – and both had far more extensive investigations to try and find intact virus, including very large blood draws, tissue biopsies, etc. For the New York and now this COH patient, the duration off ART has been much shorter. ... But given the prior cases, it is very likely that the New York and COH patients are indeed cured. But I think it’s too early to make that call, hence my preference to use the word, ‘remission,’ “ she told this news organization.

“Although a transplant is not an option for most people with HIV, these cases are still interesting, still inspiring, and help illuminate the search for a cure,” she added.

Dr. Dickter acknowledged that the complexity of stem cell transplant procedures and their potential for significant side effects make them unsuitable as treatment options for most people with HIV, although she said the COH case is evidence that some HIV patients with blood cancers may not need such intensive pretransplant conditioning regimens.

The COH patient received a reduced-intensity fludarabine and melphalan regimen that had been designed at Dr. Dickter’s center “for older and less fit patients to make transplantation more tolerable,” she said. In addition, the graft-vs.-host disease prophylaxis that the COH patient received included only tacrolimus and sirolimus, whereas the previous patients received additional immunosuppressive therapies, and some also had undergone total body irradiation.

Dr. Dickter has disclosed no relevant financial relationships. Dr. Lewin has relationships with AbbVie, BMS, Esfam, Genentech, Gilead, Immunocore, Merck, Vaxxinity, and Viiv.

A version of this article first appeared on Medscape.com.

MONTREAL – A 66-year-old U.S. man has become the world’s fourth known HIV patient to show complete clearance of the virus after being treated for acute myelogenous leukemia with an allogeneic hematopoietic stem cell transplantation from a naturally HIV-resistant donor, U.S. researchers announced at a meeting of the International AIDS Society.

The man received the transplant nearly 3.5 years ago. Since discontinuation of antiretroviral therapy (ART) more than 17 months ago, he has shown no evidence of HIV-1 RNA rebound and no detectable HIV-1 DNA, reported lead investigator Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope, a Duarte, Calif.–based stem cell transplantation center for patients with blood cancers and patients with HIV/blood cancer.

Known as the City of Hope (COH) patient, he is different from the three previously reported patients in that “he was the oldest person to successfully undergo a stem cell transplant with HIV and leukemia and then achieve remission from both conditions,” Dr. Dickter said during a press briefing for the meeting. “He has been living with HIV the longest of any of the patients to date – more than 31 years prior to transplant – and he had also received the least immunosuppressive preparative regimen prior to transplant,” she added.

She said that, like the three previous patients, known as the Berlin, London, and New York patients, the COH patient received a transplant from a donor with natural resistance to HIV because of a rare CCR5-delta 32 mutation.

Dr. Dickter and her coinvestigators used the term “remission” but went further, suggesting that an “HIV cure is feasible” after transplant, given this and the previous cases.

“It’s a bit early to say the patient is cured, but they are clearly in remission,” said Sharon Lewin, MD, president-elect of the International AIDS Society, which runs the meeting. Nevertheless, Dr. Lewin, professor of medicine at the University of Melbourne and director of the Peter Doherty Institute for Infection and Immunity, in Melbourne, acknowledged that cure is “very likely.”

“Two of the previously reported patients have been off ART for long periods of time – Berlin, 12 years (until Timothy’s death in 2020); London, 4 years – and both had far more extensive investigations to try and find intact virus, including very large blood draws, tissue biopsies, etc. For the New York and now this COH patient, the duration off ART has been much shorter. ... But given the prior cases, it is very likely that the New York and COH patients are indeed cured. But I think it’s too early to make that call, hence my preference to use the word, ‘remission,’ “ she told this news organization.

“Although a transplant is not an option for most people with HIV, these cases are still interesting, still inspiring, and help illuminate the search for a cure,” she added.

Dr. Dickter acknowledged that the complexity of stem cell transplant procedures and their potential for significant side effects make them unsuitable as treatment options for most people with HIV, although she said the COH case is evidence that some HIV patients with blood cancers may not need such intensive pretransplant conditioning regimens.

The COH patient received a reduced-intensity fludarabine and melphalan regimen that had been designed at Dr. Dickter’s center “for older and less fit patients to make transplantation more tolerable,” she said. In addition, the graft-vs.-host disease prophylaxis that the COH patient received included only tacrolimus and sirolimus, whereas the previous patients received additional immunosuppressive therapies, and some also had undergone total body irradiation.

Dr. Dickter has disclosed no relevant financial relationships. Dr. Lewin has relationships with AbbVie, BMS, Esfam, Genentech, Gilead, Immunocore, Merck, Vaxxinity, and Viiv.

A version of this article first appeared on Medscape.com.

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference on July 26.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention and Food and Drug Administration have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there’s continual concern about how SARS-CoV-2 might evolve over time.

“Our vaccines are terrific,” Ashish K. Jha, MD, the White House’s COVID-19 response coordinator, said at the summit. “[But] we have to do better.”

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

“We’re stopping the virus from spreading right at the border,” Dr. Iwasaki said at the summit. “This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader.”

Dr. Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In an editorial in Science Immunology, Dr. Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Dr. Topol is editor-in-chief of Medscape.)

Titled “Operation Nasal Vaccine – Lightning speed to counter COVID-19,” their editorial noted the “unprecedented success” seen in the rapid development of the first two mRNA shots. Dr. Iwasaki and Dr. Topol noted that these victories had been “fueled by the $10 billion governmental investment in Operation Warp Speed.

“During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,”  wrote Dr. Iwasaki and Dr. Topol.

Recent developments have “spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots,” they added.
 

An early setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit on July 26, several participants, including Dr. Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued U.S. government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing (NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. “We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID,” he said.

At the summit, Marty Moore, PhD, cofounder and chief scientific officer for Redwood City, Calif.–based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

“No one here today can tell you that mucosal COVID vaccines work. We’re not there yet. We need clinical efficacy data to answer that question,” Dr. Moore said.

But there’s a potential for a “knockout blow to COVID, a transmission-blocking vaccine” from the intranasal approach, he said.

“The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection” from spreading, Dr. Moore said.

A version of this article first appeared on Medscape.com.

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference on July 26.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention and Food and Drug Administration have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there’s continual concern about how SARS-CoV-2 might evolve over time.

“Our vaccines are terrific,” Ashish K. Jha, MD, the White House’s COVID-19 response coordinator, said at the summit. “[But] we have to do better.”

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

“We’re stopping the virus from spreading right at the border,” Dr. Iwasaki said at the summit. “This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader.”

Dr. Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In an editorial in Science Immunology, Dr. Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Dr. Topol is editor-in-chief of Medscape.)

Titled “Operation Nasal Vaccine – Lightning speed to counter COVID-19,” their editorial noted the “unprecedented success” seen in the rapid development of the first two mRNA shots. Dr. Iwasaki and Dr. Topol noted that these victories had been “fueled by the $10 billion governmental investment in Operation Warp Speed.

“During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,”  wrote Dr. Iwasaki and Dr. Topol.

Recent developments have “spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots,” they added.
 

An early setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit on July 26, several participants, including Dr. Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued U.S. government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing (NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. “We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID,” he said.

At the summit, Marty Moore, PhD, cofounder and chief scientific officer for Redwood City, Calif.–based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

“No one here today can tell you that mucosal COVID vaccines work. We’re not there yet. We need clinical efficacy data to answer that question,” Dr. Moore said.

But there’s a potential for a “knockout blow to COVID, a transmission-blocking vaccine” from the intranasal approach, he said.

“The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection” from spreading, Dr. Moore said.

A version of this article first appeared on Medscape.com.

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference on July 26.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention and Food and Drug Administration have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there’s continual concern about how SARS-CoV-2 might evolve over time.

“Our vaccines are terrific,” Ashish K. Jha, MD, the White House’s COVID-19 response coordinator, said at the summit. “[But] we have to do better.”

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

“We’re stopping the virus from spreading right at the border,” Dr. Iwasaki said at the summit. “This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader.”

Dr. Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In an editorial in Science Immunology, Dr. Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Dr. Topol is editor-in-chief of Medscape.)

Titled “Operation Nasal Vaccine – Lightning speed to counter COVID-19,” their editorial noted the “unprecedented success” seen in the rapid development of the first two mRNA shots. Dr. Iwasaki and Dr. Topol noted that these victories had been “fueled by the $10 billion governmental investment in Operation Warp Speed.

“During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,”  wrote Dr. Iwasaki and Dr. Topol.

Recent developments have “spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots,” they added.
 

An early setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit on July 26, several participants, including Dr. Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued U.S. government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing (NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. “We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID,” he said.

At the summit, Marty Moore, PhD, cofounder and chief scientific officer for Redwood City, Calif.–based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

“No one here today can tell you that mucosal COVID vaccines work. We’re not there yet. We need clinical efficacy data to answer that question,” Dr. Moore said.

But there’s a potential for a “knockout blow to COVID, a transmission-blocking vaccine” from the intranasal approach, he said.

“The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection” from spreading, Dr. Moore said.

A version of this article first appeared on Medscape.com.