Pulmonary Health Hub

HIV increases the risk for severe COVID-19 by 6% and the risk of dying of COVID-19 in the hospital by 30%, according to a report from the World Health Organization on COVID-19 outcomes among people living with HIV. The study primarily included people from South Africa but also some data from other parts of the world, including the United States.

However, the report, presented at the 11th IAS Conference on HIV Science (IAS 2021), couldn’t answer some crucial questions clinicians have been wondering about since the COVID-19 pandemic began. For example, was the increase in COVID risk a result of the presence of HIV or because of the immune compromise caused by untreated HIV?

The report didn’t include data on viral load or CD counts, both used to evaluate the health of a person’s immune system. On effective treatment, people living with HIV have a lifespan close to their HIV-negative peers. And effective treatment causes undetectable viral loads which, when maintained for 6 months or more, eliminates transmission of HIV to sexual partners.

What’s clear is that in people with HIV, as in people without HIV, older people, men, and people with diabetes, hypertension, or obesity had the worst outcomes and were most likely to die from COVID-19.

For David Malebranche, MD, MPH, an internal medicine doctor who provides primary care for people in Atlanta, and who was not involved in the study, the WHO study didn’t add anything new. He already recommends the COVID-19 vaccine for all of his patients, HIV-positive or not.

“We don’t have any information from this about the T-cell counts [or] the rates of viral suppression, which I think is tremendously important,” he told this news organization. “To bypass that and not include that in any of the discussion puts the results in a questionable place for me.”

The results come from the WHO Clinical Platform, which culls data from WHO member country surveillance as well as manual case reports from all over the world. By April 29, data on 268,412 people hospitalized with COVID-19 from 37 countries were reported to the platform. Of those, 22,640 people are from the U.S.

A total of 15,522 participants worldwide were living with HIV, 664 in the United States. All U.S. cases were reported from the New York City Health and Hospitals system, Henry Ford Hospital in Detroit, and BronxCare Health System in New York City. Almost all of the remaining participants lived in South Africa – 14,682 of the 15,522, or 94.5%.

Of the 15,522 people living with HIV in the overall group, 37.1% of participants were male, and their median age was 45 years. More than 1 in 3 (36.2%) were admitted with severe or critical COVID-19, and nearly one quarter – 23.1% – with a known outcome died. More than half had one or more chronic conditions, including those that themselves are associated with worse COVID-19 outcomes, such as hypertension (in 33.2% of the participants), diabetes (22.7%), and BMIs above 30 (16.9%). In addition, 8.9% were smokers, 6.6% had chronic pulmonary disease, and 4.3% had chronic heart disease.

After adjusting for those chronic conditions, age, and sex, people living with HIV had a 6% higher rate of severe or critical COVID-19 illness. When investigators adjusted the analysis additionally to differentiate outcomes based on not just the presence of comorbid conditions but the number of them a person had, that increased risk rose to 13%. HIV itself is a comorbid condition, though it wasn’t counted as one in this adjusted analysis.

It didn’t matter whether researchers looked at risk for severe outcomes or deaths after removing the significant co-occurring conditions or if they looked at number of chronic illnesses (aside from HIV), said Silvia Bertagnolio, MD, medical officer at the World Health Organization and co-author of the analysis.

“Both models show almost identical [adjusted odds ratios], meaning that HIV was independently significantly associated with severe/critical presentation,” she told this news organization.

As for death, the analysis showed that, overall, people living with HIV were 30% more likely to die of COVID-19 compared with those not living with HIV. And while this held true even when they adjusted the data for comorbidities, people with HIV were more likely to die if they were over age 65 (risk increased by 82%), male (risk increased by 21%), had diabetes (risk increased by 50%), or had hypertension (risk increased by 26%).

When they broke down the data by WHO region – Africa, Europe, the Americas – investigators found that the increased risk for death held true in Africa. But there were not enough data from the other regions to model mortality risk. What’s more, when they broke the data down by country and excluded South Africa, they found that the elevated risk for death in people living with HIV did not reach statistical significance. Dr. Bertagnolio said she suspects that the small sample sizes from other regions made it impossible to detect a difference, but one could still be present.

One thing conspicuously absent from the analysis was information on viral load, CD4 T-cell count, progression of HIV to AIDS, and whether individuals were in HIV care. The first three factors were not reported in the platform, and the fourth was available for 60% of participants but was not included in the analysis. Dr. Bertagnolio pointed out that, for those 60% of participants, 91.8% were on antiretroviral treatment (ART).

“The majority of patients come from South Africa, and we know that in South Africa, over 90% of people receiving ART are virologically suppressed,” she told this news organization. “So we could speculate that this effect persists despite the use of ART, in a population likely to be virally suppressed, although we cannot assess this with certainty through the data set we had.”

A much smaller study of 749 people living with HIV and diagnosed with SARS-CoV-2, also presented at the conference, found that detectable HIV viral load was significantly associated with a slightly higher risk of severe outcomes (P < .039), but CD4 counts less than 200 cells/mm³ was not (P = .15).

And although both Dr. Bertagnolio and conference organizers presented this data as proof that HIV increases the risk for poor COVID-19 outcomes, Dr. Malebranche isn’t so sure. He estimates that only about half his patients have received the COVID-19 vaccine. But this study is unlikely to make him forcefully recommend a COVID-19 vaccination with young, otherwise healthy, and undetectable people in his care who express particular concern about long-term effects of the vaccine. He also manages a lot of people with HIV who have undetectable viral loads and CD4 counts of up to 1,200 but are older, with diabetes, obesity, and high blood pressure. Those are the people he will target with stronger messages regarding the vaccine.

“The young patients who are healthy, virally suppressed, and doing well may very much argue with me, ‘I’m not going to push it,’ but I will bring it up on the next visit,” he said. The analysis “just helps reinforce in me that I need to have these conversations and be a little bit more persuasive to my older patients with comorbid conditions.”

Dr. Bertagnolio has disclosed no relevant financial relationships. Dr. Malebranche serves on the pre-exposure prophylaxis (PrEP) speakers bureau for Gilead Sciences and has consulted and advised for ViiV Healthcare. This study was funded by the World Health Organization.

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

HIV increases the risk for severe COVID-19 by 6% and the risk of dying of COVID-19 in the hospital by 30%, according to a report from the World Health Organization on COVID-19 outcomes among people living with HIV. The study primarily included people from South Africa but also some data from other parts of the world, including the United States.

However, the report, presented at the 11th IAS Conference on HIV Science (IAS 2021), couldn’t answer some crucial questions clinicians have been wondering about since the COVID-19 pandemic began. For example, was the increase in COVID risk a result of the presence of HIV or because of the immune compromise caused by untreated HIV?

The report didn’t include data on viral load or CD counts, both used to evaluate the health of a person’s immune system. On effective treatment, people living with HIV have a lifespan close to their HIV-negative peers. And effective treatment causes undetectable viral loads which, when maintained for 6 months or more, eliminates transmission of HIV to sexual partners.

What’s clear is that in people with HIV, as in people without HIV, older people, men, and people with diabetes, hypertension, or obesity had the worst outcomes and were most likely to die from COVID-19.

For David Malebranche, MD, MPH, an internal medicine doctor who provides primary care for people in Atlanta, and who was not involved in the study, the WHO study didn’t add anything new. He already recommends the COVID-19 vaccine for all of his patients, HIV-positive or not.

“We don’t have any information from this about the T-cell counts [or] the rates of viral suppression, which I think is tremendously important,” he told this news organization. “To bypass that and not include that in any of the discussion puts the results in a questionable place for me.”

The results come from the WHO Clinical Platform, which culls data from WHO member country surveillance as well as manual case reports from all over the world. By April 29, data on 268,412 people hospitalized with COVID-19 from 37 countries were reported to the platform. Of those, 22,640 people are from the U.S.

A total of 15,522 participants worldwide were living with HIV, 664 in the United States. All U.S. cases were reported from the New York City Health and Hospitals system, Henry Ford Hospital in Detroit, and BronxCare Health System in New York City. Almost all of the remaining participants lived in South Africa – 14,682 of the 15,522, or 94.5%.

Of the 15,522 people living with HIV in the overall group, 37.1% of participants were male, and their median age was 45 years. More than 1 in 3 (36.2%) were admitted with severe or critical COVID-19, and nearly one quarter – 23.1% – with a known outcome died. More than half had one or more chronic conditions, including those that themselves are associated with worse COVID-19 outcomes, such as hypertension (in 33.2% of the participants), diabetes (22.7%), and BMIs above 30 (16.9%). In addition, 8.9% were smokers, 6.6% had chronic pulmonary disease, and 4.3% had chronic heart disease.

After adjusting for those chronic conditions, age, and sex, people living with HIV had a 6% higher rate of severe or critical COVID-19 illness. When investigators adjusted the analysis additionally to differentiate outcomes based on not just the presence of comorbid conditions but the number of them a person had, that increased risk rose to 13%. HIV itself is a comorbid condition, though it wasn’t counted as one in this adjusted analysis.

It didn’t matter whether researchers looked at risk for severe outcomes or deaths after removing the significant co-occurring conditions or if they looked at number of chronic illnesses (aside from HIV), said Silvia Bertagnolio, MD, medical officer at the World Health Organization and co-author of the analysis.

“Both models show almost identical [adjusted odds ratios], meaning that HIV was independently significantly associated with severe/critical presentation,” she told this news organization.

As for death, the analysis showed that, overall, people living with HIV were 30% more likely to die of COVID-19 compared with those not living with HIV. And while this held true even when they adjusted the data for comorbidities, people with HIV were more likely to die if they were over age 65 (risk increased by 82%), male (risk increased by 21%), had diabetes (risk increased by 50%), or had hypertension (risk increased by 26%).

When they broke down the data by WHO region – Africa, Europe, the Americas – investigators found that the increased risk for death held true in Africa. But there were not enough data from the other regions to model mortality risk. What’s more, when they broke the data down by country and excluded South Africa, they found that the elevated risk for death in people living with HIV did not reach statistical significance. Dr. Bertagnolio said she suspects that the small sample sizes from other regions made it impossible to detect a difference, but one could still be present.

One thing conspicuously absent from the analysis was information on viral load, CD4 T-cell count, progression of HIV to AIDS, and whether individuals were in HIV care. The first three factors were not reported in the platform, and the fourth was available for 60% of participants but was not included in the analysis. Dr. Bertagnolio pointed out that, for those 60% of participants, 91.8% were on antiretroviral treatment (ART).

“The majority of patients come from South Africa, and we know that in South Africa, over 90% of people receiving ART are virologically suppressed,” she told this news organization. “So we could speculate that this effect persists despite the use of ART, in a population likely to be virally suppressed, although we cannot assess this with certainty through the data set we had.”

A much smaller study of 749 people living with HIV and diagnosed with SARS-CoV-2, also presented at the conference, found that detectable HIV viral load was significantly associated with a slightly higher risk of severe outcomes (P < .039), but CD4 counts less than 200 cells/mm³ was not (P = .15).

And although both Dr. Bertagnolio and conference organizers presented this data as proof that HIV increases the risk for poor COVID-19 outcomes, Dr. Malebranche isn’t so sure. He estimates that only about half his patients have received the COVID-19 vaccine. But this study is unlikely to make him forcefully recommend a COVID-19 vaccination with young, otherwise healthy, and undetectable people in his care who express particular concern about long-term effects of the vaccine. He also manages a lot of people with HIV who have undetectable viral loads and CD4 counts of up to 1,200 but are older, with diabetes, obesity, and high blood pressure. Those are the people he will target with stronger messages regarding the vaccine.

“The young patients who are healthy, virally suppressed, and doing well may very much argue with me, ‘I’m not going to push it,’ but I will bring it up on the next visit,” he said. The analysis “just helps reinforce in me that I need to have these conversations and be a little bit more persuasive to my older patients with comorbid conditions.”

Dr. Bertagnolio has disclosed no relevant financial relationships. Dr. Malebranche serves on the pre-exposure prophylaxis (PrEP) speakers bureau for Gilead Sciences and has consulted and advised for ViiV Healthcare. This study was funded by the World Health Organization.

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

HIV increases the risk for severe COVID-19 by 6% and the risk of dying of COVID-19 in the hospital by 30%, according to a report from the World Health Organization on COVID-19 outcomes among people living with HIV. The study primarily included people from South Africa but also some data from other parts of the world, including the United States.

However, the report, presented at the 11th IAS Conference on HIV Science (IAS 2021), couldn’t answer some crucial questions clinicians have been wondering about since the COVID-19 pandemic began. For example, was the increase in COVID risk a result of the presence of HIV or because of the immune compromise caused by untreated HIV?

The report didn’t include data on viral load or CD counts, both used to evaluate the health of a person’s immune system. On effective treatment, people living with HIV have a lifespan close to their HIV-negative peers. And effective treatment causes undetectable viral loads which, when maintained for 6 months or more, eliminates transmission of HIV to sexual partners.

What’s clear is that in people with HIV, as in people without HIV, older people, men, and people with diabetes, hypertension, or obesity had the worst outcomes and were most likely to die from COVID-19.

For David Malebranche, MD, MPH, an internal medicine doctor who provides primary care for people in Atlanta, and who was not involved in the study, the WHO study didn’t add anything new. He already recommends the COVID-19 vaccine for all of his patients, HIV-positive or not.

“We don’t have any information from this about the T-cell counts [or] the rates of viral suppression, which I think is tremendously important,” he told this news organization. “To bypass that and not include that in any of the discussion puts the results in a questionable place for me.”

The results come from the WHO Clinical Platform, which culls data from WHO member country surveillance as well as manual case reports from all over the world. By April 29, data on 268,412 people hospitalized with COVID-19 from 37 countries were reported to the platform. Of those, 22,640 people are from the U.S.

A total of 15,522 participants worldwide were living with HIV, 664 in the United States. All U.S. cases were reported from the New York City Health and Hospitals system, Henry Ford Hospital in Detroit, and BronxCare Health System in New York City. Almost all of the remaining participants lived in South Africa – 14,682 of the 15,522, or 94.5%.

Of the 15,522 people living with HIV in the overall group, 37.1% of participants were male, and their median age was 45 years. More than 1 in 3 (36.2%) were admitted with severe or critical COVID-19, and nearly one quarter – 23.1% – with a known outcome died. More than half had one or more chronic conditions, including those that themselves are associated with worse COVID-19 outcomes, such as hypertension (in 33.2% of the participants), diabetes (22.7%), and BMIs above 30 (16.9%). In addition, 8.9% were smokers, 6.6% had chronic pulmonary disease, and 4.3% had chronic heart disease.

After adjusting for those chronic conditions, age, and sex, people living with HIV had a 6% higher rate of severe or critical COVID-19 illness. When investigators adjusted the analysis additionally to differentiate outcomes based on not just the presence of comorbid conditions but the number of them a person had, that increased risk rose to 13%. HIV itself is a comorbid condition, though it wasn’t counted as one in this adjusted analysis.

It didn’t matter whether researchers looked at risk for severe outcomes or deaths after removing the significant co-occurring conditions or if they looked at number of chronic illnesses (aside from HIV), said Silvia Bertagnolio, MD, medical officer at the World Health Organization and co-author of the analysis.

“Both models show almost identical [adjusted odds ratios], meaning that HIV was independently significantly associated with severe/critical presentation,” she told this news organization.

As for death, the analysis showed that, overall, people living with HIV were 30% more likely to die of COVID-19 compared with those not living with HIV. And while this held true even when they adjusted the data for comorbidities, people with HIV were more likely to die if they were over age 65 (risk increased by 82%), male (risk increased by 21%), had diabetes (risk increased by 50%), or had hypertension (risk increased by 26%).

When they broke down the data by WHO region – Africa, Europe, the Americas – investigators found that the increased risk for death held true in Africa. But there were not enough data from the other regions to model mortality risk. What’s more, when they broke the data down by country and excluded South Africa, they found that the elevated risk for death in people living with HIV did not reach statistical significance. Dr. Bertagnolio said she suspects that the small sample sizes from other regions made it impossible to detect a difference, but one could still be present.

One thing conspicuously absent from the analysis was information on viral load, CD4 T-cell count, progression of HIV to AIDS, and whether individuals were in HIV care. The first three factors were not reported in the platform, and the fourth was available for 60% of participants but was not included in the analysis. Dr. Bertagnolio pointed out that, for those 60% of participants, 91.8% were on antiretroviral treatment (ART).

“The majority of patients come from South Africa, and we know that in South Africa, over 90% of people receiving ART are virologically suppressed,” she told this news organization. “So we could speculate that this effect persists despite the use of ART, in a population likely to be virally suppressed, although we cannot assess this with certainty through the data set we had.”

A much smaller study of 749 people living with HIV and diagnosed with SARS-CoV-2, also presented at the conference, found that detectable HIV viral load was significantly associated with a slightly higher risk of severe outcomes (P < .039), but CD4 counts less than 200 cells/mm³ was not (P = .15).

And although both Dr. Bertagnolio and conference organizers presented this data as proof that HIV increases the risk for poor COVID-19 outcomes, Dr. Malebranche isn’t so sure. He estimates that only about half his patients have received the COVID-19 vaccine. But this study is unlikely to make him forcefully recommend a COVID-19 vaccination with young, otherwise healthy, and undetectable people in his care who express particular concern about long-term effects of the vaccine. He also manages a lot of people with HIV who have undetectable viral loads and CD4 counts of up to 1,200 but are older, with diabetes, obesity, and high blood pressure. Those are the people he will target with stronger messages regarding the vaccine.

“The young patients who are healthy, virally suppressed, and doing well may very much argue with me, ‘I’m not going to push it,’ but I will bring it up on the next visit,” he said. The analysis “just helps reinforce in me that I need to have these conversations and be a little bit more persuasive to my older patients with comorbid conditions.”

Dr. Bertagnolio has disclosed no relevant financial relationships. Dr. Malebranche serves on the pre-exposure prophylaxis (PrEP) speakers bureau for Gilead Sciences and has consulted and advised for ViiV Healthcare. This study was funded by the World Health Organization.

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

Lower doses of linezolid in the BPaL drug regimen (bedaquiline, pretomanid, and linezolid) significantly reduce the adverse events associated with the treatment for patients with highly drug-resistant tuberculosis (TB) without compromising its high efficacy, new research shows.

“The ZeNix trial shows that reduced doses and/or shorter durations of linezolid appear to have high efficacy and improved safety,” said first author Francesca Conradie, MB, BCh, of the clinical HIV research unit, faculty of health sciences, University of Witwatersrand, Johannesburg, South Africa, in presenting the findings at the virtual meeting of the International AIDS Society conference.

As recently reported in the pivotal Nix-TB trial, the BPaL regimen yielded a 90% treatment success rate among people with highly drug-resistant forms of TB.

However, a 6-month regimen that included linezolid 1,200 mg resulted in toxic effects: 81% of patients in the study experienced peripheral neuropathy, and myelosuppression occurred in 48%. These effects often led to dose reductions or treatment interruption.

Adjustments in the dose of linezolid in the new ZeNix trial substantially reduced peripheral neuropathy to 13% and myelosuppression to 7%, with no significant reduction in the treatment response.

Importantly, the results were similar among patients with and those without HIV. This is of note because TB is the leading cause of death among patients with HIV.

“In the ZeNix trial, only 20% of patients were HIV infected, but in the [previous] Nix-TB trial, 30% were infected, so we have experience now in about 70 patients who were infected, and the outcomes were no different,” Dr. Conradie said in an interview.

Experts say the findings represent an important turn in the steep challenge of tackling highly resistant TB.

“In our opinion, these are exciting results that could change treatment guidelines for highly drug-resistant tuberculosis, with real benefits for the patients,” said Hendrik Streeck, MD, International AIDS Society cochair and director of the Institute of Virology and the Institute for HIV Research at the University Bonn (Germany), in a press conference.

Payam Nahid, MD, MPH, director of the Center for Tuberculosis at theUniversity of California, San Francisco, agreed.

“The results of this trial will impact global practices in treating drug-resistant TB as well as the design and conduct of future TB clinical trials,” Dr. Nahid said in an interview.
 

ZeNix trial

The phase 3 ZeNix trial included 181 patients with highly resistant TB in South Africa, Russia, Georgia, and Moldova. The mean age of the patients was 37 years; 67.4% were men, 63.5% were White, and 19.9% were HIV positive.

All patients were treated for 6 months with bedaquiline 200 mg daily for 8 weeks followed by 100 mg daily for 18 weeks, as well as pretomanid 200 mg daily.

The patients were randomly assigned to receive one of four daily doses of linezolid: 1,200 mg for 6 months (the original dose from the Nix-TB trial; n = 45) or 2 months (n = 46), or 600 mg for 6 or 2 months (45 patients each).

Percentages of patients with HIV were equal among the four groups, at about 20% each.

The primary outcomes – resolution of clinical disease and a negative culture status after 6 months – were observed across all linezolid dose groups. The success rate was 93% for those receiving 1,200 mg for 6 months, 89% for those receiving 1,200 mg for 2 months, 91% for those receiving 600 mg for 6 months, and 84% for those receiving 600 mg for 2 months.

With regard to the key adverse events of peripheral neuropathy and myelosuppression, manifested as anemia, the highest rates were among those who received linezolid 1,200 mg for 6 month, at 38% and 22%, respectively, compared with 24% and 17.4% among those who received 1,200 mg for 2 months, 24% and 2% among those who received 600 mg for 6 months, and 13% and 6.7% among those who received 600 mg for 2 months.

Four cases of optic neuropathy occurred among those who received 1,200 mg for 6 months; all cases resolved.

Patients who received 1,200 mg for 6 months required the highest number of linezolid dose modifications; 51% required changes that included reduction, interruption, or discontinuation, compared with 28% among those who received 1,200 mg for 2 months and 13% each in the other two groups.

On the basis of these results, “my personal opinion is that 600 mg at 6 months [of linezolid] is most likely the best strategy for the treatment of this highly resistant treatment population group,” Dr. Conradie told this news organization.
 

Findings represent ‘great news’ in addressing concerns

Dr. Nahid further commented that the results are highly encouraging in light of the ongoing concerns about the effects of linezolid in the BPaL regimen.

“This is great news,” he said. “The ZeNix trial addresses a key concern that providers and patients have had regarding the safety and tolerability of taking 6 months of linezolid at 1200 mg/d as part of the BPaL regimen.

“The findings that doses lower and durations shorter than the current 1,200 mg linezolid daily for 6 months will significantly expand the usability of the BPaL regimen worldwide.”

The inclusion of patients with HIV was essential in the trial, he noted.

“There are drug-drug interactions to be considered, among other factors that impact drug exposure,” Dr. Nahid said.

“Inclusion of patients living with HIV in this study means that any modifications to the BPaL regimen considered by the WHO [World Health Organization] and other policy decision makers will include data from this key population,” he said. “Of course, more data are needed on safety, tolerability, and efficacy on BPaL in general, and there are international cohorts and demonstration projects underway that will enhance our understanding of the regimen in HIV and in other special populations.”

The authors, Dr. Streeck, and Dr. Nahid have disclosed no relevant financial relationships.

This article was updated 7/21/21.

Lower doses of linezolid in the BPaL drug regimen (bedaquiline, pretomanid, and linezolid) significantly reduce the adverse events associated with the treatment for patients with highly drug-resistant tuberculosis (TB) without compromising its high efficacy, new research shows.

“The ZeNix trial shows that reduced doses and/or shorter durations of linezolid appear to have high efficacy and improved safety,” said first author Francesca Conradie, MB, BCh, of the clinical HIV research unit, faculty of health sciences, University of Witwatersrand, Johannesburg, South Africa, in presenting the findings at the virtual meeting of the International AIDS Society conference.

As recently reported in the pivotal Nix-TB trial, the BPaL regimen yielded a 90% treatment success rate among people with highly drug-resistant forms of TB.

However, a 6-month regimen that included linezolid 1,200 mg resulted in toxic effects: 81% of patients in the study experienced peripheral neuropathy, and myelosuppression occurred in 48%. These effects often led to dose reductions or treatment interruption.

Adjustments in the dose of linezolid in the new ZeNix trial substantially reduced peripheral neuropathy to 13% and myelosuppression to 7%, with no significant reduction in the treatment response.

Importantly, the results were similar among patients with and those without HIV. This is of note because TB is the leading cause of death among patients with HIV.

“In the ZeNix trial, only 20% of patients were HIV infected, but in the [previous] Nix-TB trial, 30% were infected, so we have experience now in about 70 patients who were infected, and the outcomes were no different,” Dr. Conradie said in an interview.

Experts say the findings represent an important turn in the steep challenge of tackling highly resistant TB.

“In our opinion, these are exciting results that could change treatment guidelines for highly drug-resistant tuberculosis, with real benefits for the patients,” said Hendrik Streeck, MD, International AIDS Society cochair and director of the Institute of Virology and the Institute for HIV Research at the University Bonn (Germany), in a press conference.

Payam Nahid, MD, MPH, director of the Center for Tuberculosis at theUniversity of California, San Francisco, agreed.

“The results of this trial will impact global practices in treating drug-resistant TB as well as the design and conduct of future TB clinical trials,” Dr. Nahid said in an interview.
 

ZeNix trial

The phase 3 ZeNix trial included 181 patients with highly resistant TB in South Africa, Russia, Georgia, and Moldova. The mean age of the patients was 37 years; 67.4% were men, 63.5% were White, and 19.9% were HIV positive.

All patients were treated for 6 months with bedaquiline 200 mg daily for 8 weeks followed by 100 mg daily for 18 weeks, as well as pretomanid 200 mg daily.

The patients were randomly assigned to receive one of four daily doses of linezolid: 1,200 mg for 6 months (the original dose from the Nix-TB trial; n = 45) or 2 months (n = 46), or 600 mg for 6 or 2 months (45 patients each).

Percentages of patients with HIV were equal among the four groups, at about 20% each.

The primary outcomes – resolution of clinical disease and a negative culture status after 6 months – were observed across all linezolid dose groups. The success rate was 93% for those receiving 1,200 mg for 6 months, 89% for those receiving 1,200 mg for 2 months, 91% for those receiving 600 mg for 6 months, and 84% for those receiving 600 mg for 2 months.

With regard to the key adverse events of peripheral neuropathy and myelosuppression, manifested as anemia, the highest rates were among those who received linezolid 1,200 mg for 6 month, at 38% and 22%, respectively, compared with 24% and 17.4% among those who received 1,200 mg for 2 months, 24% and 2% among those who received 600 mg for 6 months, and 13% and 6.7% among those who received 600 mg for 2 months.

Four cases of optic neuropathy occurred among those who received 1,200 mg for 6 months; all cases resolved.

Patients who received 1,200 mg for 6 months required the highest number of linezolid dose modifications; 51% required changes that included reduction, interruption, or discontinuation, compared with 28% among those who received 1,200 mg for 2 months and 13% each in the other two groups.

On the basis of these results, “my personal opinion is that 600 mg at 6 months [of linezolid] is most likely the best strategy for the treatment of this highly resistant treatment population group,” Dr. Conradie told this news organization.
 

Findings represent ‘great news’ in addressing concerns

Dr. Nahid further commented that the results are highly encouraging in light of the ongoing concerns about the effects of linezolid in the BPaL regimen.

“This is great news,” he said. “The ZeNix trial addresses a key concern that providers and patients have had regarding the safety and tolerability of taking 6 months of linezolid at 1200 mg/d as part of the BPaL regimen.

“The findings that doses lower and durations shorter than the current 1,200 mg linezolid daily for 6 months will significantly expand the usability of the BPaL regimen worldwide.”

The inclusion of patients with HIV was essential in the trial, he noted.

“There are drug-drug interactions to be considered, among other factors that impact drug exposure,” Dr. Nahid said.

“Inclusion of patients living with HIV in this study means that any modifications to the BPaL regimen considered by the WHO [World Health Organization] and other policy decision makers will include data from this key population,” he said. “Of course, more data are needed on safety, tolerability, and efficacy on BPaL in general, and there are international cohorts and demonstration projects underway that will enhance our understanding of the regimen in HIV and in other special populations.”

The authors, Dr. Streeck, and Dr. Nahid have disclosed no relevant financial relationships.

This article was updated 7/21/21.

Lower doses of linezolid in the BPaL drug regimen (bedaquiline, pretomanid, and linezolid) significantly reduce the adverse events associated with the treatment for patients with highly drug-resistant tuberculosis (TB) without compromising its high efficacy, new research shows.

“The ZeNix trial shows that reduced doses and/or shorter durations of linezolid appear to have high efficacy and improved safety,” said first author Francesca Conradie, MB, BCh, of the clinical HIV research unit, faculty of health sciences, University of Witwatersrand, Johannesburg, South Africa, in presenting the findings at the virtual meeting of the International AIDS Society conference.

As recently reported in the pivotal Nix-TB trial, the BPaL regimen yielded a 90% treatment success rate among people with highly drug-resistant forms of TB.

However, a 6-month regimen that included linezolid 1,200 mg resulted in toxic effects: 81% of patients in the study experienced peripheral neuropathy, and myelosuppression occurred in 48%. These effects often led to dose reductions or treatment interruption.

Adjustments in the dose of linezolid in the new ZeNix trial substantially reduced peripheral neuropathy to 13% and myelosuppression to 7%, with no significant reduction in the treatment response.

Importantly, the results were similar among patients with and those without HIV. This is of note because TB is the leading cause of death among patients with HIV.

“In the ZeNix trial, only 20% of patients were HIV infected, but in the [previous] Nix-TB trial, 30% were infected, so we have experience now in about 70 patients who were infected, and the outcomes were no different,” Dr. Conradie said in an interview.

Experts say the findings represent an important turn in the steep challenge of tackling highly resistant TB.

“In our opinion, these are exciting results that could change treatment guidelines for highly drug-resistant tuberculosis, with real benefits for the patients,” said Hendrik Streeck, MD, International AIDS Society cochair and director of the Institute of Virology and the Institute for HIV Research at the University Bonn (Germany), in a press conference.

Payam Nahid, MD, MPH, director of the Center for Tuberculosis at theUniversity of California, San Francisco, agreed.

“The results of this trial will impact global practices in treating drug-resistant TB as well as the design and conduct of future TB clinical trials,” Dr. Nahid said in an interview.
 

ZeNix trial

The phase 3 ZeNix trial included 181 patients with highly resistant TB in South Africa, Russia, Georgia, and Moldova. The mean age of the patients was 37 years; 67.4% were men, 63.5% were White, and 19.9% were HIV positive.

All patients were treated for 6 months with bedaquiline 200 mg daily for 8 weeks followed by 100 mg daily for 18 weeks, as well as pretomanid 200 mg daily.

The patients were randomly assigned to receive one of four daily doses of linezolid: 1,200 mg for 6 months (the original dose from the Nix-TB trial; n = 45) or 2 months (n = 46), or 600 mg for 6 or 2 months (45 patients each).

Percentages of patients with HIV were equal among the four groups, at about 20% each.

The primary outcomes – resolution of clinical disease and a negative culture status after 6 months – were observed across all linezolid dose groups. The success rate was 93% for those receiving 1,200 mg for 6 months, 89% for those receiving 1,200 mg for 2 months, 91% for those receiving 600 mg for 6 months, and 84% for those receiving 600 mg for 2 months.

With regard to the key adverse events of peripheral neuropathy and myelosuppression, manifested as anemia, the highest rates were among those who received linezolid 1,200 mg for 6 month, at 38% and 22%, respectively, compared with 24% and 17.4% among those who received 1,200 mg for 2 months, 24% and 2% among those who received 600 mg for 6 months, and 13% and 6.7% among those who received 600 mg for 2 months.

Four cases of optic neuropathy occurred among those who received 1,200 mg for 6 months; all cases resolved.

Patients who received 1,200 mg for 6 months required the highest number of linezolid dose modifications; 51% required changes that included reduction, interruption, or discontinuation, compared with 28% among those who received 1,200 mg for 2 months and 13% each in the other two groups.

On the basis of these results, “my personal opinion is that 600 mg at 6 months [of linezolid] is most likely the best strategy for the treatment of this highly resistant treatment population group,” Dr. Conradie told this news organization.
 

Findings represent ‘great news’ in addressing concerns

Dr. Nahid further commented that the results are highly encouraging in light of the ongoing concerns about the effects of linezolid in the BPaL regimen.

“This is great news,” he said. “The ZeNix trial addresses a key concern that providers and patients have had regarding the safety and tolerability of taking 6 months of linezolid at 1200 mg/d as part of the BPaL regimen.

“The findings that doses lower and durations shorter than the current 1,200 mg linezolid daily for 6 months will significantly expand the usability of the BPaL regimen worldwide.”

The inclusion of patients with HIV was essential in the trial, he noted.

“There are drug-drug interactions to be considered, among other factors that impact drug exposure,” Dr. Nahid said.

“Inclusion of patients living with HIV in this study means that any modifications to the BPaL regimen considered by the WHO [World Health Organization] and other policy decision makers will include data from this key population,” he said. “Of course, more data are needed on safety, tolerability, and efficacy on BPaL in general, and there are international cohorts and demonstration projects underway that will enhance our understanding of the regimen in HIV and in other special populations.”

The authors, Dr. Streeck, and Dr. Nahid have disclosed no relevant financial relationships.

This article was updated 7/21/21.

Early treatment with low-molecular-weight heparin (LMWH) reduces the risk for death in patients with COVID-19, a retrospective cohort study shows.

Heparin could reduce the risk for blood clots, Andrea De Vito, MD, of the unit of infectious diseases at the University of Sassari, Italy, said during his online presentation of the findings at the 31st European Congress of Clinical Microbiology & Infectious Diseases.

“Several studies try to describe the role played by coagulopathies in COVID-19 death,” but the mechanism causing them is still unclear, Dr. De Vito explained.

Some guidelines have suggested heparin as a treatment for hospitalized COVID-19 patients, but few have looked at nonhospitalized patients. In fact, the National Institutes of Health discourages the use of heparin in nonhospitalized COVID-19 patients, and guidance for the home care of COVID-19 patients from the World Health Organization doesn’t mention heparin treatment at all, he said.

To examine the benefits of early heparin – whether administered at home or in the hospital – Dr. De Vito and colleagues looked at a cohort of older adults with COVID-19 who were evaluated or treated at an Italian university hospital.

“Some patients were hospitalized immediately after symptoms onset; other people preferred to call their general practitioner and started the treatment at home,” Dr. De Vito said in an interview. “Other people were hospitalized for worsening of symptoms later in the course of the disease.”

Of the 734 patients, 296 received heparin within 5 days of the onset of symptoms or a positive COVID-19 test. Of the remaining 438 patients, 196 received LMWH treatment later during the disease course, and the rest never received LMWH.

All patients who received early heparin were treated with LMWH 4,000 IU, or 6,000 IU if their body mass index was above 30 kg/m². This was reduced to 2,000 IU if estimated glomerular filtration rate (eGFR) dropped below 30 mL/min. None of the patients had previously received heparin.

Median age was slightly younger for patients who received early heparin than for those who did not (76.8 vs. 78.5 years).

Other demographic characteristics, such as sex and BMI, were similar in the two groups, as were rates of comorbidities, such as hypertension, cardiovascular disease, diabetes, chronic obstructive pulmonary disease, kidney disease, and neurologic conditions. Also similar were the frequency of symptoms (such as fever, cough, and shortness of breath) and rates of treatment with remdesivir or steroids.

Rates of hospital admission were not significantly different between patients who received early heparin and those who did not (65% vs. 61%). There was also no significant difference in use of a venturi mask (35% vs. 28%), noninvasive ventilation (13% vs. 14%), or intubation (5% vs. 8%).

However, rates of death were significantly lower in patients who received early heparin than in those who did not (13% vs. 25%; P < .0001).

There was a trend toward shorter hospital stays for patients treated with early heparin, but the difference was not significant (median, 10 vs. 13 days; P = .08).

Researchers also conducted a separate analysis of 219 COVID-19 patients who received LMWH at home, regardless of when during their disease course they received it. These patients were significantly less likely to be hospitalized than were patients who did not receive LMWH at home (odds ratio, 0.2; P < .0001).

Comparatively, early heparin treatment had a greater effect on the risk for death and the risk for hospitalization than did other factors.

“Thromboemboli are a major complication of COVID. There is good consensus that hospitalized patients with COVID should receive anticoagulants prophylactically, although the best dose is being studied,” said Judy Stone, MD, an infectious disease physician and journalist who was not involved in the study.

“This study extends those findings of benefit from anticoagulants to nonhospitalized patients, with fewer deaths in those treated with low-molecular-weight heparin,” Dr. Stone told this news organization. “The major limitation is that the study is retrospective and observational. The next step would be to confirm these findings prospectively, randomizing a similar group to LMWH or no anticoagulation.”

Another limitation of the study is that some of the patients lived in nursing homes and might have received care from nurses that eliminated the need for hospitalization, Dr. De Vito added.

The study did not note any external funding. The authors have disclosed no relevant financial relationships. Dr. Stone is a member of the advisory committee for the C-Path CURE Drug Repurposing Collaboratory (CDRC) program and has written for Medscape.

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

Early treatment with low-molecular-weight heparin (LMWH) reduces the risk for death in patients with COVID-19, a retrospective cohort study shows.

Heparin could reduce the risk for blood clots, Andrea De Vito, MD, of the unit of infectious diseases at the University of Sassari, Italy, said during his online presentation of the findings at the 31st European Congress of Clinical Microbiology & Infectious Diseases.

“Several studies try to describe the role played by coagulopathies in COVID-19 death,” but the mechanism causing them is still unclear, Dr. De Vito explained.

Some guidelines have suggested heparin as a treatment for hospitalized COVID-19 patients, but few have looked at nonhospitalized patients. In fact, the National Institutes of Health discourages the use of heparin in nonhospitalized COVID-19 patients, and guidance for the home care of COVID-19 patients from the World Health Organization doesn’t mention heparin treatment at all, he said.

To examine the benefits of early heparin – whether administered at home or in the hospital – Dr. De Vito and colleagues looked at a cohort of older adults with COVID-19 who were evaluated or treated at an Italian university hospital.

“Some patients were hospitalized immediately after symptoms onset; other people preferred to call their general practitioner and started the treatment at home,” Dr. De Vito said in an interview. “Other people were hospitalized for worsening of symptoms later in the course of the disease.”

Of the 734 patients, 296 received heparin within 5 days of the onset of symptoms or a positive COVID-19 test. Of the remaining 438 patients, 196 received LMWH treatment later during the disease course, and the rest never received LMWH.

All patients who received early heparin were treated with LMWH 4,000 IU, or 6,000 IU if their body mass index was above 30 kg/m². This was reduced to 2,000 IU if estimated glomerular filtration rate (eGFR) dropped below 30 mL/min. None of the patients had previously received heparin.

Median age was slightly younger for patients who received early heparin than for those who did not (76.8 vs. 78.5 years).

Other demographic characteristics, such as sex and BMI, were similar in the two groups, as were rates of comorbidities, such as hypertension, cardiovascular disease, diabetes, chronic obstructive pulmonary disease, kidney disease, and neurologic conditions. Also similar were the frequency of symptoms (such as fever, cough, and shortness of breath) and rates of treatment with remdesivir or steroids.

Rates of hospital admission were not significantly different between patients who received early heparin and those who did not (65% vs. 61%). There was also no significant difference in use of a venturi mask (35% vs. 28%), noninvasive ventilation (13% vs. 14%), or intubation (5% vs. 8%).

However, rates of death were significantly lower in patients who received early heparin than in those who did not (13% vs. 25%; P < .0001).

There was a trend toward shorter hospital stays for patients treated with early heparin, but the difference was not significant (median, 10 vs. 13 days; P = .08).

Researchers also conducted a separate analysis of 219 COVID-19 patients who received LMWH at home, regardless of when during their disease course they received it. These patients were significantly less likely to be hospitalized than were patients who did not receive LMWH at home (odds ratio, 0.2; P < .0001).

Comparatively, early heparin treatment had a greater effect on the risk for death and the risk for hospitalization than did other factors.

“Thromboemboli are a major complication of COVID. There is good consensus that hospitalized patients with COVID should receive anticoagulants prophylactically, although the best dose is being studied,” said Judy Stone, MD, an infectious disease physician and journalist who was not involved in the study.

“This study extends those findings of benefit from anticoagulants to nonhospitalized patients, with fewer deaths in those treated with low-molecular-weight heparin,” Dr. Stone told this news organization. “The major limitation is that the study is retrospective and observational. The next step would be to confirm these findings prospectively, randomizing a similar group to LMWH or no anticoagulation.”

Another limitation of the study is that some of the patients lived in nursing homes and might have received care from nurses that eliminated the need for hospitalization, Dr. De Vito added.

The study did not note any external funding. The authors have disclosed no relevant financial relationships. Dr. Stone is a member of the advisory committee for the C-Path CURE Drug Repurposing Collaboratory (CDRC) program and has written for Medscape.

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

Early treatment with low-molecular-weight heparin (LMWH) reduces the risk for death in patients with COVID-19, a retrospective cohort study shows.

Heparin could reduce the risk for blood clots, Andrea De Vito, MD, of the unit of infectious diseases at the University of Sassari, Italy, said during his online presentation of the findings at the 31st European Congress of Clinical Microbiology & Infectious Diseases.

“Several studies try to describe the role played by coagulopathies in COVID-19 death,” but the mechanism causing them is still unclear, Dr. De Vito explained.

Some guidelines have suggested heparin as a treatment for hospitalized COVID-19 patients, but few have looked at nonhospitalized patients. In fact, the National Institutes of Health discourages the use of heparin in nonhospitalized COVID-19 patients, and guidance for the home care of COVID-19 patients from the World Health Organization doesn’t mention heparin treatment at all, he said.

To examine the benefits of early heparin – whether administered at home or in the hospital – Dr. De Vito and colleagues looked at a cohort of older adults with COVID-19 who were evaluated or treated at an Italian university hospital.

“Some patients were hospitalized immediately after symptoms onset; other people preferred to call their general practitioner and started the treatment at home,” Dr. De Vito said in an interview. “Other people were hospitalized for worsening of symptoms later in the course of the disease.”

Of the 734 patients, 296 received heparin within 5 days of the onset of symptoms or a positive COVID-19 test. Of the remaining 438 patients, 196 received LMWH treatment later during the disease course, and the rest never received LMWH.

All patients who received early heparin were treated with LMWH 4,000 IU, or 6,000 IU if their body mass index was above 30 kg/m². This was reduced to 2,000 IU if estimated glomerular filtration rate (eGFR) dropped below 30 mL/min. None of the patients had previously received heparin.

Median age was slightly younger for patients who received early heparin than for those who did not (76.8 vs. 78.5 years).

Other demographic characteristics, such as sex and BMI, were similar in the two groups, as were rates of comorbidities, such as hypertension, cardiovascular disease, diabetes, chronic obstructive pulmonary disease, kidney disease, and neurologic conditions. Also similar were the frequency of symptoms (such as fever, cough, and shortness of breath) and rates of treatment with remdesivir or steroids.

Rates of hospital admission were not significantly different between patients who received early heparin and those who did not (65% vs. 61%). There was also no significant difference in use of a venturi mask (35% vs. 28%), noninvasive ventilation (13% vs. 14%), or intubation (5% vs. 8%).

However, rates of death were significantly lower in patients who received early heparin than in those who did not (13% vs. 25%; P < .0001).

There was a trend toward shorter hospital stays for patients treated with early heparin, but the difference was not significant (median, 10 vs. 13 days; P = .08).

Researchers also conducted a separate analysis of 219 COVID-19 patients who received LMWH at home, regardless of when during their disease course they received it. These patients were significantly less likely to be hospitalized than were patients who did not receive LMWH at home (odds ratio, 0.2; P < .0001).

Comparatively, early heparin treatment had a greater effect on the risk for death and the risk for hospitalization than did other factors.

“Thromboemboli are a major complication of COVID. There is good consensus that hospitalized patients with COVID should receive anticoagulants prophylactically, although the best dose is being studied,” said Judy Stone, MD, an infectious disease physician and journalist who was not involved in the study.

“This study extends those findings of benefit from anticoagulants to nonhospitalized patients, with fewer deaths in those treated with low-molecular-weight heparin,” Dr. Stone told this news organization. “The major limitation is that the study is retrospective and observational. The next step would be to confirm these findings prospectively, randomizing a similar group to LMWH or no anticoagulation.”

Another limitation of the study is that some of the patients lived in nursing homes and might have received care from nurses that eliminated the need for hospitalization, Dr. De Vito added.

The study did not note any external funding. The authors have disclosed no relevant financial relationships. Dr. Stone is a member of the advisory committee for the C-Path CURE Drug Repurposing Collaboratory (CDRC) program and has written for Medscape.

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

In April, 92 people gathered in Texas for a wedding. To lower the chances of COVID-19 infection, the festivities were held outside under a large, open-air tent. All 92 guests were required to be fully vaccinated.

Despite those precautions, six people tested positive for the coronavirus and one of them died, Forbes magazine reported, citing a preprint published in medRxiv.

Researchers from Baylor College of Medicine said viral sequencing suggests “the strain containing the Delta variant was transmitted to wedding guests from two patients traveling from India. With no history of vaccine failure in these patients, our observations suggest these are true cases of vaccine breakthrough, mediated by the Delta variant.”

Three females and three males aged 53-69 tested positive for COVID-19. Three were overweight, but none had significant comorbidities or a history of failed vaccination.

The first people to get sick were a man and woman who traveled from India, Forbes reported. The man had no health problems, but the woman had diabetes. Both had gotten two doses of the Covaxin BBV152 vaccine before leaving India.

They tested positive for COVID-19 4 days after the wedding, and the man became so ill he was hospitalized. Six days after the wedding, he died, according to Forbes.

Two people who’d gotten the Pfizer/BioNTech vaccine and two people who received the Moderna vaccine interacted with the first two people, and they also tested positive. One of them, a man in his 60s, had to be hospitalized.

The researchers said their findings suggest the Delta variant “may possess immune evasion” in patients that received the Pfizer, Moderna, or Covaxin vaccines.

Forbes summed it up this way: “While the available COVID-19 vaccines can offer good protection against COVID-19, the protection is not perfect. As long as the pandemic is continuing, it is better to maintain multiple layers of COVID-19 precautions when you can.”
 

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

In April, 92 people gathered in Texas for a wedding. To lower the chances of COVID-19 infection, the festivities were held outside under a large, open-air tent. All 92 guests were required to be fully vaccinated.

Despite those precautions, six people tested positive for the coronavirus and one of them died, Forbes magazine reported, citing a preprint published in medRxiv.

Researchers from Baylor College of Medicine said viral sequencing suggests “the strain containing the Delta variant was transmitted to wedding guests from two patients traveling from India. With no history of vaccine failure in these patients, our observations suggest these are true cases of vaccine breakthrough, mediated by the Delta variant.”

Three females and three males aged 53-69 tested positive for COVID-19. Three were overweight, but none had significant comorbidities or a history of failed vaccination.

The first people to get sick were a man and woman who traveled from India, Forbes reported. The man had no health problems, but the woman had diabetes. Both had gotten two doses of the Covaxin BBV152 vaccine before leaving India.

They tested positive for COVID-19 4 days after the wedding, and the man became so ill he was hospitalized. Six days after the wedding, he died, according to Forbes.

Two people who’d gotten the Pfizer/BioNTech vaccine and two people who received the Moderna vaccine interacted with the first two people, and they also tested positive. One of them, a man in his 60s, had to be hospitalized.

The researchers said their findings suggest the Delta variant “may possess immune evasion” in patients that received the Pfizer, Moderna, or Covaxin vaccines.

Forbes summed it up this way: “While the available COVID-19 vaccines can offer good protection against COVID-19, the protection is not perfect. As long as the pandemic is continuing, it is better to maintain multiple layers of COVID-19 precautions when you can.”
 

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

In April, 92 people gathered in Texas for a wedding. To lower the chances of COVID-19 infection, the festivities were held outside under a large, open-air tent. All 92 guests were required to be fully vaccinated.

Despite those precautions, six people tested positive for the coronavirus and one of them died, Forbes magazine reported, citing a preprint published in medRxiv.

Researchers from Baylor College of Medicine said viral sequencing suggests “the strain containing the Delta variant was transmitted to wedding guests from two patients traveling from India. With no history of vaccine failure in these patients, our observations suggest these are true cases of vaccine breakthrough, mediated by the Delta variant.”

Three females and three males aged 53-69 tested positive for COVID-19. Three were overweight, but none had significant comorbidities or a history of failed vaccination.

The first people to get sick were a man and woman who traveled from India, Forbes reported. The man had no health problems, but the woman had diabetes. Both had gotten two doses of the Covaxin BBV152 vaccine before leaving India.

They tested positive for COVID-19 4 days after the wedding, and the man became so ill he was hospitalized. Six days after the wedding, he died, according to Forbes.

Two people who’d gotten the Pfizer/BioNTech vaccine and two people who received the Moderna vaccine interacted with the first two people, and they also tested positive. One of them, a man in his 60s, had to be hospitalized.

The researchers said their findings suggest the Delta variant “may possess immune evasion” in patients that received the Pfizer, Moderna, or Covaxin vaccines.

Forbes summed it up this way: “While the available COVID-19 vaccines can offer good protection against COVID-19, the protection is not perfect. As long as the pandemic is continuing, it is better to maintain multiple layers of COVID-19 precautions when you can.”
 

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

With only a quarter of all children aged 12-15 years fully vaccinated against COVID-19, first vaccinations continued to drop and new cases for all children rose for the second consecutive week.

Just under 25% of children aged 12-15 had completed the vaccine regimen as of July 12, and just over one-third (33.5%) had received at least one dose. Meanwhile, that age group represented 11.5% of people who initiated vaccination during the 2 weeks ending July 12, down from 12.1% a week earlier, the Centers for Disease Control and Prevention said. The total number of new vaccinations for the week ending July 12 was just over 201,000, compared with 307,000 for the previous week.

New cases of COVID-19, however, were on the rise in children. The 19,000 new cases reported for the week ending July 8 were up from 12,000 a week earlier and 8,000 the week before that, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

That report also shows that children made up 22.3% of all new cases during the week of July 2-8, compared with 16.8% the previous week, and that there were nine deaths in children that same week, the most since March. COVID-related deaths among children total 344 in the 46 jurisdictions (43 states, New York City, Puerto Rico, and Guam) that are reporting such data by age. “It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states,” the two groups noted.

Such data are available from the CDC’s COVID Data Tracker, however, and they show that children aged 16-17 years, who became eligible for COVID vaccination before the younger age group, are further ahead in the process. Among the older children, almost 46% had gotten at least one dose and 37% were fully vaccinated by July 12.

[email protected]

With only a quarter of all children aged 12-15 years fully vaccinated against COVID-19, first vaccinations continued to drop and new cases for all children rose for the second consecutive week.

Just under 25% of children aged 12-15 had completed the vaccine regimen as of July 12, and just over one-third (33.5%) had received at least one dose. Meanwhile, that age group represented 11.5% of people who initiated vaccination during the 2 weeks ending July 12, down from 12.1% a week earlier, the Centers for Disease Control and Prevention said. The total number of new vaccinations for the week ending July 12 was just over 201,000, compared with 307,000 for the previous week.

New cases of COVID-19, however, were on the rise in children. The 19,000 new cases reported for the week ending July 8 were up from 12,000 a week earlier and 8,000 the week before that, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

That report also shows that children made up 22.3% of all new cases during the week of July 2-8, compared with 16.8% the previous week, and that there were nine deaths in children that same week, the most since March. COVID-related deaths among children total 344 in the 46 jurisdictions (43 states, New York City, Puerto Rico, and Guam) that are reporting such data by age. “It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states,” the two groups noted.

Such data are available from the CDC’s COVID Data Tracker, however, and they show that children aged 16-17 years, who became eligible for COVID vaccination before the younger age group, are further ahead in the process. Among the older children, almost 46% had gotten at least one dose and 37% were fully vaccinated by July 12.

[email protected]

With only a quarter of all children aged 12-15 years fully vaccinated against COVID-19, first vaccinations continued to drop and new cases for all children rose for the second consecutive week.

Just under 25% of children aged 12-15 had completed the vaccine regimen as of July 12, and just over one-third (33.5%) had received at least one dose. Meanwhile, that age group represented 11.5% of people who initiated vaccination during the 2 weeks ending July 12, down from 12.1% a week earlier, the Centers for Disease Control and Prevention said. The total number of new vaccinations for the week ending July 12 was just over 201,000, compared with 307,000 for the previous week.

New cases of COVID-19, however, were on the rise in children. The 19,000 new cases reported for the week ending July 8 were up from 12,000 a week earlier and 8,000 the week before that, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

That report also shows that children made up 22.3% of all new cases during the week of July 2-8, compared with 16.8% the previous week, and that there were nine deaths in children that same week, the most since March. COVID-related deaths among children total 344 in the 46 jurisdictions (43 states, New York City, Puerto Rico, and Guam) that are reporting such data by age. “It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states,” the two groups noted.

Such data are available from the CDC’s COVID Data Tracker, however, and they show that children aged 16-17 years, who became eligible for COVID vaccination before the younger age group, are further ahead in the process. Among the older children, almost 46% had gotten at least one dose and 37% were fully vaccinated by July 12.

[email protected]

People receiving the Johnson and Johnson COVID-19 vaccine could be at increased risk for developing Guillain-Barré syndrome, the Food and Drug Administration is expected to announce as early as July 13, according to multiple media reports.

Although the FDA is projected to add the new warning to the labeling for the vaccine, the agency still calculates the benefit of vaccination with the J&J product continues to outweigh the risk. Benefits include protection against the Delta variant and serious COVID-19 outcomes.

More than 100 cases of Guillain-Barré reported to the Vaccine Adverse Event Reporting System, a federal program for reporting vaccine issues, spurred the FDA to act.

Men and people older than 50 appear to be at highest risk, according to reports of a July 12 Centers for Disease Control and Prevention statement. The CDC also revealed that most cases occur about 2 weeks following immunization.

Guillain-Barré syndrome often causes muscle weakness and sometimes temporary paralysis. Most people who develop the rare syndrome recover.

Such was not the case for a 57-year-old man, the New York Times reported July 12. He had a history of both a heart attack and stroke in the previous 4 years and died in April after vaccination with the J&J vaccine and developing Guillain-Barré.

The new warning comes in the wake of a number of setbacks for the company’s COVID-19 vaccine. On April 13, the FDA and CDC both recommended a 10-day pause on administration of the J&J vaccine after reports of rare blood clot events emerged. In mid-June, the FDA requested that Johnson and Johnson discard millions of vaccine doses produced at a manufacturing facility in Baltimore.

The mRNA vaccines from Pfizer/BioNTech and Moderna are not affected by the new FDA warning.

The Biden administration is expected to make a formal announcement of the new warning for the Johnson and Johnson vaccine as early as July 13, the Times reports.

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

People receiving the Johnson and Johnson COVID-19 vaccine could be at increased risk for developing Guillain-Barré syndrome, the Food and Drug Administration is expected to announce as early as July 13, according to multiple media reports.

Although the FDA is projected to add the new warning to the labeling for the vaccine, the agency still calculates the benefit of vaccination with the J&J product continues to outweigh the risk. Benefits include protection against the Delta variant and serious COVID-19 outcomes.

More than 100 cases of Guillain-Barré reported to the Vaccine Adverse Event Reporting System, a federal program for reporting vaccine issues, spurred the FDA to act.

Men and people older than 50 appear to be at highest risk, according to reports of a July 12 Centers for Disease Control and Prevention statement. The CDC also revealed that most cases occur about 2 weeks following immunization.

Guillain-Barré syndrome often causes muscle weakness and sometimes temporary paralysis. Most people who develop the rare syndrome recover.

Such was not the case for a 57-year-old man, the New York Times reported July 12. He had a history of both a heart attack and stroke in the previous 4 years and died in April after vaccination with the J&J vaccine and developing Guillain-Barré.

The new warning comes in the wake of a number of setbacks for the company’s COVID-19 vaccine. On April 13, the FDA and CDC both recommended a 10-day pause on administration of the J&J vaccine after reports of rare blood clot events emerged. In mid-June, the FDA requested that Johnson and Johnson discard millions of vaccine doses produced at a manufacturing facility in Baltimore.

The mRNA vaccines from Pfizer/BioNTech and Moderna are not affected by the new FDA warning.

The Biden administration is expected to make a formal announcement of the new warning for the Johnson and Johnson vaccine as early as July 13, the Times reports.

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

People receiving the Johnson and Johnson COVID-19 vaccine could be at increased risk for developing Guillain-Barré syndrome, the Food and Drug Administration is expected to announce as early as July 13, according to multiple media reports.

Although the FDA is projected to add the new warning to the labeling for the vaccine, the agency still calculates the benefit of vaccination with the J&J product continues to outweigh the risk. Benefits include protection against the Delta variant and serious COVID-19 outcomes.

More than 100 cases of Guillain-Barré reported to the Vaccine Adverse Event Reporting System, a federal program for reporting vaccine issues, spurred the FDA to act.

Men and people older than 50 appear to be at highest risk, according to reports of a July 12 Centers for Disease Control and Prevention statement. The CDC also revealed that most cases occur about 2 weeks following immunization.

Guillain-Barré syndrome often causes muscle weakness and sometimes temporary paralysis. Most people who develop the rare syndrome recover.

Such was not the case for a 57-year-old man, the New York Times reported July 12. He had a history of both a heart attack and stroke in the previous 4 years and died in April after vaccination with the J&J vaccine and developing Guillain-Barré.

The new warning comes in the wake of a number of setbacks for the company’s COVID-19 vaccine. On April 13, the FDA and CDC both recommended a 10-day pause on administration of the J&J vaccine after reports of rare blood clot events emerged. In mid-June, the FDA requested that Johnson and Johnson discard millions of vaccine doses produced at a manufacturing facility in Baltimore.

The mRNA vaccines from Pfizer/BioNTech and Moderna are not affected by the new FDA warning.

The Biden administration is expected to make a formal announcement of the new warning for the Johnson and Johnson vaccine as early as July 13, the Times reports.

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

A standard medical face mask is more effective at preventing the wearer from inhaling aerosols without causing substantial breathing resistance than various cloth, medical, or respirator masks, new research shows.

“Medical face masks with good filtration efficacies can provide even better protective effects than KN95 respirators,” Christian Sterr, MD, from Philipps University of Marburg (Germany), and colleagues wrote. “FFP2 respirators, on the other hand, could be useful in high-risk situations but require greater breathing effort and therefore physical stress for users.”

Extensive evidence has shown that face masks are an excellent form of source control, preventing infectious people from spreading the SARS-CoV-2 virus into the environment. But evidence has been less clear about how well masks protect the wearer from inhaling particles containing the virus.

The researchers conducted three experiments to test 32 different face masks. The findings were presented at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published online in PLOS One .

First they tested pressure drop, which “relates to how easily air can pass through the material,” said Chris Cappa, PhD, professor of civil and environmental engineering at the University of California, Davis, who was not involved with the study.

“Higher pressure drops mean that there is greater resistance to the air passing through. A higher pressure drop will typically mean breathing through the material will be slightly more challenging, compared to a low pressure drop. There is no relationship between pressure drop and the mask effectiveness,” he said in an interview.

Pressure drop was lowest with type II medical face masks, the typical three-ply surgical masks designed to stop large particles expelled by the wearer from entering the environment, was highest with respirators, including KN95 and FFP2 masks, and varied with the different cloth masks tested.

Next the researchers compared filtration efficacy, which “refers to how well the material removes particles from the air that passes through the mask material,” Dr. Cappa explained. They did this by placing each mask over the opening to an air collector that measured how many particles got through. “A mask that has 100% filtration efficacy will remove all particles from the air that passes through it and 0% means that no particles are removed.”

Cloth masks had the lowest filtration efficacy, at 28%. Certified face masks that met European Standards had a relatively high efficacy, at 70%; for uncertified face masks, filtration efficacy was 63%. As expected, KN95 and FFP2 masks had the highest filtration efficacy, at 94% and 98%, respectively.Finally, the researchers tested as-worn filtration efficacies. They placed each mask on a dummy head with an artificial airway that collected airborne particles. They then pumped a mixture of aerosol particles – ranging in size from 0.3 to 2.0 mcm – and particle-free pressurized air into the air-proof acrylic chamber in which the head was placed.

In this experiment, cloth masks and noncertified face masks were least effective, filtering less than 20% of aerosols. Interestingly, the cloth face mask with the highest filtration on its own (84%) had the lowest filtration efficacy (9%), apparently because of its very high pressure drop (breathing resistance). When more effort is required to breathe through a mask, more air can bypass the filtration system.

A standard medical face mask is more effective at preventing the wearer from inhaling aerosols without causing substantial breathing resistance than various cloth, medical, or respirator masks, new research shows.

“Medical face masks with good filtration efficacies can provide even better protective effects than KN95 respirators,” Christian Sterr, MD, from Philipps University of Marburg (Germany), and colleagues wrote. “FFP2 respirators, on the other hand, could be useful in high-risk situations but require greater breathing effort and therefore physical stress for users.”

Extensive evidence has shown that face masks are an excellent form of source control, preventing infectious people from spreading the SARS-CoV-2 virus into the environment. But evidence has been less clear about how well masks protect the wearer from inhaling particles containing the virus.

The researchers conducted three experiments to test 32 different face masks. The findings were presented at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published online in PLOS One .

First they tested pressure drop, which “relates to how easily air can pass through the material,” said Chris Cappa, PhD, professor of civil and environmental engineering at the University of California, Davis, who was not involved with the study.

“Higher pressure drops mean that there is greater resistance to the air passing through. A higher pressure drop will typically mean breathing through the material will be slightly more challenging, compared to a low pressure drop. There is no relationship between pressure drop and the mask effectiveness,” he said in an interview.

Pressure drop was lowest with type II medical face masks, the typical three-ply surgical masks designed to stop large particles expelled by the wearer from entering the environment, was highest with respirators, including KN95 and FFP2 masks, and varied with the different cloth masks tested.

Next the researchers compared filtration efficacy, which “refers to how well the material removes particles from the air that passes through the mask material,” Dr. Cappa explained. They did this by placing each mask over the opening to an air collector that measured how many particles got through. “A mask that has 100% filtration efficacy will remove all particles from the air that passes through it and 0% means that no particles are removed.”

Cloth masks had the lowest filtration efficacy, at 28%. Certified face masks that met European Standards had a relatively high efficacy, at 70%; for uncertified face masks, filtration efficacy was 63%. As expected, KN95 and FFP2 masks had the highest filtration efficacy, at 94% and 98%, respectively.Finally, the researchers tested as-worn filtration efficacies. They placed each mask on a dummy head with an artificial airway that collected airborne particles. They then pumped a mixture of aerosol particles – ranging in size from 0.3 to 2.0 mcm – and particle-free pressurized air into the air-proof acrylic chamber in which the head was placed.

In this experiment, cloth masks and noncertified face masks were least effective, filtering less than 20% of aerosols. Interestingly, the cloth face mask with the highest filtration on its own (84%) had the lowest filtration efficacy (9%), apparently because of its very high pressure drop (breathing resistance). When more effort is required to breathe through a mask, more air can bypass the filtration system.

A standard medical face mask is more effective at preventing the wearer from inhaling aerosols without causing substantial breathing resistance than various cloth, medical, or respirator masks, new research shows.

“Medical face masks with good filtration efficacies can provide even better protective effects than KN95 respirators,” Christian Sterr, MD, from Philipps University of Marburg (Germany), and colleagues wrote. “FFP2 respirators, on the other hand, could be useful in high-risk situations but require greater breathing effort and therefore physical stress for users.”

Extensive evidence has shown that face masks are an excellent form of source control, preventing infectious people from spreading the SARS-CoV-2 virus into the environment. But evidence has been less clear about how well masks protect the wearer from inhaling particles containing the virus.

The researchers conducted three experiments to test 32 different face masks. The findings were presented at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published online in PLOS One .

First they tested pressure drop, which “relates to how easily air can pass through the material,” said Chris Cappa, PhD, professor of civil and environmental engineering at the University of California, Davis, who was not involved with the study.

“Higher pressure drops mean that there is greater resistance to the air passing through. A higher pressure drop will typically mean breathing through the material will be slightly more challenging, compared to a low pressure drop. There is no relationship between pressure drop and the mask effectiveness,” he said in an interview.

Pressure drop was lowest with type II medical face masks, the typical three-ply surgical masks designed to stop large particles expelled by the wearer from entering the environment, was highest with respirators, including KN95 and FFP2 masks, and varied with the different cloth masks tested.

Next the researchers compared filtration efficacy, which “refers to how well the material removes particles from the air that passes through the mask material,” Dr. Cappa explained. They did this by placing each mask over the opening to an air collector that measured how many particles got through. “A mask that has 100% filtration efficacy will remove all particles from the air that passes through it and 0% means that no particles are removed.”

Cloth masks had the lowest filtration efficacy, at 28%. Certified face masks that met European Standards had a relatively high efficacy, at 70%; for uncertified face masks, filtration efficacy was 63%. As expected, KN95 and FFP2 masks had the highest filtration efficacy, at 94% and 98%, respectively.Finally, the researchers tested as-worn filtration efficacies. They placed each mask on a dummy head with an artificial airway that collected airborne particles. They then pumped a mixture of aerosol particles – ranging in size from 0.3 to 2.0 mcm – and particle-free pressurized air into the air-proof acrylic chamber in which the head was placed.

In this experiment, cloth masks and noncertified face masks were least effective, filtering less than 20% of aerosols. Interestingly, the cloth face mask with the highest filtration on its own (84%) had the lowest filtration efficacy (9%), apparently because of its very high pressure drop (breathing resistance). When more effort is required to breathe through a mask, more air can bypass the filtration system.

Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.

The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.

However, it is important to consider the findings in context, experts cautioned.

“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.

“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.

Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.

“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.

Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.

“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.

In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
 

Unrealistic expectations?

People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.

Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.

The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.

This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.

How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.

“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.

Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.

In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.

Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
 

Next steps

Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.

Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.

“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
 

A call for better global surveillance

A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.

One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.

“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”

Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.

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

Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.

The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.

However, it is important to consider the findings in context, experts cautioned.

“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.

“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.

Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.

“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.

Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.

“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.

In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
 

Unrealistic expectations?

People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.

Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.

The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.

This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.

How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.

“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.

Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.

In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.

Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
 

Next steps

Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.

Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.

“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
 

A call for better global surveillance

A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.

One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.

“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”

Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.

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

Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.

The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.

However, it is important to consider the findings in context, experts cautioned.

“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.

“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.

Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.

“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.

Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.

“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.

In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
 

Unrealistic expectations?

People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.

Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.

The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.

This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.

How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.

“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.

Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.

In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.

Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
 

Next steps

Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.

Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.

“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
 

A call for better global surveillance

A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.

One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.

“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”

Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.

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

Sublingual immunotherapy (SLIT) emerged over a century ago as a gentler alternative to allergy shots. It uses the same antigens found in allergy shots, delivering them through tablets or drops under the tongue rather than by injecting them into the skin.

Yet injection immunotherapy has been the mainstay of allergy treatment in the United States. Allergy shots are “the bread and butter, keeping the lights on at allergy practices,” said allergist Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in the Chicago area. So even “when environmental SLIT showed quite clearly that it had efficacy, people were so slow to adapt.”

SLIT – a daily treatment that builds protection from allergens gradually over years with few side effects – is popular around the globe, particularly for environmental allergies. But only a handful of clinics offer food SLIT. Even though recent trials in peanut-allergic children show that SLIT is far safer than oral immunotherapy and about as effective as the Food and Drug Administration–approved peanut-allergy product and has lasting benefits for toddlers, many allergists lack experience with customized immunotherapies and hesitate to offer an unregulated treatment for which the evidence base is still emerging.
 

Why hasn’t food allergy SLIT caught on?

One issue is that there is scant evidence from randomized, controlled trials. The treatments that clinics offer often hinge on insurance coverage, and increasingly, insurers only cover FDA-approved products. FDA approval requires thousands of patients being enrolled in long, expensive studies to prove the treatment’s merit. In a similar vein, doctors are trained to question methods that lack a strong publication base, for good reason.

Yet SLIT caught the attention of pioneering physicians who were intrigued by this “low-and-slow” immune-modifying approach, despite limited published evidence, and they sought real-world experience.

The late physician David Morris, MD, came across SLIT in the 1960s while searching for alternative ways to help mold-allergic farmers who were suffering terrible side effects from allergy shots. Dr. Morris attended conferences, learned more about sublingual techniques, got board certified in allergy, and opened Allergy Associates of La Crosse (Wis.), in 1970 to offer SLIT as a treatment for food and environmental allergies.

Dr. Morris and colleagues developed a protocol to create custom SLIT drops tailored to individual patients’ clinical histories and allergy test results. The method has been used to treat more than 200,000 patients. It has been used by allergist Nikhila Schroeder, MD, MEng, who learned SLIT methods while treating nearly 1,000 patients at Allergy Associates. In 2018, she opened her own direct-care SLIT practice, Allergenuity Health, in the Charlotte metropolitan area of North Carolina (see part 2 of this series).

Dr. Bajowala’s clinic offers SLIT in addition to oral immunotherapy (OIT). She was encouraged by the recent toddler SLIT data but wondered whether it would translate to a real-world setting. According to her calculations, the published protocol – according to which participants receive up to 4 mg/d over 6 months and continue receiving a daily maintenance dose of 4 mg for 3 years – would cost $10,000 per patient.

With this dosing regimen, the intervention is unaffordable, Dr. Bajowala said. And “there’s no way to make it cheaper because that’s the raw materials cost. It does not include labor or bottles or profit at all. That’s just $10,000 in peanut extract.”

Owing to cost, Dr. Bajowala’s clinic generally uses SLIT as a bridge to OIT. Her food allergy patients receive up to 1 mg/d and remain at that dose for a month or so before transitioning to OIT, “for which the supplies are orders of magnitude cheaper,” she said.

Dr. Schroeder said there is evidence for efficacy at microgram and even nanogram dosing – much lower than used in the recent food SLIT trials. Maintenance doses range from 50 ng/d to 25 mcg/d for environmental SLIT and 4-37 mcg/d for food SLIT, she said. The La Crosse method uses even lower dose ranges.

However, dosing information is not readily available, Dr. Schroeder noted. She has spent years scrutinizing articles and compiling information from allergen extract suppliers – all the while treating hundreds of SLIT patients. “I have had to expend a lot of time and effort,” said Dr. Schroeder. “It’s really hard to explain quickly.”

In the published literature, SLIT dosing recommendations vary widely. According to a 2007 analysis, environmental allergy symptoms improved with doses over a 1,000-fold range. What’s more, success did not scale with increased dosing and seemed to depend more on frequency and duration of treatment.

There are fewer studies regarding food SLIT. The most promising data come from recent trials of peanut-allergic children led by Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill. Still, “I am nervous to tell people to go do this based on 150 kids at one site,” Dr. Kim said. “We need to have a gigantic study across multiple sites that actually confirms what we have found in our single center.”

Because there are few published trials of food SLIT, confusion about which doses are optimal, how early to start, and how long the benefits last will be a barrier for many clinicians, said Douglas Mack, MD, FRCPC, assistant clinical professor in pediatrics at McMaster University, Hamilton, Ont.

Much could be learned from Allergy Associates of La Crosse, Allergenuity Health, and other clinics with SLIT experience involving thousands of patients. But that real-world data are messy and difficult to publish. Plus, it is hard for private allergists to find time to review charts, analyze data, and draft papers alongside seeing patients and running a clinic – especially without students and interns, who typically assist with academic research, Dr. Schroeder said.

Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern University, Chicago, and colleagues worked with a La Crosse team 6 or 7 years ago to try to analyze and publish SLIT outcomes for 121 peanut-allergic children who were treated for food and environmental allergies at the Wisconsin clinic. The researchers had hoped to publish an article describing caregiver-reported and clinical outcomes.

Among 73 caregivers who responded to a survey, more than half reported improved eczema, asthma, and environmental allergy symptoms, and virtually all families said SLIT calmed anxieties and minimized fear of allergic reactions. However, the clinical outcomes – skinprick test results, immune changes, and oral food challenges – were not as robust. And the data were incomplete. Some patients had traveled to La Crosse for SLIT drops but underwent skin and blood testing with their local allergist. Compiling records is “so much harder when you’re not doing a prospective clinical trial,” Dr. Gupta said.

The caregiver-reported outcomes were presented as a poster at the 2015 annual meeting of the American College of Allergy, Asthma, and Immunology and the 2016 annual meeting of the Pediatric Academic Society, said Jeff Kessler, MBA, FACHE, who is practice executive at La Crosse. However, with only self-reported data and no convincing lab metrics, the findings were never submitted for publication.

Others are eager to see clearer proof that SLIT works at doses lower than those published in the most recent trials. “If we can get efficacy with lower doses, that means we can increase accessibility, because we can lower the cost,” Dr. Bajowala said.

Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins University, Baltimore, has a pending grant proposal for a multifood trial of SLIT. “It’s a big missing piece,” he said.

Dr. Mack said that in Canada there was “almost an instant change in group think” when the Canadian Society of Allergy and Clinical Immunology published guidelines in support of OIT. With the new guidelines, “people are less concerned about liability. Once they start getting into OIT, I think you’re going to see SLIT coming right along for the ride.”

The shift will be slower in the United States, which has 20 times as many practicing allergists as Canada. Nevertheless, “I totally think SLIT has a place at the table,” Dr. Mack said. “I hope we start to see more high-quality data and people start to use it and experiment with it a bit and see how it works.”

A version of this article first appeared on Medscape.com. This is part three of a three-part series. Part one is here. Part two is here.

Sublingual immunotherapy (SLIT) emerged over a century ago as a gentler alternative to allergy shots. It uses the same antigens found in allergy shots, delivering them through tablets or drops under the tongue rather than by injecting them into the skin.

Yet injection immunotherapy has been the mainstay of allergy treatment in the United States. Allergy shots are “the bread and butter, keeping the lights on at allergy practices,” said allergist Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in the Chicago area. So even “when environmental SLIT showed quite clearly that it had efficacy, people were so slow to adapt.”

SLIT – a daily treatment that builds protection from allergens gradually over years with few side effects – is popular around the globe, particularly for environmental allergies. But only a handful of clinics offer food SLIT. Even though recent trials in peanut-allergic children show that SLIT is far safer than oral immunotherapy and about as effective as the Food and Drug Administration–approved peanut-allergy product and has lasting benefits for toddlers, many allergists lack experience with customized immunotherapies and hesitate to offer an unregulated treatment for which the evidence base is still emerging.
 

Why hasn’t food allergy SLIT caught on?

One issue is that there is scant evidence from randomized, controlled trials. The treatments that clinics offer often hinge on insurance coverage, and increasingly, insurers only cover FDA-approved products. FDA approval requires thousands of patients being enrolled in long, expensive studies to prove the treatment’s merit. In a similar vein, doctors are trained to question methods that lack a strong publication base, for good reason.

Yet SLIT caught the attention of pioneering physicians who were intrigued by this “low-and-slow” immune-modifying approach, despite limited published evidence, and they sought real-world experience.

The late physician David Morris, MD, came across SLIT in the 1960s while searching for alternative ways to help mold-allergic farmers who were suffering terrible side effects from allergy shots. Dr. Morris attended conferences, learned more about sublingual techniques, got board certified in allergy, and opened Allergy Associates of La Crosse (Wis.), in 1970 to offer SLIT as a treatment for food and environmental allergies.

Dr. Morris and colleagues developed a protocol to create custom SLIT drops tailored to individual patients’ clinical histories and allergy test results. The method has been used to treat more than 200,000 patients. It has been used by allergist Nikhila Schroeder, MD, MEng, who learned SLIT methods while treating nearly 1,000 patients at Allergy Associates. In 2018, she opened her own direct-care SLIT practice, Allergenuity Health, in the Charlotte metropolitan area of North Carolina (see part 2 of this series).

Dr. Bajowala’s clinic offers SLIT in addition to oral immunotherapy (OIT). She was encouraged by the recent toddler SLIT data but wondered whether it would translate to a real-world setting. According to her calculations, the published protocol – according to which participants receive up to 4 mg/d over 6 months and continue receiving a daily maintenance dose of 4 mg for 3 years – would cost $10,000 per patient.

With this dosing regimen, the intervention is unaffordable, Dr. Bajowala said. And “there’s no way to make it cheaper because that’s the raw materials cost. It does not include labor or bottles or profit at all. That’s just $10,000 in peanut extract.”

Owing to cost, Dr. Bajowala’s clinic generally uses SLIT as a bridge to OIT. Her food allergy patients receive up to 1 mg/d and remain at that dose for a month or so before transitioning to OIT, “for which the supplies are orders of magnitude cheaper,” she said.

Dr. Schroeder said there is evidence for efficacy at microgram and even nanogram dosing – much lower than used in the recent food SLIT trials. Maintenance doses range from 50 ng/d to 25 mcg/d for environmental SLIT and 4-37 mcg/d for food SLIT, she said. The La Crosse method uses even lower dose ranges.

However, dosing information is not readily available, Dr. Schroeder noted. She has spent years scrutinizing articles and compiling information from allergen extract suppliers – all the while treating hundreds of SLIT patients. “I have had to expend a lot of time and effort,” said Dr. Schroeder. “It’s really hard to explain quickly.”

In the published literature, SLIT dosing recommendations vary widely. According to a 2007 analysis, environmental allergy symptoms improved with doses over a 1,000-fold range. What’s more, success did not scale with increased dosing and seemed to depend more on frequency and duration of treatment.

There are fewer studies regarding food SLIT. The most promising data come from recent trials of peanut-allergic children led by Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill. Still, “I am nervous to tell people to go do this based on 150 kids at one site,” Dr. Kim said. “We need to have a gigantic study across multiple sites that actually confirms what we have found in our single center.”

Because there are few published trials of food SLIT, confusion about which doses are optimal, how early to start, and how long the benefits last will be a barrier for many clinicians, said Douglas Mack, MD, FRCPC, assistant clinical professor in pediatrics at McMaster University, Hamilton, Ont.

Much could be learned from Allergy Associates of La Crosse, Allergenuity Health, and other clinics with SLIT experience involving thousands of patients. But that real-world data are messy and difficult to publish. Plus, it is hard for private allergists to find time to review charts, analyze data, and draft papers alongside seeing patients and running a clinic – especially without students and interns, who typically assist with academic research, Dr. Schroeder said.

Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern University, Chicago, and colleagues worked with a La Crosse team 6 or 7 years ago to try to analyze and publish SLIT outcomes for 121 peanut-allergic children who were treated for food and environmental allergies at the Wisconsin clinic. The researchers had hoped to publish an article describing caregiver-reported and clinical outcomes.

Among 73 caregivers who responded to a survey, more than half reported improved eczema, asthma, and environmental allergy symptoms, and virtually all families said SLIT calmed anxieties and minimized fear of allergic reactions. However, the clinical outcomes – skinprick test results, immune changes, and oral food challenges – were not as robust. And the data were incomplete. Some patients had traveled to La Crosse for SLIT drops but underwent skin and blood testing with their local allergist. Compiling records is “so much harder when you’re not doing a prospective clinical trial,” Dr. Gupta said.

The caregiver-reported outcomes were presented as a poster at the 2015 annual meeting of the American College of Allergy, Asthma, and Immunology and the 2016 annual meeting of the Pediatric Academic Society, said Jeff Kessler, MBA, FACHE, who is practice executive at La Crosse. However, with only self-reported data and no convincing lab metrics, the findings were never submitted for publication.

Others are eager to see clearer proof that SLIT works at doses lower than those published in the most recent trials. “If we can get efficacy with lower doses, that means we can increase accessibility, because we can lower the cost,” Dr. Bajowala said.

Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins University, Baltimore, has a pending grant proposal for a multifood trial of SLIT. “It’s a big missing piece,” he said.

Dr. Mack said that in Canada there was “almost an instant change in group think” when the Canadian Society of Allergy and Clinical Immunology published guidelines in support of OIT. With the new guidelines, “people are less concerned about liability. Once they start getting into OIT, I think you’re going to see SLIT coming right along for the ride.”

The shift will be slower in the United States, which has 20 times as many practicing allergists as Canada. Nevertheless, “I totally think SLIT has a place at the table,” Dr. Mack said. “I hope we start to see more high-quality data and people start to use it and experiment with it a bit and see how it works.”

A version of this article first appeared on Medscape.com. This is part three of a three-part series. Part one is here. Part two is here.

Sublingual immunotherapy (SLIT) emerged over a century ago as a gentler alternative to allergy shots. It uses the same antigens found in allergy shots, delivering them through tablets or drops under the tongue rather than by injecting them into the skin.

Yet injection immunotherapy has been the mainstay of allergy treatment in the United States. Allergy shots are “the bread and butter, keeping the lights on at allergy practices,” said allergist Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in the Chicago area. So even “when environmental SLIT showed quite clearly that it had efficacy, people were so slow to adapt.”

SLIT – a daily treatment that builds protection from allergens gradually over years with few side effects – is popular around the globe, particularly for environmental allergies. But only a handful of clinics offer food SLIT. Even though recent trials in peanut-allergic children show that SLIT is far safer than oral immunotherapy and about as effective as the Food and Drug Administration–approved peanut-allergy product and has lasting benefits for toddlers, many allergists lack experience with customized immunotherapies and hesitate to offer an unregulated treatment for which the evidence base is still emerging.
 

Why hasn’t food allergy SLIT caught on?

One issue is that there is scant evidence from randomized, controlled trials. The treatments that clinics offer often hinge on insurance coverage, and increasingly, insurers only cover FDA-approved products. FDA approval requires thousands of patients being enrolled in long, expensive studies to prove the treatment’s merit. In a similar vein, doctors are trained to question methods that lack a strong publication base, for good reason.

Yet SLIT caught the attention of pioneering physicians who were intrigued by this “low-and-slow” immune-modifying approach, despite limited published evidence, and they sought real-world experience.

The late physician David Morris, MD, came across SLIT in the 1960s while searching for alternative ways to help mold-allergic farmers who were suffering terrible side effects from allergy shots. Dr. Morris attended conferences, learned more about sublingual techniques, got board certified in allergy, and opened Allergy Associates of La Crosse (Wis.), in 1970 to offer SLIT as a treatment for food and environmental allergies.

Dr. Morris and colleagues developed a protocol to create custom SLIT drops tailored to individual patients’ clinical histories and allergy test results. The method has been used to treat more than 200,000 patients. It has been used by allergist Nikhila Schroeder, MD, MEng, who learned SLIT methods while treating nearly 1,000 patients at Allergy Associates. In 2018, she opened her own direct-care SLIT practice, Allergenuity Health, in the Charlotte metropolitan area of North Carolina (see part 2 of this series).

Dr. Bajowala’s clinic offers SLIT in addition to oral immunotherapy (OIT). She was encouraged by the recent toddler SLIT data but wondered whether it would translate to a real-world setting. According to her calculations, the published protocol – according to which participants receive up to 4 mg/d over 6 months and continue receiving a daily maintenance dose of 4 mg for 3 years – would cost $10,000 per patient.

With this dosing regimen, the intervention is unaffordable, Dr. Bajowala said. And “there’s no way to make it cheaper because that’s the raw materials cost. It does not include labor or bottles or profit at all. That’s just $10,000 in peanut extract.”

Owing to cost, Dr. Bajowala’s clinic generally uses SLIT as a bridge to OIT. Her food allergy patients receive up to 1 mg/d and remain at that dose for a month or so before transitioning to OIT, “for which the supplies are orders of magnitude cheaper,” she said.

Dr. Schroeder said there is evidence for efficacy at microgram and even nanogram dosing – much lower than used in the recent food SLIT trials. Maintenance doses range from 50 ng/d to 25 mcg/d for environmental SLIT and 4-37 mcg/d for food SLIT, she said. The La Crosse method uses even lower dose ranges.

However, dosing information is not readily available, Dr. Schroeder noted. She has spent years scrutinizing articles and compiling information from allergen extract suppliers – all the while treating hundreds of SLIT patients. “I have had to expend a lot of time and effort,” said Dr. Schroeder. “It’s really hard to explain quickly.”

In the published literature, SLIT dosing recommendations vary widely. According to a 2007 analysis, environmental allergy symptoms improved with doses over a 1,000-fold range. What’s more, success did not scale with increased dosing and seemed to depend more on frequency and duration of treatment.

There are fewer studies regarding food SLIT. The most promising data come from recent trials of peanut-allergic children led by Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill. Still, “I am nervous to tell people to go do this based on 150 kids at one site,” Dr. Kim said. “We need to have a gigantic study across multiple sites that actually confirms what we have found in our single center.”

Because there are few published trials of food SLIT, confusion about which doses are optimal, how early to start, and how long the benefits last will be a barrier for many clinicians, said Douglas Mack, MD, FRCPC, assistant clinical professor in pediatrics at McMaster University, Hamilton, Ont.

Much could be learned from Allergy Associates of La Crosse, Allergenuity Health, and other clinics with SLIT experience involving thousands of patients. But that real-world data are messy and difficult to publish. Plus, it is hard for private allergists to find time to review charts, analyze data, and draft papers alongside seeing patients and running a clinic – especially without students and interns, who typically assist with academic research, Dr. Schroeder said.

Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern University, Chicago, and colleagues worked with a La Crosse team 6 or 7 years ago to try to analyze and publish SLIT outcomes for 121 peanut-allergic children who were treated for food and environmental allergies at the Wisconsin clinic. The researchers had hoped to publish an article describing caregiver-reported and clinical outcomes.

Among 73 caregivers who responded to a survey, more than half reported improved eczema, asthma, and environmental allergy symptoms, and virtually all families said SLIT calmed anxieties and minimized fear of allergic reactions. However, the clinical outcomes – skinprick test results, immune changes, and oral food challenges – were not as robust. And the data were incomplete. Some patients had traveled to La Crosse for SLIT drops but underwent skin and blood testing with their local allergist. Compiling records is “so much harder when you’re not doing a prospective clinical trial,” Dr. Gupta said.

The caregiver-reported outcomes were presented as a poster at the 2015 annual meeting of the American College of Allergy, Asthma, and Immunology and the 2016 annual meeting of the Pediatric Academic Society, said Jeff Kessler, MBA, FACHE, who is practice executive at La Crosse. However, with only self-reported data and no convincing lab metrics, the findings were never submitted for publication.

Others are eager to see clearer proof that SLIT works at doses lower than those published in the most recent trials. “If we can get efficacy with lower doses, that means we can increase accessibility, because we can lower the cost,” Dr. Bajowala said.

Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins University, Baltimore, has a pending grant proposal for a multifood trial of SLIT. “It’s a big missing piece,” he said.

Dr. Mack said that in Canada there was “almost an instant change in group think” when the Canadian Society of Allergy and Clinical Immunology published guidelines in support of OIT. With the new guidelines, “people are less concerned about liability. Once they start getting into OIT, I think you’re going to see SLIT coming right along for the ride.”

The shift will be slower in the United States, which has 20 times as many practicing allergists as Canada. Nevertheless, “I totally think SLIT has a place at the table,” Dr. Mack said. “I hope we start to see more high-quality data and people start to use it and experiment with it a bit and see how it works.”

A version of this article first appeared on Medscape.com. This is part three of a three-part series. Part one is here. Part two is here.

With degrees in electrical engineering and computer science from the Massachusetts Institute of Technology, Nikhila Schroeder, MD, MEng, brings a problem-solving mindset to medicine.

Being a doctor means having to “figure out all aspects of [a patient’s] situation and do my best to come up with an answer,” said Dr. Schroeder, who founded Allergenuity Health, a solo allergy practice in Huntersville, N.C., with her husband James, who serves as practice executive. It’s “being a medical detective for your patient.”

Yet, during her training, Dr. Schroeder found that market-driven health care makes it hard to practice medicine with a patient’s best interest foremost. Procedures for diagnosing and treating disease cater to insurance companies’ reimbursement policies. “You wind up having to tailor your care to whatever insurance will cover,” she said.

Insurers, in turn, look for evidence from large, peer-reviewed studies to prove that a treatment works. Many physicians hesitate to offer therapies that aren’t covered by insurance, for both liability and financial reasons. So treatment tends to be limited to those options that were rigorously vetted in long, costly, multisite trials that are difficult to conduct without a corporate sponsor.

This is why there is still only one licensed treatment for people with food allergies – a set of standardized peanut powder capsules (Palforzia) that was approved by the Food and Drug Administration in early 2020 for peanut-allergic children aged 4-17 years. A small but growing number of allergists offer unapproved oral immunotherapy (OIT) using commercial food products to treat allergies to peanuts and other foods.

Even fewer allergists treat food allergy patients with another immune-modifying treatment, sublingual immunotherapy (SLIT), which delivers allergens through liquid drops held for several minutes under the tongue. Since 2018, Allergenuity Health, which offers SLIT to treat food and environmental allergies, has provided care to more than 400 patients. More than a third have come from out of state.

The clinic uses a direct-care approach. Rather than taking insurance, the clinic offers a monthly billing program that includes tests, SLIT bottles, and access to Dr. Schroeder via phone, email, or text. “I’m only contracted with the patient, and my only focus is the patient,” Dr. Schroeder said in an interview.
 

Unforgettable day

Allergy was not on Dr. Schroeder’s radar in medical school. She wanted to be a surgeon. But she loved working with children, so she did a pediatrics residency at the University of Virginia Children’s Hospital in Charlottesville. There Dr. Schroeder started seeing kids with eczema and allergies. While covering a friend’s clinic shift in 2010, she was thrust into an emergency. A family who didn’t speak English had just brought in their screaming 6-month-old baby, red and puffy with hives. “We didn’t know what was going on with this child,” Dr. Schroeder said. “Somehow I was elected to go in there.”

All of a sudden, things got quiet. Yet the baby was still screaming, mouth wide open. Dr. Schroeder had learned about anaphylaxis but had never witnessed it – until that day. The baby›s airways swelled so much that the crying became hoarse and soft. After working with a nurse to administer epinephrine, Dr. Schroeder saw something equally unforgettable: The baby’s heart rate soared, but within minutes the hives and swelling subsided and smiles returned. “It was incredible how quickly things changed,” Dr. Schroeder said. The baby had a reaction to rice, an uncommon allergen.

Dr. Schroeder stayed at UVA 2 more years to complete an allergy and immunology fellowship. She learned to diagnose food allergies but became frustrated having to tell patients they had little recourse but to avoid the food and to check in every year or 2. “I was, like, aren’t we specialists? Shouldn’t we have a little more expertise and maybe see if there are ways we could change this?” Dr. Schroeder said.

During those years, allergy shots were the only form of immunotherapy being taught to fellows. At clinic, Dr. Schroeder served as backup to the nurses when someone reacted to shots. She was troubled that some patients needed epinephrine to stop asthma attacks caused by injections they had received as treatment. The idea of injecting substances under the skin seemed akin to vaccination – where “you want to aggravate the immune system, you want it to get revved up, you want to build it up to fight,” she said. “But that’s not what you want for allergy. You want to tone it down. It didn’t really, to be honest, make a lot of sense to me.”

Dr. Schroeder started digging and asking questions. How does the immune system decide what is safe? Which cells and molecules communicate these decisions? She thought about babies and how they “learn” by putting stuff into their mouths. “If we don’t tolerate most of what we take in there, we wouldn’t survive,” Dr. Schroeder said. “It makes a lot of sense that a lot of tolerance begins with cells of the mouth.”

Dr. Schroeder discussed these concepts with her attendings. “They were all, like, no, there’s really no good evidence for that,” she said. But at some point, someone mentioned sublingual immunotherapy, and Schroeder came across Allergy Associates of La Crosse (Wis.).

The clinic’s late founder, David Morris, MD, learned about SLIT in the 1960s as an alternative option for farmers who suffered terrible side effects from injection immunotherapy they received to treat their mold allergies. Dr. Morris attended conferences, learned more about sublingual techniques – at times seeking advice from European allergists who offered SLIT – and became board certified in allergy before opening the La Crosse clinic in 1970. According to the clinic, more than 200,000 patients with environmental and food allergies have been treated with its SLIT protocol.

Dr. Schroeder was shocked to discover that this clinic had existed for 40 years, yet “I, as an allergist, had heard nothing about them,” she said.

Toward the end of her fellowship, OIT was becoming more well known. But she felt its risks were often downplayed. After years of talking with food allergy patients, Schroeder realized that most didn’t actually care about eating peanut butter sandwiches or sesame or walnuts. “Often I would hear, through tears: ‘I just want my child to be able to sit with their friends at lunch, to not be put at this other table, to not feel so isolated,’ ” she said. What mattered most to many families was gaining enough protection to not feel anxious about participating in social activities involving food.

Dr. Schroeder had a growing sense that SLIT – given its ease, safety, and sensible route of allergen delivery – seemed more useful. She wanted to learn more.

Her mentors urged her to stay in academia instead. “They were, like, you have a good academic reputation. You’re a solid thinker. You’re great at what you do. Do the traditional stuff,” Dr. Schroeder said.

Despite these admonitions, Dr. Schroeder left academia and took a job at La Crosse after completing her allergy fellowship. Determined to see whether SLIT could be effective, “I decided in the end, you know what, I have to go do this,” she said. “I need to know, and the only way I’m going to know is to do it, because no one was giving me good information.”

Before treating anyone with SLIT, Dr. Schroeder tried it herself – as a La Crosse patient. Growing up with severe eczema, eye swelling, and chronic nasal congestion leading to sinus infections, “I myself was a severely allergic person,” she said. Within several months, Dr. Schroeder saw dramatic improvement in her symptoms – “a night and day difference.” She experienced some mouth tingling, one of SLIT’s most common side effects, but found it “very tolerable, very mild.”

Allergenuity Health doesn’t aim to promote SLIT as the best treatment, said Dr. Schroeder, who has helped some families use avoidance or OIT as a better option. “An initial evaluation is always about proper diagnosis and education about all the treatment options available. Really, the point is education – be a detective for them and figure out what’s going on, be honest about what we know and what we don’t know, and give them the tools to figure out how to proceed.”

A version of this article first appeared on Medscape.com. This is part two of a three-part series. Part one is here. Part three is here.

With degrees in electrical engineering and computer science from the Massachusetts Institute of Technology, Nikhila Schroeder, MD, MEng, brings a problem-solving mindset to medicine.

Being a doctor means having to “figure out all aspects of [a patient’s] situation and do my best to come up with an answer,” said Dr. Schroeder, who founded Allergenuity Health, a solo allergy practice in Huntersville, N.C., with her husband James, who serves as practice executive. It’s “being a medical detective for your patient.”

Yet, during her training, Dr. Schroeder found that market-driven health care makes it hard to practice medicine with a patient’s best interest foremost. Procedures for diagnosing and treating disease cater to insurance companies’ reimbursement policies. “You wind up having to tailor your care to whatever insurance will cover,” she said.

Insurers, in turn, look for evidence from large, peer-reviewed studies to prove that a treatment works. Many physicians hesitate to offer therapies that aren’t covered by insurance, for both liability and financial reasons. So treatment tends to be limited to those options that were rigorously vetted in long, costly, multisite trials that are difficult to conduct without a corporate sponsor.

This is why there is still only one licensed treatment for people with food allergies – a set of standardized peanut powder capsules (Palforzia) that was approved by the Food and Drug Administration in early 2020 for peanut-allergic children aged 4-17 years. A small but growing number of allergists offer unapproved oral immunotherapy (OIT) using commercial food products to treat allergies to peanuts and other foods.

Even fewer allergists treat food allergy patients with another immune-modifying treatment, sublingual immunotherapy (SLIT), which delivers allergens through liquid drops held for several minutes under the tongue. Since 2018, Allergenuity Health, which offers SLIT to treat food and environmental allergies, has provided care to more than 400 patients. More than a third have come from out of state.

The clinic uses a direct-care approach. Rather than taking insurance, the clinic offers a monthly billing program that includes tests, SLIT bottles, and access to Dr. Schroeder via phone, email, or text. “I’m only contracted with the patient, and my only focus is the patient,” Dr. Schroeder said in an interview.
 

Unforgettable day

Allergy was not on Dr. Schroeder’s radar in medical school. She wanted to be a surgeon. But she loved working with children, so she did a pediatrics residency at the University of Virginia Children’s Hospital in Charlottesville. There Dr. Schroeder started seeing kids with eczema and allergies. While covering a friend’s clinic shift in 2010, she was thrust into an emergency. A family who didn’t speak English had just brought in their screaming 6-month-old baby, red and puffy with hives. “We didn’t know what was going on with this child,” Dr. Schroeder said. “Somehow I was elected to go in there.”

All of a sudden, things got quiet. Yet the baby was still screaming, mouth wide open. Dr. Schroeder had learned about anaphylaxis but had never witnessed it – until that day. The baby›s airways swelled so much that the crying became hoarse and soft. After working with a nurse to administer epinephrine, Dr. Schroeder saw something equally unforgettable: The baby’s heart rate soared, but within minutes the hives and swelling subsided and smiles returned. “It was incredible how quickly things changed,” Dr. Schroeder said. The baby had a reaction to rice, an uncommon allergen.

Dr. Schroeder stayed at UVA 2 more years to complete an allergy and immunology fellowship. She learned to diagnose food allergies but became frustrated having to tell patients they had little recourse but to avoid the food and to check in every year or 2. “I was, like, aren’t we specialists? Shouldn’t we have a little more expertise and maybe see if there are ways we could change this?” Dr. Schroeder said.

During those years, allergy shots were the only form of immunotherapy being taught to fellows. At clinic, Dr. Schroeder served as backup to the nurses when someone reacted to shots. She was troubled that some patients needed epinephrine to stop asthma attacks caused by injections they had received as treatment. The idea of injecting substances under the skin seemed akin to vaccination – where “you want to aggravate the immune system, you want it to get revved up, you want to build it up to fight,” she said. “But that’s not what you want for allergy. You want to tone it down. It didn’t really, to be honest, make a lot of sense to me.”

Dr. Schroeder started digging and asking questions. How does the immune system decide what is safe? Which cells and molecules communicate these decisions? She thought about babies and how they “learn” by putting stuff into their mouths. “If we don’t tolerate most of what we take in there, we wouldn’t survive,” Dr. Schroeder said. “It makes a lot of sense that a lot of tolerance begins with cells of the mouth.”

Dr. Schroeder discussed these concepts with her attendings. “They were all, like, no, there’s really no good evidence for that,” she said. But at some point, someone mentioned sublingual immunotherapy, and Schroeder came across Allergy Associates of La Crosse (Wis.).

The clinic’s late founder, David Morris, MD, learned about SLIT in the 1960s as an alternative option for farmers who suffered terrible side effects from injection immunotherapy they received to treat their mold allergies. Dr. Morris attended conferences, learned more about sublingual techniques – at times seeking advice from European allergists who offered SLIT – and became board certified in allergy before opening the La Crosse clinic in 1970. According to the clinic, more than 200,000 patients with environmental and food allergies have been treated with its SLIT protocol.

Dr. Schroeder was shocked to discover that this clinic had existed for 40 years, yet “I, as an allergist, had heard nothing about them,” she said.

Toward the end of her fellowship, OIT was becoming more well known. But she felt its risks were often downplayed. After years of talking with food allergy patients, Schroeder realized that most didn’t actually care about eating peanut butter sandwiches or sesame or walnuts. “Often I would hear, through tears: ‘I just want my child to be able to sit with their friends at lunch, to not be put at this other table, to not feel so isolated,’ ” she said. What mattered most to many families was gaining enough protection to not feel anxious about participating in social activities involving food.

Dr. Schroeder had a growing sense that SLIT – given its ease, safety, and sensible route of allergen delivery – seemed more useful. She wanted to learn more.

Her mentors urged her to stay in academia instead. “They were, like, you have a good academic reputation. You’re a solid thinker. You’re great at what you do. Do the traditional stuff,” Dr. Schroeder said.

Despite these admonitions, Dr. Schroeder left academia and took a job at La Crosse after completing her allergy fellowship. Determined to see whether SLIT could be effective, “I decided in the end, you know what, I have to go do this,” she said. “I need to know, and the only way I’m going to know is to do it, because no one was giving me good information.”

Before treating anyone with SLIT, Dr. Schroeder tried it herself – as a La Crosse patient. Growing up with severe eczema, eye swelling, and chronic nasal congestion leading to sinus infections, “I myself was a severely allergic person,” she said. Within several months, Dr. Schroeder saw dramatic improvement in her symptoms – “a night and day difference.” She experienced some mouth tingling, one of SLIT’s most common side effects, but found it “very tolerable, very mild.”

Allergenuity Health doesn’t aim to promote SLIT as the best treatment, said Dr. Schroeder, who has helped some families use avoidance or OIT as a better option. “An initial evaluation is always about proper diagnosis and education about all the treatment options available. Really, the point is education – be a detective for them and figure out what’s going on, be honest about what we know and what we don’t know, and give them the tools to figure out how to proceed.”

A version of this article first appeared on Medscape.com. This is part two of a three-part series. Part one is here. Part three is here.

With degrees in electrical engineering and computer science from the Massachusetts Institute of Technology, Nikhila Schroeder, MD, MEng, brings a problem-solving mindset to medicine.

Being a doctor means having to “figure out all aspects of [a patient’s] situation and do my best to come up with an answer,” said Dr. Schroeder, who founded Allergenuity Health, a solo allergy practice in Huntersville, N.C., with her husband James, who serves as practice executive. It’s “being a medical detective for your patient.”

Yet, during her training, Dr. Schroeder found that market-driven health care makes it hard to practice medicine with a patient’s best interest foremost. Procedures for diagnosing and treating disease cater to insurance companies’ reimbursement policies. “You wind up having to tailor your care to whatever insurance will cover,” she said.

Insurers, in turn, look for evidence from large, peer-reviewed studies to prove that a treatment works. Many physicians hesitate to offer therapies that aren’t covered by insurance, for both liability and financial reasons. So treatment tends to be limited to those options that were rigorously vetted in long, costly, multisite trials that are difficult to conduct without a corporate sponsor.

This is why there is still only one licensed treatment for people with food allergies – a set of standardized peanut powder capsules (Palforzia) that was approved by the Food and Drug Administration in early 2020 for peanut-allergic children aged 4-17 years. A small but growing number of allergists offer unapproved oral immunotherapy (OIT) using commercial food products to treat allergies to peanuts and other foods.

Even fewer allergists treat food allergy patients with another immune-modifying treatment, sublingual immunotherapy (SLIT), which delivers allergens through liquid drops held for several minutes under the tongue. Since 2018, Allergenuity Health, which offers SLIT to treat food and environmental allergies, has provided care to more than 400 patients. More than a third have come from out of state.

The clinic uses a direct-care approach. Rather than taking insurance, the clinic offers a monthly billing program that includes tests, SLIT bottles, and access to Dr. Schroeder via phone, email, or text. “I’m only contracted with the patient, and my only focus is the patient,” Dr. Schroeder said in an interview.
 

Unforgettable day

Allergy was not on Dr. Schroeder’s radar in medical school. She wanted to be a surgeon. But she loved working with children, so she did a pediatrics residency at the University of Virginia Children’s Hospital in Charlottesville. There Dr. Schroeder started seeing kids with eczema and allergies. While covering a friend’s clinic shift in 2010, she was thrust into an emergency. A family who didn’t speak English had just brought in their screaming 6-month-old baby, red and puffy with hives. “We didn’t know what was going on with this child,” Dr. Schroeder said. “Somehow I was elected to go in there.”

All of a sudden, things got quiet. Yet the baby was still screaming, mouth wide open. Dr. Schroeder had learned about anaphylaxis but had never witnessed it – until that day. The baby›s airways swelled so much that the crying became hoarse and soft. After working with a nurse to administer epinephrine, Dr. Schroeder saw something equally unforgettable: The baby’s heart rate soared, but within minutes the hives and swelling subsided and smiles returned. “It was incredible how quickly things changed,” Dr. Schroeder said. The baby had a reaction to rice, an uncommon allergen.

Dr. Schroeder stayed at UVA 2 more years to complete an allergy and immunology fellowship. She learned to diagnose food allergies but became frustrated having to tell patients they had little recourse but to avoid the food and to check in every year or 2. “I was, like, aren’t we specialists? Shouldn’t we have a little more expertise and maybe see if there are ways we could change this?” Dr. Schroeder said.

During those years, allergy shots were the only form of immunotherapy being taught to fellows. At clinic, Dr. Schroeder served as backup to the nurses when someone reacted to shots. She was troubled that some patients needed epinephrine to stop asthma attacks caused by injections they had received as treatment. The idea of injecting substances under the skin seemed akin to vaccination – where “you want to aggravate the immune system, you want it to get revved up, you want to build it up to fight,” she said. “But that’s not what you want for allergy. You want to tone it down. It didn’t really, to be honest, make a lot of sense to me.”

Dr. Schroeder started digging and asking questions. How does the immune system decide what is safe? Which cells and molecules communicate these decisions? She thought about babies and how they “learn” by putting stuff into their mouths. “If we don’t tolerate most of what we take in there, we wouldn’t survive,” Dr. Schroeder said. “It makes a lot of sense that a lot of tolerance begins with cells of the mouth.”

Dr. Schroeder discussed these concepts with her attendings. “They were all, like, no, there’s really no good evidence for that,” she said. But at some point, someone mentioned sublingual immunotherapy, and Schroeder came across Allergy Associates of La Crosse (Wis.).

The clinic’s late founder, David Morris, MD, learned about SLIT in the 1960s as an alternative option for farmers who suffered terrible side effects from injection immunotherapy they received to treat their mold allergies. Dr. Morris attended conferences, learned more about sublingual techniques – at times seeking advice from European allergists who offered SLIT – and became board certified in allergy before opening the La Crosse clinic in 1970. According to the clinic, more than 200,000 patients with environmental and food allergies have been treated with its SLIT protocol.

Dr. Schroeder was shocked to discover that this clinic had existed for 40 years, yet “I, as an allergist, had heard nothing about them,” she said.

Toward the end of her fellowship, OIT was becoming more well known. But she felt its risks were often downplayed. After years of talking with food allergy patients, Schroeder realized that most didn’t actually care about eating peanut butter sandwiches or sesame or walnuts. “Often I would hear, through tears: ‘I just want my child to be able to sit with their friends at lunch, to not be put at this other table, to not feel so isolated,’ ” she said. What mattered most to many families was gaining enough protection to not feel anxious about participating in social activities involving food.

Dr. Schroeder had a growing sense that SLIT – given its ease, safety, and sensible route of allergen delivery – seemed more useful. She wanted to learn more.

Her mentors urged her to stay in academia instead. “They were, like, you have a good academic reputation. You’re a solid thinker. You’re great at what you do. Do the traditional stuff,” Dr. Schroeder said.

Despite these admonitions, Dr. Schroeder left academia and took a job at La Crosse after completing her allergy fellowship. Determined to see whether SLIT could be effective, “I decided in the end, you know what, I have to go do this,” she said. “I need to know, and the only way I’m going to know is to do it, because no one was giving me good information.”

Before treating anyone with SLIT, Dr. Schroeder tried it herself – as a La Crosse patient. Growing up with severe eczema, eye swelling, and chronic nasal congestion leading to sinus infections, “I myself was a severely allergic person,” she said. Within several months, Dr. Schroeder saw dramatic improvement in her symptoms – “a night and day difference.” She experienced some mouth tingling, one of SLIT’s most common side effects, but found it “very tolerable, very mild.”

Allergenuity Health doesn’t aim to promote SLIT as the best treatment, said Dr. Schroeder, who has helped some families use avoidance or OIT as a better option. “An initial evaluation is always about proper diagnosis and education about all the treatment options available. Really, the point is education – be a detective for them and figure out what’s going on, be honest about what we know and what we don’t know, and give them the tools to figure out how to proceed.”

A version of this article first appeared on Medscape.com. This is part two of a three-part series. Part one is here. Part three is here.