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‘Exciting’ results for cancer vaccine plus pembro in melanoma
according to the latest data from the KEYNOTE-942 trial.
This recurrence-free survival benefit corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with the immunotherapy alone.
The randomized phase 2b trial is the first to show a positive result for a cancer vaccine in a randomized trial. The results, if confirmed in further studies, hold promise for treating other solid tumors with sensitivity to the programmed death-1 (PD-1) protein, investigators said.
“KEYNOTE-942 is the first randomized study to demonstrate improvement in recurrence-free survival in melanoma, or in any cancer in my view, with an individualized neoantigen vaccine approach,” trial investigator Jeffrey S. Weber, MD, PhD, of NYU Langone Perlmutter Cancer Center in New York, said during an oral abstract session at the annual meeting of the American Association for Cancer Research.
“I have every confidence that this strategy will be expanded to other histologies that are PD-1 sensitive, such as non–small cell lung cancer, renal cell cancer, hepatocellular cancer, gastroesophageal cancer, et cetera,” Dr. Weber said.
Invited discussant Margaret Callahan, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, called the results “exciting,” especially in light of previous results in cancer vaccine trials. “Despite hundreds of formulations and dozens of studies, cancer vaccines have been disappointing so far, and have largely failed to have a meaningful impact in oncology,” she said.
A promising personalized vaccine
The mRNA vaccine is individually tailored and encodes up to 34 patient-specific tumor neoantigens. The vaccine also acts as an adjuvant to strengthen the immune response.
Dr. Weber said that the “mRNA 4157 is what one would call an individualized neoantigen therapy. It will target an individual patient’s unique tumor mutations, and the revelation over the last 5-10 years, is that, for better or worse, virtually all the neoantigens are unique to an individual patient. There are very, very few true universal neoantigens, or at least universal neoantigens that could have clinical utility.”
The vaccines are developed from tumor biopsy tissues that then undergo whole exome and RNA sequencing to identify single nucleotide variants that are present in the tumor but not in normal tissue.
The findings are then fed into a computer algorithm that identifies potential neoepitope peptides that would bind well to the patient’s human leukocyte antigen (HLA) type and could evoke strong T-cell responses.
“Once they’re chosen, you concatenate the sequences together into a single-strand mRNA vaccine, it’s packaged with nanoparticles to encapsulate it, and there you have your mRNA vaccine,” Dr. Weber explained.
In the KEYNOTE-942 trial, the investigators randomly assigned patients with completely resected high-risk cutaneous melanoma on a 2:1 basis to receive mRNA-4157 via intramuscular injection every 3 weeks for a total of nine doses, plus intravenous pembrolizumab every 3 weeks for 18 cycles (107 patients) or pembrolizumab alone (50 patients). Median follow-up was 101 weeks in the combination group and 105 weeks in the pembrolizumab group.
Overall, the 18-month recurrence-free survival rates were 78.6% in the combination arm and 62.2% in the pembrolizumab arm. The recurrence-free survival rates corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with those who received only pembrolizumab (hazard ratio [HR] for recurrence, 0.561; P =.0266).
Grade 3 or greater adverse events occurred in 25% of patients in the combination group and 18% of patients in the pembrolizumab group. The most common grade 3 event associated with the vaccine was fatigue. No grade 4 adverse events or deaths were associated with the vaccine, and the addition of the vaccine to pembrolizumab did not appear to increase risk for immune-mediated adverse events.
In a subanalysis, Dr. Weber and colleagues explored the relationship between tumor mutational burden and recurrence-free survival. Higher tumor mutational burden may mean more neoepitopes to target, which is helpful when developing personalized neoantigen vaccines, explained coinvestigator Ryan Sullivan, MD, associate director of the melanoma program at Mass General Cancer Center, Boston, who presented the subanalysis results.
The investigators performed whole exome and whole transcriptome sequencing of baseline tumor biopsy samples to determine the mutational burden of tumors and defined a high mutational burden as 10 or more mutations per megabase.
Overall, in the combination group, patients with a higher tumor mutational burden at baseline showed improved outcomes (HR, 0.652; 95% confidence interval [CI], 0.284-1.494), as did patients with a lower tumor mutational burden (HR, 0.586; 95% CI, 0.243-1.415).
The authors found the same was true for patients with high vs. low tumor inflammation scores (high: HR, 0.576; 95% CI, 0.209-1.591 vs. low: HR, 0.528; 95% CI, 0.253-1.101) and higher PD-L1 expression (PD-L1 positive: HR, 0.485; 95% CI, 0.226-1.039 vs. PD-L1 negative: HR, 0.162; 95% CI, 0.038-0.685).
The hazard ratios crossed 1, which suggest that the combination was similarly effective in all patient subsets, said Dr. Sullivan.
Dr. Callahan also highlighted that the P value was based on a one-side log-rank test, “a relatively low bar to jump over” and that there were slight imbalances in both PD-1 expression status and tumor mutational burden – both of which favored the vaccine group and may be associated with better recurrence-free survival.
The 16% difference in recurrence-free survival seen with the combination vs. pembrolizumab alone, if confirmed in further studies, “is clinically meaningful for high-risk patients,” said Dr. Callahan. “The authors are to be congratulated for presenting the first randomized study of a neoantigen vaccine with a clinical efficacy primary endpoint, and this is a trial that incorporates many of the lessons we’ve learned along the years.”
Dr. Sullivan also commented on the promising results. “The field of cancer vaccines is a wasteland of failed clinical trials after some initial promising data, so to have something like this where it does appear that this vaccine strategy works is good not only for patients with melanoma but for those people who have dedicated their lives to trying to develop cancer vaccines,” he said in an interview.
KEYNOTE-942 was funded by Moderna with collaboration from Merck. Dr. Weber has financial relationships with Merck, Moderna, and other companies. Dr. Sullivan has served as a paid consultant for Merck and has received research funding from the company. Dr. Callahan disclosed a consulting/advisory role with Moderna, Merck, and others.
A version of this article first appeared on Medscape.com.
according to the latest data from the KEYNOTE-942 trial.
This recurrence-free survival benefit corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with the immunotherapy alone.
The randomized phase 2b trial is the first to show a positive result for a cancer vaccine in a randomized trial. The results, if confirmed in further studies, hold promise for treating other solid tumors with sensitivity to the programmed death-1 (PD-1) protein, investigators said.
“KEYNOTE-942 is the first randomized study to demonstrate improvement in recurrence-free survival in melanoma, or in any cancer in my view, with an individualized neoantigen vaccine approach,” trial investigator Jeffrey S. Weber, MD, PhD, of NYU Langone Perlmutter Cancer Center in New York, said during an oral abstract session at the annual meeting of the American Association for Cancer Research.
“I have every confidence that this strategy will be expanded to other histologies that are PD-1 sensitive, such as non–small cell lung cancer, renal cell cancer, hepatocellular cancer, gastroesophageal cancer, et cetera,” Dr. Weber said.
Invited discussant Margaret Callahan, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, called the results “exciting,” especially in light of previous results in cancer vaccine trials. “Despite hundreds of formulations and dozens of studies, cancer vaccines have been disappointing so far, and have largely failed to have a meaningful impact in oncology,” she said.
A promising personalized vaccine
The mRNA vaccine is individually tailored and encodes up to 34 patient-specific tumor neoantigens. The vaccine also acts as an adjuvant to strengthen the immune response.
Dr. Weber said that the “mRNA 4157 is what one would call an individualized neoantigen therapy. It will target an individual patient’s unique tumor mutations, and the revelation over the last 5-10 years, is that, for better or worse, virtually all the neoantigens are unique to an individual patient. There are very, very few true universal neoantigens, or at least universal neoantigens that could have clinical utility.”
The vaccines are developed from tumor biopsy tissues that then undergo whole exome and RNA sequencing to identify single nucleotide variants that are present in the tumor but not in normal tissue.
The findings are then fed into a computer algorithm that identifies potential neoepitope peptides that would bind well to the patient’s human leukocyte antigen (HLA) type and could evoke strong T-cell responses.
“Once they’re chosen, you concatenate the sequences together into a single-strand mRNA vaccine, it’s packaged with nanoparticles to encapsulate it, and there you have your mRNA vaccine,” Dr. Weber explained.
In the KEYNOTE-942 trial, the investigators randomly assigned patients with completely resected high-risk cutaneous melanoma on a 2:1 basis to receive mRNA-4157 via intramuscular injection every 3 weeks for a total of nine doses, plus intravenous pembrolizumab every 3 weeks for 18 cycles (107 patients) or pembrolizumab alone (50 patients). Median follow-up was 101 weeks in the combination group and 105 weeks in the pembrolizumab group.
Overall, the 18-month recurrence-free survival rates were 78.6% in the combination arm and 62.2% in the pembrolizumab arm. The recurrence-free survival rates corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with those who received only pembrolizumab (hazard ratio [HR] for recurrence, 0.561; P =.0266).
Grade 3 or greater adverse events occurred in 25% of patients in the combination group and 18% of patients in the pembrolizumab group. The most common grade 3 event associated with the vaccine was fatigue. No grade 4 adverse events or deaths were associated with the vaccine, and the addition of the vaccine to pembrolizumab did not appear to increase risk for immune-mediated adverse events.
In a subanalysis, Dr. Weber and colleagues explored the relationship between tumor mutational burden and recurrence-free survival. Higher tumor mutational burden may mean more neoepitopes to target, which is helpful when developing personalized neoantigen vaccines, explained coinvestigator Ryan Sullivan, MD, associate director of the melanoma program at Mass General Cancer Center, Boston, who presented the subanalysis results.
The investigators performed whole exome and whole transcriptome sequencing of baseline tumor biopsy samples to determine the mutational burden of tumors and defined a high mutational burden as 10 or more mutations per megabase.
Overall, in the combination group, patients with a higher tumor mutational burden at baseline showed improved outcomes (HR, 0.652; 95% confidence interval [CI], 0.284-1.494), as did patients with a lower tumor mutational burden (HR, 0.586; 95% CI, 0.243-1.415).
The authors found the same was true for patients with high vs. low tumor inflammation scores (high: HR, 0.576; 95% CI, 0.209-1.591 vs. low: HR, 0.528; 95% CI, 0.253-1.101) and higher PD-L1 expression (PD-L1 positive: HR, 0.485; 95% CI, 0.226-1.039 vs. PD-L1 negative: HR, 0.162; 95% CI, 0.038-0.685).
The hazard ratios crossed 1, which suggest that the combination was similarly effective in all patient subsets, said Dr. Sullivan.
Dr. Callahan also highlighted that the P value was based on a one-side log-rank test, “a relatively low bar to jump over” and that there were slight imbalances in both PD-1 expression status and tumor mutational burden – both of which favored the vaccine group and may be associated with better recurrence-free survival.
The 16% difference in recurrence-free survival seen with the combination vs. pembrolizumab alone, if confirmed in further studies, “is clinically meaningful for high-risk patients,” said Dr. Callahan. “The authors are to be congratulated for presenting the first randomized study of a neoantigen vaccine with a clinical efficacy primary endpoint, and this is a trial that incorporates many of the lessons we’ve learned along the years.”
Dr. Sullivan also commented on the promising results. “The field of cancer vaccines is a wasteland of failed clinical trials after some initial promising data, so to have something like this where it does appear that this vaccine strategy works is good not only for patients with melanoma but for those people who have dedicated their lives to trying to develop cancer vaccines,” he said in an interview.
KEYNOTE-942 was funded by Moderna with collaboration from Merck. Dr. Weber has financial relationships with Merck, Moderna, and other companies. Dr. Sullivan has served as a paid consultant for Merck and has received research funding from the company. Dr. Callahan disclosed a consulting/advisory role with Moderna, Merck, and others.
A version of this article first appeared on Medscape.com.
according to the latest data from the KEYNOTE-942 trial.
This recurrence-free survival benefit corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with the immunotherapy alone.
The randomized phase 2b trial is the first to show a positive result for a cancer vaccine in a randomized trial. The results, if confirmed in further studies, hold promise for treating other solid tumors with sensitivity to the programmed death-1 (PD-1) protein, investigators said.
“KEYNOTE-942 is the first randomized study to demonstrate improvement in recurrence-free survival in melanoma, or in any cancer in my view, with an individualized neoantigen vaccine approach,” trial investigator Jeffrey S. Weber, MD, PhD, of NYU Langone Perlmutter Cancer Center in New York, said during an oral abstract session at the annual meeting of the American Association for Cancer Research.
“I have every confidence that this strategy will be expanded to other histologies that are PD-1 sensitive, such as non–small cell lung cancer, renal cell cancer, hepatocellular cancer, gastroesophageal cancer, et cetera,” Dr. Weber said.
Invited discussant Margaret Callahan, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, called the results “exciting,” especially in light of previous results in cancer vaccine trials. “Despite hundreds of formulations and dozens of studies, cancer vaccines have been disappointing so far, and have largely failed to have a meaningful impact in oncology,” she said.
A promising personalized vaccine
The mRNA vaccine is individually tailored and encodes up to 34 patient-specific tumor neoantigens. The vaccine also acts as an adjuvant to strengthen the immune response.
Dr. Weber said that the “mRNA 4157 is what one would call an individualized neoantigen therapy. It will target an individual patient’s unique tumor mutations, and the revelation over the last 5-10 years, is that, for better or worse, virtually all the neoantigens are unique to an individual patient. There are very, very few true universal neoantigens, or at least universal neoantigens that could have clinical utility.”
The vaccines are developed from tumor biopsy tissues that then undergo whole exome and RNA sequencing to identify single nucleotide variants that are present in the tumor but not in normal tissue.
The findings are then fed into a computer algorithm that identifies potential neoepitope peptides that would bind well to the patient’s human leukocyte antigen (HLA) type and could evoke strong T-cell responses.
“Once they’re chosen, you concatenate the sequences together into a single-strand mRNA vaccine, it’s packaged with nanoparticles to encapsulate it, and there you have your mRNA vaccine,” Dr. Weber explained.
In the KEYNOTE-942 trial, the investigators randomly assigned patients with completely resected high-risk cutaneous melanoma on a 2:1 basis to receive mRNA-4157 via intramuscular injection every 3 weeks for a total of nine doses, plus intravenous pembrolizumab every 3 weeks for 18 cycles (107 patients) or pembrolizumab alone (50 patients). Median follow-up was 101 weeks in the combination group and 105 weeks in the pembrolizumab group.
Overall, the 18-month recurrence-free survival rates were 78.6% in the combination arm and 62.2% in the pembrolizumab arm. The recurrence-free survival rates corresponded to a 44% reduced risk of recurrence or death in patients who received the personalized vaccine plus pembrolizumab compared with those who received only pembrolizumab (hazard ratio [HR] for recurrence, 0.561; P =.0266).
Grade 3 or greater adverse events occurred in 25% of patients in the combination group and 18% of patients in the pembrolizumab group. The most common grade 3 event associated with the vaccine was fatigue. No grade 4 adverse events or deaths were associated with the vaccine, and the addition of the vaccine to pembrolizumab did not appear to increase risk for immune-mediated adverse events.
In a subanalysis, Dr. Weber and colleagues explored the relationship between tumor mutational burden and recurrence-free survival. Higher tumor mutational burden may mean more neoepitopes to target, which is helpful when developing personalized neoantigen vaccines, explained coinvestigator Ryan Sullivan, MD, associate director of the melanoma program at Mass General Cancer Center, Boston, who presented the subanalysis results.
The investigators performed whole exome and whole transcriptome sequencing of baseline tumor biopsy samples to determine the mutational burden of tumors and defined a high mutational burden as 10 or more mutations per megabase.
Overall, in the combination group, patients with a higher tumor mutational burden at baseline showed improved outcomes (HR, 0.652; 95% confidence interval [CI], 0.284-1.494), as did patients with a lower tumor mutational burden (HR, 0.586; 95% CI, 0.243-1.415).
The authors found the same was true for patients with high vs. low tumor inflammation scores (high: HR, 0.576; 95% CI, 0.209-1.591 vs. low: HR, 0.528; 95% CI, 0.253-1.101) and higher PD-L1 expression (PD-L1 positive: HR, 0.485; 95% CI, 0.226-1.039 vs. PD-L1 negative: HR, 0.162; 95% CI, 0.038-0.685).
The hazard ratios crossed 1, which suggest that the combination was similarly effective in all patient subsets, said Dr. Sullivan.
Dr. Callahan also highlighted that the P value was based on a one-side log-rank test, “a relatively low bar to jump over” and that there were slight imbalances in both PD-1 expression status and tumor mutational burden – both of which favored the vaccine group and may be associated with better recurrence-free survival.
The 16% difference in recurrence-free survival seen with the combination vs. pembrolizumab alone, if confirmed in further studies, “is clinically meaningful for high-risk patients,” said Dr. Callahan. “The authors are to be congratulated for presenting the first randomized study of a neoantigen vaccine with a clinical efficacy primary endpoint, and this is a trial that incorporates many of the lessons we’ve learned along the years.”
Dr. Sullivan also commented on the promising results. “The field of cancer vaccines is a wasteland of failed clinical trials after some initial promising data, so to have something like this where it does appear that this vaccine strategy works is good not only for patients with melanoma but for those people who have dedicated their lives to trying to develop cancer vaccines,” he said in an interview.
KEYNOTE-942 was funded by Moderna with collaboration from Merck. Dr. Weber has financial relationships with Merck, Moderna, and other companies. Dr. Sullivan has served as a paid consultant for Merck and has received research funding from the company. Dr. Callahan disclosed a consulting/advisory role with Moderna, Merck, and others.
A version of this article first appeared on Medscape.com.
FROM AACR 2023
CDC backs FDA’s call for second COVID booster for those at high risk
This backs the Food and Drug Administration’s authorization April 18 of the additional shot.
“Following FDA regulatory action, CDC has taken steps to simplify COVID-19 vaccine recommendations and allow more flexibility for people at higher risk who want the option of added protection from additional COVID-19 vaccine doses,” the CDC said in a statement.
The agency is following the recommendations made by its Advisory Committee on Immunization Practices (ACIP). While there was no vote, the group reaffirmed its commitment to boosters overall, proposing that all Americans over age 6 who have not had a bivalent mRNA COVID-19 booster vaccine go ahead and get one.
But most others who’ve already had the bivalent shot – which targets the original COVID strain and the two Omicron variants BA.4 and BA.5 – should wait until the fall to get whatever updated vaccine is available.
The panel did carve out exceptions for people over age 65 and those who are immunocompromised because they are at higher risk for severe COVID-19 complications, Evelyn Twentyman, MD, MPH, the lead official in the CDC’s COVID-19 Vaccine Policy Unit, said during the meeting.
People over 65 can now choose to get a second bivalent mRNA booster shot as long as it has been at least 4 months since the last one, she said, and people who are immunocompromised also should have the flexibility to receive one or more additional bivalent boosters at least 2 months after an initial dose.
Regardless of whether someone is unvaccinated, and regardless of how many single-strain COVID vaccines an individual has previously received, they should get a mRNA bivalent shot, Dr. Twentyman said.
If an individual has already received a bivalent mRNA booster – made by either Pfizer/BioNTech or Moderna – “your vaccination is complete,” she said. “No doses indicated at this time, come back and see us in autumn of 2023.”
The CDC is trying to encourage more people to get the updated COVID shot, as just 17% of Americans of any age have received a bivalent booster and only 43% of those age 65 and over.
The CDC followed the FDA’s lead in its statement, phasing out the original single-strain COVID vaccine, saying it will no longer be recommended for use in the United States.
‘Unnecessary drama’ over children’s recs
The CDC panel mostly followed the FDA’s guidance on who should get a booster, but many ACIP members expressed consternation and confusion about what was being recommended for children.
For children aged 6 months to 4 years, the CDC will offer tables to help physicians determine how many bivalent doses to give, depending on the child’s vaccination history.
All children those ages should get at least two vaccine doses, one of which is bivalent, Dr. Twentyman said. For children in that age group who have already received a monovalent series and a bivalent dose, “their vaccination is complete,” she said.
For 5-year-olds, the recommendations will be similar if they received a Pfizer monovalent series, but the shot regimen will have to be customized if they had previously received a Moderna shot, because of differences in the dosages.
ACIP member Sarah S. Long, MD, professor of pediatrics, Drexel University, Philadelphia, said that it was unclear why a set age couldn’t be established for COVID-19 vaccination as it had been for other immunizations.
“We picked 60 months for most immunizations in children,” Dr. Long said. “Immunologically there is not a difference between a 4-, a 5- and a 6-year-old.
“There isn’t a reason to have all this unnecessary drama around those ages,” she said, adding that having the different ages would make it harder for pediatricians to appropriately stock vaccines.
Dr. Twentyman said that the CDC would be providing more detailed guidance on its COVID-19 website soon and would be holding a call with health care professionals to discuss the updated recommendations on May 11.
New vaccine by fall
CDC and ACIP members both said they hoped to have an even simpler vaccine schedule by the fall, when it is anticipated that the FDA may have authorized a new, updated bivalent vaccine that targets other COVID variants.
“We all recognize this is a work in progress,” said ACIP Chair Grace M. Lee, MD, MPH, acknowledging that there is continued confusion over COVID-19 vaccination.
“The goal really is to try to simplify things over time to be able to help communicate with our provider community, and our patients and families what vaccine is right for them, when do they need it, and how often should they get it,” said Dr. Lee, professor of pediatrics, Stanford (Calif.) University.
A version of this article originally appeared on Medscape.com .
This backs the Food and Drug Administration’s authorization April 18 of the additional shot.
“Following FDA regulatory action, CDC has taken steps to simplify COVID-19 vaccine recommendations and allow more flexibility for people at higher risk who want the option of added protection from additional COVID-19 vaccine doses,” the CDC said in a statement.
The agency is following the recommendations made by its Advisory Committee on Immunization Practices (ACIP). While there was no vote, the group reaffirmed its commitment to boosters overall, proposing that all Americans over age 6 who have not had a bivalent mRNA COVID-19 booster vaccine go ahead and get one.
But most others who’ve already had the bivalent shot – which targets the original COVID strain and the two Omicron variants BA.4 and BA.5 – should wait until the fall to get whatever updated vaccine is available.
The panel did carve out exceptions for people over age 65 and those who are immunocompromised because they are at higher risk for severe COVID-19 complications, Evelyn Twentyman, MD, MPH, the lead official in the CDC’s COVID-19 Vaccine Policy Unit, said during the meeting.
People over 65 can now choose to get a second bivalent mRNA booster shot as long as it has been at least 4 months since the last one, she said, and people who are immunocompromised also should have the flexibility to receive one or more additional bivalent boosters at least 2 months after an initial dose.
Regardless of whether someone is unvaccinated, and regardless of how many single-strain COVID vaccines an individual has previously received, they should get a mRNA bivalent shot, Dr. Twentyman said.
If an individual has already received a bivalent mRNA booster – made by either Pfizer/BioNTech or Moderna – “your vaccination is complete,” she said. “No doses indicated at this time, come back and see us in autumn of 2023.”
The CDC is trying to encourage more people to get the updated COVID shot, as just 17% of Americans of any age have received a bivalent booster and only 43% of those age 65 and over.
The CDC followed the FDA’s lead in its statement, phasing out the original single-strain COVID vaccine, saying it will no longer be recommended for use in the United States.
‘Unnecessary drama’ over children’s recs
The CDC panel mostly followed the FDA’s guidance on who should get a booster, but many ACIP members expressed consternation and confusion about what was being recommended for children.
For children aged 6 months to 4 years, the CDC will offer tables to help physicians determine how many bivalent doses to give, depending on the child’s vaccination history.
All children those ages should get at least two vaccine doses, one of which is bivalent, Dr. Twentyman said. For children in that age group who have already received a monovalent series and a bivalent dose, “their vaccination is complete,” she said.
For 5-year-olds, the recommendations will be similar if they received a Pfizer monovalent series, but the shot regimen will have to be customized if they had previously received a Moderna shot, because of differences in the dosages.
ACIP member Sarah S. Long, MD, professor of pediatrics, Drexel University, Philadelphia, said that it was unclear why a set age couldn’t be established for COVID-19 vaccination as it had been for other immunizations.
“We picked 60 months for most immunizations in children,” Dr. Long said. “Immunologically there is not a difference between a 4-, a 5- and a 6-year-old.
“There isn’t a reason to have all this unnecessary drama around those ages,” she said, adding that having the different ages would make it harder for pediatricians to appropriately stock vaccines.
Dr. Twentyman said that the CDC would be providing more detailed guidance on its COVID-19 website soon and would be holding a call with health care professionals to discuss the updated recommendations on May 11.
New vaccine by fall
CDC and ACIP members both said they hoped to have an even simpler vaccine schedule by the fall, when it is anticipated that the FDA may have authorized a new, updated bivalent vaccine that targets other COVID variants.
“We all recognize this is a work in progress,” said ACIP Chair Grace M. Lee, MD, MPH, acknowledging that there is continued confusion over COVID-19 vaccination.
“The goal really is to try to simplify things over time to be able to help communicate with our provider community, and our patients and families what vaccine is right for them, when do they need it, and how often should they get it,” said Dr. Lee, professor of pediatrics, Stanford (Calif.) University.
A version of this article originally appeared on Medscape.com .
This backs the Food and Drug Administration’s authorization April 18 of the additional shot.
“Following FDA regulatory action, CDC has taken steps to simplify COVID-19 vaccine recommendations and allow more flexibility for people at higher risk who want the option of added protection from additional COVID-19 vaccine doses,” the CDC said in a statement.
The agency is following the recommendations made by its Advisory Committee on Immunization Practices (ACIP). While there was no vote, the group reaffirmed its commitment to boosters overall, proposing that all Americans over age 6 who have not had a bivalent mRNA COVID-19 booster vaccine go ahead and get one.
But most others who’ve already had the bivalent shot – which targets the original COVID strain and the two Omicron variants BA.4 and BA.5 – should wait until the fall to get whatever updated vaccine is available.
The panel did carve out exceptions for people over age 65 and those who are immunocompromised because they are at higher risk for severe COVID-19 complications, Evelyn Twentyman, MD, MPH, the lead official in the CDC’s COVID-19 Vaccine Policy Unit, said during the meeting.
People over 65 can now choose to get a second bivalent mRNA booster shot as long as it has been at least 4 months since the last one, she said, and people who are immunocompromised also should have the flexibility to receive one or more additional bivalent boosters at least 2 months after an initial dose.
Regardless of whether someone is unvaccinated, and regardless of how many single-strain COVID vaccines an individual has previously received, they should get a mRNA bivalent shot, Dr. Twentyman said.
If an individual has already received a bivalent mRNA booster – made by either Pfizer/BioNTech or Moderna – “your vaccination is complete,” she said. “No doses indicated at this time, come back and see us in autumn of 2023.”
The CDC is trying to encourage more people to get the updated COVID shot, as just 17% of Americans of any age have received a bivalent booster and only 43% of those age 65 and over.
The CDC followed the FDA’s lead in its statement, phasing out the original single-strain COVID vaccine, saying it will no longer be recommended for use in the United States.
‘Unnecessary drama’ over children’s recs
The CDC panel mostly followed the FDA’s guidance on who should get a booster, but many ACIP members expressed consternation and confusion about what was being recommended for children.
For children aged 6 months to 4 years, the CDC will offer tables to help physicians determine how many bivalent doses to give, depending on the child’s vaccination history.
All children those ages should get at least two vaccine doses, one of which is bivalent, Dr. Twentyman said. For children in that age group who have already received a monovalent series and a bivalent dose, “their vaccination is complete,” she said.
For 5-year-olds, the recommendations will be similar if they received a Pfizer monovalent series, but the shot regimen will have to be customized if they had previously received a Moderna shot, because of differences in the dosages.
ACIP member Sarah S. Long, MD, professor of pediatrics, Drexel University, Philadelphia, said that it was unclear why a set age couldn’t be established for COVID-19 vaccination as it had been for other immunizations.
“We picked 60 months for most immunizations in children,” Dr. Long said. “Immunologically there is not a difference between a 4-, a 5- and a 6-year-old.
“There isn’t a reason to have all this unnecessary drama around those ages,” she said, adding that having the different ages would make it harder for pediatricians to appropriately stock vaccines.
Dr. Twentyman said that the CDC would be providing more detailed guidance on its COVID-19 website soon and would be holding a call with health care professionals to discuss the updated recommendations on May 11.
New vaccine by fall
CDC and ACIP members both said they hoped to have an even simpler vaccine schedule by the fall, when it is anticipated that the FDA may have authorized a new, updated bivalent vaccine that targets other COVID variants.
“We all recognize this is a work in progress,” said ACIP Chair Grace M. Lee, MD, MPH, acknowledging that there is continued confusion over COVID-19 vaccination.
“The goal really is to try to simplify things over time to be able to help communicate with our provider community, and our patients and families what vaccine is right for them, when do they need it, and how often should they get it,” said Dr. Lee, professor of pediatrics, Stanford (Calif.) University.
A version of this article originally appeared on Medscape.com .
Cancer, heart disease vaccines may be ready by 2030, Moderna says
The announcement is yet another sign of what many are calling “the golden age” of vaccine development, which is largely credited to the pandemic’s use of mRNA technology to create COVID-19 vaccines.
“I think what we have learned in recent months is that if you ever thought that mRNA was just for infectious diseases, or just for COVID, the evidence now is that that’s absolutely not the case,” Moderna Chief Medical Officer Paul Burton, MD, PhD, told The Guardian. “It can be applied to all sorts of disease areas; we are in cancer, infectious disease, cardiovascular disease, autoimmune diseases, rare disease. We have studies in all of those areas, and they have all shown tremendous promise.”
The U.S. Food and Drug Administration recently designated two new Moderna vaccines as breakthrough therapies: a shot that prevents respiratory syncytial virus (RSV) in older people and a shot that helps prevent the recurrence of melanoma. The FDA’s breakthrough designation is given when a new treatment’s early trial results are substantially better than an existing therapy.
The mRNA vaccine technology that made headlines for its role in COVID-19 vaccines works by teaching the body how to make a specific protein to help the immune system prevent or target a certain disease.
Dr. Burton anticipates that mRNA technology will result in breakthroughs such as a cancer vaccine that can be personalized based on the features of a specific tumor.
“I think we will have mRNA-based therapies for rare diseases that were previously undruggable, and I think that 10 years from now, we will be approaching a world where you truly can identify the genetic cause of a disease and, with relative simplicity, go and edit that out and repair it using mRNA-based technology,” he said.
The Moderna executive made the statements before its annual update on its vaccine pipeline projects, which the company calls “Vaccines Day.” The Massachusetts-based drugmaker said it has given someone the first dose of a “next-generation” COVID-19 vaccine in a phase III trial, has made progress on a Lyme disease shot, and is developing a vaccine for the highly contagious norovirus.
In all, Moderna expects “six major vaccine product launches in the next few years,” the company said in a statement, adding that it expects the COVID-19 booster market alone to be valued at $15 billion.
A version of this article first appeared on WebMD.com.
The announcement is yet another sign of what many are calling “the golden age” of vaccine development, which is largely credited to the pandemic’s use of mRNA technology to create COVID-19 vaccines.
“I think what we have learned in recent months is that if you ever thought that mRNA was just for infectious diseases, or just for COVID, the evidence now is that that’s absolutely not the case,” Moderna Chief Medical Officer Paul Burton, MD, PhD, told The Guardian. “It can be applied to all sorts of disease areas; we are in cancer, infectious disease, cardiovascular disease, autoimmune diseases, rare disease. We have studies in all of those areas, and they have all shown tremendous promise.”
The U.S. Food and Drug Administration recently designated two new Moderna vaccines as breakthrough therapies: a shot that prevents respiratory syncytial virus (RSV) in older people and a shot that helps prevent the recurrence of melanoma. The FDA’s breakthrough designation is given when a new treatment’s early trial results are substantially better than an existing therapy.
The mRNA vaccine technology that made headlines for its role in COVID-19 vaccines works by teaching the body how to make a specific protein to help the immune system prevent or target a certain disease.
Dr. Burton anticipates that mRNA technology will result in breakthroughs such as a cancer vaccine that can be personalized based on the features of a specific tumor.
“I think we will have mRNA-based therapies for rare diseases that were previously undruggable, and I think that 10 years from now, we will be approaching a world where you truly can identify the genetic cause of a disease and, with relative simplicity, go and edit that out and repair it using mRNA-based technology,” he said.
The Moderna executive made the statements before its annual update on its vaccine pipeline projects, which the company calls “Vaccines Day.” The Massachusetts-based drugmaker said it has given someone the first dose of a “next-generation” COVID-19 vaccine in a phase III trial, has made progress on a Lyme disease shot, and is developing a vaccine for the highly contagious norovirus.
In all, Moderna expects “six major vaccine product launches in the next few years,” the company said in a statement, adding that it expects the COVID-19 booster market alone to be valued at $15 billion.
A version of this article first appeared on WebMD.com.
The announcement is yet another sign of what many are calling “the golden age” of vaccine development, which is largely credited to the pandemic’s use of mRNA technology to create COVID-19 vaccines.
“I think what we have learned in recent months is that if you ever thought that mRNA was just for infectious diseases, or just for COVID, the evidence now is that that’s absolutely not the case,” Moderna Chief Medical Officer Paul Burton, MD, PhD, told The Guardian. “It can be applied to all sorts of disease areas; we are in cancer, infectious disease, cardiovascular disease, autoimmune diseases, rare disease. We have studies in all of those areas, and they have all shown tremendous promise.”
The U.S. Food and Drug Administration recently designated two new Moderna vaccines as breakthrough therapies: a shot that prevents respiratory syncytial virus (RSV) in older people and a shot that helps prevent the recurrence of melanoma. The FDA’s breakthrough designation is given when a new treatment’s early trial results are substantially better than an existing therapy.
The mRNA vaccine technology that made headlines for its role in COVID-19 vaccines works by teaching the body how to make a specific protein to help the immune system prevent or target a certain disease.
Dr. Burton anticipates that mRNA technology will result in breakthroughs such as a cancer vaccine that can be personalized based on the features of a specific tumor.
“I think we will have mRNA-based therapies for rare diseases that were previously undruggable, and I think that 10 years from now, we will be approaching a world where you truly can identify the genetic cause of a disease and, with relative simplicity, go and edit that out and repair it using mRNA-based technology,” he said.
The Moderna executive made the statements before its annual update on its vaccine pipeline projects, which the company calls “Vaccines Day.” The Massachusetts-based drugmaker said it has given someone the first dose of a “next-generation” COVID-19 vaccine in a phase III trial, has made progress on a Lyme disease shot, and is developing a vaccine for the highly contagious norovirus.
In all, Moderna expects “six major vaccine product launches in the next few years,” the company said in a statement, adding that it expects the COVID-19 booster market alone to be valued at $15 billion.
A version of this article first appeared on WebMD.com.
Parents of patients with rheumatic disease, MIS-C strongly hesitant of COVID vaccination
NEW ORLEANS – Parents’ concerns about vaccinating their children against COVID-19 remain a substantial barrier to immunizing children against the disease, whether those children have chronic rheumatologic conditions or a history of multisystem inflammatory syndrome in children (MIS-C), according to two studies presented at the Pediatric Rheumatology Symposium.
Parents of children who developed MIS-C after a SARS-CoV-2 infection were particularly hesitant to vaccinate, despite strong encouragement from health care professionals at Baylor College of Medicine, Houston, said the presenter of one of the studies.
“Unfortunately, it remains unclear who is susceptible and what the mechanisms are” when it comes to MIS-C, Mariana Sanchez Villa, MS, a research coordinator at Baylor, told attendees. “Because of this, there is much hesitancy to vaccinate children with a history of MIS-C against COVID-19 out of a fear that hyperinflammation may occur.”
Ms. Sanchez Villa reported findings on the vaccination rate among patients who had been hospitalized with MIS-C. The researchers included all 295 patients who presented at the hospital with MIS-C between May 2020 and October 2022. Overall, 5% of these patients had been vaccinated against COVID-19 before they were diagnosed with MIS-C. When all these patients and their families came to outpatient follow-up appointments after discharge, the subspecialist clinicians recommended the children receive the COVID-19 vaccine 3 months after discharge. The researchers then reviewed the patients’ charts to see who did and did not receive the vaccine, which they confirmed through the state’s immunization registry.
Among the 295 patients with MIS-C, 1 died, and 99 (34%) received at least one COVID-19 vaccine dose after their diagnosis, including 7 of the 15 who had also been vaccinated prior to their MIS-C diagnosis. Just over half of the vaccinated patients (58%) were male. They received their vaccine an average 8.8 months after their hospitalization, when they were an average 10 years old, and all but one of the vaccine doses they received were the Pfizer/BioNTech mRNA vaccine.
Only 9 of the 99 vaccinated patients are fully vaccinated, defined as receiving the primary series plus the recommended boosters. Of the other patients, 13 received only one dose of the vaccine, 60 received two doses, and 17 received at least three doses of the primary series doses but no bivalent boosters. Over a subsequent average 11 months of follow-up, none of the vaccinated patients returned to the hospital with a recurrence of MIS-C or any other hyperinflammatory condition. The seven patients who had been vaccinated both before and after their MIS-C diagnosis have also not had any recurrence of a hyperinflammatory condition.
“SARS-CoV-2 vaccination is well-tolerated by children with a history of MIS-C,” the researchers concluded. Ms. Sanchez Villa referenced two other studies, in The Pediatric Infectious Disease Journal and in JAMA Network Open, with similar findings on the safety of COVID-19 vaccination in patients who have had MIS-C. “This is reassuring as SARS-CoV-2 becomes endemic and annual vaccination against SARS-CoV-2 is considered.”
Dilan Dissanayake, MD, PhD, a rheumatologist at The Hospital for Sick Children in Toronto, who attended the presentation, told this news organization that data increasingly show a “synergistic protective effect” from COVID-19 infection and vaccination. That is, “having COVID or having MIS-C once doesn’t necessarily preclude you from having it again,” thereby supporting the importance of vaccination after an MIS-C diagnosis. In talking to parents about vaccinating, he has found it most helpful for them to hear about rheumatologists’ experience regarding COVID-19 vaccination.
“Particularly as the pandemic went on, being able to comfortably say that we have this large patient group, as well as collaborators across the world who have been monitoring for any safety issues, and that all the data has been reassuring” has been most useful for parents to hear, Dr. Dissanayake said.
The other study, led by Beth Rutstein, MD, MSCE, an attending rheumatologist at Children’s Hospital of Philadelphia, focused on the population of pediatric rheumatology patients by surveying pediatric rheumatologists who were members of the Childhood Arthritis and Rheumatology Research Alliance. The survey, conducted from March to May 2022, included questions about the rheumatologists’ COVID-19 vaccination practices as well as perceptions of the vaccine by the parents of their patients.
The 219 respondents included 74% pediatric rheumatologists and 21% fellows. Nearly all the respondents (98%) believed that any disease flares after COVID-19 vaccination would be mild and/or rare, and nearly all (98%) recommend their patients be vaccinated against COVID-19.
The primary finding from the study was that “we [rheumatologists] have different concerns from the families,” coauthor and presenter Vidya Sivaraman, MD, a pediatric rheumatologist at Nationwide Children’s Hospital and the Ohio State University in Columbus, told this news organization. “We’re more worried about the efficacy of the vaccine on immunosuppressive medications,” such as rituximab, which depletes B cells, Dr. Sivaraman said, but concerns about the vaccine’s immunogenicity or efficacy were very low among parents.
Just over half the clinicians surveyed (59%) were concerned about how effective the vaccine would be for their patients, especially those receiving immunosuppressive therapy. Health care professionals were most concerned about patients on rituximab – all clinicians reported concerns about the vaccine’s effectiveness in these patients – followed by patients taking systemic corticosteroids (86%), mycophenolate mofetil (59%), and Janus kinase inhibitors (46%).
Most clinicians (88%) reported that they had temporarily modified a patient’s immunosuppressive therapy to allow for vaccination, following guidelines by the American College of Rheumatology. Aside from a small proportion of health care professionals who checked patients’ post-vaccination serology primarily for research purposes, most clinicians (82%) did not collect this serology.
In regard to adverse events, the concern cited most often by respondents was myocarditis (76%), followed by development of new autoimmune conditions (29%) and thrombosis (22%), but the clinicians ranked these adverse events as low risk.
Meanwhile, the top three concerns about vaccination among parents, as reported to physicians, were worries about side effects, lack of long-term safety data on the vaccine, and misinformation they had heard, such as anxiety about changes to their child’s genetics or vaccination causing a COVID-19 infection. “They’re seeing things on social media from other parents [saying that COVID-19 vaccines are] going to affect their fertility, so they don’t want their daughters to get it,” Dr. Sivaraman said as another example of commonly cited misinformation.
Nearly half of the respondents (47%) said more than half of their families had concerns about side effects and the lack of data on long-term outcomes after vaccination. Only 8.5% of physicians said that fewer than 10% of their families were anxious about side effects. In addition, 39% of physicians said more than half of their families had concerns about misinformation they had heard, and only 16% of physicians had heard about misinformation concerns from fewer than 10% of their patients.
Other concerns cited by parents included their child’s disease flaring; lack of data on how well the vaccine would stimulate their child’s immune system; their child having already had COVID-19; and not believing COVID-19 was a major health risk to their child. Nearly every respondent (98%) said they had parents who turned down COVID-19 vaccination, and a majority (75%) reported that more than 10% of their patients had parents who were hesitant about COVID-19 vaccination.
No external funding was noted for either study. Ms. Sanchez Villa had no relevant financial relationships, but two abstract coauthors reported financial relationships with Pfizer and Moderna, and one reported a financial relationship with Novartis. Dr. Rutstein, Dr. Sivaraman, and Dr. Dissanayake had no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – Parents’ concerns about vaccinating their children against COVID-19 remain a substantial barrier to immunizing children against the disease, whether those children have chronic rheumatologic conditions or a history of multisystem inflammatory syndrome in children (MIS-C), according to two studies presented at the Pediatric Rheumatology Symposium.
Parents of children who developed MIS-C after a SARS-CoV-2 infection were particularly hesitant to vaccinate, despite strong encouragement from health care professionals at Baylor College of Medicine, Houston, said the presenter of one of the studies.
“Unfortunately, it remains unclear who is susceptible and what the mechanisms are” when it comes to MIS-C, Mariana Sanchez Villa, MS, a research coordinator at Baylor, told attendees. “Because of this, there is much hesitancy to vaccinate children with a history of MIS-C against COVID-19 out of a fear that hyperinflammation may occur.”
Ms. Sanchez Villa reported findings on the vaccination rate among patients who had been hospitalized with MIS-C. The researchers included all 295 patients who presented at the hospital with MIS-C between May 2020 and October 2022. Overall, 5% of these patients had been vaccinated against COVID-19 before they were diagnosed with MIS-C. When all these patients and their families came to outpatient follow-up appointments after discharge, the subspecialist clinicians recommended the children receive the COVID-19 vaccine 3 months after discharge. The researchers then reviewed the patients’ charts to see who did and did not receive the vaccine, which they confirmed through the state’s immunization registry.
Among the 295 patients with MIS-C, 1 died, and 99 (34%) received at least one COVID-19 vaccine dose after their diagnosis, including 7 of the 15 who had also been vaccinated prior to their MIS-C diagnosis. Just over half of the vaccinated patients (58%) were male. They received their vaccine an average 8.8 months after their hospitalization, when they were an average 10 years old, and all but one of the vaccine doses they received were the Pfizer/BioNTech mRNA vaccine.
Only 9 of the 99 vaccinated patients are fully vaccinated, defined as receiving the primary series plus the recommended boosters. Of the other patients, 13 received only one dose of the vaccine, 60 received two doses, and 17 received at least three doses of the primary series doses but no bivalent boosters. Over a subsequent average 11 months of follow-up, none of the vaccinated patients returned to the hospital with a recurrence of MIS-C or any other hyperinflammatory condition. The seven patients who had been vaccinated both before and after their MIS-C diagnosis have also not had any recurrence of a hyperinflammatory condition.
“SARS-CoV-2 vaccination is well-tolerated by children with a history of MIS-C,” the researchers concluded. Ms. Sanchez Villa referenced two other studies, in The Pediatric Infectious Disease Journal and in JAMA Network Open, with similar findings on the safety of COVID-19 vaccination in patients who have had MIS-C. “This is reassuring as SARS-CoV-2 becomes endemic and annual vaccination against SARS-CoV-2 is considered.”
Dilan Dissanayake, MD, PhD, a rheumatologist at The Hospital for Sick Children in Toronto, who attended the presentation, told this news organization that data increasingly show a “synergistic protective effect” from COVID-19 infection and vaccination. That is, “having COVID or having MIS-C once doesn’t necessarily preclude you from having it again,” thereby supporting the importance of vaccination after an MIS-C diagnosis. In talking to parents about vaccinating, he has found it most helpful for them to hear about rheumatologists’ experience regarding COVID-19 vaccination.
“Particularly as the pandemic went on, being able to comfortably say that we have this large patient group, as well as collaborators across the world who have been monitoring for any safety issues, and that all the data has been reassuring” has been most useful for parents to hear, Dr. Dissanayake said.
The other study, led by Beth Rutstein, MD, MSCE, an attending rheumatologist at Children’s Hospital of Philadelphia, focused on the population of pediatric rheumatology patients by surveying pediatric rheumatologists who were members of the Childhood Arthritis and Rheumatology Research Alliance. The survey, conducted from March to May 2022, included questions about the rheumatologists’ COVID-19 vaccination practices as well as perceptions of the vaccine by the parents of their patients.
The 219 respondents included 74% pediatric rheumatologists and 21% fellows. Nearly all the respondents (98%) believed that any disease flares after COVID-19 vaccination would be mild and/or rare, and nearly all (98%) recommend their patients be vaccinated against COVID-19.
The primary finding from the study was that “we [rheumatologists] have different concerns from the families,” coauthor and presenter Vidya Sivaraman, MD, a pediatric rheumatologist at Nationwide Children’s Hospital and the Ohio State University in Columbus, told this news organization. “We’re more worried about the efficacy of the vaccine on immunosuppressive medications,” such as rituximab, which depletes B cells, Dr. Sivaraman said, but concerns about the vaccine’s immunogenicity or efficacy were very low among parents.
Just over half the clinicians surveyed (59%) were concerned about how effective the vaccine would be for their patients, especially those receiving immunosuppressive therapy. Health care professionals were most concerned about patients on rituximab – all clinicians reported concerns about the vaccine’s effectiveness in these patients – followed by patients taking systemic corticosteroids (86%), mycophenolate mofetil (59%), and Janus kinase inhibitors (46%).
Most clinicians (88%) reported that they had temporarily modified a patient’s immunosuppressive therapy to allow for vaccination, following guidelines by the American College of Rheumatology. Aside from a small proportion of health care professionals who checked patients’ post-vaccination serology primarily for research purposes, most clinicians (82%) did not collect this serology.
In regard to adverse events, the concern cited most often by respondents was myocarditis (76%), followed by development of new autoimmune conditions (29%) and thrombosis (22%), but the clinicians ranked these adverse events as low risk.
Meanwhile, the top three concerns about vaccination among parents, as reported to physicians, were worries about side effects, lack of long-term safety data on the vaccine, and misinformation they had heard, such as anxiety about changes to their child’s genetics or vaccination causing a COVID-19 infection. “They’re seeing things on social media from other parents [saying that COVID-19 vaccines are] going to affect their fertility, so they don’t want their daughters to get it,” Dr. Sivaraman said as another example of commonly cited misinformation.
Nearly half of the respondents (47%) said more than half of their families had concerns about side effects and the lack of data on long-term outcomes after vaccination. Only 8.5% of physicians said that fewer than 10% of their families were anxious about side effects. In addition, 39% of physicians said more than half of their families had concerns about misinformation they had heard, and only 16% of physicians had heard about misinformation concerns from fewer than 10% of their patients.
Other concerns cited by parents included their child’s disease flaring; lack of data on how well the vaccine would stimulate their child’s immune system; their child having already had COVID-19; and not believing COVID-19 was a major health risk to their child. Nearly every respondent (98%) said they had parents who turned down COVID-19 vaccination, and a majority (75%) reported that more than 10% of their patients had parents who were hesitant about COVID-19 vaccination.
No external funding was noted for either study. Ms. Sanchez Villa had no relevant financial relationships, but two abstract coauthors reported financial relationships with Pfizer and Moderna, and one reported a financial relationship with Novartis. Dr. Rutstein, Dr. Sivaraman, and Dr. Dissanayake had no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – Parents’ concerns about vaccinating their children against COVID-19 remain a substantial barrier to immunizing children against the disease, whether those children have chronic rheumatologic conditions or a history of multisystem inflammatory syndrome in children (MIS-C), according to two studies presented at the Pediatric Rheumatology Symposium.
Parents of children who developed MIS-C after a SARS-CoV-2 infection were particularly hesitant to vaccinate, despite strong encouragement from health care professionals at Baylor College of Medicine, Houston, said the presenter of one of the studies.
“Unfortunately, it remains unclear who is susceptible and what the mechanisms are” when it comes to MIS-C, Mariana Sanchez Villa, MS, a research coordinator at Baylor, told attendees. “Because of this, there is much hesitancy to vaccinate children with a history of MIS-C against COVID-19 out of a fear that hyperinflammation may occur.”
Ms. Sanchez Villa reported findings on the vaccination rate among patients who had been hospitalized with MIS-C. The researchers included all 295 patients who presented at the hospital with MIS-C between May 2020 and October 2022. Overall, 5% of these patients had been vaccinated against COVID-19 before they were diagnosed with MIS-C. When all these patients and their families came to outpatient follow-up appointments after discharge, the subspecialist clinicians recommended the children receive the COVID-19 vaccine 3 months after discharge. The researchers then reviewed the patients’ charts to see who did and did not receive the vaccine, which they confirmed through the state’s immunization registry.
Among the 295 patients with MIS-C, 1 died, and 99 (34%) received at least one COVID-19 vaccine dose after their diagnosis, including 7 of the 15 who had also been vaccinated prior to their MIS-C diagnosis. Just over half of the vaccinated patients (58%) were male. They received their vaccine an average 8.8 months after their hospitalization, when they were an average 10 years old, and all but one of the vaccine doses they received were the Pfizer/BioNTech mRNA vaccine.
Only 9 of the 99 vaccinated patients are fully vaccinated, defined as receiving the primary series plus the recommended boosters. Of the other patients, 13 received only one dose of the vaccine, 60 received two doses, and 17 received at least three doses of the primary series doses but no bivalent boosters. Over a subsequent average 11 months of follow-up, none of the vaccinated patients returned to the hospital with a recurrence of MIS-C or any other hyperinflammatory condition. The seven patients who had been vaccinated both before and after their MIS-C diagnosis have also not had any recurrence of a hyperinflammatory condition.
“SARS-CoV-2 vaccination is well-tolerated by children with a history of MIS-C,” the researchers concluded. Ms. Sanchez Villa referenced two other studies, in The Pediatric Infectious Disease Journal and in JAMA Network Open, with similar findings on the safety of COVID-19 vaccination in patients who have had MIS-C. “This is reassuring as SARS-CoV-2 becomes endemic and annual vaccination against SARS-CoV-2 is considered.”
Dilan Dissanayake, MD, PhD, a rheumatologist at The Hospital for Sick Children in Toronto, who attended the presentation, told this news organization that data increasingly show a “synergistic protective effect” from COVID-19 infection and vaccination. That is, “having COVID or having MIS-C once doesn’t necessarily preclude you from having it again,” thereby supporting the importance of vaccination after an MIS-C diagnosis. In talking to parents about vaccinating, he has found it most helpful for them to hear about rheumatologists’ experience regarding COVID-19 vaccination.
“Particularly as the pandemic went on, being able to comfortably say that we have this large patient group, as well as collaborators across the world who have been monitoring for any safety issues, and that all the data has been reassuring” has been most useful for parents to hear, Dr. Dissanayake said.
The other study, led by Beth Rutstein, MD, MSCE, an attending rheumatologist at Children’s Hospital of Philadelphia, focused on the population of pediatric rheumatology patients by surveying pediatric rheumatologists who were members of the Childhood Arthritis and Rheumatology Research Alliance. The survey, conducted from March to May 2022, included questions about the rheumatologists’ COVID-19 vaccination practices as well as perceptions of the vaccine by the parents of their patients.
The 219 respondents included 74% pediatric rheumatologists and 21% fellows. Nearly all the respondents (98%) believed that any disease flares after COVID-19 vaccination would be mild and/or rare, and nearly all (98%) recommend their patients be vaccinated against COVID-19.
The primary finding from the study was that “we [rheumatologists] have different concerns from the families,” coauthor and presenter Vidya Sivaraman, MD, a pediatric rheumatologist at Nationwide Children’s Hospital and the Ohio State University in Columbus, told this news organization. “We’re more worried about the efficacy of the vaccine on immunosuppressive medications,” such as rituximab, which depletes B cells, Dr. Sivaraman said, but concerns about the vaccine’s immunogenicity or efficacy were very low among parents.
Just over half the clinicians surveyed (59%) were concerned about how effective the vaccine would be for their patients, especially those receiving immunosuppressive therapy. Health care professionals were most concerned about patients on rituximab – all clinicians reported concerns about the vaccine’s effectiveness in these patients – followed by patients taking systemic corticosteroids (86%), mycophenolate mofetil (59%), and Janus kinase inhibitors (46%).
Most clinicians (88%) reported that they had temporarily modified a patient’s immunosuppressive therapy to allow for vaccination, following guidelines by the American College of Rheumatology. Aside from a small proportion of health care professionals who checked patients’ post-vaccination serology primarily for research purposes, most clinicians (82%) did not collect this serology.
In regard to adverse events, the concern cited most often by respondents was myocarditis (76%), followed by development of new autoimmune conditions (29%) and thrombosis (22%), but the clinicians ranked these adverse events as low risk.
Meanwhile, the top three concerns about vaccination among parents, as reported to physicians, were worries about side effects, lack of long-term safety data on the vaccine, and misinformation they had heard, such as anxiety about changes to their child’s genetics or vaccination causing a COVID-19 infection. “They’re seeing things on social media from other parents [saying that COVID-19 vaccines are] going to affect their fertility, so they don’t want their daughters to get it,” Dr. Sivaraman said as another example of commonly cited misinformation.
Nearly half of the respondents (47%) said more than half of their families had concerns about side effects and the lack of data on long-term outcomes after vaccination. Only 8.5% of physicians said that fewer than 10% of their families were anxious about side effects. In addition, 39% of physicians said more than half of their families had concerns about misinformation they had heard, and only 16% of physicians had heard about misinformation concerns from fewer than 10% of their patients.
Other concerns cited by parents included their child’s disease flaring; lack of data on how well the vaccine would stimulate their child’s immune system; their child having already had COVID-19; and not believing COVID-19 was a major health risk to their child. Nearly every respondent (98%) said they had parents who turned down COVID-19 vaccination, and a majority (75%) reported that more than 10% of their patients had parents who were hesitant about COVID-19 vaccination.
No external funding was noted for either study. Ms. Sanchez Villa had no relevant financial relationships, but two abstract coauthors reported financial relationships with Pfizer and Moderna, and one reported a financial relationship with Novartis. Dr. Rutstein, Dr. Sivaraman, and Dr. Dissanayake had no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT PRSYM 2023
Why 9 is not too young for the HPV vaccine
For Sonja O’Leary, MD, higher rates of vaccination against human papillomavirus came with the flip of a switch.
Dr. O’Leary, the interim director of service for outpatient pediatric services at Denver Health and Hospital Authority, and her colleagues saw rates of HPV and other childhood immunizations drop during the COVID-19 pandemic and decided to act. Their health system, which includes 28 federally qualified health centers, offers vaccines at any inpatient or outpatient visit based on alerts from their electronic health record.
“It was actually really simple; it was really just changing our best-practice alert,” Dr. O’Leary said. Beginning in May 2021, and after notifying clinic staff of the impending change, DHHA dropped the alert for first dose of HPV from age 11 to 9.
The approach worked. Compared with the first 5 months of 2021, the percentage of children aged 9-13 years with an in-person visit who received at least one dose of HPV vaccine between June 2021 and August 2022 rose from 30.3% to 42.8% – a 41% increase. The share who received two doses by age 13 years more than doubled, from 19.3% to 42.7%, Dr. O’Leary said.
Frustrated efforts
Although those figures might seem to make an iron-clad case for earlier vaccinations against HPV – which is responsible for nearly 35,000 cases of cancer annually – factors beyond statistics have frustrated efforts to increase acceptance of the shots.
Data published in 2022 from the U.S. Centers for Disease Control and Prevention found that 89.6% of teens aged 13-17 years received at least one dose of tetanus, diphtheria, and acellular pertussis vaccine, and 89% got one or more doses of meningococcal conjugate vaccine. However, only 76.9% had received one or more doses of HPV vaccine. The rate of receiving both doses needed for full protection was much lower (61.7%).
Both the American Academy of Pediatrics and the American Cancer Society now endorse the strategy of offering HPV vaccine as early as age 9, which avoids the need for multiple shots at a single visit and results in more kids getting both doses. In a recent study that surveyed primary care professionals who see pediatric patients, 21% were already offering HPV vaccine at age 9, and another 48% were willing to try the approach.
What was the most common objection to the earlier age? Nearly three-quarters of clinicians said they felt that parents weren’t ready to talk about HPV vaccination yet.
Noel Brewer, PhD, one of the authors of the survey study, wondered why clinicians feel the need to bring up sex at all. “Providers should never be talking about sex when they are talking about vaccine, because that’s not the point,” said Dr. Brewer, the distinguished professor in public health at the University of North Carolina at Chapel Hill. He pointed out that providers don’t talk about the route of transmission for any other vaccine.
Dr. Brewer led a randomized controlled trial that trained pediatric clinicians in the “announcement” strategy, in which the clinician announces the vaccines that are due at that visit. If the parent hesitates, the clinician then probes further to identify and address their concerns and provides more information. If the parent is still not convinced, the clinician notes the discussion in the chart and tries again at the next visit.
The strategy was effective: Intervention clinics had a 5.4% higher rate of HPV vaccination coverage than control clinics after six months. Dr. Brewer and his colleagues have trained over 1,700 providers in the technique since 2020.
A cancer – not STI – vaccine
Although DHHA hasn’t participated in Dr. Brewer’s training, Dr. O’Leary and her colleagues take a similar approach of simply stating which vaccines the child should receive that day. And they talk about HPV as a cancer vaccine instead of one to prevent a sexually transmitted infection.
In her experience, this emphasis changes the conversation. Dr. O’Leary described a typical comment from parents as, “Oh, of course I would give my child a vaccine that could prevent cancer.”
Ana Rodriguez, MD, MPH, an obstetrician, became interested in raising rates of vaccination against HPV after watching too many women battle a preventable cancer. She worked for several years in the Rio Grande Valley along the U.S. border with Mexico, an impoverished rural area with poor access to health care and high rates of HPV infection.
“I would treat women very young – not even 30 years of age – already fighting advanced precancerous lesions secondary to HPV,” said Dr. Rodriguez, an associate professor of Obstetrics & Gynecology at the University of Texas Medical Branch at Galveston.
In 2016, when Texas ranked 47th in the nation for rates of up-to-date HPV vaccination, Dr. Rodriguez helped launch a community-based educational campaign in four rural counties in the Rio Grande Valley using social media, radio, and in-person meetings with school PTA members and members of school boards to educate staff and parents about the need for vaccination against the infection.
In 2019, the team began offering the vaccine to children ages 9-12 years at back-to-school events, progress report nights, and other school events, pivoting to outdoor events using a mobile vaccine van after COVID-19 struck. They recently published a study showing that 73.6% of students who received their first dose of vaccine at age 11 or younger completed the series, compared with only 45.1% of children who got their first dose at age 12 or older.
Dr. Rodriguez encountered parents who felt 9 or 10 years old was too young because their children were not going to be sexually active anytime soon. Her response was to describe HPV as a tool to prevent cancer, telling parents, “If you vaccinate your kids young enough, they will be protected for life.”
Lifetime protection is another point in favor of giving HPV vaccine prior to Tdap and MenACWY. The response to the two-dose series of HPV in preadolescents is robust and long-lasting, with no downside to giving it a few years earlier. In contrast, immunity to MenACWY wanes after a few years, so the immunization must be given before children enter high school, when their risk for meningitis increases.
The annual toll of deaths in the United States from meningococcus, tetanus, diphtheria, and pertussis typically totals less than 100, whereas cancer deaths attributable to HPV infection number in the thousands each year. And that may be the best reason for attempting new strategies to help HPV vaccination rates catch up to the rest of the preteen vaccines.
Dr. Brewer’s work was supported by the Gillings School of Global Public Health, the Lineberger Comprehensive Cancer Center at the University of North Carolina, and from training grants from the National Cancer Institute. Dr. Brewer has received research funding from Merck, Pfizer, and GSK and served as a paid advisor for Merck. Dr. O’Leary reports no relevant financial relationships. Dr. Rodriguez received a grant from the Cancer Prevention Research Institute of Texas, and the study was supported by the Institute for Translational Sciences at the University of Texas Medical Branch.
A version of this article first appeared on Medscape.com.
For Sonja O’Leary, MD, higher rates of vaccination against human papillomavirus came with the flip of a switch.
Dr. O’Leary, the interim director of service for outpatient pediatric services at Denver Health and Hospital Authority, and her colleagues saw rates of HPV and other childhood immunizations drop during the COVID-19 pandemic and decided to act. Their health system, which includes 28 federally qualified health centers, offers vaccines at any inpatient or outpatient visit based on alerts from their electronic health record.
“It was actually really simple; it was really just changing our best-practice alert,” Dr. O’Leary said. Beginning in May 2021, and after notifying clinic staff of the impending change, DHHA dropped the alert for first dose of HPV from age 11 to 9.
The approach worked. Compared with the first 5 months of 2021, the percentage of children aged 9-13 years with an in-person visit who received at least one dose of HPV vaccine between June 2021 and August 2022 rose from 30.3% to 42.8% – a 41% increase. The share who received two doses by age 13 years more than doubled, from 19.3% to 42.7%, Dr. O’Leary said.
Frustrated efforts
Although those figures might seem to make an iron-clad case for earlier vaccinations against HPV – which is responsible for nearly 35,000 cases of cancer annually – factors beyond statistics have frustrated efforts to increase acceptance of the shots.
Data published in 2022 from the U.S. Centers for Disease Control and Prevention found that 89.6% of teens aged 13-17 years received at least one dose of tetanus, diphtheria, and acellular pertussis vaccine, and 89% got one or more doses of meningococcal conjugate vaccine. However, only 76.9% had received one or more doses of HPV vaccine. The rate of receiving both doses needed for full protection was much lower (61.7%).
Both the American Academy of Pediatrics and the American Cancer Society now endorse the strategy of offering HPV vaccine as early as age 9, which avoids the need for multiple shots at a single visit and results in more kids getting both doses. In a recent study that surveyed primary care professionals who see pediatric patients, 21% were already offering HPV vaccine at age 9, and another 48% were willing to try the approach.
What was the most common objection to the earlier age? Nearly three-quarters of clinicians said they felt that parents weren’t ready to talk about HPV vaccination yet.
Noel Brewer, PhD, one of the authors of the survey study, wondered why clinicians feel the need to bring up sex at all. “Providers should never be talking about sex when they are talking about vaccine, because that’s not the point,” said Dr. Brewer, the distinguished professor in public health at the University of North Carolina at Chapel Hill. He pointed out that providers don’t talk about the route of transmission for any other vaccine.
Dr. Brewer led a randomized controlled trial that trained pediatric clinicians in the “announcement” strategy, in which the clinician announces the vaccines that are due at that visit. If the parent hesitates, the clinician then probes further to identify and address their concerns and provides more information. If the parent is still not convinced, the clinician notes the discussion in the chart and tries again at the next visit.
The strategy was effective: Intervention clinics had a 5.4% higher rate of HPV vaccination coverage than control clinics after six months. Dr. Brewer and his colleagues have trained over 1,700 providers in the technique since 2020.
A cancer – not STI – vaccine
Although DHHA hasn’t participated in Dr. Brewer’s training, Dr. O’Leary and her colleagues take a similar approach of simply stating which vaccines the child should receive that day. And they talk about HPV as a cancer vaccine instead of one to prevent a sexually transmitted infection.
In her experience, this emphasis changes the conversation. Dr. O’Leary described a typical comment from parents as, “Oh, of course I would give my child a vaccine that could prevent cancer.”
Ana Rodriguez, MD, MPH, an obstetrician, became interested in raising rates of vaccination against HPV after watching too many women battle a preventable cancer. She worked for several years in the Rio Grande Valley along the U.S. border with Mexico, an impoverished rural area with poor access to health care and high rates of HPV infection.
“I would treat women very young – not even 30 years of age – already fighting advanced precancerous lesions secondary to HPV,” said Dr. Rodriguez, an associate professor of Obstetrics & Gynecology at the University of Texas Medical Branch at Galveston.
In 2016, when Texas ranked 47th in the nation for rates of up-to-date HPV vaccination, Dr. Rodriguez helped launch a community-based educational campaign in four rural counties in the Rio Grande Valley using social media, radio, and in-person meetings with school PTA members and members of school boards to educate staff and parents about the need for vaccination against the infection.
In 2019, the team began offering the vaccine to children ages 9-12 years at back-to-school events, progress report nights, and other school events, pivoting to outdoor events using a mobile vaccine van after COVID-19 struck. They recently published a study showing that 73.6% of students who received their first dose of vaccine at age 11 or younger completed the series, compared with only 45.1% of children who got their first dose at age 12 or older.
Dr. Rodriguez encountered parents who felt 9 or 10 years old was too young because their children were not going to be sexually active anytime soon. Her response was to describe HPV as a tool to prevent cancer, telling parents, “If you vaccinate your kids young enough, they will be protected for life.”
Lifetime protection is another point in favor of giving HPV vaccine prior to Tdap and MenACWY. The response to the two-dose series of HPV in preadolescents is robust and long-lasting, with no downside to giving it a few years earlier. In contrast, immunity to MenACWY wanes after a few years, so the immunization must be given before children enter high school, when their risk for meningitis increases.
The annual toll of deaths in the United States from meningococcus, tetanus, diphtheria, and pertussis typically totals less than 100, whereas cancer deaths attributable to HPV infection number in the thousands each year. And that may be the best reason for attempting new strategies to help HPV vaccination rates catch up to the rest of the preteen vaccines.
Dr. Brewer’s work was supported by the Gillings School of Global Public Health, the Lineberger Comprehensive Cancer Center at the University of North Carolina, and from training grants from the National Cancer Institute. Dr. Brewer has received research funding from Merck, Pfizer, and GSK and served as a paid advisor for Merck. Dr. O’Leary reports no relevant financial relationships. Dr. Rodriguez received a grant from the Cancer Prevention Research Institute of Texas, and the study was supported by the Institute for Translational Sciences at the University of Texas Medical Branch.
A version of this article first appeared on Medscape.com.
For Sonja O’Leary, MD, higher rates of vaccination against human papillomavirus came with the flip of a switch.
Dr. O’Leary, the interim director of service for outpatient pediatric services at Denver Health and Hospital Authority, and her colleagues saw rates of HPV and other childhood immunizations drop during the COVID-19 pandemic and decided to act. Their health system, which includes 28 federally qualified health centers, offers vaccines at any inpatient or outpatient visit based on alerts from their electronic health record.
“It was actually really simple; it was really just changing our best-practice alert,” Dr. O’Leary said. Beginning in May 2021, and after notifying clinic staff of the impending change, DHHA dropped the alert for first dose of HPV from age 11 to 9.
The approach worked. Compared with the first 5 months of 2021, the percentage of children aged 9-13 years with an in-person visit who received at least one dose of HPV vaccine between June 2021 and August 2022 rose from 30.3% to 42.8% – a 41% increase. The share who received two doses by age 13 years more than doubled, from 19.3% to 42.7%, Dr. O’Leary said.
Frustrated efforts
Although those figures might seem to make an iron-clad case for earlier vaccinations against HPV – which is responsible for nearly 35,000 cases of cancer annually – factors beyond statistics have frustrated efforts to increase acceptance of the shots.
Data published in 2022 from the U.S. Centers for Disease Control and Prevention found that 89.6% of teens aged 13-17 years received at least one dose of tetanus, diphtheria, and acellular pertussis vaccine, and 89% got one or more doses of meningococcal conjugate vaccine. However, only 76.9% had received one or more doses of HPV vaccine. The rate of receiving both doses needed for full protection was much lower (61.7%).
Both the American Academy of Pediatrics and the American Cancer Society now endorse the strategy of offering HPV vaccine as early as age 9, which avoids the need for multiple shots at a single visit and results in more kids getting both doses. In a recent study that surveyed primary care professionals who see pediatric patients, 21% were already offering HPV vaccine at age 9, and another 48% were willing to try the approach.
What was the most common objection to the earlier age? Nearly three-quarters of clinicians said they felt that parents weren’t ready to talk about HPV vaccination yet.
Noel Brewer, PhD, one of the authors of the survey study, wondered why clinicians feel the need to bring up sex at all. “Providers should never be talking about sex when they are talking about vaccine, because that’s not the point,” said Dr. Brewer, the distinguished professor in public health at the University of North Carolina at Chapel Hill. He pointed out that providers don’t talk about the route of transmission for any other vaccine.
Dr. Brewer led a randomized controlled trial that trained pediatric clinicians in the “announcement” strategy, in which the clinician announces the vaccines that are due at that visit. If the parent hesitates, the clinician then probes further to identify and address their concerns and provides more information. If the parent is still not convinced, the clinician notes the discussion in the chart and tries again at the next visit.
The strategy was effective: Intervention clinics had a 5.4% higher rate of HPV vaccination coverage than control clinics after six months. Dr. Brewer and his colleagues have trained over 1,700 providers in the technique since 2020.
A cancer – not STI – vaccine
Although DHHA hasn’t participated in Dr. Brewer’s training, Dr. O’Leary and her colleagues take a similar approach of simply stating which vaccines the child should receive that day. And they talk about HPV as a cancer vaccine instead of one to prevent a sexually transmitted infection.
In her experience, this emphasis changes the conversation. Dr. O’Leary described a typical comment from parents as, “Oh, of course I would give my child a vaccine that could prevent cancer.”
Ana Rodriguez, MD, MPH, an obstetrician, became interested in raising rates of vaccination against HPV after watching too many women battle a preventable cancer. She worked for several years in the Rio Grande Valley along the U.S. border with Mexico, an impoverished rural area with poor access to health care and high rates of HPV infection.
“I would treat women very young – not even 30 years of age – already fighting advanced precancerous lesions secondary to HPV,” said Dr. Rodriguez, an associate professor of Obstetrics & Gynecology at the University of Texas Medical Branch at Galveston.
In 2016, when Texas ranked 47th in the nation for rates of up-to-date HPV vaccination, Dr. Rodriguez helped launch a community-based educational campaign in four rural counties in the Rio Grande Valley using social media, radio, and in-person meetings with school PTA members and members of school boards to educate staff and parents about the need for vaccination against the infection.
In 2019, the team began offering the vaccine to children ages 9-12 years at back-to-school events, progress report nights, and other school events, pivoting to outdoor events using a mobile vaccine van after COVID-19 struck. They recently published a study showing that 73.6% of students who received their first dose of vaccine at age 11 or younger completed the series, compared with only 45.1% of children who got their first dose at age 12 or older.
Dr. Rodriguez encountered parents who felt 9 or 10 years old was too young because their children were not going to be sexually active anytime soon. Her response was to describe HPV as a tool to prevent cancer, telling parents, “If you vaccinate your kids young enough, they will be protected for life.”
Lifetime protection is another point in favor of giving HPV vaccine prior to Tdap and MenACWY. The response to the two-dose series of HPV in preadolescents is robust and long-lasting, with no downside to giving it a few years earlier. In contrast, immunity to MenACWY wanes after a few years, so the immunization must be given before children enter high school, when their risk for meningitis increases.
The annual toll of deaths in the United States from meningococcus, tetanus, diphtheria, and pertussis typically totals less than 100, whereas cancer deaths attributable to HPV infection number in the thousands each year. And that may be the best reason for attempting new strategies to help HPV vaccination rates catch up to the rest of the preteen vaccines.
Dr. Brewer’s work was supported by the Gillings School of Global Public Health, the Lineberger Comprehensive Cancer Center at the University of North Carolina, and from training grants from the National Cancer Institute. Dr. Brewer has received research funding from Merck, Pfizer, and GSK and served as a paid advisor for Merck. Dr. O’Leary reports no relevant financial relationships. Dr. Rodriguez received a grant from the Cancer Prevention Research Institute of Texas, and the study was supported by the Institute for Translational Sciences at the University of Texas Medical Branch.
A version of this article first appeared on Medscape.com.
Single bivalent COVID booster is enough for now: CDC
“If you have completed your updated booster dose, you are currently up to date. There is not a recommendation to get another updated booster dose,” the CDC website now explains.
In January, the nation’s expert COVID panel recommended that the United States move toward an annual COVID booster shot in the fall, similar to the annual flu shot, that targets the most widely circulating strains of the virus. Recent studies have shown that booster strength wanes after a few months, spurring discussions of whether people at high risk of getting a severe case of COVID may need more than one annual shot.
September was the last time a new booster dose was recommended, when, at the time, the bivalent booster was released, offering new protection against Omicron variants of the virus. Health officials’ focus is now shifting from preventing infections to reducing the likelihood of severe ones, the San Francisco Chronicle reported.
“The bottom line is that there is some waning of protection for those who got boosters more than six months ago and haven’t had an intervening infection,” said Bob Wachter, MD, head of the University of California–San Francisco’s department of medicine, according to the Chronicle. “But the level of protection versus severe infection continues to be fairly high, good enough that people who aren’t at super high risk are probably fine waiting until a new booster comes out in the fall.”
The Wall Street Journal reported recently that many people have been asking their doctors to give them another booster, which is not authorized by the Food and Drug Administration.
About 8 in 10 people in the United States got the initial set of COVID-19 vaccines, which were first approved in August 2021. But just 16.4% of people in the United States have gotten the latest booster that was released in September, CDC data show.
A version of this article originally appeared on WebMD.com.
“If you have completed your updated booster dose, you are currently up to date. There is not a recommendation to get another updated booster dose,” the CDC website now explains.
In January, the nation’s expert COVID panel recommended that the United States move toward an annual COVID booster shot in the fall, similar to the annual flu shot, that targets the most widely circulating strains of the virus. Recent studies have shown that booster strength wanes after a few months, spurring discussions of whether people at high risk of getting a severe case of COVID may need more than one annual shot.
September was the last time a new booster dose was recommended, when, at the time, the bivalent booster was released, offering new protection against Omicron variants of the virus. Health officials’ focus is now shifting from preventing infections to reducing the likelihood of severe ones, the San Francisco Chronicle reported.
“The bottom line is that there is some waning of protection for those who got boosters more than six months ago and haven’t had an intervening infection,” said Bob Wachter, MD, head of the University of California–San Francisco’s department of medicine, according to the Chronicle. “But the level of protection versus severe infection continues to be fairly high, good enough that people who aren’t at super high risk are probably fine waiting until a new booster comes out in the fall.”
The Wall Street Journal reported recently that many people have been asking their doctors to give them another booster, which is not authorized by the Food and Drug Administration.
About 8 in 10 people in the United States got the initial set of COVID-19 vaccines, which were first approved in August 2021. But just 16.4% of people in the United States have gotten the latest booster that was released in September, CDC data show.
A version of this article originally appeared on WebMD.com.
“If you have completed your updated booster dose, you are currently up to date. There is not a recommendation to get another updated booster dose,” the CDC website now explains.
In January, the nation’s expert COVID panel recommended that the United States move toward an annual COVID booster shot in the fall, similar to the annual flu shot, that targets the most widely circulating strains of the virus. Recent studies have shown that booster strength wanes after a few months, spurring discussions of whether people at high risk of getting a severe case of COVID may need more than one annual shot.
September was the last time a new booster dose was recommended, when, at the time, the bivalent booster was released, offering new protection against Omicron variants of the virus. Health officials’ focus is now shifting from preventing infections to reducing the likelihood of severe ones, the San Francisco Chronicle reported.
“The bottom line is that there is some waning of protection for those who got boosters more than six months ago and haven’t had an intervening infection,” said Bob Wachter, MD, head of the University of California–San Francisco’s department of medicine, according to the Chronicle. “But the level of protection versus severe infection continues to be fairly high, good enough that people who aren’t at super high risk are probably fine waiting until a new booster comes out in the fall.”
The Wall Street Journal reported recently that many people have been asking their doctors to give them another booster, which is not authorized by the Food and Drug Administration.
About 8 in 10 people in the United States got the initial set of COVID-19 vaccines, which were first approved in August 2021. But just 16.4% of people in the United States have gotten the latest booster that was released in September, CDC data show.
A version of this article originally appeared on WebMD.com.
Negative expectations of COVID shots may amplify side effects
It fits the psychosomatic role of “nocebo effects,” the researchers say – when “psychological characteristics including anxiety, depression, and the tendency to amplify benign bodily sensations” cause participants to report more bad effects than others.
In August 2021, researchers in Hamburg, Germany, followed 1,678 adults getting a second shot of Pfizer or Moderna mRNA-based vaccines. Participants reported symptoms in a diary, starting 2 weeks ahead of the vaccinations and going 7 days afterward.
Some participants said they weren’t expecting much benefit. Researchers said these people were more likely to “catastrophize instead of normalize benign bodily sensations.” People who’d had a bad experience with their first shot were more likely to say they felt aches, pains, and other side effects from the second.
The research was published in JAMA Network Open.
“Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines,” the researchers said. “Unfavorable nocebo-related adverse effects could then be prevented, and overall vaccine acceptance could be improved.”
More than half of participants, 52.1%, expected bad effects to happen from the shot. Another 7.6% said they would be hospitalized from those bad effects, and 10.6% said the effects would last in the long term.
The Washington Times reported that “substantial numbers of patients reported adverse effects after vaccination,” but people with positive expectations reported them as minor. “Those who scored higher for anxiety, depression, and other psychosocial factors were more likely to flag these issues as severe.”
A version of this article originally appeared on WebMD.com.
It fits the psychosomatic role of “nocebo effects,” the researchers say – when “psychological characteristics including anxiety, depression, and the tendency to amplify benign bodily sensations” cause participants to report more bad effects than others.
In August 2021, researchers in Hamburg, Germany, followed 1,678 adults getting a second shot of Pfizer or Moderna mRNA-based vaccines. Participants reported symptoms in a diary, starting 2 weeks ahead of the vaccinations and going 7 days afterward.
Some participants said they weren’t expecting much benefit. Researchers said these people were more likely to “catastrophize instead of normalize benign bodily sensations.” People who’d had a bad experience with their first shot were more likely to say they felt aches, pains, and other side effects from the second.
The research was published in JAMA Network Open.
“Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines,” the researchers said. “Unfavorable nocebo-related adverse effects could then be prevented, and overall vaccine acceptance could be improved.”
More than half of participants, 52.1%, expected bad effects to happen from the shot. Another 7.6% said they would be hospitalized from those bad effects, and 10.6% said the effects would last in the long term.
The Washington Times reported that “substantial numbers of patients reported adverse effects after vaccination,” but people with positive expectations reported them as minor. “Those who scored higher for anxiety, depression, and other psychosocial factors were more likely to flag these issues as severe.”
A version of this article originally appeared on WebMD.com.
It fits the psychosomatic role of “nocebo effects,” the researchers say – when “psychological characteristics including anxiety, depression, and the tendency to amplify benign bodily sensations” cause participants to report more bad effects than others.
In August 2021, researchers in Hamburg, Germany, followed 1,678 adults getting a second shot of Pfizer or Moderna mRNA-based vaccines. Participants reported symptoms in a diary, starting 2 weeks ahead of the vaccinations and going 7 days afterward.
Some participants said they weren’t expecting much benefit. Researchers said these people were more likely to “catastrophize instead of normalize benign bodily sensations.” People who’d had a bad experience with their first shot were more likely to say they felt aches, pains, and other side effects from the second.
The research was published in JAMA Network Open.
“Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines,” the researchers said. “Unfavorable nocebo-related adverse effects could then be prevented, and overall vaccine acceptance could be improved.”
More than half of participants, 52.1%, expected bad effects to happen from the shot. Another 7.6% said they would be hospitalized from those bad effects, and 10.6% said the effects would last in the long term.
The Washington Times reported that “substantial numbers of patients reported adverse effects after vaccination,” but people with positive expectations reported them as minor. “Those who scored higher for anxiety, depression, and other psychosocial factors were more likely to flag these issues as severe.”
A version of this article originally appeared on WebMD.com.
FROM JAMA NETWORK OPEN
Nasal COVID treatment shows early promise against multiple variants
if used within 4 hours after infection inside the nose, new research reveals.
Known as TriSb92 (brand name Covidin, from drugmaker Pandemblock Oy in Finland), the viral inhibitor also appears effective against all coronavirus variants of concern, neutralizing even the Omicron variants BA.5, XBB, and BQ.1.1 in laboratory and mice studies.
Unlike a COVID vaccine that boosts a person’s immune system as protection, the antiviral nasal spray works more directly by blocking the virus, acting as a “biological mask in the nasal cavity,” according to the biotechnology company set up to develop the treatment.
The product targets a stable site on the spike protein of the virus that is not known to mutate. This same site is shared among many variants of the COVID virus, so it could be effective against future variants as well, researchers note.
“In animal models, by directly inactivating the virus, TriSb92 offers immediate and robust protection” against coronavirus infection and severe COVID, said Anna R. Mäkelä, PhD, lead author of the study and a senior scientist in the department of virology at the University of Helsinki.
The study was published online in Nature Communications.
A potential first line of defense
Even in cases where the antiviral does not prevent coronavirus infection, the treatment could slow infection. This could happen by limiting how much virus could replicate early in the skin inside the nose and nasopharynx (the upper part of the throat), said Dr. Mäkelä, who is also CEO of Pandemblock Oy, the company set up to develop the product.
“TriSb92 could effectively tip the balance in favor of the [the person] and thereby help to reduce the risk of severe COVID-19 disease,” she said.
The antiviral also could offer an alternative to people who cannot or do not respond to a vaccine.
“Many elderly people as well as individuals who are immunodeficient for various reasons do not respond to vaccines and are in the need of other protective measures,” said Kalle Saksela, MD, PhD, senior author of the study and a virologist at the University of Helsinki.
Multiple doses needed?
TriSb92 is “one of multiple nasal spray approaches but unlikely to be as durable as effective nasal vaccines,” said Eric Topol, MD, a professor of molecular medicine and executive vice president of Scripps Research in La Jolla, Calif. Dr. Topol is also editor-in-chief of Medscape, WebMD’s sister site for medical professionals.
“The sprays generally require multiple doses per day, whereas a single dose of a nasal vaccine may protect for months,” he said.
“Both have the allure of being variant-proof,” Dr. Topol added.
Thinking small
Many laboratories are shifting from treatments using monoclonal antibodies to treatments using smaller antibody fragments called “nanobodies” because they are more cost-effective and are able to last longer in storage, Dr. Mäkelä and colleagues noted.
Several of these nanobodies have shown promise against viruses in cell culture or animal models, including as an intranasal preventive treatment for SARS-CoV-2.
One of these smaller antibodies is being developed from llamas for example; another comes from experiments with yeast to develop synthetic nanobodies; and in a third case, researchers isolated nanobodies from llamas and from mice and showed they could neutralize the SARS-CoV-2 virus.
These nanobodies and TriSb92 target a specific part of the coronavirus spike protein called the receptor-binding domain (RBD). The RBD is where the coronavirus attaches to cells in the body. These agents essentially trick the virus by changing the structure of the outside of cells, so they look like a virus has already fused to them. This way, the virus moves on.
Key findings
The researchers compared mice treated with TriSb92 before and after exposure to SARS-CoV-2. When given in advance, none of the treated mice had SARS-CoV-2 RNA in their lungs, while untreated mice in the comparison group had “abundant” levels.
Other evidence of viral infection showed similar differences between treated and untreated mice in the protective lining of cells called the epithelium inside the nose, nasal mucosa, and airways.
Similarly, when given 2 or 4 hours after SARS-CoV-2 had already infected the epithelium, TriSb92 was linked to a complete lack of the virus’s RNA in the lungs.
It was more effective against the virus, though, when given before infection rather than after, “perhaps due to the initial establishment of the infection,” the researchers note.
The company led by Dr. Mäkelä is now working to secure funding for clinical trials of TriSb92 in humans.
A version of this article first appeared on WebMD.com.
if used within 4 hours after infection inside the nose, new research reveals.
Known as TriSb92 (brand name Covidin, from drugmaker Pandemblock Oy in Finland), the viral inhibitor also appears effective against all coronavirus variants of concern, neutralizing even the Omicron variants BA.5, XBB, and BQ.1.1 in laboratory and mice studies.
Unlike a COVID vaccine that boosts a person’s immune system as protection, the antiviral nasal spray works more directly by blocking the virus, acting as a “biological mask in the nasal cavity,” according to the biotechnology company set up to develop the treatment.
The product targets a stable site on the spike protein of the virus that is not known to mutate. This same site is shared among many variants of the COVID virus, so it could be effective against future variants as well, researchers note.
“In animal models, by directly inactivating the virus, TriSb92 offers immediate and robust protection” against coronavirus infection and severe COVID, said Anna R. Mäkelä, PhD, lead author of the study and a senior scientist in the department of virology at the University of Helsinki.
The study was published online in Nature Communications.
A potential first line of defense
Even in cases where the antiviral does not prevent coronavirus infection, the treatment could slow infection. This could happen by limiting how much virus could replicate early in the skin inside the nose and nasopharynx (the upper part of the throat), said Dr. Mäkelä, who is also CEO of Pandemblock Oy, the company set up to develop the product.
“TriSb92 could effectively tip the balance in favor of the [the person] and thereby help to reduce the risk of severe COVID-19 disease,” she said.
The antiviral also could offer an alternative to people who cannot or do not respond to a vaccine.
“Many elderly people as well as individuals who are immunodeficient for various reasons do not respond to vaccines and are in the need of other protective measures,” said Kalle Saksela, MD, PhD, senior author of the study and a virologist at the University of Helsinki.
Multiple doses needed?
TriSb92 is “one of multiple nasal spray approaches but unlikely to be as durable as effective nasal vaccines,” said Eric Topol, MD, a professor of molecular medicine and executive vice president of Scripps Research in La Jolla, Calif. Dr. Topol is also editor-in-chief of Medscape, WebMD’s sister site for medical professionals.
“The sprays generally require multiple doses per day, whereas a single dose of a nasal vaccine may protect for months,” he said.
“Both have the allure of being variant-proof,” Dr. Topol added.
Thinking small
Many laboratories are shifting from treatments using monoclonal antibodies to treatments using smaller antibody fragments called “nanobodies” because they are more cost-effective and are able to last longer in storage, Dr. Mäkelä and colleagues noted.
Several of these nanobodies have shown promise against viruses in cell culture or animal models, including as an intranasal preventive treatment for SARS-CoV-2.
One of these smaller antibodies is being developed from llamas for example; another comes from experiments with yeast to develop synthetic nanobodies; and in a third case, researchers isolated nanobodies from llamas and from mice and showed they could neutralize the SARS-CoV-2 virus.
These nanobodies and TriSb92 target a specific part of the coronavirus spike protein called the receptor-binding domain (RBD). The RBD is where the coronavirus attaches to cells in the body. These agents essentially trick the virus by changing the structure of the outside of cells, so they look like a virus has already fused to them. This way, the virus moves on.
Key findings
The researchers compared mice treated with TriSb92 before and after exposure to SARS-CoV-2. When given in advance, none of the treated mice had SARS-CoV-2 RNA in their lungs, while untreated mice in the comparison group had “abundant” levels.
Other evidence of viral infection showed similar differences between treated and untreated mice in the protective lining of cells called the epithelium inside the nose, nasal mucosa, and airways.
Similarly, when given 2 or 4 hours after SARS-CoV-2 had already infected the epithelium, TriSb92 was linked to a complete lack of the virus’s RNA in the lungs.
It was more effective against the virus, though, when given before infection rather than after, “perhaps due to the initial establishment of the infection,” the researchers note.
The company led by Dr. Mäkelä is now working to secure funding for clinical trials of TriSb92 in humans.
A version of this article first appeared on WebMD.com.
if used within 4 hours after infection inside the nose, new research reveals.
Known as TriSb92 (brand name Covidin, from drugmaker Pandemblock Oy in Finland), the viral inhibitor also appears effective against all coronavirus variants of concern, neutralizing even the Omicron variants BA.5, XBB, and BQ.1.1 in laboratory and mice studies.
Unlike a COVID vaccine that boosts a person’s immune system as protection, the antiviral nasal spray works more directly by blocking the virus, acting as a “biological mask in the nasal cavity,” according to the biotechnology company set up to develop the treatment.
The product targets a stable site on the spike protein of the virus that is not known to mutate. This same site is shared among many variants of the COVID virus, so it could be effective against future variants as well, researchers note.
“In animal models, by directly inactivating the virus, TriSb92 offers immediate and robust protection” against coronavirus infection and severe COVID, said Anna R. Mäkelä, PhD, lead author of the study and a senior scientist in the department of virology at the University of Helsinki.
The study was published online in Nature Communications.
A potential first line of defense
Even in cases where the antiviral does not prevent coronavirus infection, the treatment could slow infection. This could happen by limiting how much virus could replicate early in the skin inside the nose and nasopharynx (the upper part of the throat), said Dr. Mäkelä, who is also CEO of Pandemblock Oy, the company set up to develop the product.
“TriSb92 could effectively tip the balance in favor of the [the person] and thereby help to reduce the risk of severe COVID-19 disease,” she said.
The antiviral also could offer an alternative to people who cannot or do not respond to a vaccine.
“Many elderly people as well as individuals who are immunodeficient for various reasons do not respond to vaccines and are in the need of other protective measures,” said Kalle Saksela, MD, PhD, senior author of the study and a virologist at the University of Helsinki.
Multiple doses needed?
TriSb92 is “one of multiple nasal spray approaches but unlikely to be as durable as effective nasal vaccines,” said Eric Topol, MD, a professor of molecular medicine and executive vice president of Scripps Research in La Jolla, Calif. Dr. Topol is also editor-in-chief of Medscape, WebMD’s sister site for medical professionals.
“The sprays generally require multiple doses per day, whereas a single dose of a nasal vaccine may protect for months,” he said.
“Both have the allure of being variant-proof,” Dr. Topol added.
Thinking small
Many laboratories are shifting from treatments using monoclonal antibodies to treatments using smaller antibody fragments called “nanobodies” because they are more cost-effective and are able to last longer in storage, Dr. Mäkelä and colleagues noted.
Several of these nanobodies have shown promise against viruses in cell culture or animal models, including as an intranasal preventive treatment for SARS-CoV-2.
One of these smaller antibodies is being developed from llamas for example; another comes from experiments with yeast to develop synthetic nanobodies; and in a third case, researchers isolated nanobodies from llamas and from mice and showed they could neutralize the SARS-CoV-2 virus.
These nanobodies and TriSb92 target a specific part of the coronavirus spike protein called the receptor-binding domain (RBD). The RBD is where the coronavirus attaches to cells in the body. These agents essentially trick the virus by changing the structure of the outside of cells, so they look like a virus has already fused to them. This way, the virus moves on.
Key findings
The researchers compared mice treated with TriSb92 before and after exposure to SARS-CoV-2. When given in advance, none of the treated mice had SARS-CoV-2 RNA in their lungs, while untreated mice in the comparison group had “abundant” levels.
Other evidence of viral infection showed similar differences between treated and untreated mice in the protective lining of cells called the epithelium inside the nose, nasal mucosa, and airways.
Similarly, when given 2 or 4 hours after SARS-CoV-2 had already infected the epithelium, TriSb92 was linked to a complete lack of the virus’s RNA in the lungs.
It was more effective against the virus, though, when given before infection rather than after, “perhaps due to the initial establishment of the infection,” the researchers note.
The company led by Dr. Mäkelä is now working to secure funding for clinical trials of TriSb92 in humans.
A version of this article first appeared on WebMD.com.
FROM NATURE COMMUNICATIONS
COVID-19 vaccinations lag in youngest children
Case: A 3-year-old girl presented to the emergency department after a brief seizure at home. She looked well on physical exam except for a fever of 103° F and thick rhinorrhea.
The intern on duty methodically worked through the standard list of questions. “Immunizations up to date?” she asked.
“Absolutely,” the child’s mom responded. “She’s had everything that’s recommended.”
“Including COVID-19 vaccine?” the intern prompted.
“No.” The mom responded with a shake of her head. “We don’t do that vaccine.”
That mom is not alone.
COVID-19 vaccines for children as young as 6 months were given emergency-use authorization by the Food and Drug Administration in June 2022 and in February 2023, the Advisory Committee on Immunization Practices included COVID-19 vaccine on the routine childhood immunization schedule.
COVID-19 vaccines are safe in young children, and they prevent the most severe outcomes associated with infection, including hospitalization. Newly released data confirm that the COVID-19 vaccines produced by Moderna and Pfizer also provide protection against symptomatic infection for at least 4 months after completion of the monovalent primary series.
In a Morbidity and Mortality Weekly Report released on Feb. 17, 2023, the Centers for Disease Control and Prevention reported the results of a test-negative design case-control study that enrolled symptomatic children tested for SARS-CoV-2 infection through Feb. 5, 2023, as part of the Increasing Community Access to Testing (ICATT) program.1 ICATT provides SARS-CoV-2 testing to persons aged at least 3 years at pharmacy and community-based testing sites nationwide.
Two doses of monovalent Moderna vaccine (complete primary series) was 60% effective against symptomatic infection (95% confidence interval, 49%-68%) 2 weeks to 2 months after receipt of the second dose. Vaccine effectiveness dropped to 36% (95% CI, 15%-52%) 3-4 months after the second dose. Three doses of monovalent Pfizer-BioNTech vaccine (complete primary series) was 31% effective (95% CI, 7%-49%) at preventing symptomatic infection 2 weeks to 4 months after receipt of the third dose. A bivalent vaccine dose for eligible children is expected to provide more protection against currently circulating SARS-CoV-2 variants.
Despite evidence of vaccine efficacy, very few parents are opting to protect their young children with the COVID-19 vaccine. The CDC reports that, as of March 1, 2023, only 8% of children under 2 years and 10.5% of children aged 2-4 years have initiated a COVID vaccine series. The American Academy of Pediatrics has emphasized that 15.0 million children between the ages of 6 months and 4 years have not yet received their first COVID-19 vaccine dose.
While the reasons underlying low COVID-19 vaccination rates in young children are complex, themes emerge. Socioeconomic disparities contributing to low vaccination rates in young children were highlighted in another recent MMWR article.2 Through Dec. 1, 2022, vaccination coverage was lower in rural counties (3.4%) than in urban counties (10.5%). Rates were lower in Black and Hispanic children than in White and Asian children.
According to the CDC, high rates of poverty in Black and Hispanic communities may affect vaccination coverage by affecting caregivers’ access to vaccination sites or ability to leave work to take their child to be vaccinated. Pediatric care providers have repeatedly been identified by parents as a source of trusted vaccine information and a strong provider recommendation is associated with vaccination, but not all families are receiving vaccine advice. In a 2022 Kaiser Family Foundation survey, parents of young children with annual household incomes above $90,000 were more likely to talk to their pediatrician about a COVID-19 vaccine than families with lower incomes.3Vaccine hesitancy, fueled by general confusion and skepticism, is another factor contributing to low vaccination rates. Admittedly, the recommendations are complex and on March 14, 2023, the FDA again revised the emergency-use authorization for young children. Some caregivers continue to express concerns about vaccine side effects as well as the belief that the vaccine won’t prevent their child from getting sick.
Kendall Purcell, MD, a pediatrician with Norton Children’s Medical Group in Louisville, Ky., recommends COVID-19 vaccination for her patients because it reduces the risk of severe disease. That factored into her own decision to vaccinate her 4-year-old son and 1-year-old daughter, but she hasn’t been able to convince the parents of all her patients. “Some feel that COVID-19 is not as severe for children, so the risks don’t outweigh the benefits when it comes to vaccinating their children.” Back to our case: In the ED the intern reviewed the laboratory testing she had ordered. She then sat down with the mother of the 3-year-old girl to discuss the diagnosis: febrile seizure associated with COVID-19 infection. Febrile seizures are a well-recognized but uncommon complication of COVID-19 in children. In a retrospective cohort study using electronic health record data, febrile seizures occurred in 0.5% of 8,854 children aged 0-5 years with COVID-19 infection.4 About 9% of these children required critical care services. In another cohort of hospitalized children, neurologic complications occurred in 7% of children hospitalized with COVID-19.5 Febrile and nonfebrile seizures were most commonly observed.
“I really thought COVID-19 was no big deal in young kids,” the mom said. “Parents need the facts.”
The facts are these: Through Dec. 2, 2022, more than 3 million cases of COVID-19 have been reported in children aged younger than 5 years. While COVID is generally less severe in young children than older adults, it is difficult to predict which children will become seriously ill. When children are hospitalized, one in four requires intensive care. COVID-19 is now a vaccine-preventable disease, but too many children remain unprotected.
Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She is a member of the AAP’s Committee on Infectious Diseases and one of the lead authors of the AAP’s Recommendations for Prevention and Control of Influenza in Children, 2022-2023. The opinions expressed in this article are her own. Dr. Bryant discloses that she has served as an investigator on clinical trials funded by Pfizer, Enanta, and Gilead. Email her at [email protected]. Ms. Ezell is a recent graduate from Indiana University Southeast with a Bachelor of Arts in English. They have no conflicts of interest.
References
1. Fleming-Dutra KE et al. Morb Mortal Wkly Rep. 2023;72:177-182.
2. Murthy BP et al. Morb Mortal Wkly Rep. 2023;72:183-9.
3. Lopes L et al. KFF COVID-19 vaccine monitor: July 2022. San Francisco: Kaiser Family Foundation, 2022.
4. Cadet K et al. J Child Neurol. 2022 Apr;37(5):410-5.
5. Antoon JW et al. Pediatrics. 2022 Nov 1;150(5):e2022058167.
Case: A 3-year-old girl presented to the emergency department after a brief seizure at home. She looked well on physical exam except for a fever of 103° F and thick rhinorrhea.
The intern on duty methodically worked through the standard list of questions. “Immunizations up to date?” she asked.
“Absolutely,” the child’s mom responded. “She’s had everything that’s recommended.”
“Including COVID-19 vaccine?” the intern prompted.
“No.” The mom responded with a shake of her head. “We don’t do that vaccine.”
That mom is not alone.
COVID-19 vaccines for children as young as 6 months were given emergency-use authorization by the Food and Drug Administration in June 2022 and in February 2023, the Advisory Committee on Immunization Practices included COVID-19 vaccine on the routine childhood immunization schedule.
COVID-19 vaccines are safe in young children, and they prevent the most severe outcomes associated with infection, including hospitalization. Newly released data confirm that the COVID-19 vaccines produced by Moderna and Pfizer also provide protection against symptomatic infection for at least 4 months after completion of the monovalent primary series.
In a Morbidity and Mortality Weekly Report released on Feb. 17, 2023, the Centers for Disease Control and Prevention reported the results of a test-negative design case-control study that enrolled symptomatic children tested for SARS-CoV-2 infection through Feb. 5, 2023, as part of the Increasing Community Access to Testing (ICATT) program.1 ICATT provides SARS-CoV-2 testing to persons aged at least 3 years at pharmacy and community-based testing sites nationwide.
Two doses of monovalent Moderna vaccine (complete primary series) was 60% effective against symptomatic infection (95% confidence interval, 49%-68%) 2 weeks to 2 months after receipt of the second dose. Vaccine effectiveness dropped to 36% (95% CI, 15%-52%) 3-4 months after the second dose. Three doses of monovalent Pfizer-BioNTech vaccine (complete primary series) was 31% effective (95% CI, 7%-49%) at preventing symptomatic infection 2 weeks to 4 months after receipt of the third dose. A bivalent vaccine dose for eligible children is expected to provide more protection against currently circulating SARS-CoV-2 variants.
Despite evidence of vaccine efficacy, very few parents are opting to protect their young children with the COVID-19 vaccine. The CDC reports that, as of March 1, 2023, only 8% of children under 2 years and 10.5% of children aged 2-4 years have initiated a COVID vaccine series. The American Academy of Pediatrics has emphasized that 15.0 million children between the ages of 6 months and 4 years have not yet received their first COVID-19 vaccine dose.
While the reasons underlying low COVID-19 vaccination rates in young children are complex, themes emerge. Socioeconomic disparities contributing to low vaccination rates in young children were highlighted in another recent MMWR article.2 Through Dec. 1, 2022, vaccination coverage was lower in rural counties (3.4%) than in urban counties (10.5%). Rates were lower in Black and Hispanic children than in White and Asian children.
According to the CDC, high rates of poverty in Black and Hispanic communities may affect vaccination coverage by affecting caregivers’ access to vaccination sites or ability to leave work to take their child to be vaccinated. Pediatric care providers have repeatedly been identified by parents as a source of trusted vaccine information and a strong provider recommendation is associated with vaccination, but not all families are receiving vaccine advice. In a 2022 Kaiser Family Foundation survey, parents of young children with annual household incomes above $90,000 were more likely to talk to their pediatrician about a COVID-19 vaccine than families with lower incomes.3Vaccine hesitancy, fueled by general confusion and skepticism, is another factor contributing to low vaccination rates. Admittedly, the recommendations are complex and on March 14, 2023, the FDA again revised the emergency-use authorization for young children. Some caregivers continue to express concerns about vaccine side effects as well as the belief that the vaccine won’t prevent their child from getting sick.
Kendall Purcell, MD, a pediatrician with Norton Children’s Medical Group in Louisville, Ky., recommends COVID-19 vaccination for her patients because it reduces the risk of severe disease. That factored into her own decision to vaccinate her 4-year-old son and 1-year-old daughter, but she hasn’t been able to convince the parents of all her patients. “Some feel that COVID-19 is not as severe for children, so the risks don’t outweigh the benefits when it comes to vaccinating their children.” Back to our case: In the ED the intern reviewed the laboratory testing she had ordered. She then sat down with the mother of the 3-year-old girl to discuss the diagnosis: febrile seizure associated with COVID-19 infection. Febrile seizures are a well-recognized but uncommon complication of COVID-19 in children. In a retrospective cohort study using electronic health record data, febrile seizures occurred in 0.5% of 8,854 children aged 0-5 years with COVID-19 infection.4 About 9% of these children required critical care services. In another cohort of hospitalized children, neurologic complications occurred in 7% of children hospitalized with COVID-19.5 Febrile and nonfebrile seizures were most commonly observed.
“I really thought COVID-19 was no big deal in young kids,” the mom said. “Parents need the facts.”
The facts are these: Through Dec. 2, 2022, more than 3 million cases of COVID-19 have been reported in children aged younger than 5 years. While COVID is generally less severe in young children than older adults, it is difficult to predict which children will become seriously ill. When children are hospitalized, one in four requires intensive care. COVID-19 is now a vaccine-preventable disease, but too many children remain unprotected.
Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She is a member of the AAP’s Committee on Infectious Diseases and one of the lead authors of the AAP’s Recommendations for Prevention and Control of Influenza in Children, 2022-2023. The opinions expressed in this article are her own. Dr. Bryant discloses that she has served as an investigator on clinical trials funded by Pfizer, Enanta, and Gilead. Email her at [email protected]. Ms. Ezell is a recent graduate from Indiana University Southeast with a Bachelor of Arts in English. They have no conflicts of interest.
References
1. Fleming-Dutra KE et al. Morb Mortal Wkly Rep. 2023;72:177-182.
2. Murthy BP et al. Morb Mortal Wkly Rep. 2023;72:183-9.
3. Lopes L et al. KFF COVID-19 vaccine monitor: July 2022. San Francisco: Kaiser Family Foundation, 2022.
4. Cadet K et al. J Child Neurol. 2022 Apr;37(5):410-5.
5. Antoon JW et al. Pediatrics. 2022 Nov 1;150(5):e2022058167.
Case: A 3-year-old girl presented to the emergency department after a brief seizure at home. She looked well on physical exam except for a fever of 103° F and thick rhinorrhea.
The intern on duty methodically worked through the standard list of questions. “Immunizations up to date?” she asked.
“Absolutely,” the child’s mom responded. “She’s had everything that’s recommended.”
“Including COVID-19 vaccine?” the intern prompted.
“No.” The mom responded with a shake of her head. “We don’t do that vaccine.”
That mom is not alone.
COVID-19 vaccines for children as young as 6 months were given emergency-use authorization by the Food and Drug Administration in June 2022 and in February 2023, the Advisory Committee on Immunization Practices included COVID-19 vaccine on the routine childhood immunization schedule.
COVID-19 vaccines are safe in young children, and they prevent the most severe outcomes associated with infection, including hospitalization. Newly released data confirm that the COVID-19 vaccines produced by Moderna and Pfizer also provide protection against symptomatic infection for at least 4 months after completion of the monovalent primary series.
In a Morbidity and Mortality Weekly Report released on Feb. 17, 2023, the Centers for Disease Control and Prevention reported the results of a test-negative design case-control study that enrolled symptomatic children tested for SARS-CoV-2 infection through Feb. 5, 2023, as part of the Increasing Community Access to Testing (ICATT) program.1 ICATT provides SARS-CoV-2 testing to persons aged at least 3 years at pharmacy and community-based testing sites nationwide.
Two doses of monovalent Moderna vaccine (complete primary series) was 60% effective against symptomatic infection (95% confidence interval, 49%-68%) 2 weeks to 2 months after receipt of the second dose. Vaccine effectiveness dropped to 36% (95% CI, 15%-52%) 3-4 months after the second dose. Three doses of monovalent Pfizer-BioNTech vaccine (complete primary series) was 31% effective (95% CI, 7%-49%) at preventing symptomatic infection 2 weeks to 4 months after receipt of the third dose. A bivalent vaccine dose for eligible children is expected to provide more protection against currently circulating SARS-CoV-2 variants.
Despite evidence of vaccine efficacy, very few parents are opting to protect their young children with the COVID-19 vaccine. The CDC reports that, as of March 1, 2023, only 8% of children under 2 years and 10.5% of children aged 2-4 years have initiated a COVID vaccine series. The American Academy of Pediatrics has emphasized that 15.0 million children between the ages of 6 months and 4 years have not yet received their first COVID-19 vaccine dose.
While the reasons underlying low COVID-19 vaccination rates in young children are complex, themes emerge. Socioeconomic disparities contributing to low vaccination rates in young children were highlighted in another recent MMWR article.2 Through Dec. 1, 2022, vaccination coverage was lower in rural counties (3.4%) than in urban counties (10.5%). Rates were lower in Black and Hispanic children than in White and Asian children.
According to the CDC, high rates of poverty in Black and Hispanic communities may affect vaccination coverage by affecting caregivers’ access to vaccination sites or ability to leave work to take their child to be vaccinated. Pediatric care providers have repeatedly been identified by parents as a source of trusted vaccine information and a strong provider recommendation is associated with vaccination, but not all families are receiving vaccine advice. In a 2022 Kaiser Family Foundation survey, parents of young children with annual household incomes above $90,000 were more likely to talk to their pediatrician about a COVID-19 vaccine than families with lower incomes.3Vaccine hesitancy, fueled by general confusion and skepticism, is another factor contributing to low vaccination rates. Admittedly, the recommendations are complex and on March 14, 2023, the FDA again revised the emergency-use authorization for young children. Some caregivers continue to express concerns about vaccine side effects as well as the belief that the vaccine won’t prevent their child from getting sick.
Kendall Purcell, MD, a pediatrician with Norton Children’s Medical Group in Louisville, Ky., recommends COVID-19 vaccination for her patients because it reduces the risk of severe disease. That factored into her own decision to vaccinate her 4-year-old son and 1-year-old daughter, but she hasn’t been able to convince the parents of all her patients. “Some feel that COVID-19 is not as severe for children, so the risks don’t outweigh the benefits when it comes to vaccinating their children.” Back to our case: In the ED the intern reviewed the laboratory testing she had ordered. She then sat down with the mother of the 3-year-old girl to discuss the diagnosis: febrile seizure associated with COVID-19 infection. Febrile seizures are a well-recognized but uncommon complication of COVID-19 in children. In a retrospective cohort study using electronic health record data, febrile seizures occurred in 0.5% of 8,854 children aged 0-5 years with COVID-19 infection.4 About 9% of these children required critical care services. In another cohort of hospitalized children, neurologic complications occurred in 7% of children hospitalized with COVID-19.5 Febrile and nonfebrile seizures were most commonly observed.
“I really thought COVID-19 was no big deal in young kids,” the mom said. “Parents need the facts.”
The facts are these: Through Dec. 2, 2022, more than 3 million cases of COVID-19 have been reported in children aged younger than 5 years. While COVID is generally less severe in young children than older adults, it is difficult to predict which children will become seriously ill. When children are hospitalized, one in four requires intensive care. COVID-19 is now a vaccine-preventable disease, but too many children remain unprotected.
Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She is a member of the AAP’s Committee on Infectious Diseases and one of the lead authors of the AAP’s Recommendations for Prevention and Control of Influenza in Children, 2022-2023. The opinions expressed in this article are her own. Dr. Bryant discloses that she has served as an investigator on clinical trials funded by Pfizer, Enanta, and Gilead. Email her at [email protected]. Ms. Ezell is a recent graduate from Indiana University Southeast with a Bachelor of Arts in English. They have no conflicts of interest.
References
1. Fleming-Dutra KE et al. Morb Mortal Wkly Rep. 2023;72:177-182.
2. Murthy BP et al. Morb Mortal Wkly Rep. 2023;72:183-9.
3. Lopes L et al. KFF COVID-19 vaccine monitor: July 2022. San Francisco: Kaiser Family Foundation, 2022.
4. Cadet K et al. J Child Neurol. 2022 Apr;37(5):410-5.
5. Antoon JW et al. Pediatrics. 2022 Nov 1;150(5):e2022058167.
NOVIDs: Do some have the genes to dodge COVID?
As a field service representative for a slot machine company, Ryan Alexander, 37, of Louisville, Ky., spends his working hours in casinos, covering a large territory including Norfolk, Va., Indianapolis, and Charlotte. Social distancing in the casinos is not the norm. Despite all this up-close contact with people, he said he is still COVID-free, 3 years into the pandemic.
There was one nervous night when his temperature rose to 101° F, and he figured the virus had caught up with him. “I took a test and was fine,” he said, relieved that the result was negative. The fever disappeared, and he was back to normal soon. “Maybe it was just an exhausting day.”
Mr. Alexander is one of those people who have managed – or at least think they have managed – to avoid getting COVID-19.
He is, some say, a NOVID. While some scientists cringe at the term, it’s caught on to describe these virus super-dodgers. Online entrepreneurs offer NOVID-19 T-shirts, masks, and stickers, in case these super-healthy or super-lucky folks want to publicize their good luck. On Twitter, NOVIDs share stories of how they’ve done it.
How many NOVIDs?
As of March 16, according to the CDC, almost 104 million cases of COVID – about one-third of the U.S. population – have been reported, but many cases are known to go unreported. About half of American adults surveyed said they have had COVID, according to a December report by the COVID States Project, a multiuniversity effort to supply pandemic data.
As the numbers settle over time, though, it becomes clearer that some in the U.S. have apparently managed to avoid the virus.
But some scientists bristle at the term NOVIDs. They prefer the term “resisters,” according to Elena Hsieh, MD, associate professor of pediatrics and immunology at the University of Colorado at Denver, Aurora. Currently, she said, there is much more information on who is more susceptible to contracting severe COVID than who is resistant.
Dr. Hsieh is one of the regional coordinators for the COVID Human Genetic Effort, an international consortium of more than 250 researchers and doctors dedicated to discovering the genetic and immunological bases of the forms of SARS-CoV-2 infection. These researchers and others are looking for explanations for why some people get severe COVID while others seem resistant despite repeated exposure.
Resistance research
In determining explanations for resistance to infection, “the needle in the haystack that we are looking for is a change in the genetic code that would allow for you to avoid entry of the virus into the cell,” Dr. Hsieh said. “That is what being resistant to infection is.”
Part of the reason it’s so difficult to study resistance is defining a resister, she said. While many people consider themselves among that group because they’re been exposed multiple times – even with close family members infected and sick, yet they still felt fine – that doesn’t necessarily make them a resister, she said.
Those people could have been infected but remained without symptoms. “Resistance means the virus was inside you, it was near your cell and it did not infect your cell,” Dr. Hsieh said.
“I don’t think we know a lot so far,” Dr. Hsieh said about resisters. “I do believe that, just like there are genetic defects that make someone more susceptible, there are likely to be genetic defects that make somebody less susceptible.’’
“To identify genetic variants that are protective is a really challenging thing to do,” agreed Peter K. Gregersen, MD, professor of genetics at the Feinstein Institutes for Medical Research at Northwell Health in Manhasset, N.Y. Dr. Gregersen is also a regional coordinator for the COVID Human Genetic Effort.
He suspects the number found to be truly resistant to COVID – versus dodging it so far – is going to be very small or not found at all.
“It may exist for COVID or it may not,” he said. Some people may simply have what he calls a robust immune response in the upper part of the throat, perhaps killing off the virus quickly as soon as it enters, so they don’t get a positive test.
Genetic resistance has been found for other diseases, such as HIV.
“For HIV, scientists have been able to identify a specific gene that codes for a protein that can prevent individuals from getting infected,” said Sabrina Assoumou, MD, MPH, professor of medicine at Boston University, who researches HIV.
However, she said, “we haven’t yet found a similar gene or protein that can prevent people from getting infected with SARS-CoV-2.”
What has been found “is that some people might have a mutation in a gene that encodes for what’s called human leukocyte antigen (HLA),” Dr. Assoumou said. HLA, a molecule found on the surface of most cells, has a crucial role in the immune response to foreign substances. “A mutation in HLA can make people less likely to have symptoms if they get infected. Individuals still get infected, but they are less likely to have symptoms.”
Other research has found that those with food allergies are also less likely to be infected. The researchers have speculated that the inflammation characteristic of allergic conditions may reduce levels of a protein called the ACE2 receptor on the surface of airway cells. The SARS-CoV-2 virus uses the receptor to enter the cells, so if levels are low, that could reduce the ability of the virus to infect people.
The COVID Human Genetic Effort continues to search for participants, both those who were admitted to a hospital or repeatedly seen at a hospital because of COVID, as well as those who did not get infected, even after “intense and repeated” exposure.
The number of people likely to be resistant is much smaller, Dr. Hsieh said, than the number of people susceptible to severe disease.
The testing ... or lack thereof factor
The timing of testing and a person’s “infection profile” may be factors in people incorrectly declaring themselves NOVIDs, said Anne Wyllie, PhD, a research scientist in epidemiology at the Yale School of Public Health in New Haven, Conn., and a codeveloper of a saliva PCR test for COVID.
“Infection profiles can vary between individuals,” she said. For some, the infection may start in the lower respiratory tract, others in the higher respiratory tract. “Depending on where the virus takes up residence, that can affect test results.”
Then there’s the following-instructions factor. “It’s very likely that due to tests not being done at the right time, with the right sample, or not repeated if there is ongoing evidence of symptoms, that there are individuals out there who believe they are NOVIDs but just missed catching their infection at the window of opportunity.” Dr. Wyllie said.
Susceptibility research
“The part we have proven is the genetic defect that would make you more susceptible to having severe disease,” Dr. Hsieh said.
Many published papers report that inherited and/or autoimmune deficiencies of type I interferon immunity, important for combating viral infections and modulating the immune response, can be a significant cause of life-threatening COVID pneumonia.
More recently, researchers, including Jean-Laurent Casanova, MD, PhD, professor at Rockefeller University, New York, and cofounder of the COVID Human Genome Effort, reported that deficiencies in a gene that plays a role in built-in immunity (the early response), and a gene involved in signaling within the immune cells, impair interferon production and may be the basis of severe COVID pneumonia.
NOVIDs’ habits run the gamut
As scientists continue their research, the NOVIDs have their own ideas about why they’ve dodged the pandemic bullet, and they have a variety of approaches to handling the pandemic now.
Ryan Alexander, the field rep who travels to casinos, is up to date on his vaccinations and has gotten all the recommended COVID shots. “I was wearing a mask when told to wear masks,” he said.
He still observes the social distance habit but lives life. “I’ve been to three or four concerts in the past couple of years.”
And does he worry his number will eventually be up? “Not at this point, no,” he said.
Joe Asher, 46, said he has not gotten COVID despite being in contact with about 100 people a day, on average. He works as a bartender at an Evansville, Ind., brewery.
“On a Friday night, we can get 500 people,” he said. “I feel like almost everyone at the brewery got it. There’s no way I wasn’t exposed to it all the time.”
However, he said, his coworkers who did get sick were very cautious about not infecting others, partly to help protect a coworker’s family with newborn twins, so that may have helped him stay uninfected, too.
Mr. Asher said he’s in good physical shape, and he’s worked around the public for a long time, so figures maybe that has strengthened his immune system. He’s always been careful about handwashing and said he’s perhaps a bit more conscious of germs than others might be.
Roselyn Mena, 68, a retired teacher in Richmond, Calif., about 16 miles northeast of San Francisco, said she’s managed to avoid the virus even though her husband, Jesus Mena, got infected, as did her two adult children. Now, she remains vigilant about wearing a mask. She tries not to eat inside at restaurants. “I’m super careful,” she said.
Besides her teacher training, Ms. Mena had training as a medical assistant and learned a lot about sanitizing methods. She gets an annual flu shot, washes her hands often, and uses hand sanitizer.
When she shops, she will ask salespeople not wearing masks to please mask. “Only one refused, and she got someone else [to wait on her].”
One reason she is always careful about hygiene, Ms. Mena said, is that “when I get a cold, I get really sick. It last and lasts.” Now, she does worry she might still get it, she said, with the prospect of getting long COVID driving that worry.
In the beginning of the pandemic, Rhonda Fleming, 68, of Los Angeles, lived in a “COVID bubble,” interacting with just a few close family members. As cases went down, she enlarged the bubble. Her two grown daughters got infected, but her granddaughter did not.
She has been vigilant about masking, she said, “and I do still mask in public places.” She has a mask wardrobe, including basic black as well as glittery masks for dressier occasions. “I always carry a mask because inevitably, a cougher surrounds me.”
Now, she will bypass restaurants if she doesn’t feel comfortable with the environment, choosing ones with good air flow. When she flew to Mexico recently, she masked on the plane.
At this point, she said she doesn’t worry about getting infected but remains careful.
Recently, two friends, who have been as diligent as she has about precautions, got infected, “and they don’t know how they got it.”
Bragging rights?
Until researchers separate out the true resisters from those who claim to be, some NOVIDs are simply quietly grateful for their luck, while others mention their COVID-free status to anyone who asks or who will listen, and are proud of it.
And what about those who wear a “NOVID” T-shirt?
“I would think they have a need to convey to the world they are different, perhaps special, because they beat COVID,” said Richard B. Joelson, a New York–based doctor of social work, a psychotherapist, and the author of Help Me! A Psychotherapist’s Tried-and-True Techniques for a Happier Relationship with Yourself and the People You Love. “They didn’t beat COVID, they just didn’t get it.”
Or they may be relieved they didn’t get sick, he said, because they feel defeated when they do. So “it’s a source of pride.” It might be the same people who tell anyone who will listen they never need a doctor or take no medicines, he said.
Even though science may prove many NOVIDs are inaccurate when they call themselves resisters, Dr. Hsieh understands the temptation to talk about it. “It’s kind of cool to think you are supernatural,” she said. “It’s much more attractive than being susceptible. It’s a lot sexier.” ■
A version of this article first appeared on Medscape.com.
As a field service representative for a slot machine company, Ryan Alexander, 37, of Louisville, Ky., spends his working hours in casinos, covering a large territory including Norfolk, Va., Indianapolis, and Charlotte. Social distancing in the casinos is not the norm. Despite all this up-close contact with people, he said he is still COVID-free, 3 years into the pandemic.
There was one nervous night when his temperature rose to 101° F, and he figured the virus had caught up with him. “I took a test and was fine,” he said, relieved that the result was negative. The fever disappeared, and he was back to normal soon. “Maybe it was just an exhausting day.”
Mr. Alexander is one of those people who have managed – or at least think they have managed – to avoid getting COVID-19.
He is, some say, a NOVID. While some scientists cringe at the term, it’s caught on to describe these virus super-dodgers. Online entrepreneurs offer NOVID-19 T-shirts, masks, and stickers, in case these super-healthy or super-lucky folks want to publicize their good luck. On Twitter, NOVIDs share stories of how they’ve done it.
How many NOVIDs?
As of March 16, according to the CDC, almost 104 million cases of COVID – about one-third of the U.S. population – have been reported, but many cases are known to go unreported. About half of American adults surveyed said they have had COVID, according to a December report by the COVID States Project, a multiuniversity effort to supply pandemic data.
As the numbers settle over time, though, it becomes clearer that some in the U.S. have apparently managed to avoid the virus.
But some scientists bristle at the term NOVIDs. They prefer the term “resisters,” according to Elena Hsieh, MD, associate professor of pediatrics and immunology at the University of Colorado at Denver, Aurora. Currently, she said, there is much more information on who is more susceptible to contracting severe COVID than who is resistant.
Dr. Hsieh is one of the regional coordinators for the COVID Human Genetic Effort, an international consortium of more than 250 researchers and doctors dedicated to discovering the genetic and immunological bases of the forms of SARS-CoV-2 infection. These researchers and others are looking for explanations for why some people get severe COVID while others seem resistant despite repeated exposure.
Resistance research
In determining explanations for resistance to infection, “the needle in the haystack that we are looking for is a change in the genetic code that would allow for you to avoid entry of the virus into the cell,” Dr. Hsieh said. “That is what being resistant to infection is.”
Part of the reason it’s so difficult to study resistance is defining a resister, she said. While many people consider themselves among that group because they’re been exposed multiple times – even with close family members infected and sick, yet they still felt fine – that doesn’t necessarily make them a resister, she said.
Those people could have been infected but remained without symptoms. “Resistance means the virus was inside you, it was near your cell and it did not infect your cell,” Dr. Hsieh said.
“I don’t think we know a lot so far,” Dr. Hsieh said about resisters. “I do believe that, just like there are genetic defects that make someone more susceptible, there are likely to be genetic defects that make somebody less susceptible.’’
“To identify genetic variants that are protective is a really challenging thing to do,” agreed Peter K. Gregersen, MD, professor of genetics at the Feinstein Institutes for Medical Research at Northwell Health in Manhasset, N.Y. Dr. Gregersen is also a regional coordinator for the COVID Human Genetic Effort.
He suspects the number found to be truly resistant to COVID – versus dodging it so far – is going to be very small or not found at all.
“It may exist for COVID or it may not,” he said. Some people may simply have what he calls a robust immune response in the upper part of the throat, perhaps killing off the virus quickly as soon as it enters, so they don’t get a positive test.
Genetic resistance has been found for other diseases, such as HIV.
“For HIV, scientists have been able to identify a specific gene that codes for a protein that can prevent individuals from getting infected,” said Sabrina Assoumou, MD, MPH, professor of medicine at Boston University, who researches HIV.
However, she said, “we haven’t yet found a similar gene or protein that can prevent people from getting infected with SARS-CoV-2.”
What has been found “is that some people might have a mutation in a gene that encodes for what’s called human leukocyte antigen (HLA),” Dr. Assoumou said. HLA, a molecule found on the surface of most cells, has a crucial role in the immune response to foreign substances. “A mutation in HLA can make people less likely to have symptoms if they get infected. Individuals still get infected, but they are less likely to have symptoms.”
Other research has found that those with food allergies are also less likely to be infected. The researchers have speculated that the inflammation characteristic of allergic conditions may reduce levels of a protein called the ACE2 receptor on the surface of airway cells. The SARS-CoV-2 virus uses the receptor to enter the cells, so if levels are low, that could reduce the ability of the virus to infect people.
The COVID Human Genetic Effort continues to search for participants, both those who were admitted to a hospital or repeatedly seen at a hospital because of COVID, as well as those who did not get infected, even after “intense and repeated” exposure.
The number of people likely to be resistant is much smaller, Dr. Hsieh said, than the number of people susceptible to severe disease.
The testing ... or lack thereof factor
The timing of testing and a person’s “infection profile” may be factors in people incorrectly declaring themselves NOVIDs, said Anne Wyllie, PhD, a research scientist in epidemiology at the Yale School of Public Health in New Haven, Conn., and a codeveloper of a saliva PCR test for COVID.
“Infection profiles can vary between individuals,” she said. For some, the infection may start in the lower respiratory tract, others in the higher respiratory tract. “Depending on where the virus takes up residence, that can affect test results.”
Then there’s the following-instructions factor. “It’s very likely that due to tests not being done at the right time, with the right sample, or not repeated if there is ongoing evidence of symptoms, that there are individuals out there who believe they are NOVIDs but just missed catching their infection at the window of opportunity.” Dr. Wyllie said.
Susceptibility research
“The part we have proven is the genetic defect that would make you more susceptible to having severe disease,” Dr. Hsieh said.
Many published papers report that inherited and/or autoimmune deficiencies of type I interferon immunity, important for combating viral infections and modulating the immune response, can be a significant cause of life-threatening COVID pneumonia.
More recently, researchers, including Jean-Laurent Casanova, MD, PhD, professor at Rockefeller University, New York, and cofounder of the COVID Human Genome Effort, reported that deficiencies in a gene that plays a role in built-in immunity (the early response), and a gene involved in signaling within the immune cells, impair interferon production and may be the basis of severe COVID pneumonia.
NOVIDs’ habits run the gamut
As scientists continue their research, the NOVIDs have their own ideas about why they’ve dodged the pandemic bullet, and they have a variety of approaches to handling the pandemic now.
Ryan Alexander, the field rep who travels to casinos, is up to date on his vaccinations and has gotten all the recommended COVID shots. “I was wearing a mask when told to wear masks,” he said.
He still observes the social distance habit but lives life. “I’ve been to three or four concerts in the past couple of years.”
And does he worry his number will eventually be up? “Not at this point, no,” he said.
Joe Asher, 46, said he has not gotten COVID despite being in contact with about 100 people a day, on average. He works as a bartender at an Evansville, Ind., brewery.
“On a Friday night, we can get 500 people,” he said. “I feel like almost everyone at the brewery got it. There’s no way I wasn’t exposed to it all the time.”
However, he said, his coworkers who did get sick were very cautious about not infecting others, partly to help protect a coworker’s family with newborn twins, so that may have helped him stay uninfected, too.
Mr. Asher said he’s in good physical shape, and he’s worked around the public for a long time, so figures maybe that has strengthened his immune system. He’s always been careful about handwashing and said he’s perhaps a bit more conscious of germs than others might be.
Roselyn Mena, 68, a retired teacher in Richmond, Calif., about 16 miles northeast of San Francisco, said she’s managed to avoid the virus even though her husband, Jesus Mena, got infected, as did her two adult children. Now, she remains vigilant about wearing a mask. She tries not to eat inside at restaurants. “I’m super careful,” she said.
Besides her teacher training, Ms. Mena had training as a medical assistant and learned a lot about sanitizing methods. She gets an annual flu shot, washes her hands often, and uses hand sanitizer.
When she shops, she will ask salespeople not wearing masks to please mask. “Only one refused, and she got someone else [to wait on her].”
One reason she is always careful about hygiene, Ms. Mena said, is that “when I get a cold, I get really sick. It last and lasts.” Now, she does worry she might still get it, she said, with the prospect of getting long COVID driving that worry.
In the beginning of the pandemic, Rhonda Fleming, 68, of Los Angeles, lived in a “COVID bubble,” interacting with just a few close family members. As cases went down, she enlarged the bubble. Her two grown daughters got infected, but her granddaughter did not.
She has been vigilant about masking, she said, “and I do still mask in public places.” She has a mask wardrobe, including basic black as well as glittery masks for dressier occasions. “I always carry a mask because inevitably, a cougher surrounds me.”
Now, she will bypass restaurants if she doesn’t feel comfortable with the environment, choosing ones with good air flow. When she flew to Mexico recently, she masked on the plane.
At this point, she said she doesn’t worry about getting infected but remains careful.
Recently, two friends, who have been as diligent as she has about precautions, got infected, “and they don’t know how they got it.”
Bragging rights?
Until researchers separate out the true resisters from those who claim to be, some NOVIDs are simply quietly grateful for their luck, while others mention their COVID-free status to anyone who asks or who will listen, and are proud of it.
And what about those who wear a “NOVID” T-shirt?
“I would think they have a need to convey to the world they are different, perhaps special, because they beat COVID,” said Richard B. Joelson, a New York–based doctor of social work, a psychotherapist, and the author of Help Me! A Psychotherapist’s Tried-and-True Techniques for a Happier Relationship with Yourself and the People You Love. “They didn’t beat COVID, they just didn’t get it.”
Or they may be relieved they didn’t get sick, he said, because they feel defeated when they do. So “it’s a source of pride.” It might be the same people who tell anyone who will listen they never need a doctor or take no medicines, he said.
Even though science may prove many NOVIDs are inaccurate when they call themselves resisters, Dr. Hsieh understands the temptation to talk about it. “It’s kind of cool to think you are supernatural,” she said. “It’s much more attractive than being susceptible. It’s a lot sexier.” ■
A version of this article first appeared on Medscape.com.
As a field service representative for a slot machine company, Ryan Alexander, 37, of Louisville, Ky., spends his working hours in casinos, covering a large territory including Norfolk, Va., Indianapolis, and Charlotte. Social distancing in the casinos is not the norm. Despite all this up-close contact with people, he said he is still COVID-free, 3 years into the pandemic.
There was one nervous night when his temperature rose to 101° F, and he figured the virus had caught up with him. “I took a test and was fine,” he said, relieved that the result was negative. The fever disappeared, and he was back to normal soon. “Maybe it was just an exhausting day.”
Mr. Alexander is one of those people who have managed – or at least think they have managed – to avoid getting COVID-19.
He is, some say, a NOVID. While some scientists cringe at the term, it’s caught on to describe these virus super-dodgers. Online entrepreneurs offer NOVID-19 T-shirts, masks, and stickers, in case these super-healthy or super-lucky folks want to publicize their good luck. On Twitter, NOVIDs share stories of how they’ve done it.
How many NOVIDs?
As of March 16, according to the CDC, almost 104 million cases of COVID – about one-third of the U.S. population – have been reported, but many cases are known to go unreported. About half of American adults surveyed said they have had COVID, according to a December report by the COVID States Project, a multiuniversity effort to supply pandemic data.
As the numbers settle over time, though, it becomes clearer that some in the U.S. have apparently managed to avoid the virus.
But some scientists bristle at the term NOVIDs. They prefer the term “resisters,” according to Elena Hsieh, MD, associate professor of pediatrics and immunology at the University of Colorado at Denver, Aurora. Currently, she said, there is much more information on who is more susceptible to contracting severe COVID than who is resistant.
Dr. Hsieh is one of the regional coordinators for the COVID Human Genetic Effort, an international consortium of more than 250 researchers and doctors dedicated to discovering the genetic and immunological bases of the forms of SARS-CoV-2 infection. These researchers and others are looking for explanations for why some people get severe COVID while others seem resistant despite repeated exposure.
Resistance research
In determining explanations for resistance to infection, “the needle in the haystack that we are looking for is a change in the genetic code that would allow for you to avoid entry of the virus into the cell,” Dr. Hsieh said. “That is what being resistant to infection is.”
Part of the reason it’s so difficult to study resistance is defining a resister, she said. While many people consider themselves among that group because they’re been exposed multiple times – even with close family members infected and sick, yet they still felt fine – that doesn’t necessarily make them a resister, she said.
Those people could have been infected but remained without symptoms. “Resistance means the virus was inside you, it was near your cell and it did not infect your cell,” Dr. Hsieh said.
“I don’t think we know a lot so far,” Dr. Hsieh said about resisters. “I do believe that, just like there are genetic defects that make someone more susceptible, there are likely to be genetic defects that make somebody less susceptible.’’
“To identify genetic variants that are protective is a really challenging thing to do,” agreed Peter K. Gregersen, MD, professor of genetics at the Feinstein Institutes for Medical Research at Northwell Health in Manhasset, N.Y. Dr. Gregersen is also a regional coordinator for the COVID Human Genetic Effort.
He suspects the number found to be truly resistant to COVID – versus dodging it so far – is going to be very small or not found at all.
“It may exist for COVID or it may not,” he said. Some people may simply have what he calls a robust immune response in the upper part of the throat, perhaps killing off the virus quickly as soon as it enters, so they don’t get a positive test.
Genetic resistance has been found for other diseases, such as HIV.
“For HIV, scientists have been able to identify a specific gene that codes for a protein that can prevent individuals from getting infected,” said Sabrina Assoumou, MD, MPH, professor of medicine at Boston University, who researches HIV.
However, she said, “we haven’t yet found a similar gene or protein that can prevent people from getting infected with SARS-CoV-2.”
What has been found “is that some people might have a mutation in a gene that encodes for what’s called human leukocyte antigen (HLA),” Dr. Assoumou said. HLA, a molecule found on the surface of most cells, has a crucial role in the immune response to foreign substances. “A mutation in HLA can make people less likely to have symptoms if they get infected. Individuals still get infected, but they are less likely to have symptoms.”
Other research has found that those with food allergies are also less likely to be infected. The researchers have speculated that the inflammation characteristic of allergic conditions may reduce levels of a protein called the ACE2 receptor on the surface of airway cells. The SARS-CoV-2 virus uses the receptor to enter the cells, so if levels are low, that could reduce the ability of the virus to infect people.
The COVID Human Genetic Effort continues to search for participants, both those who were admitted to a hospital or repeatedly seen at a hospital because of COVID, as well as those who did not get infected, even after “intense and repeated” exposure.
The number of people likely to be resistant is much smaller, Dr. Hsieh said, than the number of people susceptible to severe disease.
The testing ... or lack thereof factor
The timing of testing and a person’s “infection profile” may be factors in people incorrectly declaring themselves NOVIDs, said Anne Wyllie, PhD, a research scientist in epidemiology at the Yale School of Public Health in New Haven, Conn., and a codeveloper of a saliva PCR test for COVID.
“Infection profiles can vary between individuals,” she said. For some, the infection may start in the lower respiratory tract, others in the higher respiratory tract. “Depending on where the virus takes up residence, that can affect test results.”
Then there’s the following-instructions factor. “It’s very likely that due to tests not being done at the right time, with the right sample, or not repeated if there is ongoing evidence of symptoms, that there are individuals out there who believe they are NOVIDs but just missed catching their infection at the window of opportunity.” Dr. Wyllie said.
Susceptibility research
“The part we have proven is the genetic defect that would make you more susceptible to having severe disease,” Dr. Hsieh said.
Many published papers report that inherited and/or autoimmune deficiencies of type I interferon immunity, important for combating viral infections and modulating the immune response, can be a significant cause of life-threatening COVID pneumonia.
More recently, researchers, including Jean-Laurent Casanova, MD, PhD, professor at Rockefeller University, New York, and cofounder of the COVID Human Genome Effort, reported that deficiencies in a gene that plays a role in built-in immunity (the early response), and a gene involved in signaling within the immune cells, impair interferon production and may be the basis of severe COVID pneumonia.
NOVIDs’ habits run the gamut
As scientists continue their research, the NOVIDs have their own ideas about why they’ve dodged the pandemic bullet, and they have a variety of approaches to handling the pandemic now.
Ryan Alexander, the field rep who travels to casinos, is up to date on his vaccinations and has gotten all the recommended COVID shots. “I was wearing a mask when told to wear masks,” he said.
He still observes the social distance habit but lives life. “I’ve been to three or four concerts in the past couple of years.”
And does he worry his number will eventually be up? “Not at this point, no,” he said.
Joe Asher, 46, said he has not gotten COVID despite being in contact with about 100 people a day, on average. He works as a bartender at an Evansville, Ind., brewery.
“On a Friday night, we can get 500 people,” he said. “I feel like almost everyone at the brewery got it. There’s no way I wasn’t exposed to it all the time.”
However, he said, his coworkers who did get sick were very cautious about not infecting others, partly to help protect a coworker’s family with newborn twins, so that may have helped him stay uninfected, too.
Mr. Asher said he’s in good physical shape, and he’s worked around the public for a long time, so figures maybe that has strengthened his immune system. He’s always been careful about handwashing and said he’s perhaps a bit more conscious of germs than others might be.
Roselyn Mena, 68, a retired teacher in Richmond, Calif., about 16 miles northeast of San Francisco, said she’s managed to avoid the virus even though her husband, Jesus Mena, got infected, as did her two adult children. Now, she remains vigilant about wearing a mask. She tries not to eat inside at restaurants. “I’m super careful,” she said.
Besides her teacher training, Ms. Mena had training as a medical assistant and learned a lot about sanitizing methods. She gets an annual flu shot, washes her hands often, and uses hand sanitizer.
When she shops, she will ask salespeople not wearing masks to please mask. “Only one refused, and she got someone else [to wait on her].”
One reason she is always careful about hygiene, Ms. Mena said, is that “when I get a cold, I get really sick. It last and lasts.” Now, she does worry she might still get it, she said, with the prospect of getting long COVID driving that worry.
In the beginning of the pandemic, Rhonda Fleming, 68, of Los Angeles, lived in a “COVID bubble,” interacting with just a few close family members. As cases went down, she enlarged the bubble. Her two grown daughters got infected, but her granddaughter did not.
She has been vigilant about masking, she said, “and I do still mask in public places.” She has a mask wardrobe, including basic black as well as glittery masks for dressier occasions. “I always carry a mask because inevitably, a cougher surrounds me.”
Now, she will bypass restaurants if she doesn’t feel comfortable with the environment, choosing ones with good air flow. When she flew to Mexico recently, she masked on the plane.
At this point, she said she doesn’t worry about getting infected but remains careful.
Recently, two friends, who have been as diligent as she has about precautions, got infected, “and they don’t know how they got it.”
Bragging rights?
Until researchers separate out the true resisters from those who claim to be, some NOVIDs are simply quietly grateful for their luck, while others mention their COVID-free status to anyone who asks or who will listen, and are proud of it.
And what about those who wear a “NOVID” T-shirt?
“I would think they have a need to convey to the world they are different, perhaps special, because they beat COVID,” said Richard B. Joelson, a New York–based doctor of social work, a psychotherapist, and the author of Help Me! A Psychotherapist’s Tried-and-True Techniques for a Happier Relationship with Yourself and the People You Love. “They didn’t beat COVID, they just didn’t get it.”
Or they may be relieved they didn’t get sick, he said, because they feel defeated when they do. So “it’s a source of pride.” It might be the same people who tell anyone who will listen they never need a doctor or take no medicines, he said.
Even though science may prove many NOVIDs are inaccurate when they call themselves resisters, Dr. Hsieh understands the temptation to talk about it. “It’s kind of cool to think you are supernatural,” she said. “It’s much more attractive than being susceptible. It’s a lot sexier.” ■
A version of this article first appeared on Medscape.com.