The US is clamping down on Covid vaccinations, with the Food and Drug Administration (FDA) announcing that it would allow the use of Covid vaccines in over-65s and those with certain medical conditions, but might require additional studies before approving the shots for other healthy Americans.
The jab will also no longer be recommended for healthy children or healthy pregnant women, ending a pandemic-era policy aimed at protecting all Americans from the coronavirus.
At the same time, the FDA has asked Pfizer and Moderna to expand the warning labels on their Covid-19 vaccines about the risk of a possible heart injury side effect linked to the mRNA shots, primarily in teen boys and young men, citing findings from a study published last year and new agency data (see story below).
Health Secretary Robert F Kennedy Jr announced the new policy on Tuesday, saying the Centres for Disease Control and Prevention would drop its years-long guidance that the vaccine be offered to children six months and older.
He also withdrew the additional recommendation for immunising pregnant women intended to shield mothers and younger infants, who can be at higher risk of severe illness, reports The New York Times.
In his video announcement posted on X, Kennedy, flanked by Dr Marty Makary and Dr Jay Bhattacharya who lead the FDA and the National Institutes of Health, said that there were no clinical data to support additional shots for healthy children.
Overall, the absolute numbers of children who became seriously ill from Covid are low.
Some public health experts immediately denounced the decision, pointing out that the risk of severe disease and hospitalisation among infants is comparable to that among adults 65 and older. Others roundly condemned the decision to stop recommending the shots for pregnant women, who are at high risk of severe illness and complications from Covid.
The new policy follows last week’s decision by the FDA to require new data before approving the jabs for children. It also rolled back eligibility for this coming winter season’s Covid vaccine, saying it should be administered only to people over 65 and those with certain medical conditions.
Writing in The New England Journal of Medicine, Dr Vinay Prasad, the FDA’s vaccine division chief, and Makary said that “at this point, the additional doses offer uncertain benefits to many young and middle-aged people who have already been vaccinated or have had Covid”.
They added that the FDA would approve vaccines for high-risk persons but would, at the same time, “demand robust, gold-standard data on persons at low risk”.
During the pandemic, both Prasad and Makary criticised vaccine mandates and other public health measures intended to fight the coronavirus.
According to CDC data, about 13% of children and just more than 14% of pregnant women have received the updated Covid shot offered since last winter.
Dr Denise Jamieson, who is on the immunisation committee of the American College of Obstetricians and Gynaecologists and an adviser to the CDC on vaccines, noted that pregnant women were at higher risk of hospitalisation, including intensive care, and of dying.
Covid infection during pregnancy is also “associated with a number of adverse pregnancy outcomes including pre-eclampsia, preterm birth and stillbirth”, especially among women with severe disease, according to the CDC.
“With Covid still circulating, pregnant women and their babies who are born too young to be vaccinated are going to be at risk for Covid and for the severe complications,” Jamieson said.
“I’m disappointed that this won’t remain an option for pregnant women who would like to protect themselves,” she added.
Vaccinating pregnant women extends the protection to their unborn until the babies are about six months old.
From birth to six months, those youngest infants face a risk of hospitalisation on par with adults aged 65 to 74, according to Dr Sean O'Leary, a paediatric vaccine expert for the American Academy of Paediatrics.
The CDC had also recommended a series of Covid shots beginning at six months for children who had never had Covid.
About three-quarters of the mothers of infants who were hospitalised for Covid had not received an updated vaccine, said Dr Naima Joseph, a maternal-foetal medicine specialist and expert in perinatal infectious diseases.
“That just goes to show that infants really remain at high risk for hospitalisation, and that the only source of protective immunity is through vaccination,” she added.
Federal health officials did not offer an explanation for removing the vaccine from the list of shots recommended for pregnant women, focusing instead on children.
Makary said there was “no evidence healthy kids need it today, and most countries have stopped recommending it for children”.
The WHO recommends a single shot for children and adolescents with medical conditions that may increase their risk from Covid. In Europe, many countries do not recommend the vaccines for healthy children under five, but the shots are approved for everyone six months and older.
“At this stage, we have not seen really a significant burden of disease in young kids, and particularly with the new version of the virus,” said Marco Cavaleri, who heads the office of biological health threats and vaccines strategy at the European Medicines Agency.
“Vaccination of pregnant women is still very relevant, and I would push for that, but vaccination of kids, for me, is less important.”
Reasonable
During a livestreamed event recently, Prasad said he thought the new approach to Covid vaccination was “a reasonable compromise”, leaving the shots available to many Americans “but also generating evidence”.
Some Americans are worried that the FDA has “not fully documented and interrogated the safety harms” of the vaccines, while others “are desperate for additional protection”, he added, describing himself as an “extreme pro-vaccine person”.
Before approving Covid vaccines for wider use, the FDA “anticipates the need” for new clinical trials in which participants under 65 are randomly assigned to receive the new shots or a placebo, Prasad and Makary wrote in the journal.
A spokesman for the agency later said that clinical trials would be required, not just recommended or anticipated.
Vaccine manufacturers should follow participants for at least six months and evaluate whether the effect of the vaccine persists over that time, Prasad said.
However, some experts believe the new criteria go too far, erecting barriers for people who will want the shots.
“This is overly restrictive and will deny vaccines to many people who want to be vaccinated,” said Dr Anna Durbin, director of the Centre for Immunisation Research at Johns Hopkins University.
Dr Daniel Griffin, a physician in New York who has treated thousands of Covid patients, said: “I think that changes like this will lead to more unnecessary deaths. What they’re really doing is very slowly reducing vaccination in the country.”
Some experts said that while they agreed with aspects of the agency’s rationale, the new restrictions would unnecessarily limit access for healthy Americans who may be at high risk from Covid because of their jobs or for other reasons.
Favourable safety profile
In a statement, Pfizer said it was evaluating the details and was in ongoing discussion with the FDA. The company said its Covid vaccines have been given to more than 1bn people, “generating robust data demonstrating a favourable safety profile”.
Moderna, maker of another widely-used Covid vaccine, said it appreciated the FDA’s clear guidance and would work with the agency to provide the data to ensure access to its vaccine for Americans.
The new recommendations mark a departure from the previous policy of offering annual Covid shots to everyone six months and older, the “most aggressive” strategy when compared with the standards used in other nations, the FDA officials noted.
Makary and Prasad have often been described as Covid contrarians. But recommending the vaccine for every American six months and older, regardless of health status, is in fact the “contrarian” approach, they said in their livestream.
“Now we are back in line with the rest of the world,” Prasad said. Other high-income nations have long adopted “risk-based” recommendations targeting the shots to those most in need.
The original vaccine trials were conducted years ago, at the onset of the pandemic. The virus was very different, and most people had not yet been exposed. It’s unclear whether the shots would still prove as beneficial now, the officials said.
Yet federal agencies do have robust data showing that even now Covid vaccines offer modest protection against hospitalisation and death even at younger ages, some scientists noted.
“We need to also include the role of observational data and the role of the CDC in continuously monitoring vaccine safety and efficacy,” Jamieson said. “We have a lot of accumulated data at this point.”
But Prasad cast doubt on the quality of such data, saying those studies are “at high risk of bias and broadly uninformative”.
He and Makary also said there was insufficient evidence that getting the vaccine would prevent transmission of the virus to others at risk from the virus.
Deaths from Covid have fallen each year since the start of the pandemic, but there were still roughly 1 000 deaths per week last winter, most of them 75 and older.
In the year ending in August, the CDC reported 150 paediatric deaths, a number comparable to deaths among children in a typical flu season.
Children under four remain at high risk from Covid, but the absolute numbers of seriously affected children are low, the officials said, and children with medical conditions would still qualify for the vaccine.
The proposed regulations align with the agency’s recent decision to narrow the eligibility for the Novavax Covid vaccine.
Antibiotics and Covid
Meanwhile, a recent large cohort study was undertaken to ascertain whether antibiotics targeting community-acquired bacterial pneumonia were associated with clinical benefit to hospitalised patients across the USA as part of treatment for non-severe Covid.
It was led by the University of Wisconsin-Madison (Michael Pulia, MD, PhD; Meggie Griffin MS et al), who wrote in JAMA Network Open that patients admitted with non-severe Covid continue to receive community-acquired pneumonia (CAP) antibiotic treatment, despite a low risk of bacterial co-infection.
This unnecessary prescribing contributes to global antibiotic resistance and also poses a threat to individual patients, they said, finding no benefit associated with antibiotic treatment for patients hospitalised with non-severe Covid-19, and thus arguing against its routine use, given the known harms.
And while their research, with target trial emulation including 520 405 patients, did not find clinically significant absolute differences, it did find statically significantly higher odds of clinical deterioration and in-hospital mortality associated with antibiotic treatment for Covid infection using propensity score-weighted and matched models.
In an editorial comment from Sean Ong MBS and Steven Tong PhD (University of Melbourne and University of Toronto), the authors wrote that while some of these patients may be co-infected or secondarily infected with bacteria, there is no criterion standard laboratory test or biomarker than can reliably distinguish between viral or bacterial causes of pneumonia.
As a result, most patients hospitalised with pneumonia receive antibiotic coverage, even though some do not require it.
“The findings from Pulia et al support an approach in which hospitalised patients with Covid-19 should not routinely receive antibiotic treatment, unless there is another clear indication for antibiotics, e.g, microbiologically confirmed bacterial pneumonia or diagnosis of other non-pneumonia bacterial infection,” they wrote.
This same management conundrum applies to Covid-19 pneumonia, they added. A meta-analysis of 171 studies including 171 262 patients, estimated that 5.1% of patients with Covid-19 had bacterial co-infection at presentation, while 13.1% had secondary bacterial infection.
Despite these low proportions, the prevalence of antibiotic prescribing was high (74.6%; 95% CI, 68.3%-80.0%).
They agreed that this may stem from a clinician’s understandable fear of missing organisms, but said it unnecessarily exposed a group of patients to the potential harms of antibiotic treatment and contributes to the global issue of antimicrobial resistance.
“The truth is that not all clinical questions can be answered using prospective randomised clinical trials (RCTs); carefully designed observational studies may make important contributions in understanding the causal impact of interventions.
“This study … the largest to our knowledge evaluating the association of antibiotic treatment with clinical outcomes in Covid-19, is an excellent example.
“In their target trial emulation study, Pulia et al demonstrated that for many patients, the receipt or not of antibiotics for acute Covid-19 did not change clinical outcomes.
“The massive sample size of 520 405 patients across 1 053 hospitals highlights a key strength of population-based studies using health administrative databases: the ability to attain sample sizes that are impossible with RCTs.
“Observational studies using health administrative databases use data collected as part of routine clinical care, resulting in minimal additional cost for study conduct, beyond that needed for data linkage and analysis.”
These studies, they added, “have an additional advantage over RCTs in that they may have potentially better generalisability, since they avoid issues with trial recruitment procedures that may bias toward inclusion of younger, healthier patients with less severe disease”.
Meanwhile, letters were sent to Pfizer and BioNTech about their Comirnaty vaccine and Moderna about its Spikevax jab, reports CBS.
Both vaccines previously carried warnings about how the risk of the heart side effects – myocarditis (an inflammation of the heart muscle) and pericarditis (inflammation of the membrane surrounding the heart) – appeared higher in young men, generally within the first week after vaccination.
While the earlier labels specified ages 18 to 24 for Moderna’s vaccine and 12 to 17 for Pfizer’s, the new warning will apply to males aged 16 to 25 for both vaccines.
The rate of myocarditis and pericarditis was around eight cases per million doses for children and adults under 65 after use of that season’s vaccines, the FDA said.
The “highest estimated incidence was in males 16 to 25”, with a rate of 38 cases per million.
The CDC had previously described rates of myocarditis and pericarditis as rare after Covid-19 vaccination.
CDC officials told the agency’s vaccine advisers last month that acute myocarditis “tends to resolve quickly” after vaccination, and no increased risk had been seen in data from recent seasons in people 12 to 39.
Pfizer and Moderna had “within 30 calendar days of the date of this letter” to try to rebut the demand.
The letters appeared on the FDA’s website hours ahead of a hearing organised by the Senate Homeland Security and Governmental Affairs Committee on “how health officials downplayed and hid myocarditis and other adverse events associated with the Covid-19 vaccines”.
The FDA says the warnings were spurred by new data from the agency’s safety surveillance system and results published in October from scientists following up with people who developed Covid-19 vaccine-associated myocarditis.
Scientists in that study followed up with people who had faced chest pain and elevated amounts of troponin in their blood, a protein that usually signals some kind of heart damage. They were predominantly young adolescent males.
“While their clinical course was nearly always mild with a low prevalence and extent of cardiac dysfunction, myocardial injury was common,” the scientists wrote in the study, which was co-authored by FDA officials.
Similar to what the study described, the FDA’s new warning also says that the heart MRI findings showed “improvement over time in most people”.
“It is not known if these heart MRI findings might predict long-term heart effects of myocarditis. Studies are under way to find out if there are long-term heart effects in people who have had myocarditis after receiving an mRNA Covid-19 vaccine,” the agency said.
The New York Times article – FDA poised to restrict access to Covid vaccines (Restricted access)
CBS – FDA expands COVID vaccine warning about heart side effect risk for young males
See more from MedicalBrief archives:
Antibiotics over-used in ICU before and during Covid – SA study
Over-prescribed antibiotics cause significant harm – large US analysis
Vaccines provide ongoing prevention of hospitalisation and death – Large US study
Covid-19 vaccines don’t cause many harms, US review finds
Boosters up to 68% effective against hospitalisation following Omicron reinfection – CDC study