Who’ll Get Long COVID? Just a Look at a Patient Gives Clues

Authors: Dennis Thompson Jul 19, 2022 The Indiana Gazette

ometimes just looking at a person can give clues to their likelihood of developing long COVID after a bout with the virus.

For example, obese people are five times more likely to suffer long COVID symptoms that persist at least three months after their infection clears, a major new U.S. study finds.

Another risk factor: Experiencing hair loss during COVID-19 illness, the same study found.

Headache and sore throat during infection also greatly increase a person’s risk of long-haul symptoms, the researchers added.

However, the results also showed that other risk factors for COVID-19 infection do not necessarily mean a person will develop long COVID, noted senior researcher Eileen Crimmins, chair of gerontology for the University of Southern California and director of the USC/UCLA Center on Biodemography and Population Health.

“What’s somewhat more interesting are the things that didn’t matter,” Crimmins said. “Gender didn’t predict long COVID. Race/ethnicity didn’t predict long COVID. And having conditions like hypertension [high blood pressure], heart disease, cancer, they didn’t predict long COVID.”

Overall, 23% of people infected with COVID-19 can be expected to develop long-haul symptoms, regardless of whether their infection was severe enough to require hospitalization, Crimmins and her colleagues reported. The study was published online recently in the journal Scientific Reports.

The World Health Organization defines long COVID as symptoms that last 12 weeks or longer after the initial infection has cleared, the researchers said.

“A significant number of people may have trouble working, taking care of their families, doing the things they need to do day-to-day because they’ve had the condition,” Crimmins said. “So, it’s not a nothing disease.”

These numbers are based on the Understanding America Study COVID-19 National Panel, an ongoing regular survey of more than 8,400 U.S. adults.

Starting every two weeks in March 2020, panel members were asked to fill out a questionnaire detailing their health status and any symptoms they might be having.

During the following year, about 10% of total participants reported that they’d been diagnosed with or tested positive for COVID-19.

The researchers focused in on 308 people who had COVID-19 and had reported their health status and symptoms before, during, and at least three months after their initial diagnosis.

What factors influenced the odds of long COVID the most? Obesity increased a person’s risk of long COVID by nearly five and a half times, the results showed. Other prominent risk factors included hair loss during infection, which increased sevenfold the risk of long COVID. Headache and sore throat each increased a person’s risk by more than three times.

It’s likely that obesity and hair loss are both tied to the amount of inflammation a person suffers during their COVID-19 infection, which can wreak havoc on their body’s organs, explained Dr. William Schaffner, medical director of the National Foundation for Infectious Diseases.

“Perhaps obesity allows that inflammation to persist for a longer period of time, therefore resulting in symptoms,” Schaffner said. “Hair loss is kind of new to me, but that’s obviously going to be some sort of symptom that relates somehow to inflammation.”

Surprisingly, age, gender, race, education, smoking, and preexisting health conditions like diabetes or asthma didn’t appear to influence the risk of long COVID.

The most common symptoms people developed during COVID that persisted months later included:

  • Headache (22%)
  • Runny or stuffy nose (19%)
  • Abdominal discomfort (18%)
  • Fatigue (17%)
  • Diarrhea (13%)

The study did not find other symptoms that have been commonly reported by long COVID-19 patients, including brain fog and joint pain, Schaffner noted.

“So there are some things that reinforce what’s in the literature and some other things that are a little different,” Schaffner said.

Despite that, Schaffner praised the study as a “noteworthy addition to the literature” that should help the many long COVID centers that have opened up around the country to deal with this phenomenon.

“The main thing I take away from this is that long COVID is not unusual. In fact, it’s rather common,” Schaffner said. “It’s persistent and it will require a great deal of medical attention going forward. A lot of medical resources will have to be devoted to this, and those resources will largely be outside the hospital, including supportive care, physical therapy and even some psychological support for these patients.”

Crimmins added it could take years, and even decades, to fully understand the long-term effects of COVID-19.

Research into the 1918 influenza pandemic found that fetuses in utero when moms caught the flu had a 25% higher risk of heart disease by the time they were in their 70s, Crimmins noted.

“There are things that may happen in this population to their underlying health that may not be immediately obvious, but could have relatively significant long-term effects,” Crimmins said of long COVID patients.

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The CDC Is Breaking Trust in Childhood Vaccination

With its unscientific push to vaccinate all infants and toddlers against COVID, the agency will harm vaccine uptake for more significant diseases

Authors: LESLIE BIENEN, TRACY BETH HØEG JULY 05, 2022 Tablet

On June 18, the U.S. Centers for Disease Control and Prevention (CDC) officially recommended Pfizer and Moderna COVID-19 vaccines for all children between the ages of 6 months and 5 years. While the Food and Drug Administration (FDA) is the agency responsible for authorizing emergency use of vaccines, it’s the CDC that crafts subsequent messaging, makes specific recommendations, and prioritizes who can, should, or should not get vaccinated. In her briefing, CDC Director Rochelle Walensky strongly urged all parents of the nearly 20 million American children in this age group to vaccinate them as soon as possible.

For some parents, Walensky’s briefing came as a huge relief. But if polling from May is anything to go by, a larger number of parents likely greeted the recommendation with skepticism. Even before the underwhelming trial results came out, only 18% of surveyed parents reported that they planned to vaccinate their babies and toddlers. Nationally, uptake in minors between the ages of 5 and 11 as of June 22, 2022, was 29% receiving two doses, and 36% receiving one, but vaccine requirements for sports, camps, and other activities likely drove an unknown percentage of vaccination in this age group.

There remains, moreover, no solid consensus among physicians about the importance of vaccinating healthy children against COVID-19. A survey from December 2021 indicates that as many as 30%-40% may not be recommending COVID vaccination for children ages 5 to 17, to say nothing of infants. A recent editorial in The Lancet expressed uncertainty about whether the benefits of vaccinating healthy 5- to 11-year-olds outweigh the risks, especially in those with a history of infection.

The gap between the CDC’s enthusiasm for vaccinating all children against COVID and that of parents and health care providers is unlikely to be bridged by approval under Emergency Use Authorization. Approval for the COVID vaccines in infants and toddlers is based on two trials that used changes in antibody levels as an estimate of efficacy, but did not assess protection from severe disease, hospitalization, or multisystem inflammatory syndrome in children (MIS-C), important outcomes that parents worry about. In a Food and Drug Administration (FDA) meeting on June 28, Pfizer Vice President for Viral Vaccines Kena Swanson even acknowledged that “there is no established correlate” between antibody levels and protection from disease.

In the Pfizer trial, the confidence interval—which shows the possible range of protection level—was alarmingly wide, with the lower bound suggesting the possibility of a 380% increase in the chance of infection after the third dose. Additionally, neither trial met the 50% efficacy requirement established by the FDA for approval of adult COVID vaccines. Peter Marks, the FDA’s top vaccine official, told Congress in May that the efficacy requirement would be lowered for the pediatric vaccine simply because vaccine efficacy against the omicron variant was lower in general.

With rates of severe disease now much lower in children than at the start of the pandemic—due to higher levels of natural immunity and lower rates of severe disease caused by omicron—trials would have needed to enroll hundreds of thousands of children, if not over a million, in order to detect a significant impact of the pediatric vaccine against severe disease. Vaccine companies could have conducted such time-consuming and costly trials, especially if there had been interest in international collaboration. But there was no economic incentive to do so, and every economic incentive not to: Speed, not providing meaningful information to parents and physicians about safety and efficacy, was the priority of U.S. regulatory agencies.

Because Pfizer and Moderna were permitted to seek approval for pediatric COVID vaccines under the emergency use pathway, Moderna only enrolled 6,300 total children in trials (4,700 in the vaccine group and 1,600 in the placebo group), and Pfizer only enrolled 4,526 total (2,750 in the vaccine group and 1,776 in the placebo), with two-thirds dropping out before the third dose. The trials, in other words, enrolled only a fraction of the number of participants that would have been required to determine efficacy against end points like severe disease, hospitalization, and rare adverse events such as myocarditis, which has been linked to COVID vaccination in males in the 12- to 17-year-old age group at a rate of up to 1 in 2,700.

Furthermore, the follow-up time after the second dose of Moderna and the third dose of Pfizer was only 1-3 months. Data from adults show protection against infection is transient, though protection against severe disease so far seems longer lasting. For the Moderna vaccine, efficacy against infection was not statistically significant for children between 6 months and 2 years, according to one of the company’s two analyses. In the Pfizer trial, there was no evidence of efficacy for the first two doses against omicron for this age group; the “effect” seen after the third dose was so uncertain that it is impossible to draw firm conclusions about how well the vaccine worked to prevent cases.

Still more puzzling is the fact that neither Pfizer nor Moderna—despite continued assurances that mRNA vaccines are uniquely flexible, allowing manufacturers to quickly tweak vaccines to match new variants—has released an updated version of their product: The pediatric vaccines now being administered target an outdated variant. In addition, the infant and toddler trials were mostly limited to children who had not been previously infected with COVID (estimates based on blood work showed less than 15% of children enrolled had previously been infected). With 75% of children nationally having already been infected by February 2022, the immune-naïve children enrolled in the trial were not representative of their age group at large.

Even in the already troubled context of the last two years, the CDC’s unqualified recommendation to vaccinate every young child against COVID may further contribute to the profound chasm of trust between U.S. citizens and their public health agencies. In January, a Hart poll found that only 44% of respondents said they believe what the CDC says; a March Gallup poll put it at 32%. Evidence of trust slippage can be seen even in highly vaccinated places like Portland, Oregon, where CDC recommendations were for the most part embraced unquestioningly during the pandemic. Despite the CDC’s recommendation that all children 5 and up should receive a booster, as of June 26 only 8.7% of children ages 5-11 in the Portland area are boosted, compared to 3.9% in the entire state of Oregon. (The CDC and American Academy of Pediatrics have not made nationwide data available.)

The general trust deficit is more troubling than skepticism toward this particular vaccine, because it could conceivably drive down uptake of other childhood vaccines that we know are more important to children’s health, such as those against measles, mumps, rubella, diphtheria, polio, and Haemophilus influenza type b (Hib). This is not an alarmist or trivial concern, as vaccinations are one of the most lifesaving medical interventions in human history, rivaled perhaps only by antibiotics. In 1800, 46% of American children did not make it to age 5, and the majority died from what are now vaccine-preventable diseases. The smallpox vaccine alone is estimated to have saved 150 million to 200 million lives. Rates of diseases such as tetanus, rubella, polio, Haemophilus influenza type b (Hib) have declined by 99% since widespread childhood vaccination became commonplace in the 20th century.

It is therefore worth our attention when, for example, a recent letter in the New England Journal of Medicine noted that flu shot uptake has decreased over the pandemic, which the authors suspect may be due to growing vaccine hesitancy in general. The CDC published a study in April showing that childhood vaccination rates fell by only 1% in 2021, a small proportion of the total when spread over 70 million children. But given that many of these vaccines require two or three doses for full coverage, this still translates to several million missing doses, and could threaten herd immunity for diseases such as measles, which require very high percentages of the population to be vaccinated. It is also difficult to separate out the factors behind this drop in coverage, because schools and local clinics—where many low-income children receive vaccines—were closed for much of the last two years. But it is reasonable to at least assume that low trust in the CDC, the agency responsible for making evidence-based recommendations about vaccines, is not helping.

Compare the CDC’s response to vaccine hesitancy during COVID to a similar challenge in the late 1990s and early 2000s: rotavirus. Only a year after Andrew Wakefield’s false claims in 1998 that the MMR vaccines caused autism—leading to one of the most disastrous setbacks for vaccination uptake in history—Wyeth’s RotaShield vaccine was pulled off the market due to evidence it caused a rare and serious intestinal malfunction (intussusception) in babies. The effect of the RotaShield withdrawal so hard on the heels of the Wakefield disaster is hard to isolate, but CDC officials acknowledged that the combined events led to “a particularly turbulent period” for U.S. vaccine programs. Referring to vaccine hesitancy that might result from the RotaShield adverse events, the CDC’s Dr. John Livengood remarked at the time that the CDC “shouldn’t be seen as withholding information right now.”

The original trial for RotaShield had enrolled 10,054 vaccine recipients and 4,633 placebo recipients. During a February 1998 meeting of the CDC’s Advisory Committee on Immunization Practices (the same body that recently met to discuss the pediatric COVID vaccines), an FDA panel member, Dr. Margaret Rennels, noted that more babies in the vaccine group experienced intestinal intussusception than in the placebo group by about 2.5-fold, with a rate of 1/2011 (0.05%) in the vaccine group compared with 1/4633 (0.02%) in the placebo. But because the absolute numbers were small, and the trial was also relatively small, intestinal intussusception did not achieve statistical significance. RotaShield was licensed by the FDA in 1998, widely rolled out, and championed by the CDC in the spring of 1999. Intussusception was not mentioned further, and the issue was buried in a 19-page document where it was listed as a side effect that did not occur significantly more often in vaccinated babies than in the control group.

By summer, however, officials at the CDC grew concerned about a growing number of intussusception reports from the Vaccine Adverse Event Reporting System (VAERS), and were anxious not to lose gains made during the Carter and Clinton administrations in raising general childhood vaccination rates. By the end of President Clinton’s first term, toddler immunization rates had achieved what was then an all-time high, thanks to Vaccines for Children, a program that expanded access to free and low-cost vaccination.

The CDC was also cognizant that Wakefield’s false claims were continuing to spur a growing movement of vaccine hesitancy. As a result, the CDC—then under the direction of Dr. Jeffrey Koplan—immediately launched a large-scale investigation into the RotaShield VAERS reports. The investigation concluded that one additional case of intussusception was attributable to the vaccine for every 5,000-10,000 infants vaccinated—lower than rates of myocarditis due to vaccine injury in COVID-vaccinated adolescent males age 12-17.

RotaShield was pulled off the market that October. To justify the decision to pull a vaccine that was 85% effective at preventing hospitalization from a viral infection that had killed hundreds of thousands of infants worldwide, CDC personnel wrote the following:

At a time when many parents express concerns about the safety of vaccines and vaccine adverse events are the focus of increasing attention by the public, media, and U.S. Congress, the wisdom of recommending a vaccine that causes a severe adverse reaction in an estimated 1 in 10,000 infants must be considered.

The next vaccine against rotavirus—RotaTeq, made by Merck and released in 2004—was only released after the Rotavirus Efficacy and Safety Trial (REST) trial, which was notable for its “[randomized] design, large sample size, detailed execution, continuous safety monitoring, and lengthy duration,” and was undertaken in direct response to the perceived failures of the RotaShield trial. The authors of a paper describing its execution wrote, “The design and conduct of this study may serve as a useful tool for planning other future clinical trials, especially those evaluating uncommon adverse events.” The REST trial was conducted in 11 countries at more than 500 study sites and enrolled 70,000 subjects (including over 35,000 infants from the United States), making it one of the largest vaccine clinical trials ever conducted pre-approval. Post-approval, Merck conducted an additional study enrolling more than 85,000 infants.

The obvious drawback of a trial like REST is that it took four years to complete (though today it could almost certainly be completed faster due to advances in recruitment methods). A multiyear trial was simply not an option during COVID, which is why the notably small and short COVID vaccine trials were allowed to serve as the basis for approval under the emergency use provision. But because COVID so rarely causes severe disease in children, and current COVID vaccines do not reliably prevent transmission, especially after a few months, it is difficult to understand how such small trials could be justified without meaningful endpoints for this age group.

Consider the case of rotavirus again. Prior to vaccination, rotavirus was a significant cause of morbidity and mortality in infants in the United States (and still is globally). Until 15 years ago, it was the leading cause of gastrointestinal hospitalization in babies in the United States and, prior to rotavirus vaccines, caused an estimated 50,000-70,000 hospitalizations per year in infants. Compare this figure with the number of children age 0-4 hospitalized with COVID: The CDC places the cumulative total during the entire pandemic at approximately 130 in 100,000, or about 26,000 children. The CDC estimates that during omicron, at least 14% of COVID hospitalizations for children ages 6 months to 4 years were incidental (meaning the need for hospitalization was due to something other than COVID itself), though this is likely an underestimate, as 63% of current COVID hospitalizations in the U.K. for all ages are “incidental.” Thus, at the time rotavirus vaccines were being trialed, there were 2-4 times more hospitalizations for rotavirus in this age group than there have been for COVID since the pandemic began. (The CDC estimates the death rate from COVID in 6-month- to 4-year-olds to be 86 per year, compared with 20-60 per year from rotavirus, but the COVID estimate does not separate out deaths primarily due to another cause, nor does it adjust for the reduction in severity associated with omicron for children in this age group.)

The rotavirus experience taught the CDC a hard-earned lesson: Speaking in absolutes about vaccine safety and efficacy regardless of trial standards can backfire. In nearly every dimension by which trial data are measured—proper endpoints, size, rigorous randomization, and other factors—the RotaShield trial was far more robust than the Pfizer and Moderna infant and toddler COVID vaccine trials. Furthermore, if the identification of safety signals is not quickly acknowledged, it becomes even harder to recover trust. More and more Americans are wondering, for example, why Canada and several European countries have advised against the Moderna vaccine for people under 30 due to myocarditis risks, while the U.S. government still won’t even acknowledge the higher risk of myocarditis.

Clinical trial data expert and Tablet contributor Dr. Vinay Prasad has pointed out many times that “expedited pathways do not always benefit people, but they always benefit companies.” This might help explain why no other country in the world has started vaccinating infants against COVID, and only a handful have vaccinated toddlers. (In addition to the United States, the only countries vaccinating 2- to 3-year-olds against COVID right now are Cuba, China, Argentina, Bahrain, Venezuela, Colombia, Hong Kong, and Chile, none of which are using mRNA vaccines.) It is perhaps especially damning that no other country collaborated with the United States on the mRNA COVID-19 vaccine trials for infants and toddlers, which could have quickly enabled enough trial participation to study effects of the vaccines against severe disease, as was done in the RotaTeq trial. Tellingly, the Danish minister of health recently claimed that it was a “mistake” to vaccinate children under 16 against COVID at all, saying, “we’ve gotten smarter and would not recommend the same today.”

In June, the CDC had the chance to help rebuild public trust: In the absence of trials and data that would have met the gold standard for scientific rigor, the CDC could have made a softer recommendation based on the data it does have. It could have been honest about the trials’ shortcomings and what these data do and do not show. It could have told the public that the data are preliminary, do not establish efficacy against severe disease or long COVID, and do not rule out the possibility of a rare adverse event. Perhaps it could have recommended COVID vaccines for high-risk children, and remained cautious about the benefits for healthy children who have already had COVID infections. The CDC and FDA together could have insisted that blanket approval and recommendations would only come after a properly conducted vaccination trial—one that would give pediatricians and public health officials the confidence to make the evidence-based recommendations parents are seeking.

In 1999, the CDC, working closely with the FDA, took such steps to shore up parents’ confidence in their recommendations. After the RotaShield withdrawal, the FDA requested that future trials of any rotavirus vaccine enroll at least 60,000 children. This level of accountability and collaboration between the two agencies responsible for vaccines in the United States resulted in the delivery of a widely trusted vaccine against a virus that posed a similar or greater danger to young children than COVID-19. This level of accountability was what the American public reasonably expected of its public health agencies two decades ago. It’s not too much to expect today.

Diabetes may increase long COVID risk; COVID while pregnant linked to baby brain development issues

Authors: Nancy Lapid Thu, June 9, 2022,

The following is a summary of some recent studies on COVID-19. They include research that warrants further study to corroborate the findings and that has yet to be certified by peer review.

Diabetes may increase the risk of long COVID, new analyses of seven previous studies suggest.

Researchers reviewed studies that tracked people for at least four weeks after COVID-19 recovery to see which individuals developed persistent symptoms associated with long COVID such as brain fog, skin conditions, depression, and shortness of breath. In three of the studies, people with diabetes were up to four times more likely to develop long COVID compared to people without diabetes, according to a presentation https://eppro02.ativ.me/web/page.php?page=IntHtml&project=ADA22&id=1683 on Sunday at the annual Scientific Sessions of the American Diabetes Association. The researchers said diabetes appears to be “a potent risk factor” for long COVID but their findings are preliminary because the studies used different methods, definitions of long COVID, and follow-up times, and some looked at hospitalized patients while others focused on people with milder cases of COVID-19.

“More high-quality studies across multiple populations and settings are needed to determine if diabetes is indeed a risk factor” for long COVID, the researchers said. “In the meantime, careful monitoring of people with diabetes… may be advised” after COVID-19.

COVID-19 in pregnancy linked with babies’ learning skills

Babies born to mothers who had COVID-19 while pregnant may be at higher than average risk for problems with brain development involved in learning, focusing, remembering, and developing social skills, researchers have found.

They studied 7,772 infants delivered in Massachusetts between March and September 2020, tracking the babies until age 12 months. During that time, 14.4% of the babies born to the 222 women with a positive coronavirus test during pregnancy were diagnosed with a neurodevelopmental disorder, compared to 8.7% of babies whose mothers avoided the virus while pregnant. After accounting for other neurodevelopmental risk factors, including preterm delivery, SARS-CoV-2 infection during pregnancy was linked with an 86% higher risk of a neurodevelopmental disorder diagnosis in offspring, the researchers reported on Thursday in JAMA Network Open https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2793178. The risk was more than doubled when the infection occurred in the third trimester.

The researchers point out that their study was brief and cannot rule out the possibility that additional neurodevelopmental effects will become apparent as the children grow up. On the other hand, they note, larger and more rigorous studies are needed to rule out other potential causes and prove that the coronavirus is to blame.

The rare but life-threatening inflammatory syndrome seen in some children after a coronavirus infection has become even more rare with the Omicron variant causing most infections and more kids vaccinated, according to a new study.

Researchers looked at data from Denmark on more than half a million children and adolescents infected after Omicron became dominant, about half of whom experienced breakthrough infections after vaccination. Overall, only one vaccinated child and 11 unvaccinated children developed Multisystem Inflammatory Syndrome in Children (MIS-C), which causes inflammation in the heart, lungs, kidneys and brain after a mild or asymptomatic SARS-CoV-2 infection. That translates to rates of 34.9 MIS-C cases per million unvaccinated children with COVID-19 and 3.7 cases per million vaccinated young COVID-19 patients, the researchers said on Wednesday in JAMA Pediatrics https://jamanetwork.com/journals/jamapediatrics/fullarticle/2793024. By comparison, rates of MIS-C cases when Delta was predominant were 290.7 per million unvaccinated infected kids and 101.5 per million among the vaccinated who had COVID, they said.

The fact that MIS-C risk was significantly lower in vaccinated children suggests the vaccine is helping to keep the immune system from causing the deadly inflammatory reaction that is an MIS-C hallmark, the researchers said.

Association of Prior BNT162b2 COVID-19 Vaccination With Symptomatic SARS-CoV-2 Infection in Children and Adolescents During Omicron Predominance

Authors: Katherine E. Fleming-Dutra, MD1Amadea Britton, MD1,2Nong Shang, PhD1et al May 13, 2022 JAMA. Published online May 13, 2022. doi:10.1001/jama.2022.7493

Key Points

Question  Does the estimated effectiveness of 2 doses of the BNT162b2 COVID-19 vaccine against symptomatic SARS-CoV-2 Omicron variant infection (based on the odds ratio for the association of prior vaccination and infection) wane rapidly among children and adolescents, as has been observed for adults?

Findings  In a test-negative, case-control study conducted from December 2021 to February 2022 during Omicron variant predominance that included 121 952 tests from sites across the US, estimated vaccine effectiveness against symptomatic infection for children 5 to 11 years of age was 60.1% 2 to 4 weeks after dose 2 and 28.9% during month 2 after dose 2. Among adolescents 12 to 15 years of age, estimated vaccine effectiveness was 59.5% 2 to 4 weeks after dose 2 and 16.6% during month 2; estimated booster dose effectiveness in adolescents 2 to 6.5 weeks after the booster was 71.1%.

Meaning  Among children and adolescents, estimated vaccine effectiveness for 2 doses of BNT162b2 against symptomatic infection decreased rapidly, and among adolescents increased after a booster dose.Abstract

Importance  Efficacy of 2 doses of the BNT162b2 COVID-19 vaccine (Pfizer-BioNTech) against COVID-19 was high in pediatric trials conducted before the SARS-CoV-2 Omicron variant emerged. Among adults, estimated vaccine effectiveness (VE) of 2 BNT162b2 doses against symptomatic Omicron infection was reduced compared with prior variants, waned rapidly, and increased with a booster.

Objective  To evaluate the association of symptomatic infection with prior vaccination with BNT162b2 to estimate VE among children and adolescents during Omicron variant predominance.

Design, Setting, and Participants  A test-negative, case-control analysis was conducted using data from 6897 pharmacy-based, drive-through SARS-CoV-2 testing sites across the US from a single pharmacy chain in the Increasing Community Access to Testing platform. This analysis included 74 208 tests from children 5 to 11 years of age and 47 744 tests from adolescents 12 to 15 years of age with COVID-19–like illness who underwent SARS-CoV-2 nucleic acid amplification testing from December 26, 2021, to February 21, 2022.

Exposures  Two BNT162b2 doses 2 weeks or more before SARS-CoV-2 testing vs no vaccination for children; 2 or 3 doses 2 weeks or more before testing vs no vaccination for adolescents (who are recommended to receive a booster dose).

Main Outcomes and Measures  Symptomatic infection. The adjusted odds ratio (OR) for the association of prior vaccination and symptomatic SARS-CoV-2 infection was used to estimate VE: VE = (1 − OR) × 100%.

Results  A total of 30 999 test-positive cases and 43 209 test-negative controls were included from children 5 to 11 years of age, as well as 22 273 test-positive cases and 25 471 test-negative controls from adolescents 12 to 15 years of age. The median age among those with included tests was 10 years (IQR, 7-13); 61 189 (50.2%) were female, 75 758 (70.1%) were White, and 29 034 (25.7%) were Hispanic/Latino. At 2 to 4 weeks after dose 2, among children, the adjusted OR was 0.40 (95% CI, 0.35-0.45; estimated VE, 60.1% [95% CI, 54.7%-64.8%]) and among adolescents, the OR was 0.40 (95% CI, 0.29-0.56; estimated VE, 59.5% [95% CI, 44.3%-70.6%]). During month 2 after dose 2, among children, the OR was 0.71 (95% CI, 0.67-0.76; estimated VE, 28.9% [95% CI, 24.5%-33.1%]) and among adolescents, the OR was 0.83 (95% CI, 0.76-0.92; estimated VE, 16.6% [95% CI, 8.1%-24.3%]). Among adolescents, the booster dose OR 2 to 6.5 weeks after the dose was 0.29 (95% CI, 0.24-0.35; estimated VE, 71.1% [95% CI, 65.5%-75.7%]).

Conclusions and Relevance  Among children and adolescents, estimated VE for 2 doses of BNT162b2 against symptomatic infection was modest and decreased rapidly. Among adolescents, the estimated effectiveness increased after a booster dose.Introduction

In December 2021 and January 2022, the spread of the SARS-CoV-2 Omicron variant led to the highest rates of COVID-19 cases among children 5 to 15 years old1 and the highest rate of pediatric hospitalizations (age ≤17 years) with COVID-19 to this point in the pandemic.2,3 Randomized trials of the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech), the only COVID-19 vaccine authorized for use in children and adolescents 5 to 15 years of age, were conducted before the emergence of the Omicron variant and demonstrated high efficacy of 2 doses against COVID-19 (100% and 91% among those aged 12-15 and 5-11 years, respectively).4,5 The US Food and Drug Administration issued Emergency Use Authorization for BNT162b2 (2 doses of 30 μg) for those aged 12 to 15 years on May 10, 2021,6 and for those aged 5 to 11 years (2 doses of 10 μg) on October 29, 2021.7 Evidence that estimated vaccine effectiveness (VE) waned over time among adults and adolescents8 contributed to a recommendation on January 5, 2022, for a booster (30-μg dose) 5 months or more after the second dose for adolescents 12 to 15 years old.9

Observational studies in adults documented lower protection from mRNA vaccines against the Omicron variant compared with the Delta variant and rapid waning of protection.10,11 However, observational estimates of VE among children 5 to 11 years old and adolescents 12 to 15 years old during Omicron variant predominance are lacking but needed to inform COVID-19 vaccine policy and use of nonpharmaceutical interventions in these age groups. The objectives of this analysis were to use the odds ratio (OR) for the association of prior vaccination and symptomatic infection to estimate BNT162b2 VE during Omicron variant predominance of (1) 2 doses among children 5 to 11 years old and adolescents 12 to 15 years old over time since the second dose and (2) 3 doses among adolescents 12 to 15 years old.Methods

This activity was determined to be public health surveillance as defined in 45 CFR §46.102(l) (US Department of Health and Human Services [HHS], Title 45 Code of Federal Regulations, §46 Protection of Human Subjects); thus, it was not submitted for institutional review board approval and informed consent was not needed.Data Source

Data from the Increasing Community Access to Testing (ICATT) platform were used. ICATT is an HHS program that contracts with 4 commercial pharmacy chains to facilitate drive-through SARS-CoV-2 testing nationally.8,10,12,13 No-cost testing is available to anyone regardless of symptom or exposure status, and sites were selected to address COVID-19 health disparities by increasing access in racially and ethnically diverse communities and areas with moderate to high social vulnerability based on the Social Vulnerability Index (SVI).14 During the analysis period, contracted pharmacy chains used different versions of the registration questionnaire and not all captured data on booster doses. This analysis was, therefore, limited to a single chain, which collected data on booster doses and provided 82% of tests platform-wide for children and adolescents aged 5 to 15 years during the analysis period.

When registering for SARS-CoV-2 testing, individuals or parents/guardians of minors answered a questionnaire (available in English or Spanish) to self-report demographic information (including race and ethnicity selected from fixed categories, shown in the Table), COVID-19–like illness symptoms (fever, cough, shortness of breath, recent loss of sense of smell or taste, muscle pain, fatigue, chill, headache, sore throat, congestion or runny nose, vomiting, or diarrhea; reported to HHS as asymptomatic or symptomatic with ≥1 symptom), and vaccination status.10 Race and ethnicity were collected as part of the HHS COVID-19 laboratory reporting requirements.15 Self-reported COVID-19 vaccination data included number of doses received up to 4, and for each dose, vaccine product and month and year received. For doses reported in the same month or the month before test registration, the registrant was asked whether the most recent dose was administered at least 2 weeks before the test date. Reporting of vaccination status was neither mandatory nor verified. Test registrants were also asked to self-report underlying health conditions, including immunocompromising conditions (defined in the questionnaire as “immunocompromising medications, solid organ or blood stem cell transplant, HIV, or other immunocompromising conditions”), and whether they had previously tested positive for SARS-CoV-2 (within 90 days and/or >90 days before test registration); answers were not verified.

Nasal swabs were self-collected at drive-through sites and tested for SARS-CoV-2 either onsite with the ID Now (Abbott Diagnostics Scarborough Inc) rapid nucleic acid amplification test (NAAT) or at contracted laboratories using laboratory-based NAAT (TaqPath COVID-19 Combo Kit [Thermo Fischer Scientific Inc] or COVID-19 RT-PCR Test [Laboratory Corporation of America]). Deidentified questionnaire data, specimen collection date, test type, test result, and testing site location and census tract SVI14 were reported to HHS with an approximate 3-day lag.Study Design

A test-negative, case-control analysis16 was conducted to estimate BNT162b2 VE against symptomatic infection. This analysis used rapid and laboratory-based NAATs from children and adolescents aged 5 to 15 years reporting 1 or more symptoms tested at the pharmacy chain from December 26, 2021, to February 21, 2022 (data downloaded February 22, 2022). The unit of analysis was tests, because unique identifiers for individuals were not available. Cases were defined as those with positive SARS-CoV-2 NAAT results, and controls were those with negative NAAT results. Tests from children and adolescents meeting any of the following criteria were excluded: indeterminate test results, missing assay type, reported an immunocompromising condition (because COVID-19 vaccine recommendations differ for these individuals),9 unknown vaccination status, vaccine product other than BNT162b2, receipt of 1 vaccine dose or receipt of the second or third dose within 2 weeks of the test date, vaccination before the month of the recommendation by the Advisory Committee on Immunization Practices (for children 5-11 years, November 2021; for adolescents 12-15 years, May 2021 for the primary series and January 2022 for the booster dose),9,17,18 receipt of more than the authorized number of doses for nonimmunocompromised individuals (>2 for children 5-11 years, >3 for adolescents 12-15 years), receipt of a third dose less than 4 months after the second dose (for adolescents 12-15 years),9 or inconsistent vaccination information (eg, reported vaccine receipt but missing dose dates, reported no vaccine receipt but doses reported).Exposure

The exposures of interest were 2 BNT162b2 doses for children 5 to 11 years old and 2 or 3 BNT162b2 doses for adolescents 12 to 15 years old. Cases and controls were considered unvaccinated if tests were from children and adolescents who received no COVID-19 vaccine before the SARS-CoV-2 test. Cases and controls were considered vaccinated with 2 or 3 doses if tests were from children and adolescents who reported receiving the second or third dose 2 weeks or more before their SARS-CoV-2 test.Outcome

The outcome measure was symptomatic SARS-CoV-2 infection determined by positive NAAT result in a person reporting COVID-19–like illness.Statistical Analysis

Associations between symptomatic SARS-CoV-2 infection and BNT162b2 vaccination were estimated by comparing the odds of prior vaccination with 2 or 3 doses (exposed) vs no vaccination (unexposed) in cases vs controls using multivariable logistic regression. The OR was used to estimate VE, where VE = (1 – OR) × 100%. Logistic regression models were adjusted for calendar day of test (continuous variable), race, ethnicity, sex, testing site region, and testing site census tract SVI (continuous variable).14 Tests with missing sex and site census tract SVI were not included in adjusted analyses. Unknown race and ethnicity were coded as categorical levels within each variable to retain those tests in regression models.

Adjusted OR and corresponding VE of 2 doses were estimated by age group (5-11 years and 12-15 years) and month since the second dose. Because only vaccination month and year but not exact calendar dates of each dose were reported, month since the second dose was calculated as the difference between the month and year of testing and the month and year of the second vaccine dose (at least 2 weeks after the second dose). The range of possible days after the second dose for month 0 was 14 to 30 days; month 1, 14 to 60 days; month 2, 30 to 90 days; month 3, 60 to 120 days, and so on (assuming 30 days per month). Because of potential imprecision of month since vaccination based on calendar month of vaccination and testing rather than exact dates, a simulation analysis (of scenarios with rapid vs slow vaccine uptake and varying date of vaccine introduction) and an analysis of previously published data from this platform8 were conducted to compare VE estimates using this approach with those with exact number of days since the second dose (eAppendix in the Supplement).

The maximum difference between calendar month of SARS-CoV-2 test and calendar month of the second dose was 3 months for children 5 to 11 years old (tested during February 2022 and second dose received in November 2021) and 9 months for adolescents 12 to 15 years old (tested during February 2022 and second dose received in May 2021). However, VE was not calculated for the last month since the second dose (month 3 for children and month 9 for adolescents) because the number of possible days since the second dose was limited in the last month. This was a result of both the timing of vaccine authorization (children became eligible for second doses in late November 202118 and adolescents in late May 202117) and by the timing of the end of the study period (test dates were only included through February 21, 2022) (eAppendix in the Supplement). For adolescents 12 to 15 years of age, the maximum possible time after a booster was 6.5 weeks (tested February 21, 2022, and booster dose received after recommendation by the Advisory Committee on Immunization Practices on January 5, 2022).9

To assess the effect of reported prior SARS-CoV-2 infection on estimated 2-dose VE (by age group and month since the second dose), 3 sensitivity analyses were conducted. The first analysis included only tests from individuals without any reported prior SARS-CoV-2–positive test result. The second analysis included only tests from individuals without reported prior SARS-CoV-2–positive test result within 90 days, because a recent prior positive test result could have been due to prolonged NAAT positivity,19 multiple tests within the same illness episode (eg, confirming an at-home test), or reinfection with a different variant in the setting of Omicron variant emergence. The third analysis included only tests from individuals without reported prior SARS-CoV-2–positive test result more than 90 days prior to the test date, because prior SARS-CoV-2 infection provides infection-induced immunity in both vaccinated and unvaccinated individuals.20

The adjusted OR and corresponding VE of 3 doses among adolescents 12 to 15 years old were estimated overall (ie, not by month since the second dose) due to the short timeframe (6.5 weeks) since booster recommendation.

Statistical analyses were performed in R (version 4.1.2; R Foundation) and SAS (version 9.4; SAS Institute Inc). OR and VE estimates were presented with 95% CIs. To compare the waning pattern for estimated VE since the second dose between children and adolescents, an interaction term between age group (5-11 vs 12-15 years) and month after the second dose (for months 0, 1, and 2) was added to the model; a likelihood ratio test comparing the models with and without the interaction term was used to evaluate the interaction. Two-sided P values comparing the magnitude of the association of vaccination and infection between the 2 age groups and across study months were estimated; a P value less than .05 was considered significant. Because of the potential for type I error due to multiple comparisons, findings should be interpreted as exploratory.Results

A total of 121 952 tests from children and adolescents aged 5 to 15 years at 6897 sites across 49 states (all states except North Dakota), Washington, DC, and Puerto Rico, met inclusion criteria (Figure 1), including 53 272 cases (43.7%) and 68 680 controls (56.3%). The median age among individuals with included tests was 10 years (IQR, 7-13); 61 189 (50.2%) were female, 75 758 (70.1%) were White, and 29 034 (25.7%) were Hispanic/Latino. Among 74 208 included tests from children 5 to 11 years old, 58 430 (78.4%) were from unvaccinated children and 15 778 (21.3%) from those vaccinated with 2 doses. Among 47 744 included tests from adolescents 12 to 15 years old, 24 767 (51.9%) were from unvaccinated adolescents, 22 072 (46.2%) from those vaccinated with 2 doses, and 905 (1.9%) from those with booster doses.

Included tests were more frequently rapid NAAT (66.3%) than laboratory-based NAAT (33.7%), and controls were more often tested by rapid NAAT than cases (70.5% vs 60.2% for children; 71.5% vs 60.8% for adolescents) (Table). Cases vs controls were more often tests from persons from the South Atlantic region (27.6% vs 22.3% for children; 27.9% vs 23.7% for adolescents). Report of prior positive SARS-CoV-2 test result within 90 days of the test date was more common among cases than controls (22.0% vs 13.0% for children; 21.1% vs 15.5% for adolescents), while report of a positive test result more than 90 days before the test date was less common among cases than controls (4.9% vs 11.1% for children; 6.5% vs 13.4% for adolescents).

Among children 5 to 11 years old, the adjusted OR for symptomatic infection for tests performed during month 0 after the second dose was 0.40 (95% CI, 0.35-0.45; estimated VE, 60.1% [95% CI, 54.7%-64.8%]) and during month 2 after the second dose was 0.71 (95% CI, 0.67-0.76; estimated VE, 28.9% [95% CI, 24.5%-33.1%]) (Figure 2). For adolescents 12 to 15 years old, the adjusted OR during month 0 after the second dose was 0.40 (95% CI, 0.29-0.56; estimated VE, 59.5% [95% CI, 44.3%-70.6%]), during month 2 after the second dose was 0.83 (95% CI, 0.76-0.92; estimated VE, 16.6% [95% CI, 8.1%-24.3%]), and was no longer significantly different from 0 during month 3 after the second dose (OR, 0.90 [95% CI, 0.82-1.00]; estimated VE, 9.6% [95% CI, −0.1% to 18.3%]). Estimated VE was not significantly different between children and adolescents during months 0 and 1 after the second dose, but estimated VE in children was significantly higher than in adolescents during month 2 (P value for month 0: .99; month 1: .40; month 2: .01; and for months 0-2 combined: .06).

The simulation analysis showed that estimated VE waning curves that used either the exact number of days or calculated months since the second dose were in close agreement in scenarios with rapid and slow vaccine uptake and vaccine introduction on day 1 and day 16 of month 0 (eFigures 1-2 in the Supplement). The analysis of previously published data from this platform showed estimated monthly VE waning curves aligned well with daily VE waning curves (eFigures 3-4 in the Supplement).

Sensitivity analyses limited to those without any prior SARS-CoV-2–positive test result (eFigure 5 in the Supplement), without prior SARS-CoV-2–positive test result within 90 days of test date (eFigure 6 in the Supplement), and without prior SARS-CoV-2–positive test result more than 90 days prior to test date (eFigure 7 in the Supplement) yielded estimated VE at month 0 of 60.4% to 66.4% among children 5 to 11 years old and 58.3% to 64.3% among adolescents 12 to 15 years old. These were similar to the main analysis results that did not take prior infection into account. However, estimated VE in the sensitivity analyses was somewhat more sustained over time relative to the main analysis, particularly for the model limited to tests from individuals without any reported prior infection (estimated VE among children was 39.8% during month 2; among adolescents, estimated VE was significantly different from 0 until month 7) and the model limited to tests from those without infection within 90 days (estimated VE among children was 39.8% at month 2; among adolescents, estimated VE was significantly different from 0 until month 5).

Among adolescents, the adjusted OR for a booster dose 2 to 6.5 weeks after the dose was 0.29 (95% CI, 0.24-0.35; estimated VE, 71.1% [95% CI, 65.5%-75.7%]).Discussion

This analysis estimated BNT162b2 VE among children 5 to 11 years old and adolescents 12 to 15 years old with COVID-19–like illness tested for SARS-CoV-2 using NAAT at drive-through US pharmacy sites from December 26, 2021, to February 21, 2022. It found the estimated VE of the BNT162b2 2-dose primary series against symptomatic infection with the Omicron variant was modest and decreased over time since vaccination in both age groups, similar to the pattern observed in adults during Omicron variant predominance.10 A booster dose was associated with increased protection against symptomatic infection in adolescents.

Previous analyses among adults have shown lower estimated VE against the Omicron variant than against the Delta variant and waning of mRNA vaccine protection against symptomatic infection, regardless of predominant variant.8,10,11 A recent analysis from the same testing platform as this analysis demonstrated the estimated VE of the 2-dose BNT162b2 primary series against symptomatic Omicron infection among adults 18 years or older was 42% at 2 to 4 weeks after the second dose. This decreased to not significantly different from 0 by 3 months after the second dose.10 In this analysis, the estimated VE against symptomatic infection among adolescents 12 to 15 years old also was not significantly different from 0 during month 3 after the second dose. Among children 5 to 11 years old, the duration of protection could only be assessed up through month 2 since the second dose, and continued monitoring will be important.

Among adolescents 12 to 15 years old, the estimated VE against symptomatic infection increased after a booster dose. This finding is consistent with data on adults from this platform and from other studies among adults and adolescents during Omicron variant predominance, which provide evidence of increased protection following mRNA vaccine booster dose.10,21,22 Given the well-established pattern of waning mRNA VE after 2 doses and early evidence of waning of booster dose protection in adults,22 monitoring the duration of protection from booster doses in adolescents will be important. Booster doses may be needed to optimize protection against symptomatic infection with the Omicron variant in children 5 to 11 years old as well.

Children aged 5 to 11 years receive a lower-dose formulation (10 μg) of BNT162b2 than adolescents and adults (30 μg), and limited observational data are available on VE with the 10-μg dose. In this analysis, the similar starting VE among children and adolescents and slower waning seen in children than adolescents suggest the 10-μg dose performed as well or better in children than the 30-μg dose in adolescents. These findings are consistent with the phase 2-3 trial in which immunogenicity of the 10-μg dose among children 5 to 11 years old, as measured by geometric mean titers of neutralizing antibodies 1 month after the second dose, was not significantly different from that generated by 30 μg in persons 16 to 25 years old.4 Furthermore, recent studies indicate estimated 2-dose BNT162b2 VE is similar among children 5 to 11 years old and adolescents 12 to 15 years old against any Omicron infection with or without symptoms (31% and 59%, respectively, with overlapping CIs)23 and against emergency department and urgent care visits due to COVID-19 (51% among children 5-11 years vs 45% among adolescents 12-15 years, with overlapping CIs).21

Prior SARS-CoV-2 infection may influence estimated VE in various ways. Unvaccinated persons with prior infection may have infection-induced immunity, which could bias VE estimates toward the null, whereas vaccinated persons with prior infection may have higher levels of protection than those with vaccination alone.20 Additionally, the proportion of the population with prior infection and how protective prior infection from a previous variant is against currently circulating variants can also influence estimated VE. The sensitivity analysis including only children and adolescents without any reported prior infection showed that waning of estimated VE was less pronounced than in the main analysis, which may provide the clearest picture of protection provided by vaccination. However, prior SARS-CoV-2 infection is increasingly common; the estimated SARS-CoV-2 infection–induced antibody seroprevalence among US children 0 to 17 years old who had blood specimens tested at commercial laboratories (for reasons unrelated to COVID-19) was 45% in December 2021.24 Although history of SARS-CoV-2 infection was self-reported in this analysis and is an imperfect measure, 27% of tests were from persons reporting prior infection. Thus, inclusion of tests from persons with prior infection may more accurately reflect vaccine performance under current conditions in the US.

Although estimated VE against symptomatic infection waned quickly in this analysis, vaccine protection against symptomatic infection is harder to achieve than protection against severe disease. For mRNA vaccines including BNT162b2, estimated VE against severe disease and hospitalization has been higher and waned more slowly than estimated VE against infection among adolescents and adults during Delta predominance25 and Omicron predominance.21,22 While estimated VE against symptomatic infection is an important end point to inform nonpharmaceutical intervention policy decisions and can provide an early warning signal of declining VE, estimated VE against severe disease is needed for children and adolescents during Omicron variant predominance.Limitations

This analysis is subject to several limitations. First, vaccination status was self-reported, which may lead to misclassification. Second, approximately 12% of tests were from people who did not report vaccination status, and 8% had missing symptom data. Exclusion of these tests may have biased results. Third, vaccination dose dates were provided as month and year rather than exact calendar date, which could affect the estimated VE over time through imprecise classification of months since vaccination. A simulation analysis and an analysis of previously published data from this platform8 (eAppendix in the Supplement) suggested that the magnitude and patterns of estimated VE over time would be similar when estimated by day or month since second dose and additionally would be robust to different speeds of vaccine uptake and timing of vaccine authorization.

Fourth, person-level identifiers were not available; therefore, the unit of analysis was tests, not individuals. The analysis was restricted to symptomatic children and adolescents tested within a 2-month timeframe, likely reducing the number of individuals contributing multiple tests. Fifth, these data are from children and adolescents who sought testing at ICATT sites and may not be generalizable to the US population. Nonetheless, these data represent a large sample of children and adolescents 5 to 15 years old tested at 6897 sites nationally. Sixth, primary series vaccine coverage among children 5 to 11 years old and booster coverage among adolescents 12 to 15 years old remained low in the US during the time of this study.26 Children who received the primary series and boosted adolescents may differ in meaningful and unmeasured ways from unvaccinated children and unboosted adolescents.

Seventh, due to the short time (6.5 weeks) since adolescents 12 to 15 years old were recommended for a booster dose, this analysis was unable to estimate booster VE over time in adolescents. Eighth, this analysis includes both rapid and laboratory-based NAAT. While there may be slight variation in the sensitivity of assays performed at different laboratories, NAAT, including rapid NAAT, is the most sensitive method available for detection of SARS-CoV-2 infection.27 Simulations of the effect of test sensitivity on influenza VE estimates using the test-negative design suggest that estimated VE remains relatively stable over a range of test sensitivity from 80% to 100%.28Conclusions

Among children and adolescents, estimated VE for 2 doses of BNT162b2 against symptomatic infection was modest and decreased rapidly. Among adolescents, the estimated effectiveness increased after a booster dose.

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12.Miller  MF, Shi  M, Motsinger-Reif  A, Weinberg  CR, Miller  JD, Nichols  E.  Community-based testing sites for SARS-CoV-2: United States, March 2020-November 2021.   MMWR Morb Mortal Wkly Rep. 2021;70(49):1706-1711. doi:10.15585/mmwr.mm7049a3PubMedGoogle ScholarCrossref

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Children get long Covid, too, and it can show up in unexpected ways

Authors: Jen Christensen, Fri May 6, 2022 CNN

November 10 is a day Kim Ford remembers too well. It was the day last year when her 9-year-old son, Jack, was scheduled to get his Covid-19 vaccine at the school clinic. They were excited that he’d finally have some protection, but on November 9, he had the sniffles. “When he woke up [November 10] and he was feeling even worse, I said, ‘You know what, let’s test you before you go in, because I don’t want you to get the Covid vaccine if you actually have Covid,’ ” the Michigan mom said.

Jack tested positive for Covid-19 that day and he’s lived with the symptoms ever since. it has kept him from staying at school all day. He has to limit how much he plays baseball with the other neighborhood kids. Even playing Fortnite for too long can leave him feeling sick the next day.

He’s one of potentially millions of kids with long Covid.

“My stomach hurts. It’s kind of hard to breathe. You have a stuffy nose. It’s just an absurd amount of things that you can feel,” Jack Ford said. “It’s really annoying at times. It’s not like a cold, you know, it feels like Covid.”People may think you’re feeling faking it, but you’re not faking it. You feel like you have Covid,” he added.

‘An undiagnosed issue’

It’s not clear how many children go on to develop long Covid, because there’s not enough research on it in this age group, some experts say.

Almost 13 million children have tested positive for Covid-19 since the start of the pandemic, according to the American Academy of PediatricsStudies suggest that between 2% and 10% of those children will develop long Covid, but the number may be larger. Many parents may not know their child has long Covid, or the child’s pediatrician hasn’t recognized it as such. In adults, some research puts the number around 30% of cases .”I personally believe that this is a very much an undiagnosed issue,” said Dr. Sara Kristen Sexson Tejtel, who helps lead a long Covid pediatric clinic at Texas Children’s Hospital in Houston. Many doctors treating children at long Covid clinics across the country say they have long waits for appointments. Some are booked through September.

An unusual range of symptoms

There are no specific tests for long Covid. It’s not clear which children will have it, as it can happen even when a child has a mild case of Covid-19.

“It’s startling how many of these children present and have a range of symptoms that we haven’t fully appreciated. Some are coming in with heart failure after asymptomatic Covid infections,” said Dr. Jeffrey Kahn, chief of the Division of Pediatric Infectious Disease at UT Southwestern Medical Center in Dallas. “What’s striking to me is that it usually occurs about four weeks after infection, and infection can be really asymptomatic, which is really startling. “Even when kids with long Covid are tested for ailments that might cause these symptoms, it’s possible nothing will show up.”The tested me, and it looked like nothing was wrong with me, but they tried their best to find something,” Jack Ford said. His pulmonary function test and EKG came back normal. “The Covid clinic said this is very common in kids with long Covid. Sometimes, all the tests come back normal,” Kim Ford said.

Dr. Amy Edwards, who runs the pediatric long Covid clinic at UH Rainbow Babies & Children’s Hospital in Cleveland, agreed that it happens a lot. “We also scoped them, and their GI tracts are normal. I do a big immune workup, and their immune system appears normal. Everything ‘looks normal,’ but the kids aren’t functioning like normal,” Edwards said. “I tell the families, ‘you have to remember, there are limits to what medical science understands and can test for.’ Sometimes, we’re just not smart enough to know where to look for it. Adults’ problems tend to be more obvious, Edwards said, because they are more likely to have organ dysfunction that shows up on tests. Doctors are still trying to understand why long Covid happens this way in children. They are also figuring out what symptoms define long Covid in children. Some studies in adults show a range of 200 symptoms, but there is no universal clinical case definition.

Public health leaders hope stories about long Covid will motivate more young people to get vaccinatedAt Sexson Tejte’s clinic in Texas, children tend to fall into a few categories. Some have fatigue, brain fog and severe headaches, “to the point where the some kids aren’t able to go to school, grades are failing, those types of issues,” she said.Another group has cardiac issues like heart palpitations, chest pains and dizziness, especially when they go back to their regular activities.Another group has stomach problems. A lot of these kids also have a change in their sense of taste and smell.Sexson Tejte said it isn’t totally different from the symptoms adults have, “but it’s not the mixed bag of different organ system involvement with adults.”

‘Once that bucket is empty, that’s it’

One of Jack Ford’s symptoms affects the amount of energy he has for typical activities.

“Long Covid patients have post-exertional malaise, which is Jack’s biggest issue,” Kim Ford said. “So if he overdoes it — and it doesn’t even have to be physically overdoing it. It could be he was really upset about something the day before, or he could be really mentally engaged with something like watching TV or playing video games sitting in his chair — will knock him out. “Energy has become such a problem that Jack can’t go to school for a full day. His parents started him back with one to two hours a day and have gradually increased it to about 5½ hours a day. “We’ve been trying to bump him up to six, but it hasn’t worked so far,” Kim Ford said. “He’s woken up pretty miserable the next day. “Edwards, who runs the long Covid clinic in Cleveland, says she has to talk to parents about carefully balancing how much energy their children expend. Most healthy people can push through if they’re tired, but those with long Covid can’t. “It’s like they have one bucket of energy, and it has to be used carefully for school, for play, to watch TV. Every single thing they do takes energy, and once that bucket is empty, that’s it,” Edwards said.

‘I barely function some days’: Covid ‘long haulers’ struggle to work amid labor of her teen patients are exhausted just dealing with typical drama at school. “Long-haulers have to think about every single aspect of their day and when they can expend that energy. They have to have that balance. Otherwise, they run out. “Many also have anxiety. Some of that may stem from the ailment itself or from the doubt they’ve heard from doctors or adults when they say they don’t feel well. Experts across the country say they’ve heard from patients whose complaints are ignored, even after a stark change in their health. They’ve been told that they are being dramatic or seeking attention, or that the symptoms are all in their head.

I don’t want to be too critical, but there are some doctors out there who just dismiss it outright,” said Dr. Alexandra Yonts, director of the post-Covid clinic at Children’s National in Washington. “The kids then just struggle. They get passed around from place to place.”Yonts thinks there needs to be better acknowledgment among doctors that long Covid can be a real problem .”I’ve got two kids in wheelchairs after having had Covid who were never in wheelchairs before. There’s one kid on crutches. I’ve got a kid who lost the use of her hands,” Edward said. “These kids should be believed.”

Help is available, but not all have access

There’s no specific treatment for long Covid, but most of these clinics are multi-disciplinary. Interactive: The things Covid victims left behind At Edwards’ clinic, which opened last year, experts can address pulmonary issues, digestive problems, physical rehabilitation, sleep issues, mental health problems and others. There’s a nutritionist on staff, as well as an acupuncturist and a pediatrician who is licensed in Chinese herbal medicine. In addition to working up a child’s schedule so they can determine where to spend their energy and when to take breaks, Edwards’ clinic teaches kids to meditate. They do massage therapy and mind-body exercises. “Children need multiple elements of help. They get significantly better, really they do, if we’re aggressive and they get intensive wraparound support and therapy,” Edwards said. But not all children are able to get into a clinic. “I’ve talked to so many people working with pediatric Covid recovery, and they all say the same thing: ‘We are worried about the kids who aren’t getting the help, who don’t have the parents who can advocate for them or navigate the medical system.’ It keeps me up at night,” Edwards said.

A lot of what her clinic does is to encourage kids to get enough sleep and to eat healthy food, but not all families can afford healthy food.”It terrifies me for those families in particular, because they’re already starting behind. And now they have kids with Covid long-haul,” Edwards said. “You just have to hope more people will become aware of the problem and try to help.”

SARS-CoV-2 mRNA Vaccination-Associated Myocarditis in Children Ages 12-17: A Stratified National Database Analysis

Authors: RALPH TURCHIANO    • 

Abstract

Establishing the rate of post-vaccination cardiac myocarditis in the 12-15 and 16-17-year-old population in the context of their COVID-19 hospitalization risk is critical for developing a vaccination recommendation framework that balances harms with benefits for this patient demographic. Design, Setting and Participants: Using the Vaccine Adverse Event Reporting System (VAERS), this retrospective epidemiological assessment reviewed reports filed between January 1, 2021, and June 18, 2021, among adolescents ages 12-17 who received mRNA vaccination against COVID-19. Symptom search criteria included the words myocarditis, pericarditis, and myopericarditis to identify children with evidence of cardiac injury. The word troponin was a required element in the laboratory findings. Inclusion criteria were aligned with the CDC working case definition for probable myocarditis. Stratified cardiac adverse event (CAE) rates were reported for age, sex and vaccination dose number. A harm-benefit analysis was conducted using existing literature on COVID-19-related hospitalization risks in this demographic. Main outcome measures: 1) Stratified rates of mRNA vaccine-related myocarditis in adolescents age 12-15 and 16-17; and 2) harm-benefit analysis of vaccine-related CAEs in relation to COVID-19 hospitalization risk. Results: A total of 257 CAEs were identified. Rates per million following dose 2 among males were 162.2 (ages 12-15) and 94.0 (ages 16-17); among females, rates were 13.0 and 13.4 per million, respectively. For boys 12-15 without medical comorbidities receiving their second mRNA vaccination dose, the rate of CAE is 3.7-6.1 times higher than their 120-day COVID-19 hospitalization risk as of August 21, 2021 (7-day hospitalizations 1.5/100k population) and 2.6-4.3-fold higher at times of high weekly hospitalization risk (2.1/100k), such as during January 2021. For boys 16-17 without medical comorbidities, the rate of CAE is currently 2.1-3.5 times higher than their 120-day COVID-19 hospitalization risk, and 1.5-2.5 times higher at times of high weekly COVID-19 hospitalization. Conclusions: Post-vaccination CAE rate was highest in young boys aged 12-15 following dose two. For boys 12-17 without medical comorbidities, the likelihood of post vaccination dose two CAE is 162.2 and 94.0/million respectively. This incidence exceeds their expected 120-day COVID-19 hospitalization rate at both moderate (August 21, 2021 rates) and high COVID-19 hospitalization incidence. Further research into the severity and long-term sequelae of post-vaccination CAE is warranted. Quantification of the benefits of the second vaccination dose and vaccination in addition to natural immunity in this demographic may be indicated to minimize harm.

Millennials Experienced the “Worst-Ever Excess Mortality in History” – An 84% Increase In Deaths After Vaccine Mandates

The most recent data from the CDC shows that U.S. millennials, aged 25-44, experienced a record-setting 84% increase in excess mortality during the final four months of 2021, according to the analysis of financial expert and Blackrock whistleblower, Edward Dowd,

Dowd, with the assistance of an insurance industry expert, compiled data from the CDC showing that, in just the second half of 2021, the total number of excess deaths for millennials was higher than the number of Americans who died in the entirety of the Vietnam War. Between August and December, there were over 61,000 deaths in this age group, compared to 58,000 over the course of 10 years in Vietnam.

In all, excess death among those who are traditionally the healthiest Americans is up by 84%.

Spotting Long COVID Symptoms in Children

Authors: Katie Sweeney Published on November 17, 2021 Categories: COVID-19Hospital Programs

It’s one of the more mysterious aspects of COVID-19—a condition called long COVID. While most people recover from the virus within two to four weeks, others can struggle for months afterward with lingering, often debilitating symptoms.

Long COVID has been most commonly talked about in adults, but children can experience it, too—even if they didn’t have any symptoms with their initial COVID infection. That can make the condition challenging to diagnose.

“Many children don’t have any symptoms when they have a COVID infection,” says Sindhu Mohandas, MD, a pediatric infectious disease specialist and Attending Physician at Children’s Hospital Los Angeles. “So if the symptoms of long COVID appear later, it can be difficult to link them to the coronavirus.”

Is it long COVID?

Unlike COVID-19, there is no simple nasal swab or other diagnostic test for long COVID. Doctors instead look at a child’s pattern of symptoms, as well as past exposure to the virus.

Those symptoms can vary widely from patient to patient, but in children, the most common long COVID symptoms are:

  • Unusual tiredness/fatigue
  • Headaches
  • Difficulty concentrating, or “brain fog”

Children can also experience:

  • Shortness of breath
  • Sore throat
  • Unexplained fevers
  • Exercise intolerance
  • Fast heartbeat
  • Chest pain
  • Loss of smell or taste
  • Muscle or nerve pain
  • Sleep disorders
  • Diarrhea, vomiting or constipation
  • Anxiety
  • Depression

Long COVID symptoms are persistent, lasting more than four weeks after a COVID-19 infection. Symptoms can vary between children. For example, one child may have a headache for a couple of hours every day, where another may have a headache a few times a week.

The condition also interferes with normal activities. A child who was previously a strong student may now have difficulty completing assignments. An athlete may no longer have the energy to take part in sports.

“Long COVID can be more severe in some patients than in others,” Dr. Mohandas notes. “But it can significantly impact the quality of life for the child, and consequently the entire family.”

Past exposure to COVID

Symptoms alone are not enough to diagnose long COVID, though, especially since they can be caused by other conditions. That’s why doctors also look for whether a child was previously exposed to the coronavirus.

This link is much easier to make for children who had a positive COVID-19 test or clear COVID symptoms in the past. For those who were never tested or never felt sick, doctors look closely at the family history and whether there were any known virus exposures for the child.

Antibody tests can indicate a past COVID infection, too. “The one caveat is that if a child is vaccinated, the antibodies may be because of the vaccine and not infection,” Dr. Mohandas explains. “However, we can order a test that distinguishes between those different antibodies.”

Long COVID treatment

Although there is no definitive cure for long COVID, But it is still important for children to be diagnosed, because often the symptoms can be managed.

“If you think your child might have long COVID, or you’re just worried about the symptoms, see your pediatrician,” she says. “Even if it’s not long COVID, there could be something else going on. Your doctor will be able to evaluate your child and decide if the child needs to be seen at a specialized center.”

This past summer, Children’s Hospital Los Angeles launched a dedicated Long COVID Recovery Care service—one of only a few of its kind for children in California. Dr. Mohandas says many families she’s seen struggled for months to find a diagnosis before coming to Children’s Hospital.

“These families are so grateful to finally understand what is happening with their child,” she adds.

A thorough exam can help rule out other causes for a child’s symptoms or help pinpoint if specific organs are affected. For example, if a child is having chest pain, an EKG and echocardiogram (ultrasound of the heart) can check for structural changes or damage to the heart.

Fortunately, children with long COVID typically do get better, though it can sometimes take many months.

“The most important thing is time and rest,” Dr. Mohandas says. “But we may also be able to provide supportive care to help manage a child’s symptoms. All this can be done safely if we’ve ruled out other conditions or causes.”

‘The million-dollar question’

So far, it seems that long COVID is more common in adolescents 12 and older than in younger children. But that’s not known for sure. In fact, little is understood about how many children get long COVID—or why they get it in the first place.

“That’s the million-dollar question right now,” Dr. Mohandas says. “The most important thing is defining how prevalent this problem is in children, and then we need to understand why it’s occurring. If we can understand the cause, we can then develop treatments.”

Children’s Hospital Los Angeles is actively trying to find those answers. Recently, the hospital was awarded $8.3 million from the National Institutes of Health to participate in a national study called RECOVER (Researching COVID to Enhance Recovery). The study aims to better understand the after-effects of COVID-19 infection.

In the meantime, Dr. Mohandas stresses that the best strategy for long COVID is prevention.

“It is critically important to get children vaccinated when they are eligible, and to follow local masking and distancing guidelines,” she says. “The best thing you can do to prevent long COVID is to prevent COVID-19.”

What Happens When Kids Get Long COVID?

Authors: KATHY KATELLA  NOVEMBER 2, 2021

Yale’s pediatric post-COVID program provides care, while doctors aim to learn more.

Doctors are working to understand why some children and adolescents who get COVID-19 make a clean recovery, while others go on to develop long COVID, a condition marked by new, returning, or ongoing symptoms such as brain fog and chronic fatigue. The question of why some kids (just like some adults) wrestle with health problems for weeks or months is one of the pandemic’s biggest mysteries—and one that causes worry for parents.

With long COVID, many kids suddenly find themselves struggling to keep up with their schoolwork or skipping sports. Others can’t sleep or have difficulty walking, while yet others struggle with aches and pains, breathlessness, dizziness, and other troubling symptoms.

Yale Medicine doctors are treating children with long COVID, as well as studying the causes and potential solutions for it, in the Children’s Post-COVID Comprehensive Care Program, offered in the Pediatric Specialty Clinic in Yale New Haven Children’s Hospital. The program, which opened in June of this year, is one of a handful in the country specializing in treating pediatric long COVID patients. They’ve seen patients from infancy through the teenage years.

Severity of symptoms has ranged widely. Some of these patients didn’t even know they had COVID until their long COVID symptoms developed. Others had been diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C), a rare, but serious condition that affects multiple organs. Then, there are children who struggle with a long list of post-COVID-19 symptoms that include lingering physical, neurological, and mental problems.

Treatment for pediatric long COVID is a work in progress, but doctors have already learned a great deal about how to help these patients. Here are some common questions parents are asking about the condition and some answers, based on the most current knowledge.  

How common is long COVID in kids?

As of the end of October, nearly 6.4 million children had been diagnosed with COVID-19, according to the American Academy of Pediatrics (AAP)—but studies quantifying the number of cases of long COVID in kids have varied widely. Geography is one factor. “Different studies have shown different results, depending on what parts of the world or which parts of the country you’re looking at,” says Carlos Oliveira, MD, a pediatric infectious diseases specialist.

Another issue is the lack of a clear definition—or even a consistent name—for the disease. It has been called long-haul COVID, post-acute COVID-19, and post-acute sequelae of SARS-CoV-2 infection (PASC), the latter being a research term (“sequelae” means, simply, a medical condition that results from a prior disease). “If you include every child who has been hospitalized with MIS-C, [by definition a complication of acute COVID], you’ll come up with a higher prevalence,” Dr. Oliveira says. As of October 4, there had been more than 5,210 cases of MIS-C and 46 deaths, according to the Centers for Disease Control and Prevention (CDC).

Only a fraction of children with long COVID seek medical attention, which makes tracking its incidence very challenging, he adds. Also, because infants and toddlers can’t always verbalize what they are feeling, it makes matters more complicated. Symptoms like fatigue, for instance, can manifest in young children as hyperactivity rather than sluggishness, making it difficult for parents to detect the problem. “As a result, we are likely only identifying the adolescents who can self-report their symptoms,” he says. 

Are post-COVID symptoms different in kids than in adults?

Dr. Oliveira says that kids often display different symptoms than adults, with no single standout symptom that makes a case easy to identify. The AAP reports that children and adolescents have experienced chest pain, cough, exercise-induced dyspnea (or labored breathing), as well as changes to smell or taste (although this is more common in adolescents), among other things. Affected children and teens have reported fatigue, brain fog, anxiety, joint pain, headache, and sore throat, among other symptoms—all varying in intensity and duration, in some cases lasting for months. 

Ian Ferguson, MD, a Yale Medicine rheumatologist has been caring for pediatric patients with long COVID who have joint and bone pain. “What I tend to see is a generalized achiness and a decrease in physical conditioning,” Dr. Ferguson says. “They might say, ‘I just feel achy. I don’t feel right.’ An otherwise healthy child may say, ‘I don’t feel like I should get out of bed in the morning.’ Or they say, ‘I used to be on the high school cross country team. And now I can barely make it down the street before I have to take a break.’”

“Sometimes the expectation from a parent is that their pediatrician will know everything about this… But, this is a new disease, and doctors are still learning.”— Carlos Oliveira, MD, a pediatric infectious diseases specialist

Some children experience subtle symptoms but, when diagnostic testing is done, no abnormalities are found, Dr. Oliveira says. For example, a child may have pain, fatigue, or trouble concentrating, but their imaging and bloodwork come back normal. “Often, we call these symptoms ‘medically unexplained,’ but they are still obviously very significant to the patient’s health,” he says. “The child may not be able to go to school or may not be able to walk, and we can’t find a reason why.”

A very small percentage of children even develop serious complications, since COVID-19 can affect organs including the brain, heart, kidneys, and liver—and any of those organs can be damaged if the child doesn’t receive proper care. “The post-COVID clinic is meant to identify these symptoms caused by residual organ damage and treat them,” Dr. Oliveira says.

Is inflammation a cause of post-COVID symptoms in children?

Experts are still trying to figure out what causes long COVID in kids. “The main hypothesis—I say hypothesis because we don’t yet know—is that there’s some continual trigger of inflammation,” Dr. Oliveira says.

He explains that some of the different ways that COVID manifests in children may contribute to a greater likelihood of ongoing inflammation. For instance, when a child gets COVID, the virus is more apt to concentrate in the gut than in the lungs, making symptoms more likely to be gastrointestinal than respiratory. It may also take longer to clear the virus from a child’s system than it does for an adult, he adds. “We don’t fully understand why, but we know that with kids, if we were to test their stool three or four months post-infection, for many of them, we would still find noninfectious remnants of the virus. It may be nonviable virus, but the remnants are still there.”  

“You can look at the lab tests… and they’re not showing anything. But that doesn’t mean that the immune system didn’t ramp up… and cause those symptoms.”— Ian Ferguson, MD, a Yale Medicine rheumatologist

And those pieces of remnant virus can continually trigger inflammation. “The immune system will attack those pieces of remnant virus and cause inflammation, because it can’t distinguish between a live virus and the remnants of one. The immune system just sees viral antigens [the molecular structures on the surface of the virus] and wants to get rid of them,” Dr. Oliveira says.

The hypothesis is that there may be continual exposure of viral antigens to the immune system in some children with long COVID, triggering persistent or intermittent inflammation, albeit at a milder level since the remnant virus is not able to make copies of itself, he says. “This kind of inflammation is more like a ‘slow burn’ for a long period of time, rather than the acute inflammation of MIS-C,” he adds. Treatment with anti-inflammatories may be helpful in this situation, he says, but studies are still ongoing.

There is support for the “slow burn” theory in that some long COVID symptoms tend to improve after patients receive a COVID-19 vaccine, which triggers a boost in antibodies that presumably clears the viral antigens more effectively.

What is the treatment for kids with long COVID?

There is no typical case of long COVID in kids, and no one-size-fits-all treatment. Young patients who visit the Yale program come in with any combination of symptoms.

Typically, after a full evaluation, patients are referred to one or more subspecialists with expertise in a particular area. Long COVID can affect different organs and parts of the body, so in addition to pediatric infectious diseases specialists, the team can include cardiologists, neurologists, pulmonologists, rheumatologists, psychologists, and others.

Treatment tends to be most effective when it addresses each symptom individually. A child with chest pain and decreasing physical conditioning will be referred for a cardiac evaluation, for instance, while one with cognitive challenges will be seen by a neurologist. 

Treatment strategies can also draw from those used for other illnesses that bring lingering symptoms, such as the prolonged fatigue after mononucleosis (or ‘mono’). “In rheumatology, we see a lot of unexplained achiness, which provides us with a fairly reasonable framework,” says Dr. Ferguson. “You can look at the lab tests or at the imaging studies, and they’re really not showing anything. That doesn’t necessarily mean that the immune system didn’t ramp up at some point and cause those symptoms. Therefore, many of our recommendations are framed as, ‘Let’s figure out how to build this child’s health back up.’”

So, for example, once a cardiologist says a patient’s heart is fine and a breathing test shows their oxygen exchange is good, doctors may tell them to gradually increase their physical conditioning by adding aerobic and muscular exercise over time. “Physical therapy is a great resource because the physical therapists not only observe patients in the clinic, they give patients a home exercise program that will help them build back up over time,” Dr. Ferguson says. “We anticipate most people will be able to regain their conditioning—albeit on a timeline that we really can’t dictate.” 

What helps when children with long COVID have mental health symptoms?

It’s common for children with long COVID to face mental health challenges as well—although whether that’s a direct result of COVID-19 is still unclear. “There is a worldwide increase in children’s behavioral health needs, especially around anxiety and depression, and that’s not only in children who have had COVID,” says Linda Mayes, MD, chair of the Yale Child Study Center (CSC), which participates in treating patients in the post-COVID treatment program. “We just don’t really know yet how COVID impacts basic psychological development overall.”

But there are ways doctors can help, regardless of the cause, she adds. For children who have learning needs or challenges, or problems paying attention, CSC specialists might work with the child’s school to help adjust curriculum or educational approaches for that child. If there are behavioral health needs, they provide psychotherapy and medications, as needed, and work directly with parents and families. “None of this is COVID-specific,” Dr. Mayes says. “It’s what we do every day. Over time, what will be important to know is, are those issues greater among children who have had COVID-19?”

In addition, CSC counselors provide strategies to help children in the program manage unexplained medical symptoms, including chronic pain. Biofeedback, cognitive behavioral therapy, and mindfulness techniques can all help, Dr. Mayes says. “Regardless of the origin, if a problem is related to COVID or anxiety, we have well-tested, evidence-based approaches,” she says. 

How long do children with long COVID need treatment?

It’s impossible to predict a long-term recovery timeline for children with long COVID, since doctors have only had a year and a half of experience with it. But the good news is that, so far, the children treated in the program are doing well, Dr. Oliveira says. “By numbers, relative to the adults, kids usually recover faster, within a few months.”

That said, he notes that some patients may continue to need monitoring for cardiac issues, and cardiologists may restrict their activities until they are confident that a child’s heart function is back to normal.

The doctors encourage pediatricians and parents to contact Yale’s pediatric post-COVID program if they have any serious physical or mental concerns about a child that could be related to having had COVID-19.

Even if they aren’t sure the child has had the illness, there may be some unknown association that is worth investigating. “Sometimes the expectation from a parent is that their pediatrician will know everything about this, and be able to diagnose it and treat it, just as they would with an ear infection,” Dr. Oliveira says. “But this is a new disease, and doctors are still learning.”