The duration [of the flu season] would be prolonged when there is a transition of the dominating virus strain, the centre said. It is believed that the current influenza season will persist for a period of time and more outbreaks and severe cases might be recorded in the upcoming weeks.
While the city entered the current flu season in early January this year, the extension meant that it would last longer than the average flu period of eight to 12 weeks.
Dr Mike Kwan Yat-wah, an honorary associate professor at the University of Hong Kongs department of paediatrics and adolescent medicine, said a relatively low vaccination rate could give rise to alternating flu strains.
He said about 50 per cent of the citys population had been inoculated with the latest seasonal flu vaccine.
If we need to build an immunity barrier to prevent infections of alternating viruses, an overall vaccination rate would need to reach 70 to 80 per cent to do so, Kwan said.
He added that as the city experienced a peak of H1 infections starting from March last year, the immunity against the virus subtype would decline roughly six months later, suggesting that people could also be more susceptible to the strain.
When the populations immunity is low, the flu season could be longer we could see a majority of people getting infected before the transmission stops, he said.
Kwan added there was no significant difference in terms of transmissibility or virulence between H1 and H3.
Hong Kong, global experts to work on longer-lasting flu vaccines, Post learns
Professor Ivan Hung Fan-ngai, an infectious disease expert from the same university, pointed out it was quite common to have two different flu virus strains in one season, especially when community immunity was low after Covid-19.
He said the low immunity was caused by a lack of thorough flu infections in the community during Covid-19 pandemic, together with the low flu vaccination rate.
Health authorities said Hong Kong underwent a 16-week winter flu season in 2015-16 after the dominance of flu A virus was overtaken by flu B later.
The six-year-old girl died this week after having contracted the H1 subtype virus and developing encephalopathy, also known as altered brain function.
The girl had a history of good health and had received a flu vaccine for this season, authorities said.
The news came just five days after the announcement of the death of an unvaccinated eight-year-old girl, who had also caught the H1 strain.
Girl, 6, in critical condition after contracting flu in Hong Kong
Kwan explained that a person could still develop complications following a flu jab under certain conditions, such as undiagnosed congenital immunodeficiency or metabolic disorders, a severe flu infection or another bacterial infection.
Health authorities said there had already been a significant increase in the number of flu-like outbreaks at schools and institutions in the week ending April 20 compared with the first week of the month, rising from 10 to 29.
The [centre] appealed again to members of the public to heighten their vigilance, and people belonging to high-risk priority groups should receive seasonal influenza vaccination as soon as possible for prevention of severe disease and death.
If you want to get the most out of your flu vaccine, you might want to cut out the red meat and butter, new research suggests.
A new study showed that feeding obese mice a low-fat menu before getting vaccinated made them better at fighting off the flu virus.
A low fat diet focuses on eating items where only 30 percent of calories are from fat,according to the American Cancer Society.This means including products like skim milk, lean meats like chicken, whole grains and plenty of fresh fruits and vegetables.
Experts conducting the research found that a low-fat diet results in significant, sustained weight loss which strengthens the immune system.
Vaccinations work by training the body's defense cells to recognize and fight viral material - which is why they are effective when introduced to a healthy immune system.
Switching to a low fat diet before flu vaccination gave obese mice a better chance at surviving the flu virus.
A low fat diet stands in contrast to the western diet, which is traditionally high in fat and processed foods, according to Dr Stacey Schultz-Cherry, the deputy director of the WHO's Collaborating Centre for Studies on the Ecology of Influenza in Animals and Birds, who co-authored the new study.
Overweight people are twice as likely to catch the flu than average weight people, even when both groups have been vaccinated, according to 2017 research from the Human Vaccine Institute.
Roughly 370,000 Americans were hospitalized by the flu in 2023, and roughly 24,000 died, according to the CDC.
Though the agency didn't report specifics, it estimates 95 percent of those hospitalized had an underlying condition that worsens flu severity - like obesity, high blood pressure or heart disease.
The study was performed on two groups of 20 mice. The mice that lost weight before getting vaccinated all survived a brush with the flu- but those who didn't diet did not.
Dr Shultz-Cherry's research, which took place at St. Jude Childrens Research Hospital, addresses this flu vaccine gap for obese people.
She and her colleagues dove into the issue by giving the flu vaccine to 20 obese mice.
Half of those mice were put on a low fat diet prior to being vaccinated. About a month later, all of the mice were exposed to the flu.
The ten mice that went on the low-fat diet survived. But all ten mice who continued eating a fatty-diet died.
Interestingly, when the researchers put a different group of mice on a diet after being vaccinated, the results weren't nearly as effective.
The American Heart Association (AHA) scored 10 popular diets for their potential benefits in staving off heart disease.
Only two of the mice on the diet survived, the remaining 18 mice - both those on a low-fat and high-fat diet - died.
'Weight loss can impact the effectiveness of the vaccine, but the timing of the weight loss makes a very big difference' Dr Schultz-Cherrytold New Scientist.
However, there's still a long way to go before we can assume that the same will hold true in humans, Dr Schultz-Cherry said.
Mice and humans have a lot of biological similarities, but human bodies are much more complex, Dr Ri Scarborough, a veterinarian and cancer researcher at Monash University, wrote for the Conversation.
'Because of species differences, something that is effective and safe in an animal might not be so in a human,' Dr Scarborough said.
Mice, for example, only live about two years. That means that a month for a mouse would be years for a human, Schultz-Cherry said.
All told, this could be a new avenue to explore in the future for better protecting people with obesity.
'We don't know for sure, but if the outcome of using GLP-1 drugs is weight loss and improved metabolic health, we would hypothesize that it will help.'
Chalk it up to shot sickness, or maybe just an inflated sense of immunity.
Either way, fewer Rhode Island adults rolled up their sleeves for a flu shot this year, though the state remains a national leader in its influenza vaccination rate, Rhode Island Department of Health Deputy Director Seema Dixit told state lawmakers during a budget presentation Tuesday night.
Just over one-third of Rhode Island adults ages 20 and older got a flu shot during the 2023-2024 season, which began in mid-September, according to RIDOH data. By comparison, 64% of Rhode Island adults got flu shots during both the 2020-2021 and 2021-2022 seasons, according to data with the Centers for Disease Control and Prevention.
Thats higher than the national rate, which ranged from 37.1% in the 2017-2018 season to a peak of 50.2% during the 2020-2021 flu season.
Two months ago, a commentary published in the scientific journal Vaccine named Rhode Island as a model in flu vaccination. The February piece by a pair of Virginia-based researchers touted Rhode Islands ranking as the state with the highest flu vaccine rate from 2017 through 2022. During that five-year period, state officials helped boost adoption of flu shots through Medicaid expansion, a 2020 mandate requiring health care facilities to offer flu shots to employees, and the states Health Equity Zone program, which made flu shots more readily available to underserved neighborhoods through school and community-based clinics, according to the article.
Those measures remain in place with higher vaccination rates among health care workers and older adults than the average population. Indeed, residents 65 and older were the only demographic whose flu shot rate increased slightly in the last year, up to 55% for this season, according to RIDOH data. Three-quarters of health care workers across all facilities were vaccinated during the 2022-2023 season; more recent data on this group was not available.
Dixit appeared unfazed by the drop in vaccine uptake, explaining to lawmakers Tuesday that Rhode Island continues to see higher vaccination rates, with fewer flu-related doctors visits and deaths compared with the region and nation.
There is a vaccine fatigue we have noted, Dixit said. Could we do more? Possibly, yes. I cant really pinpoint what we didnt end up doing.
Dr. Michael Fine, former state health director who now serves as board chair and president for a national advocacy group called Primary Care for All Americans, agreed with Dixits assessment.
We dont know if our actions lead to boosting vaccination rates, Fine said in an interview on Wednesday.
Not that it wasnt worth trying to improve. Fine specifically named outreach by primary care physicians as an effective way to gain public trust and participation in vaccines, including the flu shot.
Nationally, the CDC has reported fewer flu vaccines given out in medical offices and pharmacies; the 60 million doses distributed as of Jan. 13 represents an 11% drop over the 2019-2020 flu season, considered a benchmark because it was the last year before the COVID-19 pandemic. State-specific data through the end of the 2023-2024 flu season was not available.
Primary or urgent care offices and pharmacies were the most popular options for Rhode Islanders to get their flu shot this year, chosen by roughly 45% apiece. White, non-Hispanic residents also had a higher flu vaccination rate, just over 40%, compared with 29% of Black residents and 27% of Hispanic or Latino residents.
The latest COVID-19 booster was given to 17% of Rhode Island adults as of April 23, while 15% of residents 60 and older have received the RSV vaccine this year.
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Scientists at UC Riverside have demonstrated a new, RNA-based vaccine strategy that is effective against any strain of a virus and can be used safely even by babies or the immunocompromised.
Every year, researchers try to predict the four influenza strains that are most likely to be prevalent during the upcoming flu season. And every year, people line up to get their updated vaccine, hoping the researchers formulated the shot correctly.
The same is true of COVID vaccines, which have been reformulated to target sub-variants of the most prevalent strains circulating in the U.S.
This new strategy would eliminate the need to create all these different shots, because it targets a part of the viral genome that is common to all strains of a virus. The vaccine, how it works, and a demonstration of its efficacy in mice is described in apaperpublished today in the Proceedings of the National Academy of Sciences.
What I want to emphasize about this vaccine strategy is that it is broad, said UCR virologist and paper author Rong Hai. It is broadly applicable to any number of viruses, broadly effective against any variant of a virus, and safe for a broad spectrum of people. This could be the universal vaccine that we have been looking for.
Traditionally, vaccines contain either a dead or modified, live version of a virus. The bodys immune system recognizes a protein in the virus and mounts an immune response. This response produces T-cells that attack the virus and stop it from spreading. It also produces memory B-cells that train your immune system to protect you from future attacks.
The new vaccine also uses a live, modified version of a virus. However, it does not rely on the vaccinated body having this traditional immune response or immune active proteins which is the reason it can be used by babies whose immune systems are underdeveloped, or people suffering from a disease that overtaxes their immune system. Instead, this relies on small, silencing RNA molecules.
A host a person, a mouse, anyone infected will produce small interfering RNAs as an immune response to viral infection. These RNAi then knock down the virus, said Shouwei Ding, distinguished professor of microbiology at UCR, and lead paper author.
The reason viruses successfully cause disease is because they produce proteins that block a hosts RNAi response. If we make a mutant virus that cannot produce the protein to suppress our RNAi, we can weaken the virus. It can replicate to some level, but then loses the battle to the host RNAi response, Ding said. A virus weakened in this way can be used as a vaccine for boosting our RNAi immune system.
When the researchers tested this strategy with a mouse virus called Nodamura, they did it with mutant mice lacking T and B cells. With one vaccine injection, they found the mice were protected from a lethal dose of the unmodified virus for at least 90 days. Note that some studies show nine mouse days are roughly equivalent to one human year.
There are few vaccines suitable for use in babies younger than six months old. However, even newborn mice produce small RNAi molecules, which is why the vaccine protected them as well.UC Riversidehas now been issued a US patent on this RNAi vaccine technology.
In 2013, the same research team published a paper showing that flu infections also induce us to produce RNAi molecules. Thats why our next step is to use this same concept to generate a flu vaccine, so infants can be protected. If we are successful, theyll no longer have to depend on their mothers antibodies, Ding said.
Their flu vaccine will also likely be delivered in the form of a spray, as many people have an aversion to needles. Respiratory infections move through the nose, so a spray might be an easier delivery system, Hai said.
Additionally, the researchers say there is little chance of a virus mutating to avoid this vaccination strategy. Viruses may mutate in regions not targeted by traditional vaccines. However, we are targeting their whole genome with thousands of small RNAs. They cannot escape this, Hai said.
Ultimately, the researchers believe they can cut and paste this strategy to make a one-and-done vaccine for any number of viruses.
There are several well-known human pathogens; dengue, SARS, COVID. They all have similar viral functions, Ding said. This should be applicable to these viruses in an easy transfer of knowledge.
(Precision Vaccinations News)
CureVac N.V. today announced the start of the Phase 1 part of a combined Phase 1/2 clinical trialof an investigational influenza A (H5N1) pre-pandemic vaccine candidate developed in collaboration with GSK.
In the initial Phase 1 dose-escalation part of the study, up to five dose levels will be assessed compared to a placebo control. The study will be conducted in the United States.
The monovalent vaccine candidate is based on CureVac's proprietary second-generationmessenger ribonucleic acid (mRNA) backbone and encodes an influenzaA H5-antigen.
Dr. Myriam Mendila, CureVac's Chief Development Officer, commented in a press release on April 24, 2024,"This clinical milestone, in collaboration with GSK, expands the application of our mRNA technology into an additional indication in infectious diseases and addresses the need to be prepared for potential future pandemics."
The H5N1 avian influenza virus is considered a potentialpandemic threat. It is known to sporadically cross-species from its original bird host to other animal hosts, such as bears, cows, foxes, and humans worldwide.
The combined Phase 1/2 study will evaluate the safety, reactogenicity, and immunogenicity of an investigational influenza A (H5N1) pre-pandemic vaccine candidate in healthy younger and older adults.
The broad CureVac-GSK infectious disease collaboration was first announced in July 2020.
As of April 2024, the U.S. government has approved a bird flu vaccine (Audenz) and invested hundreds of millions in preparing avian influenza vaccine candidates.
Australian Medical Association President Professor Steve Robson said after many years of the Covid pandemic, it would be understandable if many Australians had a sense of vaccine fatigue.
I know it can be tiring keeping up to date with flu shots after receiving several rounds of the Covid vaccine, but it is absolutely the best and easiest way to protect yourself and the ones you love from serious illness, Professor Robson said.
Influenza is no joke, and it can have devastating effects for vulnerable Australians, including the elderly and children.
There really is no time to waste when it comes to getting your flu shot, and I urge as many people as possible to go book your flu shot today.
Professor Robson said the Covid booster vaccine could be administered on the same day as the flu jab.
The best time to defend yourself against Covid is when you get your flu shot. It is perfectly safe and effective to have the two shots administered one after the other in the same appointment, he said.
This week is World Immunisation Week (2430 April), which really is the ideal reminder to go and get your influenza and Covid vaccines. Its fast, its simple and its safe.
Free vaccines are available for people most at risk of complications through the Australian Governments National Immunisation Program.
Professor Paul Kelly, the head of the interim Australian Centre for Disease Control, said the highest notification rates for flu last year were in children under 14 years, and concerningly, the vaccine uptake in this same population group was very low.
Professor Robson urged parents to ensure their kids are protected.
Influenza can be extremely serious and dangerous for children, especially for those under five years of age, so it is crucial they get their flu shots as soon as possible, he said.
The flu is not just a cold, it is an extremely serious virus that can lead to hospitalisation and death but the good news is, there is a very simple form of protection available. Go book your flu shot today.
Mobile Operations Manager Parsia Jahanbani gives the monkeypox vaccine to Henry Tran at Families Together of Orange County in Tustin, CA on Tuesday, August 16, 2022. The Jynneos vaccine consists of two doses administered 28 days apart. (Photo by Paul Bersebach, Orange County Register/SCNG)
As a health communications researcher specializing in vaccine hesitancy, the last few years in my field have been paradoxical. Vaccinations played a large part in ushering us into the post-pandemic world, yet a misinfodemic against vaccines persists. Misinformation about vaccines has eroded confidence in vaccines prevention promise and has inflicted even our progressive state of California. As of August 2023, about 73% of Californians have received the initial series of COVID-19 vaccines, compared to only 38% of children between ages 5 to 11. In recognition of World Immunization Week taking place annually during the last week of April I want to highlight the collective action needed to improve vaccine uptake to protect people of all ages.
Our biggest threat to improving vaccine uptake is the rise in misinformation mostly propagated on social media platforms. Having taken root during the 2016 U.S. presidential election, continuing during the COVID-19 pandemic, and the devastating aftermath of the 2020 U.S. Presidential election misinformation is pervasive.
In my research scrubbing one of the more popular microblogging services, X (formerly Twitter), misinformation around the COVID-19 vaccine clocked in nearly 14.9 million tweets. Our research published in the Journal of Behavioral Medicine delineated the kinds of vaccine misinformation spread on social media. Falsehoods about vaccination ranged across nine categories that undermine vaccine confidence, including falsehoods about vaccine ingredients, safety, side effects, testing of the vaccine, alternatives to vaccinating, effects on the immune system, vaccine efficacy, vaccine information being concealed and doubts about the necessity of the vaccine. When users questions and concerns are not rapidly addressed and information voids ensue, such an environment is conducive to the adoption of pervasive misinformation being turned to and accepted.
Now what were seeing is that the misinfodemic has slowly made its way off our phones and into pediatrician offices nationwide. During the 2022-23 school year, kindergarten vaccination rates did not return to pre-pandemic levels and our nation is now reporting the highest rate of vaccine exemptions, including medical and nonmedical, ever seen. Of the kindergartners with vaccine exemptions, over 93% had a nonmedical exemption. Parents are choosing to exempt their children from life-saving vaccines at the cost of our communitys safety.
Higher rates of unvaccinated people in a community are associated with a greater incidence of vaccine-preventable diseases like measles, which has made a startling return. Take for example the 2014 measles outbreak that began at Disneyland, California, or in 2019, the largest measles outbreak in the U.S. that occurred in a New York City community with a cluster of unvaccinated children. And now, in the first three months of 2024, as reported by the Associated Press, the CDC shows that the number of measles cases is 17 times higher than in the previous three years of the same timeframe.
Why are parents hesitating in getting their children vaccinated or avoiding them altogether? Addressing the scourge of misinformation requires a multi-faceted approach to improve vaccine uptake across the nation.
In a society where facts are distorted and falsehoods proliferate, individuals are robbed of the ability to make sound judgments based on reality. We cannot afford to be passive bystanders in the fight for the truth our communitys health depends on it.
Suellen Hopfer is Associate Professor of Health, Society, and Behavior, with the UC Irvine Program in Public Health. She has affiliated appointments with the UCI School of Medicines Department of Pediatrics and the UCI School of Humanities Department of Asian American Studies.
Just when you thought the modern world couldnt become more cartoonish, the Centers for Disease Control and Prevention (CDC) Foundation released the most bizarre advertisement for Mpox vaccinations Tuesday.
For some reason, the CDC Foundation captioned their social media post containing the borderline seizure-inducing ad with the sentence family comes first, even though there is not a single thing about the subject matter that has anything to do with actual families. The entire production is centered on HBOs Dashaun Wesley who the CDC Foundation and apparently other people believe is the King of Vogue (thats Madonna and Ill die on this hill) and the fact he didnt get his second dose of the Mpox vaccine.
Originally called monkeypox, Mpox is a predominantly sexually transmitted disease that has spread mostly through men who have sex with other men. (RELATED: Mans Nose Rots After Monkeypox, Syphilis And HIV Infection)
And it seems that the CDC Foundation ad is specifically targeted to this demographic in a pretty stereotypical way. Personally, the gay men I know wouldnt be seen dead in the pants worn by Wesleys chosen family in the ad, but perhaps thats just a personal bias.
Despite having almost 150,000 followers, the CDC Foundations post received just 31 likes, even though they probably (hopefully) paid Wesley to appear in it to boost engagement. What a weirdo, wrote one user in the comments. Such an odd PSA.
The CDC lists Mpox as a potentially serious disease and is part of the smallpox family. Symptoms range from a rash and flu-like feeling that can last some two to four weeks. The available vaccinations for Mpox have a host of common side effects that all sound pretty similar to the flu.
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Key Points
Question Was implementation of the pediatric COVID-19 immunization program of California associated with reductions in the reported pediatric COVID-19 incidence and hospitalizations?
Finding In this case series including 3.9 million children, pediatric vaccination was estimated to avert 146210 cases of COVID-19 among adolescents aged 12 to 15 years during a 141-day postvaccine evaluation period and 230134 cases among children aged 5 to 11 years during a 199-day postvaccine evaluation period. In addition, an estimated 168 hospitalizations were averted among children aged 6 to 59 months during a 225-day evaluation period.
Meaning The findings of this study suggest that vaccination against SARS-CoV-2 was associated with significant reductions in COVID-19 incidence and hospitalizations among children in California.
Importance A SARS-CoV-2 vaccine was approved for adolescents aged 12 to 15 years on May 10, 2021, with approval for younger age groups following thereafter. The population level impact of the pediatric COVID-19 vaccination program has not yet been established.
Objective To identify whether California's pediatric COVID-19 immunization program was associated with changes in pediatric COVID-19 incidence and hospitalizations.
Design, Setting, and Participants A case series on COVID-19 vaccination including children aged 6 months to 15 years was conducted in California. Data were obtained on COVID-19 cases in California between April 1, 2020, and February 27, 2023.
Exposure Postvaccination evaluation periods spanned 141 days (June 10 to October 29, 2021) for adolescents aged 12 to 15 years, 199 days (November 29, 2021, to June 17, 2022) for children aged 5 to 11 years, and 225 days (July 17, 2022, to February 27, 2023) for those aged 6 to 59 months. During these periods, statewide vaccine coverage reached 53.5% among adolescents aged 12 to 15 years, 34.8% among children aged 5 to 11 years, and 7.9% among those aged 6 to 59 months.
Main Outcomes and Measures Age-stepped implementation of COVID-19 vaccination was used to compare observed county-level incidence and hospitalization rates during periods when each age group became vaccine eligible to counterfactual rates predicted from observations among other age groups. COVID-19 case and hospitalization data were obtained from the California reportable disease surveillance system.
Results Between April 1, 2020, and February 27, 2023, a total of 3913063 pediatric COVID-19 cases and 12740 hospitalizations were reported in California. Reductions of 146210 cases (95% prediction interval [PI], 136056-158948) were estimated among adolescents aged 12 to 15 years, corresponding to a 37.1% (35.5%-39.1%) reduction from counterfactual predictions. Reductions of 230134 (200170-265149) cases were estimated among children aged 5 to 11 years, corresponding to a 23.7% (20.6%-27.3%) reduction from counterfactual predictions. No evidence of reductions in COVID-19 cases statewide were found among children aged 6 to 59 months (estimated averted cases, 259; 95% PI, 1938 to 1019), although low transmission during the evaluation period may have limited the ability to do so. An estimated 168 hospitalizations (95% PI, 42-324) were averted among children aged 6 to 59 months, corresponding to a 24.4% (95% PI, 6.1%-47.1%) reduction. In meta-analyses, county-level vaccination coverage was associated with averted cases for all age groups. Despite low vaccination coverage, pediatric COVID-19 immunization in California averted 376 085 (95% PI, 348355-417328) reported cases and 273 (95% PI, 77-605) hospitalizations among children aged 6 months to 15 years over approximately 4 to 7 months following vaccination availability.
Conclusions and Relevance The findings of this case series analysis of 3913063 cases suggest reduced pediatric SARS-CoV-2 transmission following immunization. These results support the use of COVID-19 vaccines to reduce COVID-19 incidence and hospitalization in pediatric populations.
Vaccination is among the most important interventions to reduce the public health impact of infectious diseases.1 SARS-CoV-2 mRNA vaccines, including mRNA1273 (Moderna) and BNT162b2 (Pfizer BioNTech), were approved for adult use in December 2020.2 On May 10, 2021, the first mRNA COVID-19 vaccine was approved for use in adolescents aged 12 to 15 years. Vaccines were subsequently approved for children aged 5 to 11 years on October 29, 2021, and for children aged 6 to 59 months on June 17, 2022 (Figure 1).2
COVID-19 vaccines are safe for children.3 However, concerns over vaccine-related adverse events, lower vaccine effectiveness against illness in children, and perceptions of a milder disease course in children have resulted in high rates of parental vaccine hesitancy4-6 and resistance to pediatric vaccine mandates.7 While California has among the highest rates of vaccination in the US,8 pediatric vaccination coverage lags that of adults substantially, with only 8.2% of children younger than 5 years and 37.8% of children aged 5 to 11 years fully vaccinated as of May 2023.8 Severe manifestations of COVID-19 are rare among children, but can occur.9 Understanding the population-level impact of COVID-19 vaccinations in SARS-CoV-2 infections and hospitalizations in pediatric populations would aid in public health decision-making on pediatric vaccine and booster policy and provide pediatric-specific information on vaccine outcomes that could be applied to future SARS-CoV-2 variants.
Herein, we analyze data on 3913063 pediatric cases of COVID-19 and 12740 hospitalizations from California. Using the phased introduction of the vaccine to individuals aged 12 to 15 years, 5 to 11 years, and 6 to 59 months, we estimated statewide and county-specific outcomes associated with vaccination on pediatric incidence and hospitalizations in California.
We obtained deidentified information on all pediatric COVID-19 cases reported in California between April 1, 2020, and February 27, 2023, from the California COVID-19 Reporting System, along with the patients county of residence, age, and hospitalization status. Each case was confirmed using a nucleic acid amplification test. Because the research constitutes a public health surveillance activity, the study did not constitute human research and does not require institutional review board review or exemption according to the Common Rule (45 CFR 46). We followed the reporting guideline for case series studies.
Daily cases were aggregated by county and age groups based on dates of vaccination eligibility: 0 to 5 months (vaccine ineligible), 6 to 59 months, 5 to 11 years, 12 to 15 years, and older than 16 years (nonpediatric). To remove variation due to differential health care seeking by day of week, we calculated 7-day moving averages of case counts per county and age group. Due to small counts for pediatric hospitalizations, we aggregated hospitalizations by week and age group within 5 California-designated regions (eFigure 1 in Supplement 1). Descriptions of other covariate data are covered in the eMethods in Supplement 1).
Training and Prediction Periods
For each age group of interest (6-59 months, 5-11 years, and 12-15 years), we split data into age-eligible and age-ineligible periods. The prevaccine eligibility period encompassed data up to the date of vaccine eligibility. The evaluation period for the outcome associated with the vaccine lasted from 1 month following the date of vaccine eligibility (to allow time to complete 2 doses) until the date that the next age group became eligible or until the time of analysis (February 27, 2023) (Figure 1). Ending the evaluation period at the vaccine eligibility date of the next eligible age group permitted that age group to be selected as a control time series in our predictive models.
Candidate Model Generation and Selection
We developed a set of candidate predictive generalized linear models, which are described in greater detail in the eMethods in Supplement 1. Predictors eligible for selection within candidate models included (1) log-incidence series for other age groups (ie, <6 months, 6-59 months, 5-11 years, 12-15 years, and 16 years, omitting the group being modeled) included as either covariates or as an offset term for any 1 age group; (2) an indicator of vaccine age eligibility for other age groups; (3) an indicator for in-person school being in session; (4) interactions between school and vaccine introduction indicators and time series for other age groups, aiming to account for differences in constant proportionality during school periods or when 1 age group became vaccinated; and (5) seasonal controls. Eligible predictors are summarized in eTable 1 in Supplement 1. Quasi-Poisson distributions were fit for the outcome to account for overdispersion. Models were developed separately for each California county.
Candidate models for hospitalizations included similar eligible predictors, with 2 main differences: log weekly case incidence series for other age groups was lagged by 2 weeks in accordance with the expected lag between infection and hospitalization10 and unlagged weekly hospitalizations across other age groups were included as possible predictors. Models were developed separately for each of the 5 regions.
We used a time series with a 1-year gap cross-validation approach (eMethods and eFigure 2 in Supplement 1) to select the best predictive model for each age group and geographic area (county or region) within the prevaccine period.11-13 For each area-age group combination, we selected the model with the lowest out-of-sample mean square error across holdout folds. For this model, we also calculated the coefficient of determination, r2, a goodness-of-fit metric. The selected predictors varied by area and age group. Selected models for each area-age group combination are included in eTable 2 (for cases) and eTable 3 (for hospitalizations) in Supplement 1.
Calculation of Vaccine Outcomes and Association Between Averted Cases and Vaccination Coverage
Selected models were fit to prevaccine eligibility data for their age group and geographic area and then used to predict counterfactual incidence or hospitalization in the postvaccine period or the expected case or hospitalization counts had vaccination not occurred. For inference, we computed 95% prediction intervals (PIs) around the counterfactual predictions, using a sandwich estimator to account for overdispersion when computing SEs (eMethods in Supplement 1).14 Prediction intervals, which are wider than CIs, capture the uncertainty around each future predicted value. Statewide estimates were obtained by summing predictions across geographies (eMethods in Supplement 1).
We estimated the absolute and relative differences between predicted counterfactual values and observed values for each county or region during the postvaccine evaluation period. To understand the association between vaccination coverage and averted cases, we fit regression models relating the reduction in cases within each age and county to county-level vaccination coverage within the same age group, using a fixed-effects meta-analysis with weights equal to the inverse estimated SE of the estimates per county. We used segmented regression models (eMethods in Supplement 1) to examine whether there were coverages below which reductions in cases could not be identified or above which diminishing returns on vaccination were observed.15
To examine whether postvaccine predictions from a different, but well predictive model, yielded similar estimates of vaccination outcomes, we repeated model selection using the mean absolute error instead of the mean square error in our cross-validation algorithm. We conducted jackknife analyses to examine whether postvaccine predictions from any one county were driving observed effects, dropping each county in turn from the overall pool of counties and recalculating the primary analytic end point of cases averted.
All analyses were conducted in R, version 3.6.0 (R Foundation for Statistical Computing).16
Between April 1, 2020, and February 27, 2023, a total of 3913063 COVID-19 cases were reported in California among individuals aged 18 years or younger. Of these, 47174 cases (1.2%) were among children younger than 6 months, 517447 (13.2%) in children aged 6 to 59 months, 1590806 (40.7%) in children aged 5 to 11 years, and 1511690 (38.6%) in adolescents aged 12 to 15 years. A total of 12740 hospitalizations were reported: 1443 (11.3%) were among children younger than 6 months, 3428 (26.9%) in children aged 6 to 59 months, 2536 (19.9%) in children aged 5 to 11 years, and 3921 (30.8%) in adolescents aged 12 to 15 years.
Vaccine-Attributable Averted Cases and Hospitalizations by Pediatric Age Group
As shown in eFigure 3 in Supplement 1, r2 values for models fit to daily case data were 0.92 (IQR, 0.79-0.96) for children aged 6 to 59 months, 0.89 (IQR, 0.78-0.95) for children aged 5 to 11 years, and 0.79 (IQR, 0.62-0.90) for adolescents aged 12 to 15 years. eFigure 4 in Supplement 1 shows the model fit for hospitalizations. More details on model fit are included in the eResults in Supplement 1.
Adolescents Aged 12 to 15 Years
Individuals aged 12 to 15 years were eligible to be vaccinated against SARS-CoV-2 as of May 10, 2021. By October 29, 2021, when the next age group became eligible, 53.5% of this population had completed the 2-dose primary series of the vaccine, corresponding to 1712686 individuals. County-level vaccination rates ranged from 11.5% to 85.7%.8 During the 141 days spanning June 10 to October 29, 2021, 247700 COVID-19 cases were observed among individuals aged 12 to 15 years. We estimated that 394506 (95% PI, 392545-396467) cases of COVID-19 would have occurred absent vaccination, corresponding to 146210 (95% PI, 136056-158948) cases averted statewide or 37.1% (95% PI, 34.5%-40.3%) of expected cases (Table, Figure 2C). Incidence plots from all counties are included as eFigures 9-14 in Supplement 1.
During this same 141-day period, 688 hospitalizations were observed among adolescents. We estimated that 59 (95% PI, 65 to 244) hospitalizations were averted or a reduction of 7.9% (95% PI, 8.7% to 32.7%) from expectation (Table, Figure 3C). Hospitalization plots from all regions are included as eFigures 12-14 in Supplement 1.
Children Aged 5 to 11 Years
Children aged 5 to 11 years were eligible for vaccination on October 29, 2021. By June 17, 2022, 1219432 individuals (34.8% of this population) had completed a primary series of the vaccine, with a range of 10.0% to 74.7% by county.8 During the 199-day period following November 29, 2021, we estimated that 230134 (95% PI, 200170-265149) cases were averted due to the vaccine corresponding to a reduction of 23.7% (95% PI, 20.6%-27.3%) from counterfactual expectations (Table, Figure 2B). During this same period, we estimated that 46 (95% PI, 79 to 221) hospitalizations were averted, corresponding to 5.8% (95% PI, 10.2% to 28.6%) of expected hospitalizations (Table, Figure 3B).
Children Aged 6 to 59 Months
Children aged 6 to 59 months were eligible for vaccination on June 17, 2022. By February 27, 2023, 177087 (7.9%) individuals had received both doses of the primary series, with a range of 0.7% to 38.5% across counties.8 In the 225 days following July 17, 2022, we did not detect any significant changes in cases from counterfactual expectations in the postvaccine period (estimated averted cases: 259; 95% PI, 1938 1019) (Table). The postvaccine evaluation period for this age group did not include a surge in COVID-19 cases as it did for the other age groups (Figure 2A). However, we estimated that 168 (95% PI, 42-324) hospitalizations were averted following vaccination, or a reduction of 24.4% (95% PI, 6.1%-47.1%) from counterfactual expectations (Table and Figure 3A). Summing across all age groups, we estimated that pediatric vaccination was associated with reductions of 376 085 (95% PI, 348 355-417 328) reported cases and 273 (95% PI, 77-605) hospitalizations among children aged 6 months to 15 years during the 4 to 7 months following vaccine availability. This represents a reduction of 26.3% of the number of cases and 12.4% of the hospitalizations that would have been seen in this population absent the vaccine.
As indicated in the eResults and eFigures 5 and 6 in Supplement 1, results for individuals aged 5 to 15 years were not sensitive to the inclusion of any single county, although results for children aged 6 to 59 months were sensitive to the inclusion of Los Angeles (eFigure 7 in Supplement 1). Estimated cases (eTable 4 in Supplement 1) and hospitalizations (eTable 5 in Supplement 1) were consistent when model selection was done using mean absolute error as the loss function for children aged 5 to 15 years. Estimated averted cases in children aged 6 to 59 months were slightly lower using mean absolute error, but hospitalization results were consistent (eResults in Supplement 1). Estimates of cases averted (eTable 6 in Supplement 1) and hospitalizations averted (eTable 7 in Supplement 1) made using the mean absolute error as the loss function for each county or region are available, along with plots of observed and counterfactual case and hospitalization series for all geographic areas (eFigures 9-14 in Supplement 1).
Association Between Averted Cases and Vaccination
County-level vaccination coverage explained 26% of variation of cases averted for children aged 6 to 59 months, 28% for children aged 5 and 11 years, and 12% for adolescents aged 12 to 15 years (Figure 4). On average, every increase of 10 vaccinations per 1000 children corresponded to a reduction of 0.9 (95% CI, 0.3-1.4) cases per 1000 children for individuals aged 6 to 59 months, 3.5 (95% CI, 1.9-5.1) cases per 1000 children for those aged 5 and 11 years, and 2.0 (95% CI, 0.6-3.4) cases per 1000 children for adolescents aged 12 to 15 years. Linear model fits had lower Akaike information criterion and bayesian information criterion values than segmented regression model fits for all age groups. Across all age groups, pediatric vaccination rates in California were generally highest among Bay Area counties (eFigure 8 in Supplement 1), which also ranked highest for averted cases due to vaccination (eResults in Supplement 1).
We provide evidence that Californias pediatric COVID-19 immunization program averted 376 085 (95% PI, 348355-417328) reported cases and 273 (95% PI, 77-605) hospitalizations among children aged 6 months to 15 years during the 4 to 7 months following vaccine availability. This represents a reduction of 26.3% of the number of cases that would have been seen in this population absent the vaccine. Prior work has similarly reported a high impact of widespread administration of mRNA vaccines in adult populations. In California, COVID-19 vaccines were estimated to avert more than 1.5 million cases, 72 000 hospitalizations, and 19 000 deaths statewide during the first 10 months of vaccination (through October 16, 2021).17 In the US, each 10% increase in vaccination coverage among individuals aged 18 years or older at the county level was associated with an 8% reduction in mortality and a 7% reduction in incidence.18 Similarly, a study in Israel estimated that nearly 650 000 cases of COVID-19 were averted in the first 2 months following vaccination introduction,19
Earlier studies have estimated vaccine effectiveness in pediatric populations by comparing incidence rates among vaccinated children with those in unvaccinated children using test-negative designs,20-22 or retrospective23,24 or prospective cohort studies.25 Our counterfactual case series approach, which has been used in other studies to estimate the population-level impact of interventions with a clearly specified rollout time,26,27 enables calculation of vaccine program impact at the population level, without information on individual vaccine status.
The cumulative effect of vaccination at the population level may be meaningful even if individual vaccine effectiveness is low. While influenza vaccine effectiveness was estimated at 29% in 2017-2018,28 it was estimated that widespread vaccination averted more than 3.1 million cases of influenza in the US.29 Nevertheless, overall impact depends on vaccine coverage. We identified positive associations between county-level vaccination coverage and averted cases in each age group, whereby each 10 additional vaccinations per 1000 children corresponded to an average reduction of 0.9 to 3.5 cases per 1000 children. Segmented regression models associating vaccine coverage with averted cases did not identify break points, suggesting that over the range of vaccination coverages examined (0%-85%), we saw neither diminishing returns on increased coverage owing to the acquisition of sufficient population-level immunity nor a threshold below which vaccination has limited public health impact. This is consistent with the persistence of SARS-CoV-2 circulation in populations with high vaccination coverage and resulting value of direct protection.
Results for individuals aged 6 to 59 months differed from those of older age groups in that we found a significant reduction in hospitalizations, but not cases, following vaccination. One explanation for this discrepancy could be that postvaccine evaluation period for children aged 6 to 59 months did not include a surge in COVID-19 cases as it did for the other age groups (Figure 2), potentially making it difficult to detect statistically significant reductions from the counterfactual. However, vaccine effectiveness of early mRNA vaccines was lower against Omicron variants compared with Alpha and Delta variants,30,31 and the Omicron variant dominated during the postvaccine period for children aged 6 months to 11 years (Figure 1). The detection of significant reductions in hospitalization in this age group, but not others, may be due, in part, to the fact that COVID-19 mortality disproportionately affects very young children compared with older children.32 For older age groups, we also estimated reductions in hospitalizations, although the 95% PI spans 0. However, we note that 95% CIs are narrower than PIs and may not have encompassed the null.
This study has limitations. Case data represented individuals who sought testing, which may be differential across unvaccinated and vaccinated groups, geographies, and time. Access to at-home testing likely resulted in further case underascertainment. If individuals were, on average, less likely to seek care for mild illness following vaccination, our analysis could have overestimated the absolute effect of the vaccine on cases averted. Overestimation of the relative effect of the vaccine may have resulted if vaccine recipients were disproportionately represented in the surveillance record both before and after vaccine eligibility compared with never-vaccinated individuals being more connected to care. Data on hospitalizations are less likely to be subjected to biases from differential case ascertainment. We estimated significant reductions in hospitalizations following vaccine introduction compared with counterfactual predictions.
Several considerations could lead to underestimates of the association between vaccination and child long-term health. First, asymptomatic cases are less likely to be reported, yet remain an important outcome, as postCOVID-19 condition symptoms may present after asymptomatic infections.33-35 Second, we were unable to estimate indirect outcomes associated with the vaccine in other age groups or control for social contacts. If children increased social contacts following receipt of the vaccine, as has been shown elsewhere,36 they may be challenged more frequently with SARS-CoV-2. Third, we assessed the outcomes of the vaccine over a short postvaccination period, limiting our ability to examine vaccine responses under waning immunity.
Two important limitations relate to model functional form. First, attributing differences between the observed and the predicted counterfactual cases to the vaccine assumes that the associations between incidence in the age group being modeled and incidence in the age groups selected as model predictors would, absent the vaccine, remain constant over the pre-to-post vaccine periods. This would not occur if one age group developed increased immunity or if different variants had differential age-disease associations. This is especially salient for the 5- to 11-year age group, as the models were primarily trained on data from the period when the Delta variant predominated, yet the Omicron variant, which is less reliant on angiotensin-converting enzyme 2 binding for entry37 and disproportionately influenced children younger than 5 years, prevailed in the evaluation period. Accordingly, the effect of vaccination may have been overestimated for this age group in counties where the incidence in children younger than 5 years was selected as a predictor (eTable 2 in the Supplement).
Second, there is potential for unstable predictions in the evaluation period if the predictive model was faced with values of selected predictors that fell outside the range of data used to fit the model. Our time series with a gap cross-validation approach guards against both of these limitations by prioritizing selection of generalized linear models that do well predicting values in periods that follow the training period, and in periods where the predictors may fall outside the range of what they were during the training period.11-13,38 Moreover, generalized linear models selected using different loss functions resulted in similar model predictions during the postevaluation period, suggesting that results are robust to differences in the nature of the association between incidence in the modeled age group and incidence in the predictor age groups.
In this case series analysis of 3913063 pediatric cases, we provide evidence suggesting that programmatic vaccination against SARS-CoV-2 was associated with significant reductions in COVID-19 incidence among children in California in the 4 to 7 months following vaccine eligibility. At the county level, we found associations of higher vaccine coverage with greater reductions in pediatric cases. Our results support the use of COVID-19 vaccines to reduce COVID-19 incidence and hospitalization in pediatric populations.
Accepted for Publication: February 23, 2024.
Published: April 23, 2024. doi:10.1001/jamanetworkopen.2024.7822
Open Access: This is an open access article distributed under the terms of the CC-BY License. 2024 Head JR et al. JAMA Network Open.
Corresponding Author: Justin V. Remais, PhD, 2121 Berkeley Way, #5302, Berkeley, CA 94720 (jvr@berkeley.edu).
Author Contributions: Dr Head had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Head, Len, Lewnard, Remais.
Acquisition, analysis, or interpretation of data: Head, Collender, Len, White, Sud, Camponuri, Lee, Remais.
Drafting of the manuscript: Head, Remais.
Critical review of the manuscript for important intellectual content: All authors.
Statistical analysis: Head, Collender, Len, Camponuri, Lee.
Obtained funding: Head, Remais.
Administrative, technical, or material support: Collender, Len, White, Sud, Camponuri, Remais.
Supervision: Remais.
Conflict of Interest Disclosures: Dr Len reported having been an employee of the California Department of Public Health (CDPH). No other disclosures were reported.
Funding/Support: This project was supported by a grant from the CDPH through the University of California Health & CDPH COVID Modeling Consortium. Dr Head was supported by the National Institute of Allergy and Infectious Diseases (NIAID) National Institutes of Health (NIH) award K01AI173529. Dr Remais was supported by NIAID NIH award R01AI148336.
Role of the Funder/Sponsor: The funding organizations did not play a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 2.
