乌鸦传媒

CDC epidemiologists conducted extensive data reviews to inform the recommendations from the Advisory Committee on Immunization Practices (ACIP) on this season's updated monovalent COVID vaccines -- and 乌鸦传媒 captured some of the highlights regarding burden of disease in adults and children, vaccine efficacy and safety, and long COVID.

The bulk of the evidence comes from a by Megan Wallace, DrPH, MPH, a CDC epidemiologist who discussed the "evidence-to-recommendations" framework supporting ACIP's final decision. Interspersed are presentations from other epidemiologists (mostly from CDC, but also from one outside expert) that were largely concordant with Wallace's presentation.

Who's at Risk of Severe Disease?

In general, U.S. hospitalization rates for COVID are highest for people ages 75 and up, followed by infants under 6 months and adults ages 65 to 74, Wallace reported.

She cited data from through August 26, 2023. (Parent database RESP-NET includes COVID, RSV, and flu subcategories, and pulls data from more than 300 acute care hospitals from 13 U.S. states.)

In the most recent weeks, which may still have some delayed reporting, there were about 25 hospitalizations per 100,000 population among people ages 75 and up, and about 10 hospitalizations per 100,000 population for those ages 6 months and under and those ages 65 to 74.

Currently there are about 20,000 new admissions per week in the U.S., based on data from the National Healthcare Safety Network, which is much lower than this time last year, Wallace said. In addition, there are about 600 deaths per week, which is also very low compared with past summers. But both of these parameters are expected to tick up as the U.S. heads into respiratory virus season.

Wallace noted that a sizeable proportion of kids hospitalized with COVID had no underlying conditions. Citing COVID-NET data, she reported that rates were worst for kids ages 6 months to 2 years, with 57% of hospitalized kids in this age group having no underlying conditions. Kids ages 5 to 11 had the lowest rate, with 25% having no underlying conditions.

Fiona Havers, MD, MHS, the team lead for RESP-NET hospitalization surveillance at CDC's National Center for Immunization and Respiratory Disease (NCIRD), shared for kids under age 6 months: 75% of hospitalized kids in this age group had no underlying conditions, according to COVID-NET, she reported.

By comparison, just 16% of hospitalized adults ages 18 to 49 had no underlying conditions, Wallace reported.

She noted, however, that not many children have underlying conditions to begin with, which may have an impact on the data.

Using National Vital Statistics System data, Wallace shared information on COVID-related deaths among kids ages 19 and under, with 221 deaths in 2020; 638 deaths in 2021; and 549 deaths in 2022. Through July 22, 2023, there have been 80 COVID-related deaths in this age group, she reported.

By comparison, flu death numbers in this population were 158 in 2020, none in 2021, 169 in 2022, and 28 through July 22, 2023, she reported.

Wallace said annual hospitalizations for other illnesses prior to the availability of a vaccine are comparable to or less than those for COVID. For instance, in 1993-1995, before a chickenpox vaccine was available, there were 29 to 42 hospitalizations per 100,000 population each year.

That compares with 92 to 220 hospitalizations per 100,000 among kids ages 4 and under; 15 to 47 per 100,000 for those ages 5 to 11; and 20 to 80 per 100,000 for those ages 12 to 17, using data from 2021-2023, she reported.

The same held true for deaths, with an average of 16 chickenpox-related deaths per year from 1990-1994, she said.

Vaccine Effectiveness

Wallace said pooled estimates from observational studies in adults and adolescents showed about 48% efficacy for monovalent and bivalent boosters against hospitalization and 61% efficacy against death after a bivalent booster. However, she noted that this was low or very low quality evidence.

Since there wasn't enough evidence for a systematic review of vaccine efficacy in kids, Wallace presented estimates using disease rates from December 2022, showing that every million doses of vaccine prevented 424 hospitalizations in kids ages 6 months to 4 years, and 56 hospitalizations among kids ages 5 to 11.

Ruth Link-Gelles, PhD, MPH, team leader for the COVID vaccine effectiveness program at NCIRD, from CDC's VISION Network of emergency department and urgent care (ED/UC) encounters, which has been (MMWR).

For last season, kids ages 6 months to 5 years who had 2 doses of Moderna saw a vaccine effectiveness against ED/UC encounters of 46% at 14-59 days after the vaccine, which fell to 24% at more than 60 days post-vaccination. Kids ages 6 months to 4 years who had 3 doses of Pfizer saw 71% vaccine effectiveness against ED/UC encounters at 14-59 days, which fell to a non-significant 16% by more than 60 days post-vaccination.

Link-Gelles' team did not assess vaccine effectiveness against hospitalization or death in kids.

For adults, she and her team reported that vaccine effectiveness for the bivalent booster against hospitalization in people ages 18 to 64 was most effective 7-59 days post-vaccine, and then waned. She cautioned, however, that later estimates are imprecise because of the small number of people included, so true efficacy "could be substantially different from the point estimates shown and estimates should be interpreted with caution."

Bivalent boosters were better for those ages 65 and up, with vaccine effectiveness against hospitalization peaking at 67% at 7-59 days post-vaccine, dropping to 28% at 120-179 days post-vaccine. And these vaccines performed well against critical illness, peaking at 69% at 7-59 days out, dropping to 46% at 120-179 days out.

Link-Gelles cautioned that there were high rates of infection-induced immunity by July-August of 2022, so "VE [vaccine effectiveness] findings should be interpreted as the incremental benefit provided by COVID-19 vaccination in a population with a high prevalence of infection-induced immunity."

Vaccine Safety

Nicola Klein, MD, PhD, director of the Kaiser Permanente Vaccine Study Center in Oakland, California, using the Vaccine Safety Datalink, which covers about 12.5 million people in the U.S.

Klein reported that the rate ratio for myocarditis/pericarditis among people ages 12 and up was elevated for both the Pfizer and Moderna primary series up to 21 days after vaccination (aRR 1.72, P<0.001) -- especially within the first 7 days, and after the second dose.

Among kids ages 5 to 11, no outcome met signaling criteria in the 21 days after primary series or monovalent booster vaccination, she reported. Nor did any outcomes meet signaling criteria in the 21 days after the primary vaccination series for kids ages 6 months to 5 years, though vaccine uptake has been low, she noted.

Wallace said the risk of all adverse cardiac outcomes was 1.8 to 5.6 times higher after COVID infection than after vaccination among males ages 12 to 17, the group most at risk of myocarditis/pericarditis following COVID vaccination.

As for other potential adverse events, the rate of anaphylaxis was about 5 cases per million doses for the mRNA primary series, and fewer than 5 cases per million doses for mRNA boosters, she reported.

And a signal for ischemic stroke that met signaling criteria consistently for 8 weeks earlier this year slowly attenuated and no longer meets signaling criteria, she reported. There was temporal clustering at 13-22 days post-vaccination, and there was some suggestion that this may be related to co-administration of COVID and flu shots, she said.

Protection Against Long COVID?

Sharon Saydah, PhD, MHS, leader of CDC's post-COVID conditions/longer-term sequelae team, reported that the U.S. prevalence of long COVID -- defined by symptoms lasting at least 3 months -- among adults fell from June 2022 to January 2023 and has remained unchanged since then.

Citing an , she noted that patients with long COVID report that ongoing symptoms decline after 3 months, but 16% of patients continue to experience ongoing symptoms at 1 year.

Data from several studies suggest that the characteristics associated with developing long COVID include being female, having a greater severity of COVID illness, having underlying health conditions prior to COVID infection, having lower socioeconomic status, and not getting the COVID vaccine, Saydah reported.

Finally, a review and meta-analysis published in showed that having 1 or 2 doses of COVID vaccine reduced the risk of developing long COVID compared with not being vaccinated.

Taking Popular Opinion Into Account

Wallace reported that her team also took into account the nation's sentiments about COVID-19. A February 2023 survey showed that the majority of the population believed COVID-19 was "getting better."

A survey from August 2023 of about 4,300 U.S. adults showed that about a quarter (24.9%) will "definitely" get the updated vaccine, while about an equal percentage (25.7%) said they "definitely" will not get it. A total of 17.6% said they "probably" will get it, 13.6% said they "probably" won't get it, and 18.2% were undecided.

A June 2023 survey of just over 4,000 adults showed that confidence in vaccine safety is higher for influenza and other routine adult vaccines than for COVID shots. Data from that same survey showed that healthcare providers had far lower rates of recommending COVID shots compared with flu or other routine vaccines: 56.2% for COVID versus just above 60% for shingles and pneumonia, and about 72% for flu.

That survey also showed that Americans are much more likely to receive vaccines when recommended by their doctor.

Wallace also presented results from modeling studies taking into account various scenarios, including high versus low rates of immune escape, and a universal versus targeted national COVID vaccine recommendation.

The modeling found that a universal vaccination recommendation would prevent 200,000 more hospitalizations and 15,000 more deaths over the next 2 years compared with recommending vaccines only for those ages 65 and up, regardless of the level of immune escape.

Wallace concluded that the burden of illness from COVID varies by age and underlying conditions, with those age 65 and up and those with multiple underlying conditions having the highest risk for severe outcomes.

While hospitalization rates are lowest in those ages 5 to 49, and the burden of illness is lowest among those ages 5 to 17, there were still "hundreds" of pediatric deaths, and about half of them occurred in kids with no underlying health conditions, she said.

COVID vaccines have a "high degree of safety," she added, and a risk-based recommendation wouldn't allow access for everyone who wanted a vaccine. And since many uncertainties remain about COVID epidemiology, she added, a non-universal recommendation would need to be quickly revisited if there was a rise in disease burden. Thus, taking all of these factors into account, the CDC and ACIP settled on a universal vaccination recommendation for the U.S. population.

Comment