Science supporting the US case for COVID boosters

U.S. health officials on Wednesday presented the scientific rationale for a third dose of COVID-19 mRNA vaccines for all U.S. adults, based on published and unpublished CDC data, as well as a study by preprint.

Overall, they said that there is some evidence that the vaccine’s effectiveness against infection – both symptomatic and asymptomatic – has waned over time, but that protection against serious disease, the hospitalization and death remains relatively high.

In anticipation of a further decline in immunity amid the continuing surge fueled by the Delta variant – which poses additional challenges – pulling the trigger on booster shots could help the United States stay ahead of the game. on the virus, they said.

During a White House COVID-19 task force briefing, CDC Director Rochelle Walensky, MD, presented five pieces of evidence to support the decision: three new studies that were published Wednesday in the Morbidity and Mortality Weekly Report (MMWR), a previously published on medRxiv, and unpublished CDC data on the Delta variant.

Protection against infections

Walensky cited New MMWR New York data which showed a decrease in the effectiveness of the vaccine against infection, from 91.7% to 79.8% during the period from May 3 to July 25.

Eli Rosenberg, PhD, of the New York State Department of Health, and colleagues linked data from several New York City surveillance systems on immunization, lab tests, and hospitalization.

During this period, they found that a total of 9,675 new cases of COVID-19 occurred in fully vaccinated adults, compared to 38,505 cases in unvaccinated adults (1.31 versus 10.69 per 100,000 person-days).

In addition, data from the Mayo Clinic, previously published on medRxiv, also found a decrease in the vaccine’s effectiveness in preventing infection in Minnesota, Walensky said. For the Moderna vaccine, the efficacy against infection increased from 86% in January-July to 76% during the month of July, while it fell from 76% to 42% for Pfizer during this period.

To finish, new data from MMWR from a nationwide network of nursing homes showed a reduction in protection against infection, from 75% in March to 53% as of Aug. 1, Walensky said.

Srinivas Nanduri, MD, of the CDC, and colleagues assessed weekly data on nursing homes and qualified nursing facilities reported by CMS to the CDC’s National Healthcare Safety Network.

They found that the adjusted efficacy against infection during the ‘pre-Delta’ period (March 1 to May 9) was 74.7% (based on 17,407 weekly reports from 3,862 facilities. ), which fell to 67.5% during the “interim” period (May 10 to June 20; based on 33,160 weekly reports from 11,581 installations), and finally to 53.1% during the dominant delta period (June 21 to August 1; based on 85,593 weekly reports from 14,917 facilities).

Nanduri and his colleagues noted that the efficacy estimates were similar for the two vaccines.

“Overall, you can see that while the exact percentage of vaccine efficacy differs across the cohort and setting studied, the data consistently show a reduction in protection against infection over time,” Walensky said. .

Protection against serious illness and hospitalization

Walensky noted that despite the decrease in efficacy against infection, the data suggests that vaccines are still very protective against serious illness and hospitalization.

New York MMWR data showed that from May 3 to July 25, the overall age-adjusted vaccine efficacy against hospitalization was relatively stable (91.9% to 95.3%).

In addition, there were a total of 1,271 new hospitalizations among those fully vaccinated, compared with 7,308 hospitalizations among the unvaccinated (0.17 versus 2.03 per 100,000 person-days), reported Rosenberg and colleagues. .

Hospitalization rates declined in the week of July 5, but increased in the weeks of July 12 and 19, they added. Hospitalization rates were also higher among those 65 and older, they found.

The Mayo Clinic preprint found that from January through July in Minnesota, Moderna and Pfizer vaccines were effective in protecting against hospitalizations associated with COVID (91.6% vs. 85%, respectively) and intensive care admission ( 93.3% vs. 87%, respectively). There were no deaths in the two cohorts.

To finish, New MMWR data from CDC’s IVY (Influenza and Other Viruses in the Acutely Ill) network reported by Mark Tenforde, MD, PhD, CDC, and colleagues showed no decrease in vaccine effectiveness against hospitalization over 24 weeks – although Walensky noted that the cohort was running out of Delta infections .

The authors evaluated data collected by IVY on 3,089 adults hospitalized in 21 hospitals in 18 states from March 11 to July 14. Of these, 1,194 were patients with COVID-19 and 1,895 were witnesses who did not have COVID-19. Overall, 11.8% of cases were fully vaccinated, as were 52.1% of controls.

The efficacy rate against hospitalization was 86% overall and 90% in adults without immunocompromised conditions, they reported.

In addition, of the 1,129 patients who received two doses of an mRNA vaccine, there was no decrease in efficacy against hospitalization over a 24-week period, with an efficacy rate of 86%. from 2 to 12 weeks after vaccination against 84%. 13 to 24 weeks after vaccination.

However, of the 454 samples that underwent whole genome sequencing, only 16.3% were found to be the Delta variant, which now accounts for the vast majority of cases. More than half (53.3%) were from the Alpha line.

“Taken together, this data confirms that while protection against infection may wane over time, protection against serious illness and hospitalization currently holds up quite well,” said Walensky. “However, when making decisions about recalls, we also need to consider the effectiveness of the vaccine in the specific context of the Delta variant.”

Double Whammy: Decreasing Immunity and Delta

Walensky then highlighted preliminary unpublished data from two of the CDC’s vaccine efficacy cohorts that included more than 4,000 healthcare workers, first responders and other frontline workers from eight locations in the United States.

Data up to August 6 showed decreasing efficacy against symptomatic and asymptomatic infections in the context of the Delta variant, from 92% before Delta, to 64% with Delta.

She noted that the analysis did not show any differences over time, suggesting that the vaccine’s effectiveness is decreased against Delta regardless of when a person was vaccinated – meaning full vaccination may. be less effective against Delta than against previous variants, she said.

Immunological basis for boosters

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, provided the immunological evidence to support the thesis of a third shot during the briefing.

Antibody levels decrease over time, he said, but mRNA booster injections would increase antibody titers by at least 10-fold.

Higher levels of antibodies are associated with better vaccine efficacy and are likely needed to protect against the Delta variant, he noted.

A article published in Science showed that antibody levels peaked around 43 days after the second dose of Moderna, but dropped by 209 days regardless of the variant involved.

In addition, a pre-publication published in medRxiv based on phase III data from the Moderna trial, examined “correlates of immunity”, concluding that a serum neutralization titer of 1: 100 produces a vaccine efficacy rate of 91%. So the higher the neutralizing titer, the higher the effectiveness of the vaccine, Fauci explained.

the Science paper, as well as Pfizer data published in the New England Journal of Medicine, showed reduced levels of neutralizing antibody titers with Delta compared to other variants, Fauci noted.

To finish, another medRxiv preprint showed that a third dose of Moderna increased antibody titers by at least 10-fold, he said, and Pfizer recently announced similar data.

The Moderna study showed a “remarkable increase in titers” 15 days after the third dose against the wild-type virus, the beta variant and the gamma variant, Fauci said, adding that Pfizer’s data also showed a good increase in titers. levels against the Delta variant, which should be similar for Moderna.

“All of this supports the use of a third booster mRNA immunization to increase the overall level of protection,” Fauci concluded.