Science supporting the US case of COVID boosters

Based on published and unpublished CDC data and preprint studies, US health officials provided the scientific basis for a third dose of COVID-19 mRNA vaccine to all US adults on Wednesday.

Overall, they have evidence that the effectiveness of the vaccine against infection (both symptomatic and asymptomatic) has diminished over time, but protection against severe illness, hospitalization, and death is relatively high. Said it remained high.

Triggering booster shots may help the United States stay ahead of the virus in anticipation of further weakening of immunity in an ongoing delta variant fuel surge that raises additional challenges. They said.

During the White House COVID-19 Task Force briefing, CDC Director Rochelle Walensky, MD, provided five pieces of evidence to support this move. Weekly morbidity and mortality report (MMWR), Previously published medRxivUnpublished CDC data for, and Delta variants.

Protection against infection

Warrensky quoted New arrival MMWR Data from New York This indicates that the effectiveness of the vaccine against infection decreased from 91.7% to 79.8% between May 3 and July 25.

Dr. Eli Rosenberg and colleagues at the New York State Department of Health have linked data from several New York surveillance systems for immunization, laboratory tests, and hospitalization.

During that period, they found that a total of 9,675 new cases of COVID-19 occurred in fully vaccinated adults, compared with 38,505 cases in unvaccinated adults (10). 1.31 vs. 10.69 per million people per day).

In addition, data from the Mayo Clinic, Previously published medRxiv, Also found a reduction in vaccine efficacy in preventing infections in Minnesota, Warensky said. For the Moderna vaccine, the efficacy against infection decreased from 86% in January-July to 76% in July, while for Pfizer it decreased from 76% to 42%.

finally, New data from MMWR A national network of nursing homes has shown that protection against infection has dropped from 75% in March to 53% as of August 1, Walensky said.

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

They had an adjusted efficacy of 74.7% (based on a 17,407-week report from 3,862 institutions) for infection during the “pre-delta” period (March 1-May 9) and an “intermediate” period (based on reports from 3,862 institutions). In May), we found that it had dropped to 67.5%. 10 to June 20; based on 33,160 week reports from 11,581 facilities), and finally during Delta domination (June 21 to August 1; based on 85,593 week reports from 14,917 facilities) 53.1 Will be%.

Nanduri et al. Stated that estimates of efficacy were similar for both vaccines.

“In summary, the exact percentage of vaccine efficacy depends on the cohort and settings studied, but the data consistently show that protection from infection declines over time,” Walensky said. Stated.

Protection against severe illness and hospitalization

Walensky said the data suggest that the vaccine remains highly protective against serious illness and hospitalization, despite its reduced effectiveness against infection.

new York MMWR The data showed that from May 3 to July 25, the overall efficacy of age-adjusted vaccines for hospitalization was relatively stable (91.9% to 95.3%).

In addition, there were a total of 1,271 new hospitalizations among fully vaccinated people, compared to 7,308 hospitalizations among unvaccinated people (0.17 vs. 2.03 per 100,000 person-day). Rosenberg et al. Reported.

Hospitalization rates declined throughout the week of July 5, but increased between the weeks of July 12 and July 19, they added. They also found that hospitalization rates were high for people over the age of 65.

In the Mayo Clinic preprint, from January to July in Minnesota, both the Moderna and Pfizer vaccines came from COVID-related hospitalizations (91.6% vs. 85%, respectively) and ICU admissions (93.3% vs. 87%, respectively). It turned out to be effective in defense. There were no deaths in either cohort.

finally, New arrival MMWR Data from the CDC IVY (Influenza and Other Viruses in Acute Diseases) Network Reported by CDC’s Mark Tenforde, MD, PhD and colleagues, there was no reduction in vaccine efficacy for hospitalization over a 24-week period, but Walensky said the cohort was deficient in delta infection.

The authors evaluated IVY collected data on 3,089 inpatient adults from 21 hospitals in 18 states from March 11 to July 14. Of these, 1,194 were COVID-19 patients and 1,895 were COVID-19-free controls. Overall, 11.8% of cases were completely vaccinated, as were 52.1% of controls.

They reported that the overall efficacy rate for hospitalization was 86% and 90% for adults without immunodeficiency.

In addition, of the 1,129 patients who received the mRNA vaccine twice, there was no reduction in efficacy for 24-week hospitalization, with an efficacy rate of 84% for 2-12 weeks after vaccination, compared to 86%. 13 to 24 weeks after vaccination.

However, of the 454 samples subjected to whole-genome sequencing, only 16.3% were found to be Delta variants, which now account for the majority of cases. More than half (53.3%) were alpha strains.

“In summary, these data confirm that protection against infections can decline over time, while protection against serious illnesses and hospitalizations is currently fairly well maintained.” Warensky said. “But when making a decision about boosters, we also need to consider the effectiveness of the vaccine in certain situations for the delta mutant.”

Double Warmy: The Decline of Immunity and Delta

Next, Warrensky is from two of the CDC’s vaccine efficacy cohorts, including more than 4,000 healthcare workers, first responders, and other front-line workers from eight locations across the United States. Emphasized preliminary unpublished data.

Data up to August 6 showed reduced efficacy against symptomatic and asymptomatic infections in the context of delta variants, from 92% prior to delta to 64% of delta.

She said the analysis showed no difference over time. This suggests that the effectiveness of the vaccine is reduced against delta, regardless of when the person was vaccinated. That is, complete vaccination may be less effective against deltas than previous variants.

Immunological basis of boosters

Dr. Anthony Fauci, MD, director of the National Institute for Allergic Infectious Diseases, provided immunological evidence to support the case of the third shot during the briefing.

Although antibody levels decline over time, mRNA booster shots will increase antibody titers by at least 10-fold, he said.

Higher levels of antibody are associated with better vaccine efficacy and are likely to be needed to protect against delta mutants, he said.

NS Papers published in Chemistry Antibody levels peaked approximately 43 days after the second dose of Moderna, but were shown to decrease by 209 days regardless of the mutants involved.

Moreover, Preprint published in medRxiv Based on Phase III data from the Moderna trial, we investigated the “immunity correlation” and found that a 1: 100 serum neutralizing titer produced a vaccine efficacy rate of 91%. Therefore, the higher the neutralizing titer, the more effective the vaccine, Fauci explained.

NS Chemistry Paper and Pfizer data Was published in New England Journal of MedicineShowed a decrease in the level of neutralizing antibody titers due to delta compared to other mutants, Forch said.

finally, another medRxiv Preprint Pfizer recently published similar data, showing that the third dose of modelna increased antibody titers by at least 10-fold.

According to Fouch, Modana’s study showed a “significant increase in titer” 15 days after the third dose to wild-type virus, beta and gamma mutants, and Pfizer data also showed levels for delta mutants. He added that he showed a good rise in the virus. , Moderna is expected to be similar.

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