More Clarity on Post-Vax COVID

Real-world risks of developing COVID-19 infection and illness after full vaccination are coming into focus as more reports come in with hard numbers.

Just on Wednesday, three such publications appeared:

• In the CDC's Morbidity and Mortality Weekly Report, health officials described 22 "breakthrough" infections diagnosed among nearly 15,000 Chicago-area nursing home residents and staff two weeks or more after they received a second mRNA COVID vaccine dose

• At one Kentucky nursing home, 22 out of 127 residents and staff developed infections at least two weeks after their second mRNA vaccine dose, with virus sequencing indicating an unusual variant was responsible, according to a separate MMWR report

• And among 417 employees and students at Rockefeller University in New York City receiving two mRNA vaccine doses, researchers identified two breakthrough infections -- notable mainly for the particular virus strains involved, as reported in the New England Journal of Medicine

Collectively, these reports provide more assurance that the phase III trial results with the Pfizer/BioNTech and Moderna vaccines did not exaggerate their effectiveness and that breakthrough infections remain rare. They're more common, however, among older individuals, and the vaccines do not offer complete protection against serious illness or death.

The Kentucky and Rockefeller University reports also suggest that virus variants may escape vaccine-induced immunity to some extent.

Chicago-Area Investigation

Beginning in February, officials in Chicago began a concerted effort to identify breakthrough cases in vaccinated nursing home residents and staff after one such infection was detected, in part to quell any outbreaks that could result because of such facilities' high-risk nature. Area nursing homes had been advised to test all residents at least monthly; staff were initially tested twice a week until early February, and then weekly for most of the subsequent investigation period, which ended March 31.

In all, 627 confirmed SARS-CoV-2 infections were detected in 75 nursing homes -- 447 of which were in residents and staff who had not been vaccinated at all. Another 145 were in individuals who had received only one dose, and 13 involved individuals who hadn't completed two weeks from their second shot.

Among the 22 with definite breakthrough infections, 12 were in residents and 10 in staff. Fourteen cases were asymptomatic, four required hospitalization, and one proved fatal. The resident who died also had a bacterial bloodstream infection as well as a urinary tract infection, plus multiple chronic conditions known to increase risk for severe COVID-19.

The investigators, led by Richard Teran, PhD, of the CDC, did not attempt to estimate vaccine efficacy from these data.

Kentucky Nursing Home

Officials noted a burst of infections at the unidentified skilled nursing facility after a vaccination program was completed Feb. 21. At that time, 90% of the facility's 83 residents and just over half of the 116 staff members had received two doses of the Pfizer/BioNTech vaccine. Residents had been routinely monitored for symptoms and staff were tested twice weekly.

On March 1, the first case of what became an outbreak was detected in an unvaccinated staff member via antigen testing. Over the next several weeks, 18 residents and four additional staff members were found to be infected, all more than two weeks after their last vaccine dose. Twelve of the cases among residents were asymptomatic; two involved hospital admission, and one resident died. Two staff members developing breakthrough infections developed symptoms that did not require hospitalization.

Investigators led by the CDC's Alyson M. Cavanaugh, DPT, PhD, sequenced virus isolates from 27 cases at the facility and determined that these were an unusual strain known as R.1. This variant "is not currently identified as a CDC variant of concern," the group wrote, but nevertheless it includes mutations such as E484K found in others known to be either more transmissible or more likely to produce serious illness than the original Wuhan strain.

Cavanaugh and colleagues did estimate vaccine efficacy for various outcomes at the nursing home:

• 66.2% for infection (including asymptomatic) in residents (95% CI 40.5%-80.8%)

• 86.5% for symptomatic COVID in residents (95% CI 65.6%-94.7%)

• 94.4% for hospitalization in residents (95% CI 73.9%-98.8%)

• 75.9% for infection in staff (95% CI 32.5%-91.4%)

• 87.1% for symptomatic COVID in staff (95% CI 46.4%-96.9%)

The researchers couldn't be certain that these figures, somewhat lower than seen in clinical studies or Israel's national experience, were because the R.1 strain is more virulent, but said it was possible.

Rockefeller University

Late in 2020, the school began testing all students and employees weekly with a saliva-based PCR assay. Beginning Jan. 21, when two weeks had elapsed since the first vaccinees had received their second doses of either the Pfizer/BioNTech or Moderna vaccines, Rockefeller researchers led by Robert B. Darnell, MD, PhD, began looking for breakthrough cases, with 417 individuals considered eligible.

By March 17, the group found two: both in previously healthy women, one age 51 and the other 65, who developed mild symptomatic illness 19 and 36 days, respectively, after their second vaccine doses.

Viral RNA sequencing showed that both women were infected with variants differing from each other as well as from the original Wuhan strain. In "Patient 1" the virus included the E484K mutation and another known as D614G, whereas virus from "Patient 2" had D614G plus S477N. Both were distinct from variants such as B.1.1.7 and B.1.526 known to be circulating in New York City.

Serology studies indicated both women mounted strong antibody responses from vaccination, according to Darnell and colleagues. Moreover, lab studies showed that serum taken from Patient 1 effectively neutralized the Wuhan strain, B.1.526, and the E484K mutant, suggesting "that the antibody response in Patient 1 recognized these variants but was nonetheless insufficient to prevent a breakthrough infection," the researchers said.

Darnell's group emphasized that the findings "in no way undermine the importance" of completing COVID vaccinations across the U.S. population, but they do "lend support" to the desirability of boosters targeting variants, as well as a "pan-coronavirus" vaccine.

"Our observations underscore the importance of the ongoing race between immunization and the natural selection of potential viral escape mutants," and thus "the need to maintain layers of mitigation strategies," the researchers wrote.