COVID Breakthrough Cases Ran the Gamut in Healthcare Workers

Breakthrough COVID-19 cases in fully vaccinated healthcare workers were rare, and generally were associated with the individual’s immune response to the vaccine in the early days of infection, an Israeli study found.

In 39 breakthrough infections of SARS-CoV-2 out of 1,497 fully vaccinated healthcare workers, neutralizing antibody titers were lower than uninfected controls during the “peri-infection period” (case-to-control ratio 0.361, 95% CI 0.165-0.787), reported Gili Regev-Yochay, MD, of Tel Aviv University in Israel, and colleagues.

Moreover, nearly one in five cases reported symptoms more than 6 weeks later, akin to “long COVID,” the authors wrote in the New England Journal of Medicine.

“Most important, we found that low titers of neutralizing antibody and S-specific IgG antibody may serve as markers of breakthrough infection,” they said.

They discussed how “no correlate of protection from breakthrough infection has been reported,” though 85% of these cases were from the Alpha variant. CDC officials in the U.S. discussed the potential for breakthrough cases with the Delta variant in fully vaccinated people as the reason for their new guidance on indoor masking in hotspots and schools.

Regev-Yochay’s group examined a group of healthcare workers at a single medical center, including employees, students, and volunteers from Dec. 19, 2020 to April 28, 2021. Nearly all (91%) of these workers received the two-dose Pfizer vaccine, and filled out daily health questionnaires. The center tested staff via RT-PCR who either had COVID symptoms or were exposed to an infected person.

A breakthrough infection was defined as a positive test for SARS-CoV-2 at 11 or more days following the second dose of Pfizer vaccine if no exposure or symptoms were reported during the first 6 days. Each case was matched with four or five uninfected controls by age, sex, and the interval between the second dose of vaccine and serologic testing, as well as immunosuppression status.

Of more than 11,000 healthcare workers, 13.1% underwent RT-PCR testing. The authors noted that 38 people were tested for every breakthrough case detected, for a test positivity of 2.6%.

Eighteen of the 39 breakthrough cases were among nursing staff, 10 were administration or maintenance workers, six were allied health professionals and five were in physicians. Mean age was 42, and almost two-thirds of cases were in women. Median interval between the second dose and reinfection was 39 days. Twenty-seven cases occurred in workers who were tested only due to exposure to someone with a known infection.

Two-thirds of breakthrough cases had mild symptoms, the most common of which was upper respiratory congestion (36%), followed by myalgia and loss of smell or taste (28% each), while 21% reported fever. There were 19% of patients reporting “long COVID” symptoms, including prolonged loss of smell, persistent cough, fatigue, weakness, dyspnea, or myalgia.

Thirty-three isolates were tested for a variant of concern, and 28 of those were identified as B.1.1.7 (Alpha variant), which accounted for nearly all of Israel’s cases.

The authors added that most infected workers had N gene Ct values that suggested they had been infectious at some point, but it might not have been detected without screening for any minor known exposure, meaning the vaccine protected against symptomatic disease, but not infection.

“However, no secondary infections were traced back to any of the breakthrough cases, which supports the inference that these workers were less contagious than unvaccinated persons,” they said.

Limitations to the data include the small sample size; the young and healthy population that limits generalizability of the findings; and the potential that asymptomatic cases may have been missed.