From the Journals

COVID-19 infection conveys imperfect immunity in young adults



Holes in immunologic armor

Full data were available for a total of 189 participants who were seropositive and 2,247 who were seronegative at enrollment.

In all, 19 of 189 seropositive recruits (10%) had at least one PCR test positive for SARS-CoV-2 infection during the 6-week follow-up period. This translated into an incidence of 1.1 cases per person-year.

Of the 2,247 participants seronegative at baseline, 1,079 tested positive (6.2 cases per person-year; incidence rate ratio 0.18).

It appeared that antibodies provided some protection for seropositive recruits, as evidenced by a higher likelihood of infection among those with lower baseline full-length spike protein IgG titers than in those with higher baseline titers (hazard ratio 0.4, P < .001).

Among the seropositive participants who did acquire a second SARS-CoV-2 infection, viral loads in mid-turbinate nasal swabs were about 10-fold lower than in seronegative recruits who acquired infections during follow-up.

“This finding suggests that some reinfected individuals could have a similar capacity to transmit infection as those who are infected for the first time. The rate at which reinfection occurs after vaccines and natural immunity is important for estimating the proportion of the population that needs to be vaccinated to suppress the pandemic,” the investigators wrote.

Baseline neutralizing antibody titers were detected in 45 of the first 54 seropositive recruits who remained PCR negative throughout follow-up, but also in 6 of 19 seropositive participants who became infected during the 6 weeks of observation.


Both Dr. Siedner and Dr. Gupta agreed with the authors that the risks for reinfection that were observed in young, physically fit people may differ for other populations, such as women (only 10% of seropositive recruits and 8% of seronegative recruits were female), older patients, or those who are immunocompromised.

Given that the adjusted odds ratio for reinfection in this study was nearly identical to that of a recent British study comparing infection rates between seropositive and seronegative health care workers, the risk of reinfection for other young adults and for the general population may be similar, Dr. Sealfon and colleagues wrote.

Adding to the challenge of reaching herd immunity is the observation that some patients who have recovered from COVID-19 are skeptical about the need for further protection.

“There are patients who feel like vaccination is of low benefit to them, and I think these are the same people who would be hesitant to get the vaccine anyway,” Dr. Gupta said.

Although no vaccine is perfect – the vaccine failure rate from the mRNA-based vaccines from Moderna and Pfizer/Biontech is about 5% – the protections they afford are unmistakable, Dr. Siedner said.

“I think it’s important to make the distinction that most postvaccination infections by and large have been very mild,” he said. “In people with normal immune systems, we have not seen an onslaught of postvaccination infections requiring hospitalization. Even if people do get infected after vaccination, the vaccines protect people from severe infection, and that’s what we want them to do.”

The investigators stated, “Young adults, of whom a high proportion are asymptomatically infected and become seropositive in the absence of known infection, can be an important source of transmission to more vulnerable populations. Evaluating the protection against subsequent SARS-CoV-2 infection conferred by seropositivity in young adults is important for determining the need for vaccinating previously infected individuals in this age group.”

The study was funded by the Defense Health Agency and Defense Advanced Research Projects Agency. Dr. Sealfon, Dr. Siedner, and Dr. Gupta have no conflicts of interest to report. Dr. Gupta is a member of the editorial advisory board for this publication.


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