Young Men Not Immune to Getting COVID Twice

Young adult men who were previously infected with COVID-19 were not completely protected against reinfection, a study of U.S. marines found.

Among 189 Marines who were seropositive but free of current SARS-CoV-2 infection at baseline, 10% tested positive for SARS-CoV-2 via PCR during a 6-week follow-up period, reported Stuart Sealfon, MD, of Icahn School of Medicine at Mount Sinai in New York City, and colleagues.

Not surprisingly, viral loads were about 10 times lower compared with initially seronegative participants who tested positive, and those who tested positive again were more likely to have a weaker immune response, Sealfon and colleagues wrote in Lancet Respiratory Medicine.

Participants were nearly all men, and most were ages 18-20. Notably, only three of 19 seropositive Marines were symptomatic.

The question of natural infection conferring immunity has been central in the discussion over whether to vaccinate previously infected people. Sealfon’s group said most individuals do mount a “sustained serological response” after initial infection, but prior research found that about 10% of individuals with antibodies to SARS-CoV-2, with a weaker immune response, failed to develop measurable neutralizing activity.

They noted that a high proportion of young adults are infected asymptomatically and “can be an important source of transmission to more vulnerable populations.”

“As vaccine rollouts continue to gain momentum, it is important to remember that, despite a prior COVID-19 infection, young people can catch the virus again and may still transmit it to others,” Sealfon said in a statement. “Immunity is not guaranteed by past infection, and vaccinations that provide additional protection are still needed for those who have had COVID-19.”

Sealfon and colleagues examined data from the COVID-19 Health Action Response for Marines (CHARM) study, in which U.S. Marine recruits had a 2-week unsupervised home quarantine, followed by a Marine-supervised 2-week quarantine on a college campus or in a hotel. They were then assessed for baseline SARS-CoV-2 IgG seropositivity and completed a questionnaire that included demographic history, risk factors, medical history, and symptoms. Participants were tested via PCR at weeks 0, 1, and 2 of quarantine and completed follow-up questionnaires about symptoms since last visit.

After quarantine, those testing negative for current SARS-CoV-2 infection entered basic training, and were tested for new infections every 2 weeks for 6 weeks and completed a follow-up symptom questionnaire. Baseline neutralizing antibody titers were performed on all newly infected seropositive participants and selected seropositive uninfected participants.

From May 11 to Nov. 2, 2020, 3,076 participants were followed up after quarantine for 6 weeks. There was a higher proportion of Hispanic and Black participants in the seropositive group.

Nineteen of 189 seropositive participants had at least one positive PCR test for SARS-CoV-2 (1.1 cases per person-year), as did 1,079 seronegative participants (6.2 cases per person-year), for an incidence rate ratio of 0.18 (95% CI 0.11-0.28).

When examining immune response within the seropositive group, Sealfon’s group found a strong link between lower titers of IgG antibodies to full-length spike protein and a subsequent positive PCR test. They also found neutralizing activity above the limit of detection in 83% of seropositive participants who never tested positive again, and in 32% of participants who were reinfected.

“Overall, these results indicate that COVID-19 does not provide an almost universal and long-lasting protective immunity, unlike that seen in measles, for example,” wrote Marìa Velasco, MD, PhD, and Carlos Guijarro, MD, PhD, of Hospital Universitario Fundación Alcorcón in Madrid, in an accompanying editorial.

However, they offered some caveats to the study, namely that a positive PCR test is most likely a new infection, but could also be “viral persistence with reappearance of virus in mucosae, or non-viable viral debris.”

“In the absence of viral sequencing with phylogenetic analyses, viral cultures, or information regarding different SARS-CoV-2 variants, a positive PCR test cannot be assumed to represent new viral infections in all settings,” the editorialists wrote, though they added that strict scientific criteria may also be underestimating the real rate of reinfection, and suggested a “pragmatic approach” for classifying cases as either reinfection, relapse, or “PCR re-positivity.”

Sealfon’s group noted that despite the closed setting, the population is representative of U.S. men ages 18-20, though it is unclear how generalizable it is to young women or older adults.

Other limitations include potential missing data, such as infections occurring between sampling every 2 weeks. The authors added that the study is also likely underestimating risk of reinfection, as the seronegative group “included an unknown number of previously infected participants who did not have significant IgG [titers] in their baseline serum sample.”