Why the Research Is Interesting: With the onset of mass SARS-CoV-2 vaccination programs and the increasing proportion of previously infected individuals, the risk of reinfection after natural infection is an important question for modeling the pandemic, estimating herd immunity, and guiding vaccination strategies. And since young adults, of whom a high percentage are asymptomatically infected and become seropositive in the absence of known infection, can therefore be a source of transmission to more vulnerable populations, it’s important to evaluate protection against subsequent SARS-CoV-2 infection conferred by seropositivity to determine the need for vaccinating previously infected individuals in this age group.
Said Mount Sinai’s Dr. Stuart Sealfon of this work: “Our findings indicate that reinfection by SARS-CoV-2 in healthy young adults is common.”
Corresponding Author: Stuart C. Sealfon, MD, Professor of Neurology, Neuroscience and Pharmacological Sciences, Icahn School of Medicine at Mount Sinai.
Bottom Line: Although antibodies induced by infection to SARS-CoV-2 are largely protective, they do not guarantee effective immunity against subsequent infection, as evidenced through a longitudinal, prospective study of young Marine recruits. Previously infected study participants identified by seropositivity are susceptible to repeat infection, with nearly one-fifth the incidence rate of those without evidence of previous infection. Among the seropositive group, those who became infected again had lower antibody titers than those that were uninfected, and most lacked detectable baseline neutralizing antibodies. Findings suggest that COVID-19 vaccination may be necessary for control of the pandemic in previously infected young adults.
Results: Among 189 seropositive participants, 19 (10.1%) had at least one positive PCR test for SARS-CoV-2 during the six-week follow-up. In contrast, 1,079 (48.0%) of the 2,246 seronegative participants tested positive. The incidence rate ratio was 0.18 (95% CI 0.11-0.28, p<0.00001). Among seropositive recruits, infection was associated with lower baseline full-length protein IgG titers (p=<0.0001). Compared with seronegative recruits, seropositive recruits had about 10-fold lower viral loads and trended towards shorter duration of PCR positivity (p=0.18) and more asymptomatic infections (p=0.13). Among seropositive participants, baseline neutralizing titers were detected in 45 of 54 (83.3%) uninfected and in 6of 19 (31.6%) infected participants during the 6 weeks of observation.
Who: Scientists from the Icahn School of Medicine at Mount Sinai, in collaboration with researchers from the Naval Medical Research Center, utilized the COVID-19 Health Action Response for Marines (CHARM) study, a longitudinal, prospective cohort study that has been previously described and published in NEJM, to examine how protective detectable antibodies are to preventing subsequent infections with SARS-CoV-2, the virus that causes COVID-19. The study population consisted of 3,249 predominantly male, 18-20-year-old Marine recruits who, upon arrival at a Marine-supervised two-week quarantine prior to entering basic training, were assessed for baseline SARS-CoV-2 IgG seropositivity (defined as a 1:150 dilution or greater on receptor binding domain and full-length spike protein enzyme-linked immunosorbent [ELISA] assays.) The presence of SARS-CoV-2 was assessed by PCR at initiation, middle and end of quarantine. After appropriate exclusions, including participants with a positive PCR during quarantine, the study team performed three bi-weekly PCR tests in both seronegative and seropositive groups once recruits left quarantine and entered basic training.
When: All study data was collected between May and October, 2020. The prospective study observation period began when Marine recruits arrived at Marine Corps Recruit Depot – Parris Island (MCRDPI) to commence basic training.
What: The study evaluated protection against subsequent SARS-CoV-2 infection conferred by seropositivity in young adults to determine the need for vaccinating previously infected individuals in this age group.
How: After appropriate exclusions, including participants with a positive PCR during quarantine, the study team performed three biweekly PCR tests in both seropositive and in seronegative groups once recruits left quarantine and entered basic training and baseline neutralizing antibody titers on all subsequently infected seropositive and selected seropositive uninfected participants.
Study Conclusions: Seropositive young adults had about one-fifth the risk of subsequent infection compared with seronegative individuals. Although antibodies inducted by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralization activity or immunity against subsequent infection. These findings may be relevant for optimization of mass vaccination strategies.
Funding: Defense Health Agency and Defense Advanced Research Projects Agency (DARPA)