SARS-CoV-2 Seropositivity and Subsequent Infection Risk in Healthy Young Adults: A Prospective Cohort Study (preprint)

ABSTRACT

Background: The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subsequent infection among seropositive young adults was studied prospectively.Methods: The study population comprised 3,249 predominantly male, 18-20-year-old Marine recruits. Upon arrival at a Marine-supervised two-week quarantine, participants were assessed for baseline SARS-CoV-2 IgG seropositivity, defined as a 1150 dilution or greater on receptor binding domain and full-length spike protein enzyme-linked immunosorbent (ELISA) assays. SARS-CoV-2 infection was assessed by PCR at initiation, middle and end of the quarantine. After appropriate exclusions, including participants with a positive PCR during quarantine, we 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.Findings: Among 189 seropositive participants, 19 (10.1%) had at least one positive PCR test for SARS-CoV-2 during the six-week follow-up (1.1 cases per person-year). In contrast, 1,079 (48.0%) of the 2,247 seronegative participants tested positive (6.2 cases per person-year). 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 spike protein IgG titers (p<0.0001). Compared with seronegative recruits, seropositive recruits had about 10-fold lower viral loads (ORF1ab gene, p<0.005), and trended towards shorter duration of PCR positivity (p=0.18) and less frequent symptomatic infections (p=0.13). Among seropositive participants, baseline neutralizing titers were detected in 45 of 54 (83.3%) uninfected and in 6 of 19 (31.6%) infected participants during the 6 weeks of observation (ID50 difference pInterpretation: Seropositive young adults had about one-fifth the risk of subsequent infection compared with seronegative individuals. Although antibodies induced 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 AgencyDeclaration of Interests AGL, YG, SV, CG, DLW, HWC, DE, MCG, WDG, FJ, RL, JM, NM, CM, SM, VDN, EN, CKP, ESA, ASS, MS, VS, MT, PS, RPT, IR and SCS declare no competing interests. DP owned stock in Co- Diagnostics Inc during the conduct of the study. DP held stock in Co-Diagnostics, Inc. DS and FK have filed a patent regarding serological assays and for SARS-CoV-2 and Icahn School of Medicine at Mount Sinai has founded a company to commercialize serological assays they developed. AGL, CG, DLW, HWC, DEW, DG, FJ, JM, EN, CKP, ESA, MS, VS, PS, RAL, SAL, and MT are military Service members or GS employees. This work was prepared as part of their official duties. Ethics Approval Statement Institutional Review Board approval was obtained from the Naval Medical Research Center (protocol number NMRC.2020.0006) in compliance with all applicable U.S. federal regulations governing the protection of human subjects. All participants provided written informed consent.