BACKGROUND: Whether young adults who are infected with SARS-CoV-2 are at risk of subsequent infection is uncertain . We investigated the risk of subsequent SARS-CoV-2 infection among young adults seropositive for a previous infection .
METHODS: This analysis was performed as part of the prospective COVID-19 Health Action Response for Marines study (CHARM). CHARM included predominantly male US Marine recruits, aged 18-20 years, following a 2-week unsupervised quarantine at home . After the home quarantine period, upon arrival at a Marine-supervised 2-week quarantine facility (college campus or hotel), participants were enrolled and were assessed for baseline SARS-CoV-2 IgG seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein ELISA . Participants also completed a questionnaire consisting of demographic information, risk factors, reporting of 14 specific COVID-19-related symptoms or any other unspecified symptom, and brief medical history . SARS-CoV-2 infection was assessed by PCR at weeks 0 , 1, and 2 of quarantine and participants completed a follow-up questionnaire, which included questions about the same COVID-19-related symptoms since the last study visit . Participants were excluded at this stage if they had a positive PCR test during quarantine . Participants who had three negative swab PCR results during quarantine and a baseline serum serology test at the beginning of the supervised quarantine that identified them as seronegative or seropositive for SARS-CoV-2 then went on to basic training at Marine Corps Recruit Depot-Parris Island . Three PCR tests were done at weeks 2 , 4, and 6 in both seropositive and seronegative groups, along with the follow-up symptom questionnaire and baseline neutralising antibody titres on all subsequently infected seropositive and selected seropositive uninfected participants (prospective study period). FINDINGS: Between May 11 , 2020, and Nov 2 , 2020, we enrolled 3249 participants, of whom 3168 (98 %) continued into the 2-week quarantine period . 3076 (95 %) participants , 2825 (92 %) of whom were men, were then followed up during the prospective study period after quarantine for 6 weeks . Among 189 seropositive participants , 19 (10 %) had at least one positive PCR test for SARS-CoV-2 during the 6-week follow-up (1·1 cases per person-year). In contrast , 1079 (48 %) of 2247 seronegative participants tested positive (6·2 cases per person-year). The incidence rate ratio was 0·18 (95% CI 0·11-0·28; p <0·001). Among seropositive recruits, infection was more likely with lower baseline full-length spike protein IgG titres than in those with higher baseline full-length spike protein IgG titres (hazard ratio 0·45 [95% CI 0·32-0·65]; p <0·001). Infected seropositive participants had viral loads that were about 10-times lower than those of infected seronegative participants (ORF1ab gene cycle threshold difference 3·95 [95% CI 1·23-6·67]; p=0·004). Among seropositive participants, baseline neutralising titres were detected in 45 (83 %) of 54 uninfected and in six (32 %) of 19 infected participants during the 6 weeks of observation (ID50 difference p <0·0001). INTERPRETATION: 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 neutralisation activity or immunity against subsequent infection . These findings might be relevant for optimisation of mass vaccination strategies .
FUNDING: Defense Health Agency and Defense Advanced Research Projects Agency.