SARS-CoV-2 seropositivity and subsequent infection risk in healthy young adults: a prospective cohort study

Abstract

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 participant...

The success of SARS-CoV-2 vaccines and challenges ahead

“…Although re-infections have been reported, symptomatic reinfections in previously infected individuals occur at a lower rate than primary infections (Dimeglio et al, 2021;Leidi et al, 2021), consistent with the demonstration of immune memory after infection (Dan et al, 2021;Turner et al, 2021). In a study of young, healthy US Marines, seropositive individuals had about one-fifth the risk of re-infection and 10-fold reduced viral loads compared with seronegative individuals (Letizia et al, 2021). Re-infection in seropositive individuals was more likely to occur when lower amounts of baseline SARS-CoV-2 antibody were observed (Letizia et al, 2021).…”

“…In a study of young, healthy US Marines, seropositive individuals had about one-fifth the risk of re-infection and 10-fold reduced viral loads compared with seronegative individuals (Letizia et al, 2021). Re-infection in seropositive individuals was more likely to occur when lower amounts of baseline SARS-CoV-2 antibody were observed (Letizia et al, 2021). Recent studies have demonstrated that a single dose of mRNA vaccine in previously infected seropositive individuals enhanced both T and B cell responses (Reynolds et al, 2021) and boosted antibody titers by up to 1,000-fold (Stamatatos et al, 2021) or to levels similar to those achieved after two doses of vaccine in seronegative individuals.…”

SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients

“…The exact correlates of protection remain to be elucidated (12,13), but circulating antibodies and memory immune cells are crucial in protection against COVID-19. Especially CORONAVIRUS SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees important are virus-specific neutralizing antibodies targeting the receptor binding domain (RBD) of the spike (S) protein, which correlate with presence of SARS-CoV-2 specific CD4 + circulating follicular helper T cells (cT FH ) (8,14) and can prevent the interaction between virus and the host cell (15). If SARS-CoV-2 establishes a reinfection, memory B and T cells rapidly proliferate and control the infection.…”

mRNA Vaccine-Induced Antibodies More Effective than Natural Immunity in Neutralizing SARS-CoV-2 and its High Affinity Variants

“…There are many studies reporting reinfection by SARS-CoV-2 [6][7][8][9] , whereas in some of the studies, the neutralizing antibodies were shown to have a protective role 10,11 . In one recent report, individuals who were SARS-CoV-2 seropositive from prior exposure had an estimated 80% reduction of subsequent risk for reinfection 12 . Several late stage clinical studies demonstrated the effectiveness of COVID-19 vaccines [13][14][15][16][17] .…”