SARS-CoV-2 Seropositivity and Subsequent Infection Risk
- A lower proportion of participants who had baseline serum antibodies against SARS-CoV-2 became infected during the 6-week study period than of those without detectable antibodies.
- Although antibodies induced by infection appear largely protective, they do not guarantee effective immunity against subsequent infection.
- Irrespective of previous SARS-CoV-2 infection or documented seropositivity, vaccination seems indicated to boost the natural immune response and prevent reinfection and reduce transmission.
What is the risk of subsequent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among young adults seropositive for a previous infection?
The investigators performed this analysis as part of the prospective CHARM (COVID-19 Health Action Response for Marines) study. 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 immunoglobulin G (IgG) seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein enzyme-linked immunosorbent assay (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 neutralizing antibody titers on all subsequently infected seropositive and selected seropositive uninfected participants (prospective study period).
Between May 11–November 2, 2020, 3,249 participants were enrolled, of whom 3,168 (98%) continued into the 2-week quarantine period. 3,076 (95%) participants, 2,825 (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 polymerase chain reaction (PCR) test for SARS-CoV-2 during the 6-week follow-up (1.1 cases per person-year). In contrast, 1,079 (48%) of 2,247 seronegative participants tested positive (6.2 cases per person-year). The incidence rate ratio was 0.18 (95% confidence interval [CI], 0.11–0.28; p < 0.001). Among seropositive recruits, infection was more likely with lower baseline full-length spike protein IgG titers than in those with higher baseline full-length spike protein IgG titers (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 neutralizing titers were detected in 45 (83%) of 54 uninfected and in 6 (32%) of 19 infected participants during the 6 weeks of observation (ID50 difference p < 0.0001).
The authors concluded that seropositive young adults had about one-fifth the risk of subsequent infection compared with seronegative individuals.
This study reports that a lower proportion of participants with baseline serum antibodies against SARS-CoV-2 became infected during the 6-week study period compared to those without detectable antibodies. It is important to note that although antibodies induced by infection are largely protective, they do not guarantee effective immunity against subsequent infection. These data imply that irrespective of previous SARS-CoV-2 infection or documented seropositivity, vaccination appears indicated to boost the natural immune response and prevent reinfection and reduce transmission.
Keywords: Antibodies, Neutralizing, Coronavirus, COVID-19, Enzyme-Linked Immunosorbent Assay, Immunity, Immunoglobulin G, Military Personnel, Polymerase Chain Reaction, Primary Prevention, Quarantine, Risk Factors, SARS-CoV-2, Serologic Tests, Spike Glycoprotein, Coronavirus, Vaccination, Viral Load, Young Adult
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