Young Adults Infected With SARS-CoV-2 May Have Higher Risk of Reinfection

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Young adults who are infected with SARS-CoV-2 have a slightly higher risk of subsequent infection with COVID-19 compared with seronegative people.

Young adults who are infected with SARS-CoV-2 have a slightly higher risk of subsequent infection with COVID-19 compared with seronegative people, despite the former population having antibodies that may be largely protective against a second infection, according to study results published in Lancet Respiratory Medicine.

Researchers analyzed data from the prospective COVID-19 Health Action Response for Marines study (CHARM), which included mostly male US Marine recruits between 18 and 20 years of age. Participants had completed a 2-week unsupervised quarantine at home prior to study entry and were subsequently enrolled upon arrival at a supervised 2-week quarantine facility (n=3168).

Researchers assessed participants for SARS-CoV-2 immunoglobulin G (IgG) seropositivity at baseline. Additionally, the investigators administered a questionnaire to collect demographic information, risk factors, occurrence of COVID-19-related symptoms or any other unspecified symptom, and a brief medical history. Participants were reassessed for SARS-CoV-2 infection by polymerase chain reaction (PCR) test at weeks 0, 1, and 2. Additional PCR tests were performed at weeks 2, 4, and 6 in seropositive and seronegative groups.

A total of 3076 participants were followed during the prospective study period and for up to 6 weeks. At baseline, a total of 225 patients were SARS-CoV-2 IgG seropositive, while 2851 participants were seronegative.

Approximately 10% (19/189) of seropositive participants and 48% (1079/2247) of seronegative participants had at least 1 positive SARS-CoV-2 PCR result during the 6 weeks, corresponding to an incidence rate ratio of 0.18 (95% CI, 0.11-0.28; P <.001) for infections in those classified as seropositive.

In the seropositive recruits, infection was statistically more likely if they had lower full-length spike protein IgG titers at baseline compared with recruits with higher baseline full-length spike protein IgG titers (hazard ratio, 0.45; 95% CI, 0.32-0.65; P <.001).

Viral loads in infected seropositive recruits were approximately 10 times lower than loads observed in infected seronegative participants (ORF1ab gene cycle threshold difference, 3.95; 95% CI, 1.23-6.67; P =.004). Baseline neutralizing titers among the seropositive participants were detected in 83% of 54 uninfected and in 32% of 19 infected recruits during the 6-week observation period (50% inhibitory dose difference P <.0001).

Limitations of this study were the greater number of male participants as well as the inclusion of only young participants, which may limit the generalizability of the findings.

Overall, the findings suggest “COVID-19 vaccination might be necessary for control of the pandemic in previously infected young adults,” the investigators wrote.


Letizia AG, Ge Y, Vangeti S, et al. SARS-CoV-2 seropositivity and subsequent infection risk in healthy young adults: a prospective cohort study. Lancet Respir Med. Published online April 15, 2021. doi:10.1016/S2213-2600(21)00158-2