#VisualAbstract: Positive Anti-Spike or Anti-Nucleocapsid Antibody Status is Associated with Reduced Incidence of SARS-CoV-2 Reinfection in Health Care Workers

1. Health care workers with anti-spike antibodies revealed no symptomatic infections during the follow-up period for at least six months.

2. Participants with anti-nucleocapsid IgG antibodies also displayed a lower risk of reinfection of COVID-19 disease during the follow-up period.

Evidence Rating Level: 2 (Good)

Study Rundown: Vaccines have been great with combating the flu every year. With the ongoing presence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, studying the immune response of those infected with COVID-19 has been essential. However, there is limited information and evidence in regard to post-infection immunity with coronavirus disease 2019 (COVID-19). This longitudinal cohort study examined the antibody status and incidence among health care workers in the United Kingdom. A baseline antibody status test was conducted upon enrollment into the study followed by the measurement of the primary analysis of anti-spike IgG assay. Most of the participants had a negative antibody result and upon completion of the follow-up period, the results revealed an inverse relationship between a high anti-spike antibody titer resulting in a seropositive assay and a positive COVID-19 polymerase chain reaction (PCR)-test. The study was limited by its short duration of 31 weeks. Moreover, outcome ascertainment bias may have happened as a result of infrequent visits of asymptomatic staff for testing. Nonetheless, the study highlighted the ability for anti-spike antibodies to confer a lower reinfection risk.

Click to read the study in NEJM

Relevant reading: Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

In-Depth [prospective cohort]: This longitudinal study was conducted in the United Kingdom across four different hospitals between March 27, 2020, and November 30, 2020. Symptomatic and asymptomatic health care workers were invited to join the study where a nasal or oropharyngeal swab was collected. A total of 12,541 participants were enrolled in the study and the samples were assessed using enzyme-linked immunosorbent assay (ELISA) to measure the anti-trimeric spike IgG and an anti-nucleocapsid IgG antibody. Of these, 90.6% had a seronegative test result and 9.4% had a seropositive result of the anti-spike protein. During the study, only 88 of these participants had a seroconversion occur. From the 90.6% with a negative anti-spike protein test, a total of 223 had a positive test – 100 were asymptomatic, 123 were symptomatic, and 88 converted into a seropositive. In seropositive health care workers, the incidence rate ratio was 0.12 with a 95% confidence interval (CI) of 0.03-0.47 (P=0.002) for a positive test. Consequently, after certain factors were adjusted for, such as age, gender, and testing month, the incidence rate ratio was 0.1 with a 95% CI of 0.03-0.44 (P=0.002) for a positive test. Anti-spike antibody titers and positive PCR tests displayed an inverse relationship. In fact, only two participants had a positive test result over the 31 weeks of the follow-up period. Both of these participants were from the asymptomatic group. Overall, health care workers with anti-spike antibodies and anti-nucleocapsid antibodies displayed a significantly lower risk of re-infection with COVID-19.

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