Rapid decline of neutralizing antibodies against SARS-CoV-2 among infected healthcare workers

Healthcare workers (HCWs) are at high risk of SARS-CoV-2 infection and potential reinfection due to their constant exposure. Understanding the duration of protective immunity, specifically the persistence of neutralizing antibodies (NAbs), is crucial for informing infection control strategies and vaccination protocols. Prior research on the persistence of NAbs in SARS-CoV-2-infected individuals has yielded varied results, necessitating further investigation, especially within high-risk populations like HCWs. This study aimed to address the knowledge gap concerning the long-term persistence of NAbs in HCWs who experienced mild COVID-19, providing valuable insights into the duration of naturally acquired immunity and informing recommendations for infection prevention and control measures, as well as potential vaccination strategies for this vulnerable group. The study's importance lies in its potential to guide public health interventions aimed at mitigating the risk of SARS-CoV-2 transmission and reinfection within healthcare settings.

Existing literature on SARS-CoV-2 immunity shows a variable duration of antibody responses. Some studies report relatively long-lasting IgG responses, while others highlight the transient nature of neutralizing antibodies. The lack of consistent data, particularly regarding the duration of NAbs in HCWs, necessitates this study. Previous research on SARS-CoV-1 suggests that antibody responses may wane over time. Understanding how these responses differ for SARS-CoV-2, especially in the context of frequent exposure in healthcare settings, is crucial for optimizing infection control and vaccination strategies.

This study enrolled 26 HCWs who experienced mild COVID-19. Blood samples were collected at three time points: three weeks (D21), two months (M2), and three months (M3) after symptom onset. The researchers measured antibody levels (IgG, IgA, IgM) against various SARS-CoV-2 viral components (N protein, S protein, RBD) using commercial immunoassays. Neutralizing antibody (NAb) titers were determined using a virus neutralization test (VNT). Statistical analysis was performed to assess changes in antibody levels and NAb titers over time and correlations between antibody isotypes and NAb titers. Further experiments involved purifying IgA and IgG antibody fractions to evaluate their individual neutralizing capacities. Specificity of the assays was tested using serum samples from individuals infected with other human coronaviruses.

All 26 HCWs exhibited seroconversion at D21, with detectable IgG, IgA, and IgM antibodies against SARS-CoV-2. A rapid decline in IgA antibodies against the receptor-binding domain (RBD) was observed, with a significant decrease in seropositivity rates from M2 onwards. Concurrently, NAb titers decreased significantly between D21 and M2, and between D21 and M3. By M3, some HCWs lost their neutralizing activity entirely. The strongest correlation with NAb titers was observed with anti-RBD IgG and IgA antibodies. Experiments with purified IgA and IgG fractions showed that IgA dominated early neutralizing activity, while IgG became more prominent at M3, although not enough to fully compensate for the decrease in IgA. The median time between symptom onset and positive RT-PCR was 2 days. The median time from symptom onset to blood sampling was 17.1 days for D21, 59 days for M2, and 97 days for M3. The study noted that anti-S and anti-RBD IgG antibody levels increased slightly at M2 before decreasing again by M3. Anti-N1 IgG levels did not change significantly between D21 and M3.

The findings reveal a transient nature of NAbs in HCWs recovering from mild COVID-19, with a significant decline in both NAb titers and IgA antibodies within two months of symptom onset. This suggests that naturally acquired immunity from a mild infection may be short-lived. The strong correlation between anti-RBD IgA and IgG antibodies and NAb titers highlights the importance of these antibodies in mediating protective immunity. The shift in neutralizing activity from IgA dominance at D21 to a more IgG-mediated response at M3 suggests a potential maturation of the antibody response over time, although this IgG increase is insufficient to maintain protective NAb levels. These results underscore the importance of maintaining stringent infection prevention and control measures among HCWs. The potential need for periodic SARS-CoV-2 vaccination boosts to sustain protection is supported by these findings.

This study demonstrates a rapid decline in neutralizing antibodies against SARS-CoV-2 among HCWs following mild COVID-19 infection. The short duration of humoral immunity necessitates sustained infection prevention measures and emphasizes the potential need for periodic vaccination boosts to ensure ongoing protection for HCWs. Future research should investigate optimal vaccination strategies and explore the role of other immune components, such as T cells, in providing longer-lasting immunity.

The study's relatively small sample size and focus on HCWs with mild COVID-19 may limit the generalizability of the findings to other populations or disease severities. Furthermore, the use of commercial immunoassays may influence the results, and longer-term follow-up would provide more conclusive data regarding the longevity of immunity.