Three Separate Spike Antigen Exposures by COVID-19 Vaccination or SARS-CoV-2 Infection Elicit Strong Humoral Immune Responses in Healthcare Workers

Background: The immunogenicity of different COVID-19 vaccine regimens and combinations in naive and convalescent individuals has not been formally tested in controlled studies, and real-life observational studies are scarce. Methods: We assessed the SARS-CoV-2 infection and COVID-19 vaccination-induced immunity of 697 hospital workers at the University Medical Center Hamburg-Eppendorf between 17 and 31 January 2022. Results: The overall prevalence of anti-NC-SARS-CoV-2 antibodies indicating prior infection was 9.8% (n = 68) and thus lower than the seroprevalence in the general population. All vaccinated individuals had detectable anti-S1-RBD-SARS-CoV-2 antibodies (median AU/mL [IQR]: 13,891 [8505-23,543]), indicating strong protection against severe COVID-19. Individuals who received three COVID-19 vaccine doses (median AU/mL [IQR]: 13,856 [8635-22,705]) and those who resolved a prior SARS-CoV-2 infection and had received two COVID-19 vaccine doses (median AU/mL [IQR] 13,409 [6934-25,000]) exhibited the strongest humoral immune responses. Conclusions: The current study indicates that three exposures to the viral spike protein by either SARS-CoV-2 infection or COVID-19 vaccination are necessary to elicit particularly strong humoral immune responses, which supports current vaccination recommendations.

Automated summary

This study indicates that three exposures to the viral spike protein through either SARS-CoV-2 infection or COVID-19 vaccination are necessary to elicit particularly strong humoral immune responses.