Exposure factors associated with SARS-CoV-2 seropositivity are not predictive for higher humoral immune responses: A cross-sectional cohort study in the general population

Introduction

Higher antibody levels, in particular antibodies directed against the receptor-binding domain (RBD) of the spike protein, protect against re-infection with SARS-CoV-2. Quantitative antibody response data provide insight into population immunity and are essential for decision-making on booster-vaccination strategies. We aimed to identify predictors for higher antibody responses such as gender, age, experienced COVID-19-compatible symptoms, disease severity and exposure to pre-determined risk factors associated with SARS-CoV-2 seropositivity.

Materials and methods

Quantitative anti-S-RBD responses were analysed in seropositive vaccine-naive individuals (n = 1,857) from a study population of 10,001 adults, including healthcare workers (n = 211) and individuals with a known date of a positive PCR (n = 214). Regression models tested associations between age, gender, the period of symptoms, disease severity, pre-identified exposure factors associated with SARS-CoV-2 seropositivity, and anti-S-RBD responses.

Results

Symptoms of more severe disease (fever and/or dyspnoea: OR 2.42 [95%CI 1.76–3.34], and hospital admission: OR 11.41 [95%CI 4.66–27.97]), and a longer interval between COVID-19-compatible symptoms and serum collection (OR 3.17 [95%CI 1.32–7.63]) were predictive for anti-S-RBD levels ≥300 U/mL. Working in healthcare was inversely associated with anti-S-RBD levels ≥300 U/mL (OR 0.51 [95%CI 0.31–0.82]). None of the pre-identified exposure factors associated with SARS-CoV-2 seropositivity could be identified as predictive of higher anti-S-RBD responses.

Conclusion

No exposure factors were identified as predictors of higher neutralising antibody responses. Nevertheless, higher neutralising antibody levels in individuals with more severe symptoms suggest better immunological protection against SARS-CoV-2 re-infection. In seroprevalence studies, that mainly include asymptomatic or mildly infected individuals, the determination of quantitative antibody responses may help in the interpretation of population immunity.