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Background and Objectives: Given the limited knowledge of antibody responses to COVID-19 and their determinants, we analyzed the relationship between the occurrence of acute-phase symptoms and infection-induced immunoglobulin (Ig) G seropositivity up to 8 months post-symptom onset. Materials and Methods: In this cross-sectional study, 661 middle-aged unvaccinated healthcare workers (HCWs) were interviewed about the presence of symptoms during the acute phase of their previously confirmed COVID-19 and were tested for specific IgG, targeting the spike protein (S1 and S2). The dependence of seropositivity on the symptom occurrence was explored through multiple logistic regression, adjusted for the interval between symptom onset and serology testing, and through classification and regression trees. Results: A total of 551 (83.4%) HCWs showed seropositivity and, inversely, 110 (16.6%) HCWs were seronegative. The chance of IgG seropositivity was increased by dyspnea (odds ratio (OR) 1.48, p &lt; 0.001) and anosmia (OR 1.52, p = 0.021). Fever in HCWs with dyspnea resulted in the highest detected seropositivity rate, and anosmia in HCWs without dyspnea significantly increased the proportion of seropositivity. Conclusion: Clinical manifestation of the acute phase of COVID-19 predisposes to the development of infection-induced antibody responses. The findings can be applied for assessing the long-term protection by IgG, and thus, for creating effective surveillance strategies.

Relationship between Acute-Phase Symptoms and Immunoglobulin G Seropositivity up to Eight Months after COVID-19