SARS-CoV-2 Antigenemia as a Confounding Factor in Immunodiagnostic Assays: A Case Study

Belogiannis, Konstantinos; Florou, Venetia A.; Fragkou, Paraskevi C.; Ferous, Stefanos; Chatzis, Loukas; Polyzou, Aikaterini; Lagopati, Nefeli; Vassilakos, Demetrios; Kittas, Christos; Tzioufas, Athanasios G.; Tsiodras, Sotirios; Sourvinos, George; Gorgoulis, Vassilis G.

Humoral immunity has emerged as a vital immune component against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nevertheless, a subset of recovered Coronavirus Disease-2019 (COVID-19) paucisymptomatic/asymptomatic individuals do not generate an antibody response, constituting a paradox. We assumed that immunodiagnostic assays may operate under a competitive format within the context of antigenemia, potentially explaining this phenomenon. We present a case where persistent antigenemia/viremia was documented for at least 73 days post-symptom onset using ‘in-house’ methodology, and as it progressively declined, seroconversion took place late, around day 55, supporting our hypothesis. Thus, prolonged SARS-CoV-2 antigenemia/viremia could mask humoral responses, rendering, in certain cases, the phenomenon of ‘non-responders’ a misnomer.