The variability of the serological response to SARS‐corona virus‐2: Potential resolution of ambiguity through determination of avidity (functional affinity)

Data on the serological response toward severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in 16 recent reports were analyzed and a high degree of variability was shown. Immunoglobulin M (IgM) responses were either found earlier than IgG, or together with IgG, later than IgG, or were missing. Therefore, clear distinctions between early, intermediate, and past infections are obviously not possible merely on the basis of IgM and IgG determinations. A review of publications on the serology of other virus groups shows that variable IgM responses can be found as well and therefore are not unique for SARS‐CoV‐2 infections. A model to explain this variability is proposed. The inclusion of avidity determination into regular diagnostic procedures has allowed to resolve such “atypical” serological constellations. The potential use of avidity determination for the diagnosis of COVID‐19, for risk assessment, epidemiological studies, analysis of cross reactions, as well as for the control of vaccination programs is suggested and discussed.