Virological Correlates of IgM-IgG Patterns of Response to SARS-CoV-2 Infection According to Targeted Antigens

The virological meaning of the different patterns of serology in COVID-19 has been little examined in clinical settings. Asymptomatic subjects with IgM-spike (S) and IgG-nucleocapsid (N) determinations by chemiluminescence were studied for SARS-CoV-2 shedding in respiratory secretions by transcription-mediated amplification (TMA). In subjects showing IgM-S positive and IgG-N negative, IgG-S was determined by lateral flow assay. A total of 712 individuals were tested: 30.0% presented IgM-S(+)/IgG-N(-), 25.8% had IgM-S(+)/IgG-N(+) and 44.2% had IgM-S(-)/IgG-N(+); the proportion with TMA(+) were comparable in these three groups: 12.1, 8.7 and 10.5%, respectively. In individuals with IgM-S(+)/IgG-N(-), IgG-S(+) was detected in 66.5%. The frequency of IgM-S(+)/IgG-S(-) in the total population was 10.0%, of whom 24.1% had TMA(+); the chances for TMA(+) in subjects with an IgM-S(+) alone pattern were 2.4%. Targeting of the same SARS-CoV-2 antigen seems to be better for the characterization of IgM/IgG patterns of response. IgM-S(+) alone reactivity is rare, and a small proportion is associated with viral shedding.