Definite COVID-19 diagnosis entails direct detection of SARS-CoV-2 RNA by nucleic acid amplification technology (NAAT)16-18. Serological assays, which detect antibodies against SARS-CoV-2, can contribute to identify individuals, which were previously infected by the virus, and to assess the extent of exposure of a population. They might thereby help to decide on application, enforcement or relaxation of containment measures19.
Upon infection with SARS-CoV-2, the host mounts an immune response against the virus, including production of specific antibodies against viral antigens. Both IgM and IgG have been detected as early as day 5 after symptom onset20,21. Median seroconversion has been observed at day 10 - 13 for IgM and day 12 - 14 for IgG22-24, while maximum levels have been reported at week 2 - 3 for IgM, week 3 - 6 for IgG and week 2 for total antibody20-26. Whereas IgM seems to vanish around week 6 - 727,28, high IgG seropositivity is seen at that time20,27,28. While IgM is typically the major antibody class secreted to blood in the early stages of a primary antibody response, levels and chronological order of IgM and IgG antibody appearance seem to be highly variable for SARS-CoV-2. Anti-SARS-CoV-2 IgM and IgG often appear simultaneously, and some cases have been reported where IgG appears before IgM, limiting its diagnostic utility21,22,24,29,30.
After infection or vaccination, the binding strength of antibodies to antigens increases over time - a process called affinity maturation31. High-affinity antibodies can elicit neutralization by recognizing and binding specific viral epitopes32,33. In SARS-CoV-2 infection, antibodies targeting both the spike and nucleocapsid proteins, which correlate with a strong neutralizing response, are formed as early as day 9 onwards, suggesting seroconversion may lead to protection for at least a limited time29,34-37.