Antibody response patterns in COVID-19 patients

We analyzed antibody response patterns according to level of disease severity in patients with novel coronavirus disease 2019 (COVID-19) in Japan. We analyzed 611 serum samples from 231 patients with COVID-19 (mild, 170; severe, 31; critical, 30). Immunoglobulin M (IgM) and IgG antibodies to core protein (N) and spike protein 1 (S1) were detected by enzyme immunoassays.

The peaks of the fitted curves for the optical density (OD) values ​​of IgM and IgG antibodies against N appeared simultaneously, while those against S1 were delayed compared to N. The OD values ​​of IgM against N and IgG against N and S1 were significantly higher. in severe and critical cases than in mild cases at 11 days after the onset of symptoms.

IgG seroconversion rates were higher than IgM against N and S1 during the clinical course based on the optimal cutoff values ​​defined in this study. IgG and IgM seroconversion rates against N and S1 were higher in severe and critical cases than in mild cases. Our results show that a stronger antibody response occurred in COVID-19 patients with greater disease severity and that there were low antibody seroconversion rates against N and S1 in mild cases.

The novel coronavirus disease 2019 (COVID-19), which is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was initially reported in December 2019 in Wuhan, China,1 and it has since become an ongoing pandemic worldwide.2

Patients with COVID-19 are mostly asymptomatic or have mild symptoms, but about 20% of patients develop severe disease.3 The global scientific community is still researching the mechanism of disease pathogenesis to identify an effective treatment . Recently, several reports have suggested that antibody response against SARS-CoV-2 may be associated with disease severity.4-10 Identifying antibody response patterns of target populations and differences in these patterns between patients depending on disease severity will help clarify pathogenicity and humoral immunity for SARS-CoV-2.

The main antigens of SARS-CoV-2 are the inner core protein (N) and the outer spike protein (S), which consists of two subunits (S1 and S2). In particular, S1 contains a receptor-binding domain (RBD) that is responsible for binding to the angiotensin-converting enzyme 2 receptor on host cells early in infection11; thus, antibodies targeting S1 and RBD should inhibit angiotensin-converting enzyme 2/RBD binding and have neutralizing activity.8, 12-15

Differences in antibody response patterns against each antigen between patients with different levels of disease severity have been reported based on limited samples collected from specific countries9, 12; however, it is unclear whether these response patterns can be applied in the same way to different populations. Here, we describe differences in antibody response patterns for N and S1 and isotypes among 611 serum samples collected from 231 Japanese COVID-19 patients with different levels of disease severity.