IgG4 serum levels are not elevated in cases of Post-COVID syndrome (preprint)

The different effector functions of human IgG are closely associated with its four subtypes. Class switch towards IgG4 occurs after long-term antigen exposure, downregulates immune responses and is associated with several autoimmune diseases. Interestingly, significantly elevated IgG4 levels have recently been detected after more than two mRNA vaccinations. We here study the distribution of IgG subtypes in the context of Post-COVID syndrome. To this end, we analyzed serum samples from two cohorts of 64 patients after COVID and 64 convalescent COVID-19 patients. We found differences in the absolute levels of Spike protein-specific IgG subtypes for both cohorts. IgG1 was the most abundant subtype, followed by IgG3 and IgG2 and IgG4 in declining order. A significant difference was only detected for IgG2. When further analyzing the IgG4 levels reactive against the Spike protein receptor-binding domain (RBD) and the nucleocapsid-protein of SARS-CoV-2, a small but significant difference was detected for the RBD but not nucleocapsid proteins. Since the total IgG4 levels are very low, we do not expect a biologically relevant role in the development and progression of post-COVID syndrome. However, low IgG2 levels, as seen in the Post-COVID cohort, could contribute to the persistent presence of SARS-CoV-2 antigens, causing chronic inflammation in the setting of post-COVID.

Lack of antibodies against seasonal coronavirus OC43 nucleocapsid protein identifies patients at risk of critical COVID-19 (preprint)

Most COVID-19 patients experience a mild disease; a minority suffers from critical disease. We report about a biomarker validation study regarding 296 patients with confirmed SARS-CoV-2 infections from four tertiary care referral centers in Germany and France. Patients with critical disease had significantly less anti-HCoV OC43 nucleocapsid protein antibodies compared to other COVID-19 patients (p=0.007). In multivariate analysis, OC43 negative inpatients had an increased risk of critical disease, higher than the risk by increased age or BMI, and lower than the risk by male sex. A risk stratification based on sex and OC43 serostatus was derived from this analysis. Our results indicate that prior infections with seasonal human coronaviruses can protect against a severe course of COVID-19. Anti-OC43 antibodies should be measured for COVID-19 inpatients and considered as part of the risk assessment. We expect individuals tested negative for anti-OC43 antibodies to particularly benefit from vaccination, especially with other risk factors prevailing.