Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature

Abstract

Despite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.

Functional Contribution and Targeted Migration of Group-2 Innate Lymphoid Cells in Inflammatory Lung Diseases: Being at the Right Place at the Right Time

“…Consistent with the strong epithelial damage observed in SARS-CoV2 lungs, global transcriptomic analyses of cells within the bronchoalveolar fluid indicated that the expression of IL-33 is upregulated in lungs of patients suffering from COVID-19 disease ( 66 ). In line with this, IL-33 blood concentrations were reported to be increased during active disease ( 67 , 68 ). Moreover, the expression of IL-33 after stimulation of COVID-19 convalescent peripheral blood mononuclear cells with SARS-CoV2 peptides correlated with seropositivity for the viral spike glycoprotein ( 69 ) indicating that ILC2s or other ST2 + cells such as T cells, B cells and macrophages are functionally linked to the disease.…”

Cytokine Profiles Associated With Worse Prognosis in a Hospitalized Peruvian COVID-19 Cohort

“…Regarding to the relationship between antibodies and cytokines, anti-spike 1 IgG antibodies presented a positive correlation with EGF and IL-8 and an inverse correlation with IP-10, IFN-g and G-CSF. A previous study only found a correlation with IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity (39). However, another study hypothesized that IL-8 and overall, the inflammation acts as a mediator between the association of IgG antibodies and the clinical outcome (40).…”

IL-33 Enhances IFNγ and TNFα Production by Human MAIT Cells: A New Pro-Th1 Effect of IL-33

“…This observation is interesting in the context of the current SARS-CoV-2 epidemic, which has revealed the importance of the “cytokine storm” in severe forms of infection [ 34 ]. These gravely affected patients are likely to produce alarmins, such as IL-33, as well as IL-12 [ 35 , 36 ]. It has been reported that the number of MAIT cells, which account for up to 10% of circulating CD3+ T cells, decreased significantly in peripheral blood from COVID-19 patients, while their activation was associated with poor clinical outcome [ 37 ].…”