doi:?10.1002/jmv.26241. regarding the association of the antibody dynamics and severity of the disease in SARS-CoV-2 contamination have been raised, although many questions remain unanswered. (ANOVA)the N antigen (15). In this context, it is crucial to evaluate the differences in the SARS-CoV-2 antibody detection methods because the antigens used to identify antibodies and follow-up occasions can affect the interpretation of the outcomes. In our study, we evaluated the IgA and IgG antibodies against the S protein using a commercial ELISA kit from EUROIMMUN. A previous study using a plaque reduction neutralization test (PRNT), a reference test for serologic analysis, tested the performance of different ELISAs to detect antibodies among PCR-confirmed COVID-19 patients. The study Conteltinib showed a high correlation (Spearman value=0.93) between PRNT90 (90% plaque reduction neutralization test) and IgA EUROIMMUN ELISA and IgG EUROIMMUN ELISA (Spearman value=0.88) (5), both used in this study. Another study from the same research group, including a higher number of samples, confirmed that this S1 based IgA ELISA by EUROIMMUN had a good sensitivity to support clinical diagnosis in hospitalized patients. It also showed the best quantitative relationship with neutralizing antibodies, particularly once neutralizing titers were higher than 80 in the PRNT50 (50% plaque reduction neutralization test). Based on their data, it is also possible to observe that when the IgG OD ratio is usually 5.0, the neutralizing antibody titer in the PRNT50 is at least 640 (16). The recovered patients in our study who had severe symptoms had a mean OD ratio for IgG antibodies of 7.0, which indicates that this titers of the neutralizing antibodies are also high. The relationship between viral loads and antibody titers has been previously described (17,18). However, only a few studies have resolved the kinetics of antibody responses, suggesting that FLN2 antibody response is usually associated with disease prognosis. Herein, we showed that higher antibody indexes appear to be directly related to disease severity. The severe symptoms group had a higher index of IgG and IgA, and both were very similar. Yu et al. (8) discussed the hypothesis that enhanced IgA response in severe cases might confer damaging effects in severe COVID-19 and can be, at least in part, an IgA-mediated disease, related to IgA deposition and vasculitis. However, cytokine release syndrome (CRS) appears to be one of the major causes Conteltinib of disease severity (19,20), similar to SARS and MERS (21). CRS is also commonly associated with antibody immunotherapies, bispecific antibodies, and adoptive T-cell therapies (22). Therefore, it is interesting to determine whether the increased antibody titers in severe COVID-19 disease are just a consequence of higher viral load or one of the factors responsible for the occurrence of Conteltinib CRS, increasing COVID-19 severity. Another hypothesis in the literature associates neutralizing IgG antibodies and the severity of the disease. This association suggests that while neutralizing IgG antibodies can prevent epithelial cell computer virus infection, they might also be mediators of antibody-dependent infections of leukocytes and play a central role in dysfunctional cellular responses. This mediation suggests that high antibody titers might be more associated with disease severity than with immunological efficacy. Therefore, mild, moderate, or asymptomatic patients may have low or even no neutralizing antibodies (23). Similarly, a study evaluating SARS demonstrated the presence of IgG anti-spike proteins before viral clearance skewed the macrophage response and interleukin-8 production. The authors observed that the deceased patients displayed pulmonary pro-inflammatory Conteltinib monocyte/macrophage accumulation and faster neutralizing antibody responses (24). More recently, based on reinfection cases whose evolution was worse than the first SARS-CoV-2 infection, there has been a discussion on the possibility that antibodies produced in response to the virus could help, rather than fight, the virus during a reinfection (25). This phenomenon, called antibody-dependent enhancement, was found in SARS and MERS and.