The ongoing spread of coronavirus disease 2019 (COVID-19) constitutes an international concern on an unprecedented scale.To date, over 23 million people have been diagnosed with COVID-19 worldwide, and this disease has caused more than 800,000 deaths.Hyperinflammation elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported to contribute to illness severity and death. 1,2Humoral immune responses play important roles in therapy and prophylaxis for SARS-CoV-2 infection.Since the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein binds to angiotensinconverting enzyme 2 to trigger virion endocytosis, antibodies against this domain may be able to neutralize SARS-CoV-2 and possibly provide protective immunity in COVID-19 patients. 3linical trials investigating the administration of convalescent plasma and the interleukin (IL)-6 antagonist tocilizumab to treat COVID-19 patients are currently underway, 4 but the overly robust expansion of antibody-secreting cells (ASCs) could play a major role in the pathogenicity of SARS-CoV-2 in COVID-19 patients. 5Thus, a detailed characterization of the associations between humoral immune responses and inflammatory factors could result in a better understanding of SARS-CoV-2-host interactions in COVID-19 patients.In the current study, the levels of RBD-specific IgG, RBD-specific IgA, and the frequencies of ASCs and ICOS+ T follicular helper (TFH) cells were found to be higher in severely affected COVID-19 patients than those in nonseverely affected patients.Follow-up analysis of COVID-19 patients demonstrated that humoral immune responses were positively correlated with the levels of IL-6, C-X-C motif chemokine 10 (CXCL10), and C5a.Positive correlations between the serum CXCL13 level and the levels of IL-6 and CXCL10 were also noted in COVID-19 patients.Taken together, these results indicate that there is a close relationship between humoral immunity and inflammatory factors, and the generation of protective humoral immunity could be a double-edged sword in COVID-19 patients.A total of 54 hospital-admitted COVID-19 patients (41 nonsevere cases and 13 severe cases) were assessed in the present study.The clinical characteristics of the patients and results of their laboratory tests are summarized in Supplementary Tables 1