Abstract
BackgroundCOVID-19 pandemic continues, clarifying signatures in clinical characters and antibody responses between severe and non-severe COVID-19 cases would benefit the prognosis and treatment.MethodsIn this study, 119 serum samples from 37 severe or non-severe COVID-19 patients from the First People's Hospital of Yueyang were collected between January 25 and February 18 2020. The clinical features, antibody responses targeting SARS-CoV-2 spike protein (S) and its different domains, SARS-CoV-2-specific Ig isotypes, IgG subclasses, ACE2 competitive antibodies, binding titers with FcγIIa and FcγIIb receptors, and 14 cytokines were comprehensively investigated. The differences between severe and non-severe groups were analyzed using Mann–Whitney U test or Fisher’s exact test.ResultsSevere group including 9 patients represented lower lymphocyte count, higher neutrophil count, higher level of LDH, total bile acid (TBA) (P < 1 × 10–4), r-glutaminase (P = 0.011), adenosine deaminase (P < 1 × 10–4), procalcitonin (P = 0.004), C-reactive protein (P < 1 × 10–4) and D-dimer (P = 0.049) compared to non-severe group (28 patients). Significantly, higher-level Igs targeting S, different S domains (RBD, RBM, NTD, and CTD), FcγRIIa and FcγRIIb binding capability were observed in a severe group than that of a non-severe group, of which IgG1 and IgG3 were the main IgG subclasses. RBD-IgG were strongly correlated with S-IgG both in severe and non-severe group. Additionally, CTD-IgG was strongly correlated with S-IgG in a non-severe group. Positive RBD-ACE2 binding inhibition was strongly associated with high titers of antibody (S-IgG1, S-IgG3, NTD-IgG, RBD-IgA, NTD-IgA, and CTD-IgA) especially RBD-IgG and CTD-IgG in the severe group, while in the non-severe group, S-IgG3, RBD-IgG, NTD-IgG, and NTD-IgM were correlated with ACE2 blocking rate. S-IgG1, NTD-IgM and S-IgM were negatively associated with illness day in a severe group, while S-IgG3, RBD-IgA, CTD-IgA in the severe group (r = 0.363, P = 0.011) and S-IgG1, NTD-IgA, CTD-IgA in the non-severe group were positively associated with illness day. Moreover, GRO-α, IL-6, IL-8, IP-10, MCP-1, MCP-3, MIG, and BAFF were also significantly elevated in the severe group.ConclusionAntibody detection provides important clinical information in the COVID-19 process. The different signatures in Ig isotypes, IgG subclasses, antibody specificity between the COVID-19 severe and non-severe group will contribute to future therapeutic and preventive measures development.Graphical
Highlights
COVID-19 pandemic continues, clarifying signatures in clinical characters and antibody responses between severe and non-severe COVID-19 cases would benefit the prognosis and treatment
Serum antibody binding titers with Fc receptors To detect whether the difference of serum samples in inhibition or enhancement receptor binding domain (RBD) binding with angiotensin converting enzyme 2 (ACE2) was non- induced by Fc function of serum antibodies, we examined the binding activity of serum sample to Fc receptors, which included an activating receptor FcγRIIa and an inhibitory receptor FcγRIIb
Consistent with what was previously reported [22], we observed that lactate dehydrogenase (LDH), D-dimer, C-reactive protein (CRP), the concentration of prothrombin, total bile acid (TBA), r-glutaminase, adenosine deaminase in severe group were significantly higher than a non-severe group
Summary
COVID-19 pandemic continues, clarifying signatures in clinical characters and antibody responses between severe and non-severe COVID-19 cases would benefit the prognosis and treatment. The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) [1, 2], has been declared a threat to global health. It has caused over 300 million COVID-2019 cases and accounting for over 5 million deaths [3]. Severe cases are defined by respiratory distress with pneumonia, with respiratory rate ≥ 30 breaths/min; or S pO2 (oxygen saturation) ≤ 93% at rest; or PaO2/FIO2 (partial pressure of oxygen/fraction of inspired oxygen) ≤ 300 mmHg. It is reported that dyspnea, myalgia or fatigue, high-grade fever were the most common symptoms in severe cases
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