SARS-CoV-2 infection causes COVID-19, ranging from mild to critical disease in symptomatic subjects. It is essential to better understand the immunologic responses occurring in patients with the most severe outcomes. In this study, parameters related to the humoral immune response elicited against SARS-CoV-2 were analysed in 61 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centres in Madrid, Spain, during the first pandemic peak between April and June 2020. Subjects were allocated as mild patients without hospitalization, severe patients hospitalized or critical patients requiring ICU assistance. Critical patients showed significantly enhanced levels of B cells with memory and plasmablast phenotypes, as well as higher levels of antibodies against SARS-CoV-2 with neutralization ability, which were particularly increased in male gender. Despite all this, antibody-dependent cell-mediated cytotoxicity was defective in these individuals. Besides, patients with critical COVID-19 also showed increased IgG levels against herpesvirus such as CMV, EBV, HSV-1 and VZV, as well as detectable CMV and EBV viremia in plasma. Altogether, these results suggest an enhanced but ineffectual immune response in patients with critical COVID-19 that allowed latent herpesvirus reactivation. These findings should be considered during the clinical management of these patients due to the potential contribution to the most severe disease during SARS-CoV-2 infection.

SARS-CoV-2 感染会导致 COVID-19，在有症状的受试者中，病情从轻度到重症不等。更好地了解具有最严重结果的患者中发生的免疫反应至关重要。在这项研究中，对 61 名不同表现的 COVID-19 患者的体液免疫反应相关参数进行了分析，这些患者是在西班牙马德里的医院和初级保健中心招募的，这些患者是在2020年4月和6月。受试者被分配为未住院的轻症患者、住院的重症患者或需要ICU帮助的危重患者。危重患者的记忆B细胞和浆母细胞表型显着升高，具有中和能力的SARS-CoV-2抗体水平升高，尤其是男性。尽管如此，抗体依赖性细胞介导的细胞毒性在这些个体中仍然存在缺陷。此外，重症COVID-19患者还表现出抗CMV、EBV、HSV-1和VZV等疱疹病毒的IgG水平升高，血浆中可检测到CMV和EBV病毒血症。总而言之，这些结果表明，重症 COVID-19 患者的免疫反应增强但无效，导致潜伏的疱疹病毒重新激活。由于这些发现可能导致 SARS-CoV-2 感染期间最严重的疾病，因此在这些患者的临床管理过程中应考虑这些发现。