Immune dysregulation and system pathology in COVID-19.

The coronavirus disease 19 (COVID-19) caused by the novel coronavirus known as SARS-CoV-2 has caused a global public health crisis. As of 7 January 2021, 87,640,402 confirmed cases and 1,891,692 mortalities have been reported worldwide. Studies focusing on the epidemiological and clinical characteristics of COVID-19 patients have suggested a dysregulated immune response characterized by lymphopenia and cytokine storm in these patients. The exaggerated immune response induced by the cytokine storm causes septic shock, acute respiratory distress syndrome (ARDS), and/or multiple organs failure, which increases the fatality rate of patients with SARS-CoV-2 infection. Herein, we review the recent research progress on epidemiology, clinical features, and system pathology in COVID-19. Moreover, we summarized the recent therapeutic strategies, which are either approved, under clinical trial, and/or under investigation by the local or global health authorities. We assume that treatments should focus on the use of antiviral drugs in combination with immunomodulators as well as treatment of the underlying comorbidities.

Clinical Characteristics and Immune Injury Mechanisms in 71 Patients with COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19), caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a threat to global health. The mortality rate of severely ill patients in the early stage is 32.5%. The exacerbation of the condition and death of patients are closely associated with inflammatory cytokine storms, which are caused by excessive activation of the immune and complement systems as well as the coinfection of other pathogens. However, the immunological characteristics and the mechanisms underlying inflammatory storms have not been well elucidated. Here, we analyzed the clinical and immunological characteristics of 71 confirmed COVID-19 patients. Based on the National Health Commission of China (NHCC) guidelines, patients were stratified into mild and severe types. We compared the clinical and laboratory data obtained from electronic medical records between the two types. In regard to the hematological parameters, COVID-19 patients showed decreased erythrocyte count, hemoglobin, hematocrit, lymphocyte count, eosinophil count, and complement C1q, whereas neutrophils, C-reactive protein, and procalcitonin were significantly increased, especially in severe cases. We also found that CD3+ CD4+ T lymphocytes, CD3+ CD8+ T lymphocytes, CD19+ B lymphocytes, and CD16+ CD56+ NK cells in the peripheral blood of all patients were decreased. In addition, CD3+ CD8+ T lymphocytes, CD16+ CD56+ NK cells, and complement C1q in severely ill patients decreased more significantly. Additionally, interleukin 6 (IL-6) elevation was particularly prominent in all patients, especially in severe cases. These results suggest that CD3+ CD8+ T lymphocytes, CD16+ CD56+ NK cells, C1q as well as IL-6 may play critical roles in the inflammatory cytokine storm. The dysregulation of these aforementioned immune parameters, along with bacterial coinfection, were the important causes of exacerbation of the patients' condition and death. This study improves our understanding of the immune dysregulation of COVID-19 and provides potential immunotherapeutic strategies.IMPORTANCE The dysregulation of CD3+ CD8+ T lymphocytes, CD16+ CD56+ NK cells, C1q as well as IL-6, along with bacterial coinfection, were important causes of exacerbation of the patients' condition and death.