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

Abstract

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.

Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19

“…Multiple clinically established biomarkers, such as LDH, ferritin, CRP, and D-dimer, are currently being evaluated to assess the risk of clinical deterioration from a COVID-19 diagnosis ( 40 , 45 – 49 ). However, as products of gene expression in response to both acute and chronic stimuli, they tend to be largely nonspecific measures of systemic inflammation, with the exception of LDH, a marker of cell death.…”

Circulating Mitochondrial DNA is an Early Indicator of Severe Illness and Mortality from COVID-19

“…Multiple clinically established biomarkers such as LDH, Ferritin, CRP and D-dimers are currently being evaluated to assess the risk of clinical deterioration from a COVID-19 diagnosis (Cummings et al, 2020;Luo et al, 2020;McElvaney et al, 2020;Messner et al, 2020;Song et al, 2020;Wu et al, 2020). However, as products of gene expression in response to both acute and chronic stimuli they tend to be largely non-specific measures of systemic inflammation with the exception of LDH, a marker of cell death.…”

Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial

“… 2 High levels of interleukin (IL)-1β, IL-6, IL-18 and tumour necrosis factor (TNF) are some of the many immunological disturbances in the pathophysiology of the high inflammatory status of COVID-19, 3 which counts, moreover, with markedly elevation of serum C reactive protein (CRP) and uncommon neutrophilia and lymphopaenia. 4 5 Neutrophils release neutrophil extracellular traps (NETs), which were found to be toxic to lung epithelial cells in vitro. Furthermore, high levels of NETs were present in the plasma of patients with COVID-19 compared with healthy controls, and the presence of these cellular components was at least 10 times higher in tracheal aspirates than in plasma of the same patients, raising the question whether they have a role in the lung lesions.…”