ABSTRACT
The purpose of this study was to investigate the expression of pyroptosis-related factors (NLRP3, IL-18, NF-kappa B, HMGB-1, and GSDMD) in patients who died of COVID-19. The expression levels of NLRP3, IL-18, NF-kappa B, HMGB-1, and GSDMD in lung and spleen tissues of the COVID-19 group and the control group were detected by tissue immunofluorescence. The control group includes lung tissues and spleen tissues of two patients who died unexpectedly without SARS-CoV-2 infection, and the COVID-19 group includes the lung and spleen tissues of three patients who died of SARS-CoV-2 virus infection. The positive rates of NF-kappa B, NLRP3, IL-18, and GSDMD in the lung tissues from the control group and COVID-19 group were 9.8% vs 73.4% (p = 0.000), 5.5% vs 63.6% (p = 0.000), 24.4% vs 76.2% (p = 0.000), and 17.5% and 46.8% (p = 0.000) respectively. The positive rates of NF-kappa B, NLRP3, IL-18, HMGB-1, and GSDMD in the spleen tissues from the control group and COVID-19 group were 20.6% vs 71.2% (p = 0.000), 18.9% vs 72.0% (p = 0.000), 15.2% vs 64.8% (p = 0.000), 27.6% vs 69.2% (p = 0.000), and 23% and 48.8% (p = 0.000), respectively. The positive rates of SARS-CoV-2 spike protein in the CD68 positive cells of the lung and spleen in the control group and COVID-19 group were 2.5% vs 56.8% (p = 0.000);3.0% vs 64.9% (p = 0.000) respectively. The rates of NF-kappa B positive nuclei in the control group and COVID-19 group were 13.4% vs 51.4% (p = 0.000) in the lung and 38.2% vs 59.3% (p = 0.000) in the spleen. The rates of HMGB-1 positive cytoplasm in the control and the COVID-19 group were 19.7% vs 50.3% (p = 0.000) in the lung and 12.3% vs 45.2% (p = 0.000) in the spleen. The targets of SARS-CoV-2 are the lung and spleen, where increased macrophages could be involved in the up-regulation of pyroptosis-related inflammatory factors such as NF-kappa B, HMGB-1, NLRP3, IL-18, and GSDMD.
ABSTRACT
Objective: To analyze the data on the clinical course, risk factors, and outcomes of severe COVID‑19 patients with respiratory failure, and to built a nomogram to predict the short‑term survival rate of severe COVID‑19 patients. Methods: Adult patients with laboratory‑confirmed COVID‑19 were recruited for the study and in‑hospital data including clinical characteristics, laboratory indices, treatments, and outcomes were collected from the electronic medical record system. According to the multivariable Cox hazard regression analysis, a nomogram for predicting the short‑term survival probability of COVID‑19 patients with respiratory failure was constructed. Results: A retrospective study of 72 severe COVID⁃19 patients with respiratory failure was conducted in Wuhan Leishenshan Hospital and Wuhan No.7 Hospital. According to multivariable Cox regression analysis, independent factors associated with the risk of mortality included age (adjusted hazard ratio [aHR]: 1.052;95%CI: 1.002‑1.105), NT‑proBNP (aHR: 1.02;95%CI: 1.002‑1.039) and D‑dimer (aHR: 1.044;95%CI: 1.017‑1.071), while treatment with montelukast (aHR: 0.23;95%CI: 0.065‑0.821) decreased the risk of death. Longer ventilation time was associated with better outcomes for respiratory failure inpatients (aHR: 0.912;95%CI: 0.861‑0.965). A nomogram of short‑term survival of severe COVID‑19 patients was constructed according to the three independent risk factors. The AUC of 1‑, 4‑, and 6‑week survival of the nomogram was 0.656, 0.79, and 0.909, respectively. And a high level of consistency between nomogram prediction and actual observation was also determined by calibration curve. Conclusion: For severe COVID‑19 patients, advanced age, elevated level of D‑dimer, and NT‑proBNP were associated with higher mortality. We utilized these three independent factors to construct a nomogram of the short‑term survival probability of patients with severe COVID‑19. Patients who received mechanical ventilation support may benefit from prolonged duration of this treatment, and montelukast might be beneficial for COVID‑19 patients with respiratory failure. © 2022, Editorial Board of Medical Journal of Wuhan University. All right reserved.
ABSTRACT
Background and Purpose: Corona Virus Disease 2019 (COVID-19) is a highly contagious disease which continuously and rapidly circulating around the world now. The patients with severe COVID-19 have relatively high mortality. Therefore, there is an urgent need for methods to assess mortality risk in patients with COVID-19 accurately. Materials and methods: We conducted a retrospective study focusing on the clinical characteristics of 194 confirmed cases of severe COVID-19. Personal information, clinical data and laboratory information of patients with COVID-19 were collected by consulting case records so as to investigate the risk of death related to COVID-19. Results: In the 194 patients with COVID-19, there was no difference in prevalence between men and women. Comorbidities (such as hypertension, cerebral infarction) associated with severe clinical features and mortality are prevalent in non-survivors. 86.1% of patients with severe COVID-19 had fever and 46.9% coughed, and the proportion of chest tightness, airlessness and dyspnea in non-survivors was significantly higher than that in survivors. There were multiple laboratory indicator differences between survivors and non-survivors. Non-survivors had significantly lower lymphocyte count (including T lymphocyte). Changes in liver (aspartate aminotransferase, AST), kidney [Urea, creatinine (Cr)], and heart [lactate dehydrogenase (LDH), creatine kinase (CK), B-type natriuretic peptide (BNP)] damage markers, coagulation, and inflammation indicators in severe patients were related to their risk of death. Multivariable logistic regression model revealed that age (OR 1.082, 95% CI 1.024-1.357), interleukin-6 (IL-6). (OR 1.568, 95% CI 1.149-2.138), D-dimer (OR 1.327, 95% CI 1.087-1.621) were associated significantly with risk of death, whereas CD4 count was associated with a lower risk (OR 0.972, 95% CI 0.953-0.992). Conclusion: This study found that age, IL-6, D-dimer and CD4 counts are closely related to mortality risk in patients with severe COVID-19, and they are useful in assessing the prognosis of patients.