ABSTRACT
Severe novel coronavirus disease 2019 (COVID-19) patients have a high incidence of thrombotic complications and mortality. The pathophysiology of coagulopathy involves fibrinolytic system impairment and vascular endothelial damage. This study examined coagulation and fibrinolytic markers as outcome predictors. In an observational study of 164 COVID-19 patients admitted to our emergency intensive care unit, hematological parameters on days 1, 3, 5, and 7 were retrospectively compared between survivors and nonsurvivors. Nonsurvivors had a higher APACHE II score, SOFA score, and age than survivors. Nonsurvivors also had a significantly lower platelet count and significantly higher plasmin/α2plasmin inhibitor complex (PIC), tissue plasminogen activator/plasminogen activator inhibitor-1 complex (tPAPAI-1C), D-dimer, and fibrin/fibrinogen degradation product (FDP) levels than survivors throughout the measurement period. The 7-day maximum or minimum values of the tPAPAI-1C, FDP, and D-dimer levels were significantly higher in nonsurvivors. A multivariate logistic regression analysis showed that the maximum tPAPAI-1C (OR = 1.034;95% CI,1.014–1.061;p = 0.0041) was an independent factor affecting mortality, with an area under the curve (AUC) of 0.713 (optimum cut-off of 51 ng/mL;sensitivity, 69.2%;and specificity, 68.4%). COVID-19 patients with poor outcomes exhibit exacerbated coagulopathy with fibrinolysis inhibition and endothelial damage. Consequently, plasma tPAPAI-1C might be a useful predictor of the prognosis in patients with severe or critical COVID-19.
ABSTRACT
Severe novel coronavirus disease 2019 (COVID-19) patients have a high incidence of thrombotic complications and mortality. The pathophysiology of coagulopathy involves fibrinolytic system impairment and vascular endothelial damage. This study examined coagulation and fibrinolytic markers as outcome predictors. In an observational study of 164 COVID-19 patients admitted to our emergency intensive care unit, hematological parameters on days 1, 3, 5, and 7 were retrospectively compared between survivors and nonsurvivors. Nonsurvivors had a higher APACHE II score, SOFA score, and age than survivors. Nonsurvivors also had a significantly lower platelet count and significantly higher plasmin/α2plasmin inhibitor complex (PIC), tissue plasminogen activator/plasminogen activator inhibitor-1 complex (tPAPAI-1C), D-dimer, and fibrin/fibrinogen degradation product (FDP) levels than survivors throughout the measurement period. The 7-day maximum or minimum values of the tPAPAI-1C, FDP, and D-dimer levels were significantly higher in nonsurvivors. A multivariate logistic regression analysis showed that the maximum tPAPAI-1C (OR = 1.034; 95% CI,1.014-1.061; p = 0.0041) was an independent factor affecting mortality, with an area under the curve (AUC) of 0.713 (optimum cut-off of 51 ng/mL; sensitivity, 69.2%; and specificity, 68.4%). COVID-19 patients with poor outcomes exhibit exacerbated coagulopathy with fibrinolysis inhibition and endothelial damage. Consequently, plasma tPAPAI-1C might be a useful predictor of the prognosis in patients with severe or critical COVID-19.
ABSTRACT
Although the importance of virus-specific cytotoxic T lymphocytes (CTL) in virus clearance is evident in COVID-19, the characteristics of virus-specific CTLs related to disease severity have not been fully explored. Here we show that the phenotype of virus-specific CTLs against immunoprevalent epitopes in COVID-19 convalescents might differ according to the course of the disease. We establish a cellular screening method that uses artificial antigen presenting cells, expressing HLA-A*24:02, the costimulatory molecule 4-1BBL, SARS-CoV-2 structural proteins S, M, and N and non-structural proteins ORF3a and nsp6/ORF1a. The screen implicates SARS-CoV-2 M protein as a frequent target of IFNγ secreting CD8+ T cells, and identifies M198-206 as an immunoprevalent epitope in our cohort of HLA-A*24:02 positive convalescent COVID-19 patients recovering from mild, moderate and severe disease. Further exploration of M198-206-specific CD8+ T cells with single cell RNA sequencing reveals public TCRs in virus-specific CD8+ T cells, and shows an exhausted phenotype with less differentiated status in cells from the severe group compared to cells from the moderate group. In summary, this study describes a method to identify T cell epitopes, indicate that dysfunction of virus-specific CTLs might be an important determinant of clinical outcomes.
Subject(s)
CD8-Positive T-Lymphocytes , COVID-19 , Humans , SARS-CoV-2 , T-Lymphocytes, Cytotoxic , Epitopes, T-Lymphocyte , HLA-A AntigensABSTRACT
Aim There are few reports on the prognostic factors associated with mortality in coronavirus disease (COVID-19) patients with critical disease. This study assessed prognostic factors associated with mortality of patients with critical COVID-19 who required ventilator management. Methods This single-center, retrospective cohort study used medical record data of COVID-19 patients admitted to an emergency ICU at a hospital in Japan between March 1, 2020 and September 30, 2021, and provided with ventilator management. Multivariable logistic regression was used to identify factors associated with mortality. Results Seventy patients were included, of whom 29 (41.4%) died. The patients who died were significantly older (median: 69 years) (interquartile range [IQR]: 47-82 years) than the patients who survived (62 years [38-84 years], p<0.007). In addition, patients who died were significantly less likely to have received steroid therapy than patients who survived (25 [86.2%] vs. 41 [100%], p=0.026). In the multivariable analysis, age was identified as a significant prognostic factor for mortality and the risk of death increased by 6% for every one-year increase in age (OR: 1.06; 95% CI: 1.00-1.13; p=0.048). Medical history was not a risk factor for death. Conclusion Age was a predictor of mortality in critically ill patients with COVID-19. Therefore, the indications for critical care in older patients with COVID-19 should be carefully considered.
ABSTRACT
Introduction This study aimed to determine if tocilizumab treatment for coronavirus disease 2019 (COVID-19) increases bacteremia and suppresses fever and inflammatory reactants. Methods In this single-center, retrospective, observational study, all patients with COVID-19 admitted to our emergency intensive care unit from March 2020 to August 2021 were categorized into tocilizumab-treated and tocilizumab-naïve groups, and the incidence of bacteremia and other factors between the two groups were compared. Patients with bacteremia were further classified into tocilizumab-treated and tocilizumab-naïve groups to determine if fever and inflammatory reactants were suppressed. Results Overall, 144 patients were included in the study, 51 of whom received tocilizumab, which was administered on the day of admission. Further, of the 24 (16.7%) patients with bacteremia, 13 were in the tocilizumab-treated group. Results revealed a significant difference in the C-reactive protein level (p < 0.001) at the onset of bacteremia between the tocilizumab-treated group [median 0.42 mg/dL (0.27–0.44 mg/dL)] and the tocilizumab-naïve group [7.48 mg/dL (4.56–13.9 mg/dL)]. The median number of days from admission to onset of bacteremia was not significantly different between the tocilizumab-treated group [10 days (9–12 days)] and the tocilizumab-naïve group [9 days (7.5–11 days)] (p = 0.48). There was no significant difference in fever between the groups. Multivariate logistic analysis showed that tocilizumab treatment did not affect the probability of bacteremia. Conclusion Treatment of patients with COVID-19 with tocilizumab does not increase the risk of bacteremia. Tocilizumab suppresses C-reactive protein levels but not fever. Therefore, careful monitoring of fever can reduce the risk of missed bacteremia.
ABSTRACT
INTRODUCTION: This study aimed to determine if tocilizumab treatment for coronavirus disease 2019 (COVID-19) increases bacteremia and suppresses fever and inflammatory reactants. METHODS: In this single-center, retrospective, observational study, all patients with COVID-19 admitted to our emergency intensive care unit from March 2020 to August 2021 were categorized into tocilizumab-treated and tocilizumab-naïve groups, and the incidence of bacteremia and other factors between the two groups were compared. Patients with bacteremia were further classified into tocilizumab-treated and tocilizumab-naïve groups to determine if fever and inflammatory reactants were suppressed. RESULTS: Overall, 144 patients were included in the study, 51 of whom received tocilizumab, which was administered on the day of admission. Further, of the 24 (16.7%) patients with bacteremia, 13 were in the tocilizumab-treated group. Results revealed a significant difference in the C-reactive protein level (p < 0.001) at the onset of bacteremia between the tocilizumab-treated group [median 0.42 mg/dL (0.27-0.44 mg/dL)] and the tocilizumab-naïve group [7.48 mg/dL (4.56-13.9 mg/dL)]. The median number of days from admission to onset of bacteremia was not significantly different between the tocilizumab-treated group [10 days (9-12 days)] and the tocilizumab-naïve group [9 days (7.5-11 days)] (p = 0.48). There was no significant difference in fever between the groups. Multivariate logistic analysis showed that tocilizumab treatment did not affect the probability of bacteremia. CONCLUSION: Treatment of patients with COVID-19 with tocilizumab does not increase the risk of bacteremia. Tocilizumab suppresses C-reactive protein levels but not fever. Therefore, careful monitoring of fever can reduce the risk of missed bacteremia.