Encephalopathy Predicts Poor Prognosis Of COVID-19 Patients:A Retrospective Cohort Study And Meta-analysis

Part 1Objective: To determine whether encephalopathy at admission can predict the poor prognosis of patients with severe acute respiratory syndrome coronavirus 2(SARS-Co V-2).Methods: Electronic medical records of 1053 consecutively hospitalized patients with laboratory-confirmed infection of SARS-Co V-2from one large medical center in the USA were retrospectively analyzed.Univariable and multivariable Cox regression analyses were performed with the calculation of areas under the curve(AUC)and concordance index(C-index).Patients were stratified into subgroups based on the presence of encephalopathy and its severity using survival statistics.In sensitivity analyses,patients with mild/moderate and severe encephalopathy(defined as coma)were separately considered.Results: Of 1053 patients(mean age 52.4 years,48.0% men [n = 505),35.1%(n = 370)had neurologic manifestations at admission,including10.3%(n = 108)with encephalopathy.Encephalopathy was an independent predictor for death(hazard ratio [HR] 2.617,95% confidence interval [CI]1.481-4.625)in multivariable Cox regression.The addition of encephalopathy to multivariable models comprising other predictors for adverse outcomes increased AUCs(mortality: 0.84-0.86,ventilation/intensive care unit [ICU]: 0.76-0.78)and C-index(mortality: 0.78 to 0.81,ventilation/ICU: 0.85-0.86).In sensitivity analyses,risk stratification survival curves for mortality and ventilation/ICU based on severe encephalopathy(n = 15)versus mild/moderate encephalopathy(n = 93)versus no encephalopathy(n = 945)at admission were discriminative(p <0.001).Conclusions: Encephalopathy at admission predicts later progression to death in SARS-Co V-2 infection,which may have important implications for risk stratification in clinical practice.Part 2Objective: To explore the relationship between encephalopathy and prognosis of patients with COVID-19.Methods: We searched Pub Med,EMBASE,and Cochrane Library for studies related to encephalopathy in patients with SARS-Co V-2infection,and reported prognostic studies on the presence or absence of encephalopathy in patients with COVID-19.Odds ratios(ORs)were calculated with their 95% confidence intervals(95% CI).STATA 17.0 were used for data combination and meta-analysis.Results: Forty-eight studies involving 255163 patients were included into analysis.Encephalopathy is associated with poor prognosis in patients with COVID-19.Specifically,encephalopathy significantly increased mortality of patients with COVID-19(OR = 3.788,95% CI: 2.599-5.520,p < 0.001).Subgroup analysis revealed that severe encephalopathy is more correlated to mortality of COVID-19 patients compared with mildmoderate encephalopathy(p= 0.006).Further meta-regression upon studies of mild-moderate encephalopathy showed that higher male percent results in a lower OR of encephalopathy-mortality relationship(p = 0.007).Also,encephalopathy significantly increased intubation/mechanical ventilation rate(OR = 8.382,95% CI: 2.129-32.997,p= 0.002)and ICU admission rate(OR = 6.006,95% CI: 3.022-11.946,p < 0.001)of COVID-19 patients.Conclusions: Encephalopathy is associated with poor outcomes in patients with COVID-19.The mortality rate of Gender COVID-19 patients complicated with mild-moderate encephalopathy is significantly lower than that of their female counterparts.Intensive Care Unit should be actively administered when COVID-19 patients are complicated with severe encephalopathy to reduce their mortality.