Encephalopathy at admission predicts adverse outcomes in patients with SARS-CoV-2 infection

Abstract

Aims: To determine if neurologic symptoms at admission can predict adverse outcomes in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: Electronic medical records of 1053 consecutively hospitalized patients with laboratory-confirmed infection of SARS-CoV-2 from 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, including 10.3% (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-CoV-2 infection, which may have important implications for risk stratification in clinical practice.

Keywords: COVID-19; SARS-CoV-2; encephalopathy; neurologic symptoms.

FIGURE 1

Flow chart of inclusion/exclusion

FIGURE 2

ROC‐AUCs to predict mortality or ventilation/ICU are shown in (A) and (B). In these plots, the x‐axis is false‐positive rate and y‐axis is true‐positive rate. Curves in different colors represent ROC curves based on (1) encephalopathy (2) other factors significant on multivariable Cox regression without encephalopathy (3) encephalopathy +other factors. Other factors represent age, cardiac or cerebrovascular disease, and lactate dehydrogenase in mortality, and hypertension, malignancy, dyspnea, diastolic blood pressure, oxygen saturation, magnesium, lactate dehydrogenase, and neutrophil in ventilation/ICU. ICU, intensive care unit

FIGURE 3

Risk stratification for mortality or ventilation/ICU based on encephalopathy for (A) mortality (B) ventilation/ICU. In these plots, the x‐axis stands for time in days, and the y‐axis is survival probability that represents the probability of not progressing to mortality or ventilation/ICU. ICU, intensive care unit

FIGURE 4

Neurological complications in COVID‐19 patients. (A) Non‐contrast CT head shows diffuse loss of gray‐white differentiation and sulcal effacement, consistent with global hypoxic ischemic encephalopathy. Additionally, there are multifocal intracranial hemorrhages, including a large hematoma in the left fronto‐parietal deep white matter (red arrow); (B) T2‐FLAIR and (C) DWI MRI brain sequences in a patient show right parieto‐occipital and left posterior thalamocapsular acute infarcts (arrows)