Fewer COVID‐19 Neurological Complications with Dexamethasone and Remdesivir

OBJECTIVE: The objective of this study was to assess the impact of treatment with dexamethasone, remdesivir or both on neurological complications in acute coronavirus diease 2019 (COVID‐19). METHODS: We used observational data from the International Severe Acute and emerging Respiratory Infection Consortium World Health Organization (WHO) Clinical Characterization Protocol, United Kingdom. Hospital inpatients aged ≥18 years with laboratory‐confirmed severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection admitted between January 31, 2020, and June 29, 2021, were included. Treatment allocation was non‐blinded and performed by reporting clinicians. A propensity scoring methodology was used to minimize confounding. Treatment with remdesivir, dexamethasone, or both was assessed against the standard of care. The primary outcome was a neurological complication occurring at the point of death, discharge, or resolution of the COVID‐19 clinical episode. RESULTS: Out of 89,297 hospital inpatients, 64,088 had severe COVID‐19 and 25,209 had non‐hypoxic COVID‐19. Neurological complications developed in 4.8% and 4.5%, respectively. In both groups, neurological complications were associated with increased mortality, intensive care unit (ICU) admission, worse self‐care on discharge, and time to recovery. In patients with severe COVID‐19, treatment with dexamethasone (n = 21,129), remdesivir (n = 1,428), and both combined (n = 10,846) were associated with a lower frequency of neurological complications: OR = 0.76 (95% confidence interval [CI] = 0.69–0.83), OR = 0.69 (95% CI = 0.51–0.90), and OR = 0.54 (95% CI = 0.47–0.61), respectively. In patients with non‐hypoxic COVID‐19, dexamethasone (n = 2,580) was associated with less neurological complications (OR = 0.78, 95% CI = 0.62–0.97), whereas the dexamethasone/remdesivir combination (n = 460) showed a similar trend (OR = 0.63, 95% CI = 0.31–1.15). INTERPRETATION: Treatment with dexamethasone, remdesivir, or both in patients hospitalized with COVID‐19 was associated with a lower frequency of neurological complications in an additive manner, such that the greatest benefit was observed in patients who received both drugs together. ANN NEUROL 2023;93:88–102