ABSTRACT
Background: Remdesivir is the current recommended anti-viral treatment in moderate-to-severe COVID-19. However, data on several aspects of its use such as impact of timing of therapy, efficacy, and safety in this severity category are limited. The current study aimed to evaluate the impact of timing of remdesivir initiation (symptom-onset to remdesivir treatment [SORT] interval) on in-hospital all-cause mortality in patients with moderate-to-severe COVID-19. Methods: This retrospective study was conducted between June 25, 2020 and October 3, 2020, at a tertiary care dedicated COVID center in India. Consecutive patients with moderate-tosevere COVID-19 (moderate: SpO2 <94%;severe: SpO2 <90%) were included. Data were collected from the health records of the hospital. Remdesivir was administered along with other standard medications as per protocol. The main outcome was the impact of SORT interval on in-hospital all-cause mortality. Subgroups were formed based on SORT interval. Other measures analyzed included overall in-hospital mortality, length of hospital stay, and safety. Results: Of 350 patients treated with remdesivir, 346 were included for the final analysis (males: 270 [78.0%];median [range] age: 60 [24-94] years). Overall, 243 (70.2%) patients had ≥1 comorbidity;109 (31.5%) patients had moderate disease, 237 (68.5%) had severe disease, and 50 (14.5%) patients required mechanical ventilation. Of the 346 patients, 76 (22.0%) patients died (moderate: 3 [2.8%], severe: 73 [30.8%]). In the subset of mechanically ventilated patients, 43 (86.0%) died. All-cause mortality was significantly lower in patients with SORT interval ≤9 days (n = 260) compared with those with SORT interval >9 days (n = 86;18.1% vs 33.7%;P = .004). The odds of death were significantly lower in patients with SORT interval ≤9 days vs >9 days (odds ratio = 0.44;95% CI, 0.25-0.76;P = .004). Adverse events (transaminitis ≥5 times upper limit of normal or estimated glomerular filtration rate <30ml/min) leading to drug discontinuation were seen in 4 (1.1%) patients. Conclusion: In this large series of moderate-to-severe COVID-19, initiation of remdesivir ≤9 days from symptom-onset was associated with a significant mortality benefit. These findings indicate a treatment window and reinforce the need for earlier remdesivir initiation in moderate-to-severe COVID-19 infection.