Early remdesivir initiation optimal in moderate-to-severe COVID-19

In patients with COVID-19, starting remdesivir within 9 days of symptom onset confers benefit for survival, according to a study.

Earlier remdesivir treatment reduced the likelihood of death by more than 50 percent as compared with symptom onset-to-remdesivir treatment (SORT) interval of >9 days, the investigators said.

The findings underscore an optimal treatment window and the need for appropriately timed remdesivir administration in patients with moderate-to-severe infection, they added.

In total, 350 patients at a tertiary care COVID-dedicated centre in India received remdesivir, of which 346 (median age 60 years, 78 percent male) were included in the final analysis. The four patients excluded had serious adverse events that led to treatment discontinuation.

At baseline, oxygen saturation (SpO₂) was <94 percent among patients with moderate infection (n=109, 31.5 percent) and <90 percent among those with severe infection (n=237, 68.5 percent). Fifty patients (14.5 percent) required mechanical ventilation. The majority of the population had ≥1 comorbidity (n=243), including diabetes mellitus (50.0 percent), hypertension (47.1 percent), chronic heart disease (15.6 percent), chronic kidney disease (5.2 percent), and chronic respiratory disease (asthma/chronic obstructive pulmonary disease; 3.5 percent).

Seventy-six (22 percent) deaths were recorded overall, with the numbers higher among patients with severe than moderate COVID-19 (30.8 percent vs 2.8 percent). Length of hospital stay was longer also in the group with severe infection (median, 13 vs 9 days).

As pointed out, all-cause mortality was much lower among patients with SORT interval ≤9 days (n=260) vs >9 days (n=86; 18.1 percent vs 33.7 percent; p=0.004). The corresponding odds ratio for death was 0.43 (95 percent confidence interval [CI], 0.25–0.75; p=0.003), suggesting a survival benefit of earlier remdesivir treatment. [Int J Infect Dis 2021;106:71-77]

To date, global studies have examined the effects of remdesivir in COVID-19 by comparing with placebo or studying different durations of the antiviral drug. However, none of them evaluated mortality outcomes based on SORT interval (early vs late initiation). [N Engl J Med 2020;383:1813-1826; Lancet 2020;395:1569-1578; N Engl J Med 2020;383:1827-1837; N Engl J Med 2021;384:497-511]

“Antivirals are maximally effective in earlier stages of the disease when there is active viral replication—defining this therapeutic window is of paramount importance. Additionally, considering that the average latency between viral exposure and clinical symptoms is 5 days, minimizing the interval between symptom onset and treatment initiation is critical from an outcomes perspective,” the investigators pointed out.

The current study reflects real-world practice in the latter part of the pandemic, where the use of remdesivir and steroids and a well-prepared healthcare system have been established, they said. The findings drive home the message that rather than “date of diagnosis,” “symptom onset” must instead be considered as the target for intervention.

“The importance of early remdesivir initiation (SORT interval ≤9 days) in our study, with a clear mortality benefit, indicates an impact of the medication over and above steroids and ancillary therapies in moderate-to-severe COVID-19,” according to the investigators.