Adding Remdesivir to Dexamethasone Early Associated With Better Outcomes of Moderate COVID-19

NEW YORK (Reuters Health) – Adding remdesivir to dexamethasone is associated with better clinical outcomes of COVID-19, especially when done early in the treatment of mild to moderate disease, according to new research.

“Study findings showed the initiation of remdesivir prior to or simultaneously with dexamethasone was associated with faster time to clinical improvement (median 12 vs. 13 days), viral clearance (median 5 vs. 6 days), and reduced risks of in-hospital death and hospital length of stay (18 vs. 21 days; difference, -2.65 days) than late introduction of remdesivir after the corticosteroid or not using the antiviral at all,” Dr. Carlos Wong of The University of Hong Kong, who worked on the study, told Reuters Health by email.

Those findings, published in Clinical Infectious Diseases, were statistically significant with the exception of viral clearance, which was a non-significant trend.

Dr. Wong and colleagues reviewed patient records from Hong Kong hospitals for a period of a year starting in late January 2020. They found 10,445 COVID-19 patients, 1,544 of whom were given dexamethasone. The researchers compared 466 patients who started remdesivir before or concurrently with dexamethasone to 1,078 patients who started the antiviral a median of two days after dexamethasone (149 patients) or not at all.

The two groups shared similar clinical characteristics, including clinical severity of COVID-19, treatments while in the hospital and pre-existing comorbidities among others.

Cox regression models with inverse-probability-of-treatment weighting found significant benefits to starting remdesivir as early as possible.

The time to clinical improvement was reduced to 12 days from 13, a hazard ratio of 1.23 (95% confidence interval, 1.02 to 1.49). The risk of death in the hospital was also lower at a hazard ratio of 0.59 (95% CI, 0.36 to 0.98). And there was no significant difference between the groups in their risk of acute respiratory distress syndrome, the researchers report.

Looking at a subgroup of survivors, the length of stay in the hospital was shorter by 2.65 days for patients who started remdesivir early or concurrently (95% CI, 1.01 to 4.29).

One explanation for the findings, the researchers speculate, is that corticosteroids may dampen the immune system’s ability to clear the virus, and remdesivir may reduce the risk of a heightened immune response to the virus.

“These findings were justifiable based on the theoretical understanding of the progression of a viral infection, where early introduction of antivirals (remdesivir) might help to inhibit viral replication and possibly prevent the ‘cytokine storm’, followed by the addition of anti-inflammatory agents (dexamethasone) to suppress the hyper-inflammation should it develop,” Dr. Wong said.

Dr. Thomas Benfield, a clinical professor at the University of Copenhagen who carried out a similar study in a Danish population, said, “I believe (the study by) Wong et al. is a valuable real-world contribution.”

“In fact, our study and the study by Wong and colleagues strongly support one another. The exposure group is very similarly to our treatment group because per recommendation remdesivir and dexamethasone are co-administered in Denmark,” Dr. Benfield told Reuters Health by email.

SOURCE: Clinical Infectious Diseases, online August 22, 2021.

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