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Remdesivir, the first antiviral drug approved to treat COVID-19, curiously does not work for all patients.

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Why remdesivir works for some COVID-19 patients but not others

23 Jun 2022

Remdesivir treatment is more likely to be successful in COVID-19 patients who are naturally able to mount a strong immune response against infections.

In October 2020, the US Food and Drug Administration (FDA) approved the emergency use of the antiviral drug remdesivir to treat COVID-19. Finally, after seven months of fear and uncertainty, there appeared to be hope against the disease that had brought the world to a standstill.

Remdesivir helps patients fight COVID-19 by preventing the virus from multiplying further, effectively putting a stop to its life cycle. However, there was a curious catch: it didn’t work all the time. Many patients on oxygen support continued to deteriorate despite remdesivir treatment, suggesting that the drug was effective only in some patients. Why this was so, or what factors made these patients more responsive to remdesivir than others, remained mostly unknown.

To help answer this question, Lisa Ng, Executive Director at A*STAR Infectious Diseases Labs (ID Labs) led a research team in the search for key immune markers that could help doctors identify patients for whom remdesivir treatment would be successful.

With collaborators from the National Centre for Infectious Diseases, the researchers collected plasma samples from 28 severe COVID-19 patients who were treated with remdesivir. Those who did not deteriorate enough to need oxygen support were deemed as treatment responders.

Remdesivir turned out to be effective in 21 patients. When Ng and her team measured the levels of immune response markers of this group before and after the treatment, they found that the responders had higher levels of type 2 helper cells (Th2) than type 1 helper cells (Th1). This finding suggested that the balance between Th1 and Th2 was a potential indicator of such response to remdesivir.

“Although the exact function of Th2 in severe COVID-19 is unclear, it is known to have a vital role in the reduction of inflammation in other lung disorders,” Ng explained. “Responders had a higher Th2 response, indicating that remdesivir treatment is working and reducing their overactive inflammation.”

Other Th2-associated cytokines were also elevated in responders, further suggesting that Th2 and its related pathways play an important role in the drug’s effectiveness.

Meanwhile, non-responders were more likely to have overactive and uncontrollable inflammation that not even remdesivir could treat, suggesting that adding anti-inflammatory agents to remdesivir could be a promising treatment strategy. However, Ng and the team emphasised that more research is needed before definitive treatment guidelines can be drawn from these results.

“Our findings warrant further studies with larger cohorts to define the underlying immune response differences between responders and non-responders of remdesivir that could have prevented or limited the aggravation of COVID-19,” said Ng.

The A*STAR-affiliated researchers contributing to this research are from A*STAR Infectious Diseases Labs (ID Labs) and the Singapore Immunology Network (SIgN).

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References

Chan, Y.H., Young, B.E., Fong, S.W., Ding, Y., Goh, Y.S., et al. Differential cytokine responses in hospitalized COVID-19 patients limit efficacy of remdesivir. Frontiers in Immunology 12, 680188 (2021). | article

About the Researcher

Lisa F.P. Ng obtained her PhD in molecular virology in coronaviruses from the National University of Singapore (NUS) in 2002. After joining A*STAR’s Genome Institute of Singapore (GIS) in 2002 as a Postdoctoral Fellow, she worked on viral diseases such as hepatitis, severe acute respiratory syndrome and influenza. Ng is currently the Executive Director of A*STAR’s Biomedical Research Council (BMRC) and holds a concurrent appointment as Executive Director at A*STAR's Infectious Diseases Labs (ID Labs) where she focuses on the immune responses to arthritic arboviruses that are epidemic or highly endemic in the tropical region. Ng has won numerous accolades for her research, including the ASEAN ‘International Young Scientist and Technologist Award’ in 2008 and A*STAR’s ‘Most Inspiring Mentor Award’ in March 2013.

This article was made for A*STAR Research by Wildtype Media Group