Early use of antivirals linked to reduced risk of long COVID

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A meta-analysis of nine observational studies published late last week in the Journal of Infection shows that early use of oral antiviral drugs reduced the risk of long COVID, or post-COVID condition (PCC), by 23%, and Paxlovid may perform better than molnupiravir.

In total the nine studies included 866,066 patients, in which Paxlovid (nirmatrelvir-ritonavir, or MMV-r) and molnupiravir were evaluated in eight and two studies, respectively. 

While antivirals have been approved to use in the acute phase of illness to prevent progression to severe disease in at-risk populations, the potential use of the drugs as a way to prevent long COVID has drawn recent attention. 

In the study, the patients were not hospitalized, and early use was defined as within 5 days of COVID-19 diagnosis for most studies and within 30 days of symptom onset in one study, and it was not mentioned in two studies. 

Paxlovid outperforms molnupiravir

Studies defined long COVID differently, with five measuring PCC outcomes as symptoms 30 days after diagnosis, and four defining the condition as symptoms persisting 90 days after diagnosis. 

Overall early oral antiviral drugs reduced long-COVID risk 23% (risk ratio [RR] 0.77; 95% confidence interval [CI], 0.68 to 0.88), regardless of age or sex. 

Paxlovid and molnupiravir subgroups had RRs of 0.76 (95% CI, 0.65 to 0.88) and 0.88 (95% CI, 0.82 to 0.94), respectively—reductions of 24% and 12%—compared to no antiviral drug treatment.

"Our mixed evidence comparing two oral antiviral drugs using a network meta-analysis suggests a possible benefit of NMV-r over molnupiravir in reducing PCC risk," the authors wrote.

Long COVID has emerged as a major feature of the COVID-19 landscape, with incidence rates estimated to be 10% to 30% and 50% to 70% among non-hospitalized and hospitalized patients with COVID-19 worldwide, the authors said. 

Broader use indicated?

The findings suggest that a broader use of antivirals may be considered to prevent long COVID. Current World Health Organization guidelines strongly recommend Paxlovid in patients at a moderate to high risk of hospitalization, or molnupiravir or remdesivir if Paxlovid is not available.

Though the protective mechanisms are not fully understood, the authors said lowering the rate of viral replication in patients likely plays a role in the antivirals' ability to lower the risk of long COVID. The condition is strongly associated with severe disease and hospitalization, and antivirals limit viral progression, they said.

Our study underscores the importance of timely antiviral intervention in mitigating the long-term repercussions of COVID-19.

"Our study underscores the importance of timely antiviral intervention in mitigating the long-term repercussions of COVID-19," the authors wrote.

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