Taking the SARS-CoV-2 antiviral drug nirmatrelvir-ritonavir (Paxlovid) 3 to 5 days after COVID-19 symptom onset—not earlier or later—may result in the greatest reduction in viral loads, viral transmission, and viral rebound in hospitalized patients, a University of Hong Kong–led study finds.
For the study, posted by eLife, which publishes peer-reviewed preprints, the investigators fitted a mathematical model of in vivo Omicron variant behavior to electronic medical record data from 208 patients hospitalized with mild to moderate COVID-19 in Hong Kong from January to May 2022. The Omicron BA.2 variant was dominant during the study period.
Half of the patients received Paxlovid, and the other half were given no antiviral therapy. Participants were aged 8 to 103 years.
Low uptake despite efficacy
The study authors noted that despite the availability of antivirals within 5 miles of home for 90% of Americans through the US Test-to-Treat program, US uptake has been relatively low, with only 11% of COVID-19 patients prescribed the drugs during the study period. Paxlovid is prescribed for patients at high risk for severe disease.
"The low uptake may stem from slow rollouts in some areas, complex eligibility requirements, testing, and potential drug interactions, as well as concerns about viral rebounds following Paxlovid treatment," they wrote.
In Hong Kong, under 40% of COVID-19 patients older than 60 years had been prescribed Paxlovid by late July 2022.
"Low rates of antiviral uptake may stem from misinformation, lack of access, and the rising proportion of cases that opt for at-home rapid tests and do not seek healthcare," the researchers wrote. "Telemedicine and online healthcare services can accelerate and expand access to antivirals, but may not reach some of the older populations in Hong Kong."
Optimal use could avert over 90% of viral replication
In total, 62% of Paxlovid recipients started the drug 3 to 5 days after symptom onset. When the drug was started 3 days after symptom onset, the odds of post-treatment viral rebound was low (17%), with a 12% lower risk of transmission among non-rebound patients. The findings suggest that Paxlovid can prevent over 90% of viral replication if it is given at the optimal time, the study authors said.
But if Paxlovid is initiated before 3 days, the risk of viral rebound is significantly increased with no improvement in infectiousness, with a 74% chance of viral rebound if started the day after symptom onset. And starting the drug after 5 days of symptom emergence lowers the drug's ability to stem peak viral shedding (0% reduction at 10 days).
The development of global distribution programs that provide rapid and equitable access to antivirals could enhance our ability to combat COVID-19 as the virus and the landscape of immunity continues to evolve.
"Our findings indicate that broader global access to Paxlovid, coupled with appropriately timed treatment, can mitigate the severity and transmission of SARS-CoV-2," the researchers concluded.
Giving Paxlovid to more patients may help quell future pandemic waves without the need for socioeconomically expensive lockdowns, lead author Zhanwei Du, PhD, of the World Health Organization (WHO) Collaborating Center for Infectious Disease Epidemiology and Control at the University of Hong Kong, said in an eLife press release. "However, to get the most out of these drugs, we first need to understand the optimal timing for taking them and to encourage their wider distribution and uptake," he said.
The researchers, however, caution that their data didn't consider the potential emergence of Paxlovid resistance, which would require further research before the antiviral could be deployed more broadly.
"The development of global distribution programs that provide rapid and equitable access to antivirals could enhance our ability to combat COVID-19 as the virus and the landscape of immunity continues to evolve," they concluded.
