By IDSE News Staff
Starting antiviral treatment as late as 14 days after infection with SARS-CoV-2 may still be beneficial in immunocompromised people, who are at greatest risk of developing severe COVID-19, according to researchers in the Center for Translational Antiviral Research at Georgia State University's Institute for Biomedical Sciences (J Virol 2024. doi:10.1128/jvi.00905-24).
Although antivirals against COVID-19 infection work best when given early after symptoms start, drugs like nirmatrelvir-ritonavir (Paxlovid, Pfizer) and molnupiravir (Lagevrio, Merck) appear to inhibit viral replication even if initiated up to 14 days after infection.
The researchers sought to offer specific SARS-CoV-2 treatment plans to the immunocompromised patients and tested late-onset therapeutic options with standard-of-care nirmatrelvir-ritonavir and molnupiravir and experimental therapeutic 4'-fluorouridine (4'-FlU) in a T-cell−depleted immunocompromised mouse model of SARS-CoV-2.
The immunocompromised mice experienced low-level viral replication for 35 days after infection with SARS-CoV-2. When started on antivirals 14 days after infection, however, the duration of viral replication was significantly shortened, which could have implications for clinical use of antiviral drugs in immunocompromised patients.
The findings demonstrate that antiviral therapeutics could still have clinical value when given later in the management of persistent SARS-CoV-2 infection in immunocompromised patients, in addition to reducing the risk for progression to severe disease.
“Paxlovid, molnupiravir and preclinical candidate 4'-FlU significantly lowered virus loads in turbinates when treatment was initiated 14 days after the infection for seven days,” said Carolin M. Lieber, PhD, a postdoctoral fellow in the Center for Translational Antiviral Research at Georgia State University, in Atlanta.
“We demonstrated that late-onset antiviral treatment can provide major therapeutic benefit to an immunocompromised host infected with SARS-CoV-2,” said Richard K. Plemper, PhD, senior author of the study, Regents' Professor and the director of the Center for Translational Antiviral Research at Georgia State. “This study highlights that appropriately powered clinical trials are urgently needed to best serve the specific needs of a patient population at high risk to develop severe COVID-19.”
The study was funded by public health service grants.
