Antiviral treatment of COVID‐19 is associated with lack of immune response

Abstract

To the Editor, Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was discovered in 2019 with first oral antivirals Nirmatrelvir/Ritonavir (Paxlovid) and Molnupiravir (Lagevrio) in 2021. One of the main concerns surrounding COVID-19 is the sequelae, termed Long Covid affecting almost 20% of patients, with current Government Accountability Office estimates of up to 23 million patients before the BA.4/5 wave of Summer 2022. The current Long Covid hypothesis is viral persistence in reservoirs, mainly in the brain and the GI system. 1,2 This is akin to HIV, and SARS-CoV-2 can be CD4 dependent and infect T helper cells independent of the ACE2-TMPRSS2 pathway. 3 It is common for infections to be treated with multiple drugs (e.g., HIV or mycobacteria) to minimize resistance and sequelae. Drugs chosen target different pathways, to ensure no resistance, which may be due to selective use (e.g., oseltamivir) or patientassociated factors. Thus the development of a Paxlovid-resistant SARS-CoV-2 VOC is a matter of when not if. 4 It makes theoretical sense that combination of Paxlovid and Lagevrio would lead to better outcomes, less resistance, and prevent and treat Long Covid. In vitro studies have shown a synergistic effect, a drug