A Multicenter Randomized Controlled Trial To Evaluate the Efficacy and Safety of Nelfinavir in Patients with Mild COVID-19

Abstract

The anti-HIV drug nelfinavir suppresses the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro . However, its efficacy in patients with COVID-19 has not been studied.

Stratification of viral shedding patterns in saliva of COVID-19 patients

“…We used longitudinal saliva viral load data obtained from cohorts of the nelfinavir (NFV) clinical trial (jRCT2071200023 11,12 ) and the University of Illinois at Urbana-Champaign 5 . All infections were either mild or asymptomatic.…”

“…Because of previous work concluding that there are no significant differences in virus infection dynamics between NFV-treated and untreated participants 12 , we analyzed all data together regardless of treatment (see Methods ). To further confirm whether NFV affects the stratification of the time-course pattern of viral shedding, we compared the number of individuals belonging to each group (i.e., G1, G2 and G3) between NFV-treated and untreated participants (including the members of the University of Illinois cohort) and found no trend for the stratification (p=0.784 by the Fisher’s exact test: Fig 2E ).…”

“…Another potential limitation of this study is the timing of saliva specimen sampling, although we took great care to select and compare specimens from G1, G2, and G3 without bias. As a result of our clinical trial design (jRCT2071200023 11,12 ), participants were enrolled after the onset of symptoms, thereby restricting saliva specimen collection exclusively to the post-symptom phase. Unfortunately, we lack samples from the pre-infection, pre-symptomatic, and early infection phases.…”

“…Briefly, the NFV clinical trial was a prospective, randomized, open-label, blinded-endpoint, parallel-group trial conducted between July 2020 and October 2021 at 11 university and teaching hospitals in Japan. This study consisted of a 14-day treatment period and a 14-day follow-up period, with no significant differences in the time to viral clearance between patients who received standard-of-care plus NFV administration and those who had the standard-of-care alone 11,12 . Therefore, the participants with COVID-19 were analyzed together here.…”

“…So far, our ability to understand and characterize whole SARS-CoV-2 infection dynamics has been hindered by several limitations of the clinical data that made it impossible to capture either the early or the late phase of infection or to annotate individual-level clinical information. To overcome these limitations, here we quantified and stratified longitudinal virus dynamics in saliva 3 samples from 144 mildly symptomatic participants of two different but complementary cohorts 5,11,12 . We successfully identified three groups with significantly different durations of viral shedding (i.e., the mean durations were 11.5 days, 17.4 days, and 30.0 days, respectively), implying a large inter-participant heterogeneity in virus infection dynamics.…”