Association of Nirmatrelvir/Ritonavir Treatment on Upper Respiratory Severe Acute Respiratory Syndrome Coronavirus 2 Reverse Transcription-Polymerase Chain Reaction (SARS-Cov-2 RT-PCR) Negative Conversion Rates Among High-Risk Patients With Coronavirus Disease 2019 (COVID-19)

Abstract

Background Acceleration of negative respiratory conversion of SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19) might reduce viral transmission. Nirmatrelvir/ritonavir is a new antiviral agent recently approved for treatment of COVID-19 that has the potential to facilitate negative conversion. Methods A cohort of hospitalized adult patients with mild-to-moderate COVID-19 who had a high-risk for progression to severe disease were studied. These patients presented with COVID-19 symptoms between March 5 and April 5, 2022. The time from positive to negative upper respiratory RT-PCR conversion was assessed by Kaplan-Meier plots and Cox proportional hazards regression with the adjustment for patients baseline demographic and clinical characteristics. Results There were 258 patients treated with nirmatrelvir/ritonavir and 224 non-treated patients who had mild-to-moderate COVID-19. The median (interquartile range) time for patients who converted from positive to negative RT-PCR was 10 days (7-12 days) in patients treated ≤5 days after symptom onset and 17 days (12-21 days) in non-treated patients, respectively. The proportions of patients with a negative conversion at day 15 were 89.7% and 42.0% in treated patients and non-treated patients, corresponding to a hazard ratio of 4.33 (95% CI, 3.31-5.65). Adjustment for baseline differences between the groups had little effect on the association. Subgroup analysis on treated patients suggests that time to negative conversion did not vary with the patients’ baseline characteristics. Conclusion This cohort study of high-risk patients with mild-to-moderate COVID-19 found an association between nirmatrelvir/ritonavir treatment and accelerated negative RT-PCR respiratory SARS-CoV-2 conversion that might reduce the risk of viral shedding and disease transmission.

Viral Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Infection in mRNA-Vaccinated Individuals Treated and Not Treated with Nirmatrelvir-Ritonavir

“…The baseline incidence of rebound in the untreated group was 4% when rebound was defined as at least 2 negative (Ct≥35) PCR results followed by at least 2 positive (Ct<35) results. Estimates of the incidence of rebound vary widely across the literature because of differences in methodology 4 , 9 – 11 . Our result is consistent with the 6% rate reported in a prospective observational cohort of mRNA-vaccinated individuals infected with Omicron, where viral rebound was defined using similar PCR criteria.…”

“…Viral rebound was defined as at least 2 negative (Ct≥35) PCR results followed by at least 2 positive (Ct<35) results. These criteria were chosen to enhance comparability with data in Li et al 5 and Hay et al 6 . The incidence of viral rebound was compared between treated and untreated participants using Chi-square test.…”

“…The protease inhibitor nirmatrelvir-ritonavir (NMV-r) decreases the risk of severe COVID-19 (coronavirus disease 2019) in unvaccinated high-risk outpatients with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection 1 , 2 , but has not shown clinical benefit in low-risk and/or vaccinated individuals 3 . NMV-r accelerates time to viral suppression in a range of populations 1 , 3 , 4 , suggesting that there may be a public health benefit of NMV-r treatment if reduced viral shedding translated to decreased transmission. However, there are concerns that cases of viral rebound following NMV-r cessation with prolonged viral shedding would negate any such public health benefit.…”

“…The data on the incidence of viral rebound in treated and untreated populations is mixed, primarily due to varying definitions of rebound, methods of ascertaining events, and patient populations 1 , 4 , 9 – 11 . In the largest dataset of viral kinetics in untreated mRNA-vaccinated individuals infected with the Omicron variant, viral rebound (defined with PCR monitoring) occurred in 6% of 494 infections 10 .…”

Nirmatrelvir–ritonavir might only be effective in elderly patients

“…(2) The main populations in these studies were older patients (Table 1), [2][3][4][5] and the younger patients with relatively small sample size may result in that the significant treatment benefit were not be shown. Other reports also strengthening the clinical benefit of nirmatrelvir-ritonavir, [6][7][8][9] whereas these studies were lack of subgroup analysis according to age. Further research on the effectiveness of nirmatrelvir-ritonavir in age specific populations is needed.…”