Oral Nirmatrelvir and Ritonavir in Nonhospitalized Vaccinated Patients With Coronavirus Disease 2019

Abstract

Background Treatment of coronavirus disease-2019 (Covid-19) with nirmatrelvir plus ritonavir (NMV-r) in high-risk non-hospitalized unvaccinated patients reduced the risk of progression to severe disease. However, the potential benefits of NMV-r among vaccinated patients are unclear. Methods We conducted a comparative retrospective cohort study using the TriNetX research network. Patients ≥18 years of age who were vaccinated and subsequently developed Covid-19 between December 1, 2021, and April 18, 2022, were included. Cohorts were developed based on the use of NMV-r within five days of diagnosis. The primary composite outcome was all-cause emergency room (ER) visit, hospitalization, or death at a 30-days follow-up. Secondary outcomes included individual components of primary outcomes, multisystem symptoms, Covid-19 associated complications, and diagnostic test utilization. Results After propensity score matching, 1,130 patients remained in each cohort. A primary composite outcome of all-cause ER visits, hospitalization, or death in 30 days occurred in 89 (7.87%) patients in the NMV-r cohort as compared to 163 (14.4%) patients in the non-NMV-r cohort (OR 0.5, CI 0.39-0.67; p<0.005) consistent with 45% relative risk reduction. A significant reduction in multisystem symptom burden and subsequent complications such as lower respiratory tract infection, cardiac arrhythmia, and diagnostic radiology testing were noted in NMV-r treated patients. There was no apparent increase serious complications between days 10 to 30. Conclusion Treatment with NMV-r in non-hospitalized vaccinated patients with Covid-19 was associated with a reduced likelihood of emergency room visits, hospitalization, or death. Complications and overall resource utilization were also decreased.

Clinical efficacy of Jingyin granules, a Chinese patent medicine, in treating patients infected with coronavirus disease 2019

“…The antivirals approved by FDA such as Paxlovid can increase the mortality and improve adverse events in COVID-19 patients ( Wen et al, 2022 ). Paxlovid could be used in mild to moderate COVID-19 patients with high risk for progression to severe disease, but it is more suitable for immunosuppressed patients, old patients and COVID-19 patients with comorbidity, ( Ganatra et al, 2022 ; Huang et al, 2022 ; Najjar-Debbiny et al, 2022 ). Recent RCT study demonstrated that treating COVID-19 with Paxlovid led to an 89% decreased risk of progress to severe COVID-19 than the risk with placebo (Hammond et al, 2022).…”

Real-world effectiveness of nirmatrelvir/ritonavir use for COVID-19: A population-based cohort study in Ontario, Canada

“…(4) Studies that have stratified by vaccination status have identified similar relative risk reductions in vaccinated cohorts, but with smaller absolute risk reductions due to the lower baseline risk of hospitalization or death from COVID-19. (3,5,6) All previous observational studies have risks of bias including residual confounding and immortal time bias. (7) In Ontario, Canada nirmatrelvir/ritonavir became widely available, and universally funded for all patients, in the community by April 2022 with clinical criteria set by the government limiting access only to patients who were older, had comorbidities, and/or were undervaccinated.…”

“…(4) Studies that have stratified by vaccination status have identified similar relative risk reductions in vaccinated cohorts, but with smaller absolute risk reductions due to the lower baseline risk of hospitalization or death from COVID-19. (3,5,6) All previous observational studies have risks of bias including residual confounding and immortal time bias. (7)…”

The Paxlovid Rebound Study: A Prospective Cohort Study to Evaluate Viral and Symptom Rebound Differences Between Paxlovid and Untreated COVID-19 Participants

“…Further viral rebound and symptom rebound have also been seen in participants who did not receive any treatment leading to viral or symptom resolution [11], imploring further investigation into this rebound phenomenon. There have been some suggestions that rebound could be related to drug pharmacodynamics [12] or anti-viral mediated interactions with viral immunologic response [13], however, peer reviewed literature on Paxlovid rebound is mostly limited to retrospective case series with wide estimates [7,9,[14][15][16]. Rebound in untreated cohorts has consisted of small prospective studies [11,17].…”