The Potential and Limitations of Antiviral Treatment for COVID-19

Group of floating coronaviruses

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Nirmatrelvir combined with ritonavir is indicated for the treatment of mild-to-moderate COVID-19. The study did not demonstrate a significant difference in the time to relief of COVID-19 signs and symptoms between the treatment and placebo groups.

Of the 1,296 participants randomized, 1,288 received at least one dose of nirmatrelvir–ritonavir (654 participants) or placebo (634 participants) and had a follow-up visit post-baseline. The median time to alleviate all specified COVID-19 signs and symptoms was 12 days in the nirmatrelvir–ritonavir group and 13 days in the placebo group (P=0.60). Hospitalization or death occurred in 0.8% of the nirmatrelvir–ritonavir group compared to 1.6% in the placebo group. Adverse events were reported in 25.8% of the nirmatrelvir–ritonavir group and 24.1% of the placebo group, with taste disturbances (5.8%) and diarrhea (2.1%) being the most common in the treatment group.

“Among the patients who underwent randomization, COVID–19–related hospitalization or death from any cause occurred in 5 participants in the nirmatrelvir–ritonavir group and 10 in the placebo group,” according to investigators. “In the subgroup of high-risk participants, the numbers with this outcome were 3 and 7, respectively.”¹

In this phase 2–3 trial, adults with confirmed COVID-19 and symptom onset within the last 5 days were randomized to receive nirmatrelvir–ritonavir or a placebo every 12 hours for 5 days. Eligibility included the fully vaccinated individuals with at least one risk factor for severe COVID-19 and unvaccinated individuals or those not vaccinated within the past year, irrespective of risk factors. The primary outcome was the time to sustain the alleviation of all targeted signs and symptoms of COVID-19.

“The results with respect to the numbers of Covid-19–related hospitalizations and deaths from any cause in this trial, although not significant, are consistent with and supported by recent real-world data,” according to investigators. “5 real-world cohort studies have investigated nirmatrelvir–ritonavir in SARS-CoV-2–positive nonhospitalized patients during the period of omicron-variant dominance.”¹

Limitations include a descriptive analysis for the key secondary outcome due to the primary efficacy endpoint not being met and potential bias in blinding due to the distinct taste of nirmatrelvir–ritonavir. The trial’s initiation during the delta variant’s predominance. However, this is mitigated by subsequent studies affirming nirmatrelvir–ritonavir’s efficacy across different SARS-CoV-2 strains.

According to a previous report from Contagion, a Veterans Affairs study finds some reduction in post-COVID thromboembolic events with early use of nirmatrelvir-ritonavir but no protection against 30 other conditions.

“Use of the antiviral combination nirmatrelvir-ritonavir (Paxlovid) for early symptoms of COVID-19 offered limited protection against the development of Long COVID, in a VA study finding some reduced risk for thromboembolic events but not for 30 other potential post-COVID conditions.”²

Given the challenges such as waning vaccine immunity and emerging variants, the diverse international participant pool and the continued relevance of findings underscore the need for effective treatments for high-risk populations in the ongoing management of COVID-19.

References

1. Hammond J, Fountaine R, Yunis C, et. al. Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with Covid-19. Published April 3, 2024. Accessed April 9, 2024. The New England Journal of Medicine. Doi: 10.1056/NEJMoa2309003
2. Bender K. Paxlovid Provides Limited Protection Against Long COVID. Contagion. Published October 31, 2023. Accessed April 9, 2024. https://www.contagionlive.com/view/paxlovid-provides-limited-protection-against-long-covid