A recent study published in The Lancet reported the real-world efficacy of the oral antiviral therapies nirmatrelvir plus ritonavir and molnupiravir on the Omicron (B.1.1.529) variant of coronavirus 2 (SARS-CoV-2) syndrome severe acute respiratory syndrome, based on an observational study among patients with coronavirus disease 2019 (COVID-19) in Hong Kong.
Study: Real-world efficacy of molnupiravir and nirmatrelvir plus ritonavir against mortality, hospitalization and hospital outcomes among community outpatients with confirmed SARS-CoV-2 infection during the omicron wave in Hong Kong: an observational study. Image credit: G.Tbov/Shutterstock
background
Most of the evidence for the efficacy of oral antivirals such as nirmatrelvir plus ritonavir and molnupiravir comes from clinical trials conducted before Omicron SARS-CoV (B.1.1.529) became the predominant circulating variant . Clinical trials in more than 20 countries have shown that early administration of these two oral antiviral therapies to people with mild to moderate symptoms of COVID-19 reduces the risk of hospitalization and mortality by 30 to 89% .
A large number of the clinical trials of nirmatrelvir plus ritonavir and molnupiravir were conducted in unvaccinated individuals who were not hospitalized but were at risk of mild or moderate symptoms of COVID-19 progressing to more severe outcomes. In addition, the studies were largely conducted during the circulation of the SARS-CoV-2 delta variant (B.1.617.2). Therefore, the actual efficacy of these therapies should be investigated based on emerging SARS-CoV-2 variants and the vaccination status of individuals.
About the study
In the present study, researchers used the Hong Kong Hospital Authority database to collect information on confirmed cases of SARS-CoV-2 and associated demographic characteristics, diagnoses, prescribed treatment, vaccination status COVID-19, laboratory tests, hospitalization status and records. deaths The study was conducted between January and June 2022, which was the period of dominance of the Omicron SARS-CoV-2 variant.
People aged 18 years or older with positive reverse transcription polymerase chain reaction (RT-PCR) tests confirming SARS-CoV-2 infection were included in the study. Patients received molnupiravir or nirmatrelvir plus ritonavir within five days of the onset of mild to moderate symptoms.
Risk factors such as diabetes, obesity, other chronic diseases, age (over 60 years) and incomplete vaccination were considered as criteria for antiviral administration. The study excluded people treated with drugs that might have contraindications to nirmatrelvir plus ritonavir. Patients with severe renal or hepatic impairment were also excluded to avoid confounding the results.
The primary analysis was based on a retrospective cohort study, while the internal validation sensitivity analysis was based on a case-control study design. Participants were divided into two groups based on the prescription of molnupiravir or nirmatrelvir plus ritonavir. The date of SARS-CoV-2 positivity or onset of symptoms, whichever occurred earlier, was considered the index date. The treatment cohort was matched with a control cohort comprising SARS-CoV-2 positive individuals who were not prescribed molnupiravir or nirmatrelvir plus ritonavir.
The retrospective cohort and case-control study measured three outcomes: all-cause mortality, hospitalization for COVID-19, and a composite outcome consisting of the requirement for an intensive care unit (ICU) or invasive mechanical ventilation (IMV) or in – hospital mortality. The cohort study also included an additional outcome of individual in-hospital outcomes consisting of mortality, initiation of VMI, or need for ICU.
results
The results indicated that early administration of the oral antivirals molnupiravir or nirmatrelvir plus ritonavir significantly reduced the risk of mortality compared with no treatment with either antiviral therapy. In addition, nirmatrelvir plus ritonavir also reduced the risk of hospitalization due to COVID-19.
Early administration of both oral antiviral therapies was associated with a lower risk of mortality and hospitalization in patients aged 60 years and older. The use of molnupiravir resulted in a reduction in the onset of VMI. Updated clinical trials showed that nirmatrelvir plus ritonavir reduced the risks of death and hospitalization by 51% in unvaccinated individuals or fully vaccinated COVID-19 patients with at least one risk factor.
The study found that molnupiravir users were older and more likely to be incompletely vaccinated than nirmatrelvir and ritonavir users. The authors believe that this result was best explained by the advantage of molnupiravir first, and nirmatrelvir plus ritonavir is not as widely prescribed in the elderly because of its interactions with other drugs. However, subsequent guidelines promote nirmatrelvir plus ritonavir over molnupiravir, as it significantly reduces the risk of hospitalization, even in patients who are not fully vaccinated.
Conclusions
In conclusion, the observational study conducted in Hong Kong during the predominance of the SARS-CoV-2 Omicron BA.2.2 sublineage reported that early administration of oral antivirals nirmatrelvir plus ritonavir or molnupiravir significantly reduced disease severity and mortality risks. Nirmatrelvir plus ritonavir also reduced the risk of hospitalization.
The authors noted that, given the potential genotoxicity and mutational risks of molnupiravir, and concerns about the rapid mutation of SARS-CoV-2 developing antiviral resistance, further clinical studies and greater pharmacovigilance are needed to monitor the safety of oral antivirals.
Journal reference:
- Wong, CKH, Au, ICH, Lau, KTK, Lau, EHY, Cowling, BJ and Leung, GM (2022). Real-world effectiveness of molnupiravir and nirmatrelvir plus ritonavir against mortality, hospitalization, and hospital outcomes among community outpatients with confirmed SARS-CoV-2 infection during the omicron wave in Hong Kong: an observational study. The Lancet. doi: