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A research team comprised of members from the Department of Pharmacology and Pharmacy, School of Public Health, Department of Family Medicine and Primary Care, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong (HKUMed), and Laboratory of Data Discovery for Health (D²4H) have conducted one of the first real-world studies to explore the inpatient use of oral antivirals during a pandemic wave dominated by the SARS-CoV-2 omicron variant. Initiation of novel oral antiviral treatments in hospitalised patients with mild-to-moderate COVID-19 not requiring oxygen therapy on admission showed substantial clinical benefit to reduce mortality, disease progression, and achieve lower viral burden. The findings are now published online in the journal The Lancet Infectious Diseases [link to the publication].

Background
Use of oral antivirals in patients with COVID-19 may lower their risks of hospitalisation and death and reduce the burden on healthcare systems. Clinical trials observed no clinical benefits with molnupiravir use in the inpatient setting among patients with moderate-to-severe COVID-19, and reported reductions in the hospitalisation or death with oral antivirals use (30% for molnupiravir and 88% for nirmatrelvir–ritonavir respectively) in non-hospitalised patients with mild-to-moderate COVID-19. However, real-world evidence of oral antiviral use in patients infected with the SARS-CoV-2 omicron variant is insufficient.

Research findings
The study analysed data from a territory-wide retrospective cohort of patients in Hong Kong who were hospitalised with a confirmed diagnosis of SARS-CoV-2 infection between 26 February and 26 April 2022. Among 40,776 patients hospitalised with SARS-CoV-2 infection during the study period, we selected patients who were eligible to receive oral antivirals^[1]. This analysis included 1,856 early molnupiravir recipients (i.e. receiving molnupiravir within the first two days of admission) and 1,856 matched controls, and 890 early nirmatrelvir-ritonavir recipients and 890 matched controls.

A lower risk of all-cause mortality was observed in molnupiravir recipients versus matched controls and in nirmatrelvir–ritonavir recipients versus matched controls. Oral antiviral recipients also had lower risks of the composite disease progression outcome and need for oxygen therapy than controls. Time to achieving a low viral burden was significantly shorter among oral antiviral recipients than matched controls.

Significance of the study
‘Current guidelines are now prioritising the distribution of oral antivirals to those who do not require supplemental oxygen but at the highest risk of disease progression. Our study cohort reflected such a prescription pattern in real-world clinical practice, consisting of mostly older people with multiple pre-existing comorbidities and who had not been fully vaccinated. The antiviral effect and mortality benefit observed in this patient cohort support the use of oral antivirals in patients with COVID-19 who do not require supplemental oxygen on admission during a pandemic wave of the omicron variant.’ said Dr Carlos Wong King-ho, Assistant Professor of the Department of Pharmacology and Pharmacy, HKUMed.

In conclusion, this retrospective cohort study of hospitalised patients with COVID-19 who did not initially require supplemental oxygen showed that early initiation of oral antivirals was associated with significant reductions in risk of all-cause mortality and disease progression, and with reaching a low viral burden faster than non-use, during an epidemic dominated by the SARS-CoV-2 omicron BA.2 subvariant. These findings support the use of these antivirals in this population. As both oral antivirals are currently indicated for non-hospitalised patients with COVID-19 who are at high risk of disease progression, ongoing research will inform the safety and effectiveness of oral antivirals in specific patient populations, drug combinations, and health-care settings.

About the research team
This study was co-led by Dr Carlos Wong King-ho, Assistant Professor of the Department of Pharmacology and Pharmacy, Assistant Professor of Department of Family Medicine and Primary Care, HKUMed; Professor Benjamin John Cowling, Chair Professor and Division Head of Epidemiology and Biostatistics, School of Public Health, Director of Laboratory of Data Discovery for Health; and Professor Gabriel Matthew Leung, Honorary Clinical Professor, School of Public Health, HKUMed. The research team also includes Dr Eric Lau Ho-yin, Scientific Officer, School of Public Health, HKUMed; Ivan Au Chi-ho, MPhil student, and Kristy Lau Tsz-kwan, Senior Research Assistant, Department of Pharmacology and Pharmacy, HKUMed.

Acknowledgements
This study was supported by the Health and Medical Research Fund (reference number COVID190210) administered by the Health Bureau of the Government of the Hong Kong Special Administrative Region. The researchers are grateful for the assistance of the Department of Health and Hospital Authority for the provision of data for the research.

Media enquiries
Please contact LKS Faculty of Medicine of The University of Hong Kong by email (medmedia@hku.hk).

^[1] Those who were admitted to hospital more than 5 days after symptom onset, were younger than 18 years, had a history of oral antiviral use before admission, required supplemental oxygen on admission, had drug-related contraindications to nirmatrelvir–ritonavir use, or had severe renal or severe liver impairment were excluded.