With over 5 million deaths worldwide [
1], the COVID-19 pandemic has proven difficult to contain. Despite the development, advent, licensure, and rollout of many safe and effective vaccines [
2], controlling SARS-CoV-2 transmission has shown to be elusive for several reasons, including vaccine supply shortages in low- and middle-income countries [
3], vaccine hesitancy [
4], and the emergence of new variants [
5]. Indeed, the Delta and Omicron variants, that emerged in summer and fall of 2021, quickly became the predominant strains and have caused large epidemic outbreaks, even in highly vaccinated regions [
1]. Rapidly producing such COVID-19 vaccines has been an amazing scientific endeavor, but effective tools to treat COVID-19 disease are still urgently needed. Monoclonal antibodies, antibody cocktails and antiretroviral treatments have been, and continue to be studied to treat SARS-CoV-2 infection and to prevent progression to severe disease [
6]. Several treatments have been found to reduce hospitalizations by 30 to 89% [
7‐
10] when taken within the first five days after developing symptoms. Some of them are approved for early treatment of patients with mild-to moderate COVID-19 who are at high-risk of progression to severe disease while others are approved for hospitalized patients, with one approved as a pre-exposure prophylaxis [
11]. Furthermore, most studies have shown that these antiviral treatments significantly reduced the amount of infectious virus in the nasal mucosa of treated individuals [
12,
13]. Hence, the advent of effective antiviral drugs raises the possibility that in treating infected individuals we may reduce onward transmission (indirect population benefit) while also protecting the treated person from severe disease (direct benefit). The use of antiviral treatments as an effective means of prevention and epidemic control is not new. During the 2009 influenza A H1N1 pandemic, just a few weeks after the first case of influenza A H1N1 was identified in the US, the US government released 11 million courses of antiviral drugs for influenza (25% of the antiviral supply) from the National Stockpile as a potential tool to control transmission and mitigate disease [
14]. Treatment as Prevention is considered a primary method of epidemic control for HIV, as research has demonstrated that earliest detection and treatment suppressing HIV replication stops secondary transmission while having the the greatest effect at the individual level [
15‐
17].
Over the past several months, the availability of antigen tests has expanded considerably, facilitating the early diagnosis of SARS-CoV-2 infection and possible early treatment [
18,
19]. The US government has purchased 20 million courses of the antiviral pill paxlovid; these are expected to be delivered in early 2022. Furthermore, a “Test to Treat” initiative was recently announced as part of a new phase in the US government pandemic response [
20]. The Medicines Patent Pool and the manufacturers of molnupiravir and paxlovid (Merck and Pfizer respectively) have announced license agreements to facilitate global access for these drugs [
21,
22], and Pfizer will donate 4 million courses of paxlovid to UNICEF for use in lower-income countries in the following months [
23]. Hence, it is possible that in the next few months antiviral treatments will become widely available globally.
In this work, we use an agent-based mathematical model to evaluate the potential population impact of widespread use of antiviral treatments in reducing hospitalization risk and population-level transmission. We explored the use of antiviral treatments in four different countries (Kenya, Mexico, US and Belgium) with very different demographic composition and vastly different proportions of vaccinated individuals.
We showed that the synergistic use of vaccine and antiviral treatments can significantly reduce the burden of COVID-19. Further, our model suggested that targeted use of antiviral treatments can be used to prevent the majority of deaths.