Modeling the role of antivirals in suppressing the COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) pandemic has led to over 5 million worldwide deaths and has proved difficult to contain. Although several safe and effective vaccines have been developed, they are elusive for many reasons such as shortage of vaccine supply, the emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and vaccine hesitancy. Therefore, effective tools for the treatment of COVID-19 are still required.

Study: The role of antiviral treatment in curbing the COVID-19 pandemic: a modeling study. Image Credit: Mabeline72/ Shutterstock

Only one antiviral drug (remdesivir) and one monoclonal antibody (REGEN-COV) have been approved in the United States. Although these therapies are highly effective, they must be administered intravenously, which makes them costly.

Recently an oral antiviral treatment, molnupiravir, has been in phase 3 clinical trial.  Molnupiravir has been shown to reduce hospitalizations due to COVID-19 by 50 percent if taken within five days from the onset of symptoms. Therefore, its manufacturer has requested Emergency Use Approval (EUA) from the Federal Drug Administration (FDA).

Another oral antiviral treatment, PAXLOVID, was found to reduce hospitalizations and deaths by 89 percent in phase 3 clinical trial analysis. Furthermore, several earlier studies have also indicated that antivirals significantly reduced the viral infection in treated individuals. Therefore, the advent of effective antiviral drugs can prevent onward transmission as well as a serious disease in treated individuals.

A new study published in the pre-print server medRxiv* used an agent-based mathematical model to evaluate potential population impact on the widespread use of antiviral treatment for reducing viral load and hospitalization risk.

The study

The study included a previously developed agent-based transmission model, COVASIM. It stimulated SARS-CoV-2 transmission, vaccination, and interventions where each individual in the model in the population is modeled as an agent in a network with 500,000 agents. It involved a similar population size from four countries, the United States, Kenya, Mexico, and Belgium. The duration of the study was six months.

Furthermore, the model has four possible contact layers: home, work, school, and community. The model uses location-specific demographics and household sizes for each country. The use of antiviral treatment was also modeled.

The study included certain assumptions. First, the antiviral treatment would be deployed only under a variant similar to the Delta variant. Second, children were less likely to develop symptoms than adults but equally likely to get infected. Third, asymptomatic individuals were 30 percent less infectious as compared to symptomatic adults. Fourth, 40 percent of the population was already infected and immune for the duration of the study.

Moreover, the individuals in the network could be symptomatic, asymptomatic, presymptomatic, exposed, and susceptible at any given time. Symptomatic individuals can develop either mild, severe, or critical infections. Also, a leaky vaccination was considered, where the vaccines either reduced the probability of getting infected with SARS-CoV-2, reduced the probability of developing symptoms after getting infected, or reduced the probability of hospitalization upon infection.

Study findings

The result indicated that the use of antiviral treatment could avert a large number of deaths. It was observed that with 100 percent of the population with symptomatic infection using antiviral treatments, 59, 80, 82, and 90 percent fewer deaths were reported in Kenya, Mexico, the US, and Belgium, respectively. Even a modest coverage of 20 percent led to more than a third reduction in all the countries.

The result of the current study also found a synergy between vaccination and antiviral treatment. A major impact of antiviral treatment in the aversion of infection was not observed in Kenya as it had a very low vaccine coverage. However, for the other countries with high to moderate vaccination, infection aversion was over 50 percent.

The analysis of the difference between the early and late treatment of symptomatic infections showed that at low antiviral coverage, there was almost no difference between the two treatments. However, at moderate or high antiviral coverage, the early treatment was more important as it resulted in a higher aversion of infections. The antiviral treatment also averted hospitalization of more than 80 percent of individuals with symptomatic infection.

Therefore, the current study results indicated that antiviral treatments can serve as an extremely important tool in reducing mortality due to COVID-19. However, these treatments cannot be a substitute for vaccines. All countries around the world should focus on the implementation of higher rates of vaccination so that the use of antiviral treatment and vaccination can have a greater impact on reducing COVID-19 transmission.

Limitations

The study is subjected to certain limitations. First, the study did not consider the development of antiviral resistance, which is possible if antiviral treatments are used widely. Second, the study did not explore asymptomatic infections or prophylaxis. Third, waning immunity was not considered in the study. Finally, several assumptions in the study might be incorrect.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Suchandrima Bhowmik

Suchandrima has a Bachelor of Science (B.Sc.) degree in Microbiology and a Master of Science (M.Sc.) degree in Microbiology from the University of Calcutta, India. The study of health and diseases was always very important to her. In addition to Microbiology, she also gained extensive knowledge in Biochemistry, Immunology, Medical Microbiology, Metabolism, and Biotechnology as part of her master's degree.