Estimating the Causal Effects of Interventions for Covid-19 Prevention

Abstract

The Coronavirus Disease 2019 (Covid-19) global pandemic has led to 6.9 million deaths worldwide as of May 3, 2023. It is caused by coronavirus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) that was first identified in December 2019 in Wuhan, China. In the US, the first case of Covid-19 unrelated to travel was reported in February 2020, and by May 8, 2023, there has been 1.1 million reported Covid-19 deaths and over 104.6 million total cases. In this dissertation, we present three research projects in estimating the causal effects of antivirals and vaccine interventions for Covid-19 prevention, using nationwide data from the Department of Veterans Affairs, the largest integrated health care system in the U.S. In Chapter 1, we explore the repurposing potential of tenofovir disoproxil fumarate for prevention of Covid-19 outcomes in men with HIV. We find TDF/FTC is associated with a 35% lower risk for documented SARS-CoV-2 infection, and 57% lower risk for Covid-19 hospitalization in over 20,000 men with HIV, which suggests that in men living with HIV, TDF/FTC may provide protection against Covid-19-related events. In Chapter 2, we use Covid-19 vaccine effectiveness as an example to quantitatively compare the test-negative design and cohort design with explicit target trial emulation. We find similar estimated effectiveness under a cohort design with explicit emulation of target trial, case-control sampling of the cohort, case-control sampling with restriction to person-days with a test, and after applying additional features of a test-negative design in this particular context, where unmeasured confounding may be limited. In Chapter 3, we apply the methodological framework developed in Chapter 2 to a new question of seasonal influenza vaccination and Covid-19, to explore the reported lower Covid-19 risks among influenza vaccinated individuals in the literature. Our findings under a cohort design with explicit target trial emulation suggest that influenza vaccination does not influence Covid-19 outcomes, and the previously reported implausible estimates may be attributed to deviations from an adequate target trial emulation.