Objectives:

This study will be completed in two phases. In the first phase, the investigators will
establish a source population and comprehensively describe the temporal and geographic
utilization of COVID-19 pharmacotherapies beginning July 2021. These therapies include
casirivimab and imdevimab, bamlanivimab and etesevimab, sotrovimab, nirmatrelvir,
molnupiravir, and remdesivir. The investigators will also compare demographic and
clinical characteristics of Veterans who are treated or do not receive these therapies.
Phase 1 will inform the study design and analytic protocol of Phase 2. Phase 1 will also
inform critical policy questions and national guidance regarding COVID-19
pharmacotherapies in the VA healthcare system with the potential to inform policy across
other healthcare systems.

In the second phase, the investigators will conduct target trial emulation studies to
determine the effectiveness and comparative effectiveness of current pharmacotherapies
for COVID-19 in preventing short- and long-term adverse outcomes related to SARS-CoV-2
infection. The investigators will use a sequence of comparative effectiveness studies
through emulation to help establish a common framework sharing a similar population,
design, and outcomes for a rapid-response, adaptive observational study design to
characterize utilization and determine the effectiveness and comparative effectiveness of
novel therapeutic agents authorized for the treatment of mild to moderate COVID-19 in
Veterans. Phase 2 will provide an infrastructure upon which subsequent observational
studies can be performed, which will include other infectious diseases of interest,
ultimately ensuring the timeliness and pertinence of VA research.

Research Design and Methodology:

In the first phase, the investigators will conduct a descriptive, retrospective,
electronic health record-based study among Veterans aged 18 years with a
laboratory-confirmed positive test for SARS-CoV-2 or a diagnosis of COVID-19 documented
at any time since the beginning of the pandemic in January 2020 to present. The
investigators will describe the geographic distribution (by VISN, state, and distance
from place of residence to the closest VAMC and/ COVID-19 infusion facilities) of
Veterans receiving each of the COVID-19 antiviral and monoclonal antibody therapies
during different periods of SARS-CoV-2 variant circulation (i.e., January 1, 2022, to
present for Omicron). The investigators will also compare baseline demographic
characteristics, clinical characteristics including underlying medical conditions and
prior SARS-CoV-2 infections, SARS-CoV-2 vaccination status, National Institutes of Health
(NIH) risk group tiers for prioritization of treatments, concurrent outpatient
medications, and time from positive test to treatment among Veterans receiving different
antiviral and monoclonal antibody therapies as well as eligible Veterans who are not
treated during different periods of SARS-CoV-2 variant circulation. This established
framework will also be used to identify Veterans who tested positive for other
respiratory viruses, including influenza virus or respiratory syncytial virus (RSV), and
other infectious diseases in the same time period and describe their characteristics,
risk factors and treatments.

In the second phase, the investigators will conduct retrospective and prospective target
trial emulation studies to evaluate the effectiveness and comparative effectiveness of
different pharmacotherapies for mild-to-moderate COVID-19 in patients with documented
SARS-CoV-2 infection by period of predominant SARS-CoV-2 variant circulation. The
established framework will be used to investigate vaccine and pharmacotherapy
effectiveness for SARS-CoV-2 and other respiratory viruses, including influenza and
respiratory syncytial virus (RSV) and other infectious diseases using observational data
from the VHA electronic health records.

Impact Significance:

Data on real-world utilization and clinical outcomes in the Veteran population are needed
to inform clinical, operational and research partners in the VA and other healthcare
systems on strategies for optimizing the utilization of pharmacotherapies and vaccines
against COVID-19 and other infectious diseases. Ongoing evaluations will be essential as
new variants emerge, vaccination practices evolve, and new pharmacotherapies are
introduced. This study will establish a common framework sharing a similar population,
design, and outcomes for a rapid-response, adaptive platform observational study design
to characterize utilization and determine the effectiveness and comparative effectiveness
of novel therapeutic agents authorized for the treatment of mild to moderate COVID-19,
respiratory viruses, including RSV and influenza, and other infectious diseases in
Veterans.