Recruiting

Observational Study

Sponsor:

VA Office of Research and Development

Code:

NCT06160128

Conditions

COVID-19, SARS-CoV-2 Infection

RSV

Influenza

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Accepted

Study Details

Brief summary:

The purpose of this study is to comprehensively describe the temporal and geographic utilization of COVID-19 therapies used for mild to moderate disease during different periods of SARS-CoV-2 variant circulation as well as to compare demographic and clinical characteristics of Veterans who are treated or do not receive these different therapies. The investigators will also perform similar descriptive epidemiology for other respiratory viruses, including RSV and influenza and other infectious diseases. This first phase will critically inform feasibility and direction of the second phase, in which the investigators will use target trial emulation design to study the comparative effectiveness of therapies and vaccines for COVID-19, respiratory viruses, including RSV, and influenza, and other infectious diseases.

Conditions

COVID-19, SARS-CoV-2 Infection

RSV

Influenza

Study ID

NCT06160128

Start date

Sep 26, 2022

Status verified date

Aug, 2026

Completion date

Sep 30, 2027

Anticipated

Primary completion date

Sep 30, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Accepted

Inclusion Criteria:

Phase 1:

\- Veterans 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

Phase 2:

  • All Veterans alive and in VHA care as of January 2018
  • Specific exclusion/inclusion criteria and observation periods will be further defined for each sub-study (See outcomes/publications)

Exclusion Criteria:

  • VA employees who are not enrollees

Study Design

Enrollment

400000 participants

Anticipated

Interventions and Outcome Measures

Arms

Outpatient Veterans with risk factors for severe COVID-19 & tested positive during Jan-Feb 2022

This cohort study assessed outpatient Veterans with risk factors for severe COVID-19 who tested positive for SARS-CoV-2 during January and February 2022.

The purpose is to describe factors associated with receipt of outpatient COVID-19 pharmacotherapies in the Veterans Affairs (VA) health care system.

Nonhospitalized Veterans in VHA at risk for SARS-CoV-2 Jan-Jul 2022

Three retrospective target trial emulation studies comparing matched cohorts of nirmatrelvir-ritonavir versus no treatment, molnupiravir versus no treatment, and nirmatrelvir- ritonavir versus molnupiravir.

The purpose is to measure the effectiveness of nirmatrelvir-ritonavir and molnupiravir for outpatient treatment of COVID-19.

Outpatient Veterans who tested positive for SARS-CoV-2 from Jan 2022 through Jan 2023

This cohort study evaluated nonhospitalized Veterans in VHA care who tested positive for SARS-CoV-2 from January 2022 through January 2023 using VHA and linked Community Care and Medicare databases.

The purpose is to analyze trends and factors associated with prescription of outpatient COVID-19 pharmacotherapies within the Veterans Health Administration (VHA).

Outpatient Veterans with risk factors for severe COVID-19 & tested positive during Jan-Jul 2022

Retrospective target trial emulation study comparing matched cohorts receiving nirmatrelvir-ritonavir versus no treatment.

The purpose is to measure the effectiveness of outpatient treatment of COVID-19 with nirmatrelvir-ritonavir in preventing Post COVID conditions.

Primary outcome measure

  • Receipt of any COVID-19 pharmacotherapy, including sotrovimab, nirmatrelvir boosted with ritonavir, molnupiravir, or remdesivir [ Time Frame: January and February 2022 ]
  • Incidence of any hospitalization or all-cause mortality at 30 days and from 31 to 180 days [ Time Frame: January through July 2022 ]
  • Monthly receipt of any COVID-19 pharmacotherapy (nirmatrelvir-ritonavir, molnupiravir, sotrovimab, or bebtelovimab) [ Time Frame: January 2022 through January 2023 ]
  • Cumulative incidence of 31 potential PCCs at 31 -180 days after treatment or a matched index date, including cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, endocrine, and general conditions [ Time Frame: January through July 2022 ]
  • Incidence of any hospitalization or all-cause mortality at 30 days [ Time Frame: April 2022 through March 2023 ]
  • Prediction of 30-day COVID-19 hospitalization and death in the Omicron era for contemporary clinical and research applications [ Time Frame: March 1, 2022, and March 31, 2023 ]
  • RSVPreF3 or RSVpreF vaccination compared with no respiratory syncytial virus (RSV) vaccination for the prevention of documented RSV infection and associated health-care use among Veterans [ Time Frame: March 1, 2022, and March 31, 2023 ]
  • compare disease severity of COVID-19, influenza, and RSV among US Veterans [ Time Frame: August 1, 2022, and March 31, 2023, or between August 1, 2023, and March 31, 2024. ]
  • Determine XBB.1.5 COVID-19 vaccine effectiveness (VE) and the extent to which it declines over time [ Time Frame: October 2,2023- January 3, 2024 ]
  • Determine if severe SARS-CoV-2 infection increases risk of selected PCCs or death up to 1 year after infection in wild-type (WT), Alpha-transition, Delta, and Omicron eras [ Time Frame: March 2020 and April 2022 ]
  • Determined budget cost of providing nirmatrelvir-ritonavir to Veterans with COVID-19 on 30-day healthcare costs to inform procurement strategies in large healthcare systems [ Time Frame: April 2022 through March 2023 ]
  • Evaluate the impact of different time zero designations on results and inferences from a cohort study comparing the effectiveness of nirmatrelvir ritonavir treatment versus no COVID-19 antiviral treatment in preventing 30-day hospitalization and death [ Time Frame: April 2022-March 2023 ]
  • Asses the long-term effectiveness of a single respiratory syncytial virus (RSV) vaccine dose against RSV illness and associated health care use [ Time Frame: September 2023 to March 2024. ]
  • Estimate the long-term vaccine effectiveness (VE) of the 2024-2025 COVID-19 vaccines targeting the KP.2 Omicron variant within the Veterans Health Administration [ Time Frame: August 1, 2024- April 12, 2025 ]
  • Compared treatment with oseltamivir versus no antiviral treatment within 6 hours of a positive influenza test [ Time Frame: 1 October 2022-31 January 2023; 1 December 2023-31 March 2024 ]
  • Calculated cumulative incidence, risk differences (RDs), and risk ratios (RR) for hospitalization and intensive care unit (ICU) admission at 10 days [ Time Frame: 1 October 2022-31 January 2023; 1 December 2023-31 March 2024 ]
  • Calculated cumulative incidence, risk differences (RDs), and risk ratios (RR) for hospitalization and intensive care unit (ICU) admission at death at 30 days [ Time Frame: 1 October 2022-31 January 2023; 1 December 2023-31 March 2024 ]

Central Contacts and Locations

Central contacts

Kristina L Bajema, MD

(503) 220-8262Kristina.Bajema@va.gov

George N Ioannou, MD MS

(206) 277-3136George.Ioannou@va.gov

Locations

VA Portland Health Care System, Portland, OR

Recruiting

Portland, Oregon, United States, 97207-2964

Contacts

Kristina L Bajema, MD

(503) 220-8262Kristina.Bajema@va.gov

George N Ioannou, MD MS

(206) 277-3136George.Ioannou@va.gov

More Information

Sponsor

VA Office of Research and Development

Last update posted

Sep 4, 2026

Last verified

Aug, 2026

Keywords

  • COVID-19
  • pharmacotherapy effectiveness
  • SARS-CoV-2
  • antiviral
  • RSV
  • influenza
  • respiratory viruses

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2026-09-04.