Infections
Rates of acute respiratory infections (ARIs) and associated outbreaks among military personnel and their beneficiaries can result in substantial morbidity, as well as decreased operational readiness from reduced job performance and lost training days.
The overarching aim of the ARI Research Area is to improve the detection, prediction, treatment, and prevention of high-priority respiratory pathogens (e.g., SARS-CoV-2, influenza, and adenovirus), as well as emerging respiratory threats, to maintain Force Health Protection.
Led by Dr. Rhonda Colombo, the Epidemiology and Prevention of ARIs at the U.S. Naval Academy (ARIA) study characterizes the epidemiology of respiratory viruses causing medically-attended ARIs in this training environment using enhanced virologic testing of residual clinical swabs combined with clinical data. During 2024, analyses examined risk factors associated with training time lost due to ARIs (e.g., infecting pathogens and coinfections), and explored ARI incidence and characteristics during specific training periods (e.g., Plebe Summer). Analysis is underway to provide clinical context to wastewater surveillance sequencing efforts being conducted by collaborators at the U.S. Naval Academy. Moreover, comprehensive analyses of influenza cases examined whether partial influenza vaccine mismatch contributed to influenza clusters. Advanced machine learning approaches to more precisely define ARI symptom patterns are underway.
To inform recommendations for influenza vaccinations within the Military Health System (MHS), the open-label, randomized Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) clinical trial evaluated the relative effectiveness of three licensed inactivated influenza vaccine formulations (i.e., egg-based, cell-culture-based, and recombinant) across four influenza seasons. Led by CAPT (retired) Timothy Burgess, data collected through PAIVED are being used to characterize influenza-like-illness in MHS beneficiaries with a focus on patient-reported outcomes, including risk factors for severe symptoms (e.g., smoking and obesity). In-depth comparison of influenza-like-illness experiences in healthcare workers versus non-healthcare workers was completed. Serum from participants in the PAIVED immunogenicity substudy were used to compare neuraminidase inhibiting antibody responses elicited by egg and cell-derived influenza vaccines.
Led by Dr. Simon Pollett, the Epidemiology, Immunology and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is an observational cohort study of SARS-CoV-2 infections in active-duty service members and MHS beneficiaries. During 2024, an online survey was implemented with questions related to perceptions about MHS beneficiaries seeking ARI diagnostic testing and healthcare. Assessment of the contribution of SARS-CoV-2 T-cell specificity to acute severe COVID-19 was completed, and findings may support next-generation COVID-19 vaccines with increased T-cell specificity. Characterization of Long COVID has been a major focus with analyses on the impact of SARS-CoV-2 on sleep, herpes-zoster risk, and ocular health. In collaboration with the Department of Veterans Affairs (VA), risk factors for Long COVID-19 are being compared in a DoD/VA cross-cohort analysis. Predictors of acute COVID-19 severity (e.g., type 2 diabetes), and proteomic, autoimmune, and transcriptomic markers of acute SARS-CoV-2 myocarditis were assessed. Findings from EPICC also contributed to an international study validating use of lung ultrasound for COVID-19 prognostication.
The Military COVID-19 Registry Analysis Project (M-RAP), led by Dr. David Tribble, refined evidence-based surveillance for COVID-19 diagnoses among active-duty personnel using electronic medical records, creating a framework that can be applied to other respiratory pathogens. COVID-19 incidence over a 30-month period have been compared to regional incidence trends, demonstrating how MHS data can augment national surveillance. Current analyses are examining specific post-COVID-19 neurological complications and the impact of the pandemic on healthcare utilization. A new protocol activated in 2024 is the ARI Repository Protocol, which is compiling specimens and clinical cohort data across multiple IDCRP ARI-related protocols. The repository will enable future respiratory virus pandemic research response (e.g., rapid diagnostic design). The first analysis under this new protocol will compare COVID-19 and other respiratory virus sequelae using data collected from EPICC and PAIVED.
For 2025, a new observational pandemic contingency protocol is being developed that can be tailored to various new ARI pandemics once activated. A follow-on study to the PASS protocol, with a broader pathogen focus to identify infection-resilient hosts, is also planned. A new EPICC follow-up questionnaire will examine the impact of COVID-19 on military travel, association between repeat infections and Long COVID risk, and participant perceptions on receiving MHS care for Long COVID. The EPICC study will collect existing fitness test data from active-duty participants to identify predictors of fitness loss after SARS-CoV-2 infection. Long COVID-19 biomarker analyses will continue to examine associations with clinical outcomes, with possible utility for Long COVID risk prediction and therapeutic development.
Military Impact
Findings from EPICC, PASS, and M-RAP continue to offer insights into the detection, prediction, treatment, prevention, and functional illness outcomes of COVID-19, as well as other ARIs. Epidemiologic and surveillance findings from ARIA, including phenotypic and phylogeny data for an influenza A/H3N2 outbreak at the U.S. Naval Academy in 2024, were shared with leadership at the Naval Health Clinic Annapolis and the Armed Forces Health Surveillance Division (AFHSD). A report to the Congressional Defense Committees on Long COVID cited findings from EPICC. Moreover, data from ARIA on influenza strains were provided to the U.S. Food and Drug Administration (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) to support decision making. Immunological findings from EPICC and PASS were also provided to the FDA VRBPAC to support vaccine booster decision-making and immunologic findings from EPICC were used to validate animal models to support future COVID-19 vaccine selection methodology. Findings from PAIVED may help guide policy decisions regarding ideal vaccine formulations for use in the DoD to support Force Health Protection.