Infections
Acute respiratory infections (ARIs) are common among military personnel and their beneficiaries, imposing considerable morbidity. The occurrence of ARI outbreaks also reduces operational readiness from diminished job performance and lost training days.
Studies conducted through the ARI Research Area are focused on improving the detection, prediction, treatment, and prevention of high-priority respiratory pathogens (e.g., SARS-CoV-2, influenza, and adenovirus) and emerging respiratory threats to maintain Force Health Protection.
The Epidemiology and Prevention of ARIs at the U.S. Naval Academy (ARIA) study, led by Dr. Rhonda Colombo, assessed the epidemiology of medically-attended ARIs at the U.S. Naval Academy (USNA), including predictors of viral co-infections, time spent sick-in-quarters, and complications. Use of sequencing from residual, self-collected test swabs suggest that this method may be used to support detection of respiratory pathogens when conventional molecular diagnostic assays are negative. Examination of real-world ARI management practice patterns indicated that antiviral and non-pharmaceutical countermeasures appeared effective at mitigating influenza outbreaks at USNA.
Led by Dr. David Tribble, the Military COVID-19 Registry Analysis Project (M-RAP) refined electronic medical record-based probability tiers of COVID-19 diagnoses, resulting in enhanced capability to more accurately estimate the incidence of respiratory infectious disease. In addition, M-RAP analyses examined the incidence and risk factors of post-COVID-19 dysautonomia in Military Health System (MHS) beneficiaries and are evaluating changes in healthcare utilization during the COVID-19 pandemic. Efforts continue to identify demographic, clinical, and other predictors of post-COVID-19 illness and similar analyses focused on other ARIs are planned. The M-RAP framework is now being applied to influenza, including use of artificial intelligence-enabled analysis methods to support infection prediction and mitigation.
The objective of the open-label, randomized Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) clinical trial, led by CAPT (retired) Timothy Burgess, was to evaluate the relative effectiveness of three licensed inactivated influenza vaccine formulations (i.e., egg-based, cell-culture-based, and recombinant) across four influenza seasons and inform influenza vaccine recommendations within the MHS. During the past year, data from influenza antibody seroconversion assays collected through PAIVED were used to detect the frequency of occult/undiagnosed influenza infections in vaccinated active-duty service members (ADSMs) and MHS beneficiaries. Assessment of serum from participants in the PAIVED immunogenicity substudy showed that neuraminidase-inhibiting antibody responses elicited by influenza vaccines did not correlate with hemagglutinin-specific neutralizing antibody responses, suggesting further studies are needed to determine the impact of neuraminidase immunity on influenza vaccine effectiveness.
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 ADSMs and MHS beneficiaries. Led by Dr. Simon Pollett, an online extension survey collected data from more than 2,000 MHS beneficiaries on their perceptions about Long COVID in the MHS, as well as measuring the impact of COVID-19 on military travel, mandatory fitness scores, and long-term cognitive and mental health symptoms. Collaborative cross-study analyses with the Department of Veterans Affairs (VA) are examining risk factors for Long COVID in Department of War (DOW) and VA cohorts and the methodology may be applied to other infectious disease threats. Additional analyses assessed predictors of acute and post-acute COVID-19 complications, including the impact of SARS-CoV-2 on military fitness. Findings from EPICC continue to inform potential future Long COVID treatment strategies through bedside-to-bench laboratory studies, including transcriptomic gene expression analyses.
To support the advancement of DOW surveillance capabilities, the Prospective Assessment of SARS-CoV-2 Seroconversion (PASS) study has evaluated the prevalence of multiple ARI pathogens via a high-throughput, low-volume serological platform and is estimating the protective effect of non-pharmaceutical interventions targeted toward other ARIs on COVID-19. In collaboration with the U.S. Military HIV Research Program, analyses of B-cell biology are being conducted to support identification of pan-SARS-CoV-2 monoclonal antibodies. Data collected through PASS are also being used to evaluate vaccine immune escape for emerging variants in partnership with researchers from the U.S. Food and Drug Administration and assess mechanisms of vaccine-elicited immunity in collaboration with the University of Pennsylvania.
In 2025, the ARI Repository Protocol completed the pooling of specimens and clinical cohort data across multiple IDCRP ARI-related protocols. A pathway was also established to connect this protocol to the National Institute of Allergy and Infectious Diseases Vaccine Research Center B-cell sequencing pipeline to support broader opportunities for therapeutic monoclonal antibody development across multiple ARI pathogens. Another new protocol is the Comparative Immunogenicity of Respiratory Virus Vaccines (CIRV2), which is a Phase IV clinical trial study platform, supported by the Centers for Disease Control and Prevention, to examine differences in immunogenicity and reactogenicity between licensed vaccines. While the protocol will focus on mRNA and recombinant COVID-19 vaccines, it may examine other licensed ARI vaccines in the future.
For 2026, the final epidemiologic and laboratory analyses under the PASS, PAIVED, EPICC, and ARIA studies will be completed. A new platform protocol to examine pathogen agnostic countermeasures for outpatient ARIs is planned. Discussions are underway to expand M-RAP beyond respiratory pathogens to support surveillance, prediction, prevention, and mitigation of a broad-range of high-consequence pathogens. The ARI Research Area will also merge with the HIV/Sexually-Transmitted Infections Research Area in the coming year.
Military Impact
Findings from EPICC, PASS, and M-RAP continue to advance the understanding of ARI detection, prediction, treatment, and prevention with the goal of mitigating readiness loss in ADSMs. While surveillance was ongoing, monthly findings from ARIA were shared with leadership at the Naval Health Clinic Annapolis and the Armed Forces Health Surveillance Division (AFHSD) Global Emerging Infections Surveillance (GEIS) program, including the epidemiology and phylogeny data for an influenza outbreak that occurred at USNA during 2025. Moreover, ARIA’s collaboration with wastewater investigators at USNA also informed GEIS’ biosurveillance efforts. Investigators with M-RAP continue to engage with the Joint Trauma System with plans to broaden the focus of M-RAP to support other high-priority infectious disease surveillance and analytics. Findings from PAIVED may help guide policy decisions regarding optimal vaccine formulations for use in the DOW to support Force Health Protection.