Long COVID in the active component US military: Risk factors, effect of vaccination, and predicting incident long COVID diagnoses

Abstract: Background: Long COVID risk factors have been established in civilian populations, including female sex, older age, smoking, and certain comorbidities. However, little research has been conducted on risk in the U.S. military.Objective: To identify the rate of and risk factors for long COVID in the U.S. military.Design: Retrospective cohort studySetting: Military Health SystemPatients: 464,356 active component U.S. servicemembers with confirmed COVID-19 between January 1, 2020, and December 31, 2022.Measurement: Incidence of long COVID was measured and demographic, COVID-19 infection, and comorbidity characteristics were assessed as risk factors using Poisson regression.Results: 104,024 servicemembers developed long COVID (70.4 cases per 100,000 person-days of follow-up). Male sex (CIR, 0.72; 95% CI, 0.71 to 0.73), age ≥45 (CIR, 1.45; 95% CI, 1.39 to 1.52), non-Hispanic Black race (CIR, 1.11; 95% CI, 1.08 to 1.15), symptomatic COVID-19 infection (CIR, 1.04; 95% CI, 1.03 to 1.06), COVID-19 hospitalization (CIR, 1.25; 95% CI, 1.18 to 1.31), COVID-19 re-infection (CIR, 1.11; 95% CI, 1.08 to 1.13), vaccination against COVID-19 (CIR, 0.95; 95% CI, 0.93 to 0.98), antiviral treatment for COVID-19 (CIR, 0.82; 95% CI, 0.72 to 0.93), and any comorbidity (CIR, 1.22; 95% CI, 1.19 to 1.25) were significantly associated with incidence of long COVID.Limitation: Risk factors were assessed only through 2022, precluding investigation into more recent treatments, vaccines, and variants.Conclusions: Despite being a younger and healthier population, incidence of long COVID was high in U.S. servicemembers. Similar risk factors were observed compared to the general population, including female sex, increased age, comorbidities, and being unvaccinated against COVID-19. Additionally, characteristics of the infection, such as reinfection, symptoms, and hospitalization were associated with long COVID.Analysis 2Objective: To identify whether COVID-19 vaccination and time since last dose impact the risk of long COVID in the U.S. militaryMethods: Incidence of long COVID was measured in a cohort of active component U.S. service members with confirmed COVID-19 between January 1, 2020, and December 31, 2022. COVID-19 vaccination and length of time since last vaccine dose were assessed as risk factors for long COVID using Cox proportional hazards regression with a step function for follow-up periods.Results: Of 464,356 servicemembers with a confirmed COVID-19 event, 104,024 (22.4%) servicemembers developed long COVID within one year of follow-up. Being partially or fully vaccinated (aHR, 0.96; 95% CI, 0.94 to 0.98) and receipt of one or more booster doses (aHR, 0.91; 95% CI, 0.88 to 0.94) prior to the COVID-19 event were associated with lower rates of long COVID compared to those who were unvaccinated. The protective effect was strongest for those whose most recent dose was within 3 months of the COVID-19 event (aHR, 0.94; 95% CI, 0.91 to 0.97). However, significant reductions in long COVID risk were only seen for the first 3 months of follow-up, with nonsignificant differences between vaccinated and unvaccinated groups for the remainder of the follow-up period. Neurological (4 months of follow-up) and respiratory (7 months of follow-up) symptoms showed significant decreases in diagnoses for vaccinated servicemembers vs unvaccinated for a longer duration compared to the overall long COVID outcome.Conclusions: Vaccination against COVID-19 appears to provide modest reductions in risk of long COVID, and benefits for those vaccinated closer to their COVID-19 event may be even greater. However, the effect of vaccination on long COVID risk may wane over time, with the greatest reduction in risk in the first 3 months after infection. Protection against individual diagnostic groups, like neurological and respiratory diagnoses, may be longer.Analysis 3Long COVID represents a potentially serious threat to military readiness. Forecasts of future long COVID diagnoses could help prepare senior leaders for disruptions. However, few studies predicting long COVID have been published to date. Using existing COVID-19 and long COVID diagnoses, as well as demographic and outpatient encounter data, 1- to 6-month ahead and full 6-month forecasts were generated using time series and machine learning models trained on various covariate data. Forecasting models generated accurate predictions of long COVID diagnoses up to 6 months ahead of the forecasted date. Several model and covariate combinations were within 5% of the observed number of diagnoses over the full 6 month testing period, and monthly forecasts of long COVID diagnoses had MAPE ranging from 3-10% for the best performing model combinations. Simple forecasting models and distribution-based forecasts that utilize existing clinical databases can provide accurate predictions of long COVID up to 6 months in advance and can be used to prepare for the burden of new long COVID diagnoses.