Effectiveness of mRNA-1273, BNT162b2, and JNJ-78436735 COVID-19 Vaccines Among US Military Personnel Before and During the Predominance of the Delta Variant.

Importance: No studies to date have evaluated the effectiveness of 3 COVID-19 vaccines in the US military population, especially during the circulation of the SARS-CoV-2 Delta (B.1.617.2) variant. Objective: To estimate the effectiveness of the mRNA-1273, BNT162b2, and JNJ-78436735 vaccines among US military personnel before and during the predominance of the Delta variant in the US. Design, Setting, and Participants: This case-control study was conducted among all unvaccinated and fully vaccinated US military personnel who had a documented SARS-CoV-2 test performed in the US between January 1 and September 24, 2021. Individuals were identified using Department of Defense (DOD) electronic medical, laboratory, and surveillance databases. The pre-Delta period was defined as January 1 to May 31, 2021, and the Delta period as June 19 to September 24, 2021. Case individuals were defined by a positive polymerase chain reaction SARS-CoV-2 test result or a positive antigen test result with symptoms. Control individuals had at least 1 negative SARS-CoV-2 test result. Exposures: COVID-19 vaccination with the mRNA-1273, BNT162b2, or JNJ-78436735 vaccine, assessed from DOD electronic vaccination records. Main Outcomes and Measures: COVID-19 vaccine effectiveness overall, by vaccine type, and by outcome stratified by the pre-Delta and Delta periods in the US. Vaccine effectiveness was estimated as 100 × (1 - odds ratio) in a logistic regression model with adjustment for potential confounders. Results: The cohort included 441 379 individuals, with 290 256 in the pre-Delta period (236 555 [81%] male; median age, 25 years [range, 17-68 years]) and 151 123 in the Delta period (120 536 [80%] male; median age, 26 years [range, 17-70 years]). Adjusted vaccine effectiveness of all vaccines was significantly higher during the pre-Delta period (89.2%; 95% CI, 88.1%-90.1%) compared with the Delta period (70.2%; 95% CI, 69.3%-71.1%) for all outcomes, an overall decrease of 19%. mRNA-1273 vaccine effectiveness was highest in the pre-Delta (93.5%; 95% CI, 91.9%-94.7%) and Delta (79.4%; 95% CI, 78.3%-80.4%) periods for all outcomes, whereas the JNJ-78436735 vaccine had the lowest effectiveness during the pre-Delta (81.8%; 95% CI, 74.2%- 87.1%) and Delta (38.3%; 95% CI, 34.5%-41.9%) periods. Effectiveness for all vaccines during both periods was higher for symptomatic infection and hospitalization among individuals with SARS-CoV-2 infection. Conclusions and Relevance: In this case-control study, among US military personnel, COVID-19 vaccine effectiveness was significantly lower during the period when the Delta variant predominated compared with the period before Delta variant predominance; this was especially true for the JNJ-78436735 vaccine. These findings were confounded by time since vaccination; this and the change in effectiveness support the need for booster doses and continued evaluation of vaccine effectiveness as new variants of SARS-CoV-2 emerge.

COVID-19 and depressive symptoms among active component U.S. service members, January 2019-July 2021.

This study examined the rates of depressive symptoms in active component U.S. service members prior to and during the COVID-19 pandemic and evaluated whether SARS-CoV-2 test results (positive or negative) were associated with self-reported depressive symptoms. Depressive symptoms were measured by the Patient Health Questionnaire-2 (PHQ-2) screening instrument and were defined as positive if the total score was 3 or greater. From 1 January 2019 through 31 July 2021, 2,313,825 PHQ-2s were completed with an increase in the positive rate from 4.0% to 6.5% (absolute % difference, +2.5%; relative % change, +67.1%) from the beginning to the end of the period. While there was a gradual increase of 19.8% in the months prior to the pandemic (1.4%/month average), this increase grew to 40.4% during the pandemic (2.5%/month average). However, no association was found between a positive or negative SARS-CoV-2 test result and the PHQ-2 screening instrument result. These findings suggest that the accelerated increase in depressive symptoms is likely a function of the environment of the COVID-19 pandemic instead of the SARS-CoV-2 infection itself. Further research to better understand specific factors of the pandemic leading to depressive symptoms will improve efficient allocation of military medical resources and safeguard military medical readiness.

Update: Osteoarthritis and Spondylosis, Active Component, U.S. Armed Forces, 2016-2020.

Osteoarthritis (OA) is the most common adult joint disease and accounts for significant morbidity burdens among U.S. civilian and military populations. During 2016-2020, the crude overall rates of incident OA and spondylosis diagnoses among U.S. active component service members were 630.9 per 100,000 person-years (p-yrs) and 958.2 per 100,000 p-yrs, respectively. Crude annual rates of both conditions decreased markedly from 2016 through 2020 with declines evident in all of the demographic and military subgroups examined. Compared to their respective counterparts, crude overall rates of OA diagnoses were highest among male service members, those aged 35 or older, non-Hispanic Black service members, Army members, and those working in health care occupations. Crude overall rates of spondylosis diagnoses were highest among those aged 30 or older, non-Hispanic White and non-Hispanic Black service members, Army members, and those in health care and communications/intelligence occupations. More than two-thirds of all incident OA diagnoses involved the knee (38.8%) or shoulder (28.4%). Differences in anatomic site-specific rates of OA were apparent by sex, race/ethnicity group, service, and military occupation. Additional research to identify military-specific equipment and activities that increase the risk of acute and chronic damage to joints would be useful to develop, test, and implement practical and effective countermeasures against OA and spondylosis among military members in general and those in high-risk occupations specifically.

Acute and chronic pancreatitis, active component, U.S. Armed Forces, 2004-2018.

Pancreatitis is an inflammatory disease of the pancreas resulting from the premature activation of digestive enzymes within the pancreas. Pancreatitis occurs in both acute and chronic forms. During 2004-2018, a total of 6,471 U.S. active component service members received incident diagnoses of acute pancreatitis (AP), for a crude overall incidence rate of 31.8 per 100,000 person- years (p-yrs). Compared to their respective counterparts, overall rates of AP diagnoses were highest among females, those in older age groups, non-Hispanic blacks, Army members, and those working in healthcare occupations. Crude annual rates of AP diagnoses increased by 25.5% over the 15-year period; this trend was driven largely by a rise in outpatient rates. Of the total incident cases of AP, 9.0% received a subsequent incident diagnosis of chronic pancreatitis (CP) during the surveillance period. Between 2004 and 2018, the crude overall incidence rate of CP was 4.4 per 100,000 p-yrs. Patterns of overall rates of CP by demographic and military characteristics were generally similar to those for AP. Crude annual rates of CP fluctuated between 3.7 per 100,000 p-yrs and 5.7 per 100,000 p-yrs during the surveillance period, with no pronounced overall trend over time. To inform preventive and therapeutic strategies, continued research is needed to understand the factors that increase risk of progression from AP to CP and the importance of the interaction between genetic and environmental factors in this transition.

Summary of the 2018-2019 influenza season among Department of Defense service members and other beneficiaries.

The Armed Forces Health Surveillance Branch conducts weekly surveillance of influenza activity among Department of Defense (DoD) populations each influenza season. This report provides a summary of the data from the 2018-2019 influenza season. Ambulatory data for influenza-like illnesses (ILIs), influenza hospitalization data, and lab data for influenza-confirmed cases were used for the surveillance. The 2018-2019 season differed from past seasons in that it was much longer, had a later peak, and the predominant strain of influenza changed from influenza A(H1N1)pdm09 at the beginning of the season to influenza A(H3N2) in the middle of the season. Non-service member beneficiaries accounted for the majority of ILI-related encounters and hospitalizations. However, there were still 149 influenza-related hospitalizations among service members during the 2018- 2019 season. Continued weekly surveillance of influenza among DoD populations is crucial to track increases in activity each season and the potential emergence of new and/or severe influenza subtypes.

Vasectomy and vasectomy reversals, active component, U.S. Armed Forces, 2000-2017.

During 2000-2017, a total of 170,878 active component service members underwent a first-occurring vasectomy, for a crude overall incidence rate of 8.6 cases per 1,000 person-years (p-yrs). The most common operative procedure performed was conventional vasectomy (99.2%), with less than 1% of vasectomies categorized as minimally invasive vasectomy. Among the men who underwent incident vasectomy, 2.2% had another vasectomy performed during the surveillance period. Compared to their respective counterparts, the overall rates of vasectomy were highest among service men aged 30-39 years, non-Hispanic whites, married men, and those in pilot/air crew occupations. Male Air Force members had the highest overall incidence of vasectomy and men in the Marine Corps, the lowest. Crude annual vasectomy rates among service men increased slightly between 2000 and 2017. The largest increases in rates over the 18-year period occurred among service men aged 35-49 years and among men working as pilots/air crew. Among those who underwent vasectomy, 1.8% also had at least 1 vasectomy reversal during the surveillance period. The likelihood of vasectomy reversal decreased with advancing age. Non-Hispanic black and Hispanic service men were more likely than those of other race/ethnicity groups to undergo vasectomy reversals.

Herpes zoster, active component, U.S. Armed Forces, 2000-2016.

During 2000-2016, a total of 52,895 active component service members received incident diagnoses of herpes zoster (HZ), for an overall unadjusted incidence rate of 2.5 cases per 1,000 person-years (p-yrs). Compared to their respective counterparts, overall incidence rates of HZ were highest among females, those aged 50 years or older, and Air Force members. Overall rates generally increased with increasing age and were highest among non-Hispanic whites and Asian/Pacific Islanders and lowest among non-Hispanic blacks. Unadjusted annual incidence rates of HZ increased steadily from 2000 to a peak in 2014. From 2000 through 2016, annual rates of HZ increased in each service and increases in annual rates were seen in all race/ethnicity groups. Individuals who were identified as immunocompromised constituted 2.1% of the total incident HZ cases. During 2000-2016, the cumulative numbers of incident cases of HZ were highest during June, July, and August. The increase in HZ incidence observed in this and many other studies is a public health concern that requires a better understanding of key risk factors. Additional research focused on these factors could make trends more interpretable, suggest new approaches for prevention and treatment of HZ, and allow for better targeting of existing strategies.

Psychiatric medical evacuations in individuals with diagnosed pre-deployment family problems, active component, U.S. Armed Forces, 2002-2014.

This study evaluated incidence of pre-deployment family problem diagnoses and psychiatric medical evacuations among a population of active component service members without a history of previous mental health diagnoses, who deployed to the U.S. Central Command Area of Responsibility for the first time between 1 January 2002 and 31 December 2014. During the surveillance period, 6,182 service members received an incident family problems diagnosis during the pre-deployment period, with an overall incidence of 5.6 cases per 1,000 deployers. The incidence of pre-deployment family problem diagnoses was generally stable over the study period. Compared to their respective counterparts, rates of pre-deployment family problems were highest among females, non-Hispanic black service members, those who were married, enlisted service members, and Army members. A total of 2,190 active component service members were evacuated from theater for psychiatric reasons, with an overall incidence rate of 3.1 per 1,000 deployed person-years. Of evacuated service members, 1.7% had diagnosed pre-deployment family problems (N=38). Incidence of psychiatric medical evacuation was consistently higher among those with pre-deployment family problems among all demographic subgroups, and overall was 2.7 times the incidence among those without documented family problems.

Multiple sclerosis among service members of the active and reserve components of the U.S. Armed Forces and among other beneficiaries of the Military Health System, 2007-2016.

During 2007-2016, a total of 2,031 active component service members received incident diagnoses of multiple sclerosis (MS), for an overall unadjusted incidence rate of 14.9 cases per 100,000 p-yrs. The average overall unadjusted rate among reserve/guard members during this surveillance period was 6.9 cases per 100,000 persons. In both components, women had a higher overall incidence of MS than men across all race/ethnicity groups. Overall rates of MS were highest among non-Hispanic black service members. Crude annual incidence rates among active component members decreased slightly during 2007-2016, while rates among reserve/guard members were relatively stable. Among active component members, the annual female-to-male incidence ratios decreased during the 10-year period (3.7:1 in 2007 to 2.5:1 in 2016). Annual numbers of incident cases of MS decreased among non-service member Military Health System beneficiaries during this period. The median age at MS case-defining diagnosis was 32 years among active component members, 37 years among reserve/guard members, and 48 years among non-service member beneficiaries. The median time intervals between initial presentation and case-defining MS-related encounter ranged from 15 days among reserve/guard component members to 20 days among active component service members. This study makes a useful contribution to the literature on temporal changes in the incidence of MS by sex and race/ethnicity.

Rates of Chlamydia trachomatis infections across the deployment cycle, active component, U.S. Armed Forces, 2008-2015.

High rates of sexually transmitted infections (STIs), including Chlamydia trachomatis (CT), have been documented among U.S. military service members. However, it is unknown whether phases of the deployment cycle affect risk for CT. This article characterizes the rates of CT infections during the predeployment, deployment, and post-deployment phases for active component members of the U.S. Army, Navy, Air Force, and Marine Corps during 2008-2015. Cases of CT were defined using laboratory, reportable medical event, and prescription data in a sensitivity analysis approach. Adjusted incidence rate ratios for CT were calculated using a multivariable Poisson model. In these analyses, the crude and adjusted incidence rates of CT were found to be highest during the pre-deployment phase for both sexes. However, men's rates of CT differed only slightly across pre-, post-, and non-deployed phases, while women had substantial rate differences between phases. These analyses call for better screening and documentation of STIs during deployment, as well as continued surveillance of STIs in the Military Health System, to assess the true burden of disease.

Integrated genome-wide analysis of expression quantitative trait loci aids interpretation of genomic association studies.

BACKGROUND: Identification of single nucleotide polymorphisms (SNPs) associated with gene expression levels, known as expression quantitative trait loci (eQTLs), may improve understanding of the functional role of phenotype-associated SNPs in genome-wide association studies (GWAS). The small sample sizes of some previous eQTL studies have limited their statistical power. We conducted an eQTL investigation of microarray-based gene and exon expression levels in whole blood in a cohort of 5257 individuals, exceeding the single cohort size of previous studies by more than a factor of 2. RESULTS: We detected over 19,000 independent lead cis-eQTLs and over 6000 independent lead trans-eQTLs, targeting over 10,000 gene targets (eGenes), with a false discovery rate (FDR) < 5%. Of previously published significant GWAS SNPs, 48% are identified to be significant eQTLs in our study. Some trans-eQTLs point toward novel mechanistic explanations for the association of the SNP with the GWAS-related phenotype. We also identify 59 distinct blocks or clusters of trans-eQTLs, each targeting the expression of sets of six to 229 distinct trans-eGenes. Ten of these sets of target genes are significantly enriched for microRNA targets (FDR < 5%). Many of these clusters are associated in GWAS with multiple phenotypes. CONCLUSIONS: These findings provide insights into the molecular regulatory patterns involved in human physiology and pathophysiology. We illustrate the value of our eQTL database in the context of a recent GWAS meta-analysis of coronary artery disease and provide a list of targeted eGenes for 21 of 58 GWAS loci.

Seizures among active component service members, U.S. Armed Forces,2007-2016.

Traumatic brain injury (TBI) is a known risk factor for seizures. Evidence also shows that post-traumatic stress disorder (PTSD) is associated with seizures, but the relationship in the absence of TBI remains unclear. This retrospective study spanning 2007-2016 separately quantifies the rates of seizures diagnosed among deployed and non-deployed active component military service members to understand the factors associated with seizures and whether they differ in deployed settings. Higher rates of seizures were associated with service members who were in the Army or Marine Corps; female; black; younger; lower enlisted; in a combat-specific, armor/motor transport, or healthcare occupation; and who had no more than one previous deployment. These associations were similar among both deployed and non-deployed service members. Either a TBI or recent PTSD diagnosis was associated with a 3- to 4-fold increased seizure rate. For service members who had received both diagnoses, seizure rates among the deployed and the non-deployed were two and three times the rates among those with only one of those diagnoses, respectively. If the current results are supported by future investigations, there may be implications for both clinical care and military policy.

Fatigue and related comorbidities, active component, U.S. Armed Forces, 2007-2016.

Fatigue is a common complaint in the civilian population and may be a presenting symptom of more serious physical and mental disorders. Data from the Defense Medical Surveillance System (DMSS) were utilized to characterize the incidence and burden of fatigue in active component military members from 1 January 2007 through 31 December 2016. A subanalysis of 3 years within this surveillance period (2012-2014) was also conducted to assess the burden of comorbidities related to incident fatigue and the strength of the association between fatigue and selected comorbidities. The study identified 211,213 incident cases of fatigue with an overall incidence rate of 18.1 per 1,000 person-years between 2007 and 2016. Mental disorders and musculoskeletal disease accounted for about 35% of all medical encounters and about 40% of all hospital days within a year for those diagnosed with fatigue in 2013. The adjusted odds ratio for fatigue was highest in those with male hypogonadism, thyroid disorder, and sleep problems. These results show that fatigue is a common diagnosis with high incidence and burden among active component U.S. military. By focusing on the conditions that frequently occur and are highly associated with fatigue, more rapid diagnosis and treatment of the underlying cause of service member fatigue is possible.

Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations.

Genome-wide association studies (GWAS) have successfully identified genetic loci associated with glycemic traits. However, characterizing the functional significance of these loci has proven challenging. We sought to gain insights into the regulation of fasting insulin and fasting glucose through the use of gene expression microarray data from peripheral blood samples of participants without diabetes in the Framingham Heart Study (FHS) (n = 5,056), the Rotterdam Study (RS) (n = 723), and the InCHIANTI Study (Invecchiare in Chianti) (n = 595). Using a false discovery rate q <0.05, we identified three transcripts associated with fasting glucose and 433 transcripts associated with fasting insulin levels after adjusting for age, sex, technical covariates, and complete blood cell counts. Among the findings, circulating IGF2BP2 transcript levels were positively associated with fasting insulin in both the FHS and RS. Using 1000 Genomes-imputed genotype data, we identified 47,587 cis-expression quantitative trait loci (eQTL) and 6,695 trans-eQTL associated with the 433 significant insulin-associated transcripts. Of note, we identified a trans-eQTL (rs592423), where the A allele was associated with higher IGF2BP2 levels and with fasting insulin in an independent genetic meta-analysis comprised of 50,823 individuals. We conclude that integration of genomic and transcriptomic data implicate circulating IGF2BP2 mRNA levels associated with glucose and insulin homeostasis.

Completeness and timeliness of reporting of notifiable medical conditions, active component, U.S. Armed Forces, 2008-2014.

The complete and timely reporting of notifiable medical conditions occurring among U.S. military service members is important for the control of communicable and preventable diseases and injuries. The Defense Medical Surveillance System (DMSS) was used to identify all hospital and ambulatory care encounters among service members occurring during 2008-2014. Incident encounters with diagnoses of Department of Defense notifiable medical conditions were matched to reportable medical events entered through the Disease Reporting System Internet. Over this time period, the Services reported 47.6% of notifiable hospitalized cases and 57.2% of notifiable ambulatory care cases. Timeliness of reporting improved over the time period with 40.0% of notifiable hospitalized cases reported within 1 week in 2008 and 73.6% in 2014. For ambulatory care cases, 62.3% were reported within 1 week in 2008 and 81.3% in 2014.

Gene expression markers of age-related inflammation in two human cohorts.

INTRODUCTION: Chronically elevated circulating inflammatory markers are common in older persons but mechanisms are unclear. Many blood transcripts (>800 genes) are associated with interleukin-6 protein levels (IL6) independent of age. We aimed to identify gene transcripts statistically mediating, as drivers or responders, the increasing levels of IL6 protein in blood at older ages. METHODS: Blood derived in-vivo RNA from the Framingham Heart Study (FHS, n=2422, ages 40-92 yrs) and InCHIANTI study (n=694, ages 30-104 yrs), with Affymetrix and Illumina expression arrays respectively (>17,000 genes tested), were tested for statistical mediation of the age-IL6 association using resampling techniques, adjusted for confounders and multiple testing. RESULTS: In FHS, IL6 expression was not associated with IL6 protein levels in blood. 102 genes (0.6% of 17,324 expressed) statistically mediated the age-IL6 association of which 25 replicated in InCHIANTI (including 5 of the 10 largest effect genes). The largest effect gene (SLC4A10, coding for NCBE, a sodium bicarbonate transporter) mediated 19% (adjusted CI 8.9 to 34.1%) and replicated by PCR in InCHIANTI (n=194, 35.6% mediated, p=0.01). Other replicated mediators included PRF1 (perforin, a cytolytic protein in cytotoxic T lymphocytes and NK cells) and IL1B (Interleukin 1 beta): few other cytokines were significant mediators. CONCLUSIONS: This transcriptome-wide study on human blood identified a small distinct set of genes that statistically mediate the age-IL6 association. Findings are robust across two cohorts and different expression technologies. Raised IL6 levels may not derive from circulating white cells in age related inflammation.