Seropositivity of COVID-19 among asymptomatic healthcare workers: A multi-site prospective cohort study from Northern Virginia, United States.

BACKGROUND: Because of their direct patient contact, healthcare workers (HCW) face an unprecedented risk of exposure to COVID-19. The aim of this study was to examine incidence of COVID-19 disease among asymptomatic HCW and community participants in Northern Virginia during 6 months of follow-up. METHODS: This is a prospective cohort study that enrolled healthy HCW and residents who never had a symptomatic COVID-19 infection prior to enrolment from the community in Northern Virginia from April to November 2020. All participants were invited to enrol in study, and they were followed at 2-, and 6-months intervals. Participants were evaluated by commercial chemiluminescence SARS-CoV-2 serology assays as part of regional health system and public health surveillance program to monitor the spread of COVID-19 disease. FINDINGS: Of a total of 1,819 asymptomatic HCW enrolled, 1,473 (96%) had data at two-months interval, and 1,323 (73%) participants had data at 6-months interval. At baseline, 21 (1.15%) were found to have prior COVID-19 exposure. At two-months interval, COVID-19 rate was 2.8% and at six months follow-up, the overall incidence rate increased to 4.8%, but was as high as 7.9% among those who belong to the youngest age group (20-29 years). Seroconversion rates in HCW were comparable to the seropositive rates in the Northern Virginia community. The overall incidence of COVID-19 in the community was 4.5%, but the estimate was higher among Hispanic ethnicity (incidence rate = 15.3%) potentially reflecting different socio-economic factors among the community participants and the HCW group. Using cross-sectional logistic regression and spatio-temporal mixed effects models, significant factors that influence the transmission rate among HCW include age, race/ethnicity, resident ZIP-code, and household exposure, but not direct patient contact. INTERPRETATION: In Northern Virginia, the seropositive rate of COVID-19 disease among HCW was comparable to that in the community.

Assessment of Seroprevalence of SARS-CoV-2 and Risk Factors Associated With COVID-19 Infection Among Outpatients in Virginia.

Importance: Data from seroepidemiologic surveys measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure in diverse communities and ascertaining risk factors associated with infection are important to guide future prevention strategies. Objective: To assess the prevalence of previous SARS-CoV-2 infection across Virginia and the risk factors associated with infection after the first wave of coronavirus disease 2019 (COVID-19) infections in the US. Design, Setting, and Participants: In this statewide cross-sectional surveillance study, 4675 adult outpatients presenting for health care not associated with COVID-19 in Virginia between June 1 and August 14, 2020, were recruited to participate in a questionnaire and receive venipuncture to assess SARS-CoV-2 serology. Eligibility was stratified to meet age, race, and ethnicity quotas that matched regional demographic profiles. Main Outcomes and Measures: The main outcome was SARS-CoV-2 seropositivity, as measured by the Abbott SARS-CoV-2 immunoglobulin G assay. Results: Among 4675 adult outpatients (mean [SD] age, 48.8 [16.9] years; 3119 women [66.7%]; 3098 White [66.3%] and 4279 non-Hispanic [91.5%] individuals) presenting for non-COVID-19-associated health care across Virginia, the weighted seroprevalence was 2.4% (95% CI, 1.8%-3.1%) and ranged from 0% to 20% by zip code. Seroprevalence was notably higher among participants who were Hispanic (10.2%; 95% CI, 6.1%-14.3%), residing in the northern region (4.4%; 95% CI, 2.8%-6.1%), aged 40 to 49 years (4.4%; 95% CI, 1.8%-7.1%), and uninsured (5.9%; 95% CI, 1.5%-10.3%). Higher seroprevalence was associated with Hispanic ethnicity (adjusted odds ratio [aOR], 3.56; 95% CI, 1.76-7.21), residence in a multifamily unit (aOR, 2.55; 95% CI, 1.25-5.22), and contact with an individual with confirmed COVID-19 infection (aOR, 4.33; 95% CI, 1.77-10.58). The sensitivity of serology results was 94% (95% CI, 70%-100%) among those who reported receiving a previous polymerase chain reaction test for COVID-19 infection. Among 101 participants with seropositive results, 67 individuals (66.3%) were estimated to have asymptomatic infection. These data suggested a total estimated COVID-19 burden that was 2.8-fold higher than that ascertained by PCR-positive case counts. Conclusions and Relevance: This large statewide serologic study estimated that 2.4% of adults in Virginia had exposure to SARS-CoV-2, which was 2.8-fold higher than confirmed case counts. Hispanic ethnicity, residence in a multifamily unit, and contact with an individual with confirmed COVID-19 infection were significant risk factors associated with exposure. Most infections were asymptomatic. As of August 2020, the population in Virginia remained largely immunologically naive to the virus.

Clinical findings for fungal infections caused by methylprednisolone injections.

BACKGROUND: Since September 18, 2012, public health officials have been investigating a large outbreak of fungal meningitis and other infections in patients who received epidural, paraspinal, or joint injections with contaminated lots of methylprednisolone acetate. Little is known about infections caused by Exserohilum rostratum, the predominant outbreak-associated pathogen. We describe the early clinical course of outbreak-associated infections. METHODS: We reviewed medical records for outbreak cases reported to the Centers for Disease Control and Prevention before November 19, 2012, from the six states with the most reported cases (Florida, Indiana, Michigan, New Jersey, Tennessee, and Virginia). Polymerase-chain-reaction assays and immunohistochemical testing were performed on clinical isolates and tissue specimens for pathogen identification. RESULTS: Of 328 patients without peripheral-joint infection who were included in this investigation, 265 (81%) had central nervous system (CNS) infection and 63 (19%) had non-CNS infections only. Laboratory evidence of E. rostratum was found in 96 of 268 patients (36%) for whom samples were available. Among patients with CNS infections, strokes were associated with an increased severity of abnormalities in cerebrospinal fluid (P<0.001). Non-CNS infections were more frequent later in the course of the outbreak (median interval from last injection to diagnosis, 39 days for epidural abscess and 21 days for stroke; P<0.001), and such infections developed in patients with and in those without meningitis. CONCLUSIONS: The initial clinical findings from this outbreak suggest that fungal infections caused by epidural and paraspinal injection of a contaminated glucocorticoid product can result in a broad spectrum of clinical disease, reflecting possible variations in the pathogenic mechanism and in host and exposure risk factors. (Funded by the Centers for Disease Control and Prevention.).

Using fluorodeoxythymidine to monitor anti-EGFR inhibitor therapy in squamous cell carcinoma xenografts.

BACKGROUND: 3'-18F-fluoro-3'-deoxy-fluorothymidine (18F-FLT), a nucleoside analog, could monitor effects of molecularly targeted therapeutics on tumor proliferation. METHODS: We tested whether (18)F-FLT positron emission tomography (PET) uptake changes are associated with antitumor effects of erlotinib in A431 xenografts or cetuximab in SCC1 xenografts. RESULTS: Compared with pretreatment FLT PET scans, 3 days of erlotinib in A431 reduced the standardized uptake value (SUV) by 18%, whereas placebo increased SUV by 1% (p = .005). One week of cetuximab in SCC1 reduced SUV by 62%, whereas placebo reduced SUV by 16% (p = .005). FLT uptake suppression following anti-epidermal growth factor receptor (EGFR) treatment was associated with reduced tumor thymidine kinase-1 (TK1) activity. In vitro TK1 knockdown studies confirmed the importance of TK1 activity on intracellular FLT accumulation suppression. CONCLUSIONS: 18F-FLT PET imaging detects tumor responses to EGFR-inhibitors within days of starting therapy. This technique may identify patients likely to benefit from EGFR-inhibitors early in their treatment course.

Self-rated health and health care utilization after military deployments.

Self-rated general health is one element of the standard health assessment required of U.S. military service members upon completion of major deployments. A cohort study of 22,229 male U.S. Army and Air Force personnel returning from Europe or Southwest Asia in 2000 used survival analysis methods and Cox proportional hazard models to examine postdeployment self-rated health (SRH) status and subsequent hospitalization, separation, and ambulatory care visits. Self-rated health was fair/poor for 1.5% and good for 20.4%; 11% documented at least one health concern. During 30,433 person-years of follow-up (median, 1.5 person-years), there were 22.8 hospitalizations per 1,000 person-years and 4.0 ambulatory care visits per person-years. After adjustment, deployers with fair/poor SRH had an increased risk for hospitalization (hazard ratio [HRI, 1.6; 95% confidence interval [CI], 1.0,2.7); the risk was lower for those with good SRH (HR, 1.3; 95% CI,1.1,1.5). Deployers with fair/poor SRH health had an increased risk for illness-related ambulatory care visits (HR, 1.8, 95%; CI, 1.6,2.1) and administrative visits (HR, 1.4; 95% CI, 1.1,1.7), but not injury-related visits (HR, 1.2; 95% CI, 0.8,1.7). Self-reported low health status and other health concerns identify military members with higher levels of health care needs following return from major deployments.

The recommended role of exposure biomarkers for the surveillance of environmental and occupational chemical exposures in military deployments: policy considerations.

A lack of individual exposure information limited the evaluation of exposure-outcome relationships after the Gulf War. Exposure concerns during Operation Enduring Freedom and Iraqi Freedom deployments have increased interest in individual environmental and occupational chemical exposure assessment. Currently, deployment assessments are conducted using intermittent ambient air monitoring, occasional focused evaluations based on these results, and postdeployment questionnaire documentation of exposure and/or health concerns. Although this strategy is an improvement over previous practice, it has limitations, including a reliance on evidence of an acute problem, to initiate in-depth health evaluation. Exposure biomarkers may have the potential to overcome some of the limitations of current environmental and occupational exposure assessment tools. This article examines current exposure assessment methods, reviews emerging technologies, and recommends a phased approach to introducing exposure biomarkers into a comprehensive occupational and environmental health surveillance program.

Self-rated health and subsequent health care use among military personnel returning from international deployments.

Individual health status assessment upon completion of U.S military deployments was standardized in 1999 with a brief health assessment questionnaire. This cohort study analyzed health status responses and their relationship to postdeployment health outcomes among 16,142 military personnel who completed a health questionnaire after a deployment ending in 1999. Respondents were Army and Air Force personnel returning from Europe or Southwest Asia. Fourteen percent documented at least one health concern and 1.8% had fair/poor self-rated health. In the 6 months after deployment, 1.4% were hospitalized, 25% made five or more outpatient visits, and 4% separated from military service. Deployers with fair/poor self-rated health were at a significantly increased risk for high use of outpatient services (risk ratio, men 1.8, women 1.7) but not for hospitalization or separation. Self-report of low health status or other health concerns may help identify deployers with higher health care needs after future deployments.

Tuberculosis infection among young adults enlisting in the United States Navy.

BACKGROUND: Tuberculosis (TB) is a re-emerging infectious disease threat worldwide. To protect the health and readiness of US military personnel, policies exist to screen for and treat latent TB infection at the time of service entrance. RESULTS: of this screening programme have not been recently described. METHODS: Multivariate regression techniques were used to evaluate demographic and medical data associated with TB infection among all young adults entering US Navy enlisted service between 1 October 1997 and 30 September 1998. Results A total of 44,128 adults (ages 17-35, 81% male) were screened for TB during this 12-month period. The prevalence of latent TB infection was 3.5%. Place of birth was very strongly associated with TB infection, with foreign-born recruits eight times more likely to have a reactive tuberculin skin test or history of infection. Those who reported their race as 'Asian/Pacific Island' had 3.8 times the odds of having evidence of TB infection compared with 'Caucasian' recruits, even after adjusting for place of birth. CONCLUSIONS: The prevalence of TB infection among Navy recruits was last reported as 2.5% nearly 10 years ago. The apparent increase to 3.5% in this large cohort is likely due to a concurrent increase in the number of foreign-born recruits, and it serves to underscore the importance of comprehensive screening and treatment of latent TB infections in this population.

Synthesis and evaluation of 99mTc(CO)(3)-DTPA-folate as a folate-receptor-targeted radiopharmaceutical.

A folate-receptor-targeted 99mTc-radiopharmaceutical, [99mTc]Tc(CO)(3)DTPA-folate, was prepared by heating [99mTc]Tc(CO)(3)(H(2)O)(3)(+) in an aqueous solution of the previously reported DTPA-folate conjugate. The radiotracer was HPLC purified (> 98% radiochemical purity) and evaluated in vitro and in vivo as an agent for targeting folate-receptor-positive cells. [99mTc]Tc(CO)(3)DTPA-folate experienced high, folate-receptor-specific uptake in human KB tumor cells. Intravenous administration of [99mTc]Tc(CO)(3)DTPA-folate to athymic mice bearing KB cell tumor xenografts resulted in 99mTc tumor uptake of 1.8 +/- 0.5 and 3.3 +/- 0.2%ID/g (n = 3) at 30 minutes and 4 hours post-injection, respectively. Tumor uptake was reduced when folic acid was co-administered with the intravenous [99mTc]Tc(CO)(3)DTPA-folate, consistent with radiopharmaceutical localization being mediated by the folate receptor.

Protecting the health of United States military forces in Afghanistan: applying lessons learned since the Gulf War.

Four weeks after the terrorist attacks on the World Trade Center and the Pentagon, US combat troops began bombing missions over Afghanistan in Operation Enduring Freedom. Additional Reserve and National Guard personnel were called to active duty to support the war effort and to ensure security throughout the United States. All of these troops will require health care and assistance during and after this war on terrorism. They will benefit from recent federal legislation that has increased access to health care and from the changes implemented by the Departments of Defense and Veterans Affairs since the Gulf War. An innovative Defense Department "Force Health Protection" strategy places greater emphasis on helping service members and families stay healthy and fit and on preventing injury and illness. The two agencies also have developed new post-deployment clinical practice guidelines, established deployment research centers, and made further improvements in preventive medicine, health surveillance, and risk communication and are thus better prepared for this newest generation of war veterans.

Force health protection: 10 years of lessons learned by the Department of Defense.

The Department of Defense has applied lessons learned since the Persian Gulf War to develop the force health protection (FHP) strategy. The goal of this new, unified strategy is to protect the health of military members from medical and environmental hazards associated with military service to the maximum extent possible. FHP is an evolving strategy that seeks to balance the military health system's responsibilities to promote and sustain health and wellness throughout each person's military service; prevent acute and chronic illnesses and injuries during training and deployment; and rapidly stabilize, treat, and evacuate casualties. In addition, FHP demands a continuous assessment of the current and future health of military members through medical surveillance, longitudinal health studies, adequate medical record documentation, and clinical follow-up. Effective communication with military members, leaders, veterans, families, and the public regarding military members' health status and the health risks of military service is a key element of the FHP strategy.

The Recruit assessment Program: a program to collect comprehensive baseline health data from U.S. military personnel.

Pilot testing has begun on the Recruit Assessment Program (RAP). The RAP is a proposed Department of Defense (DoD) program for the routine collection of baseline demographic, medical, psychosocial, occupational, and health risk factor data from all U.S. military personnel at entry into the armed forces. The RAP currently uses an optically scannable paper questionnaire, which will provide data for the first building block of an electronic medical record within the DoD and the Department of Veterans Affairs. The RAP will serve several important functions, including automating enrollment into the military health care system, improving patient care and preventive medicine efforts, and providing critical data for investigations of health problems among military personnel and veterans. If the feasibility of the RAP is demonstrated and the program is fully implemented throughout the DoD, it could provide a substantial improvement in health care delivery. For the first time, DoD and Department of Veterans Affairs physicians, public health officers, and researchers will have access to comprehensive baseline health status data.