Occupational Risk Factors for SARS-CoV-2 Seropositivity in Healthcare Workers: Results of a Longitudinal Cohort.

OBJECTIVE: The aim of the study is to evaluate COVID-19 risk factors among healthcare workers (HCWs) before vaccine-induced immunity. METHODS: We conducted a longitudinal cohort study of HCWs ( N = 1233) with SARS-CoV-2 immunoglobulin G quantification by ELISA and repeated surveys over 9 months. Risk factors were assessed by multivariable-adjusted logistic regression and Cox proportional hazards models. RESULTS: SARS-CoV-2 immunoglobulin G was associated with work in internal medicine (odds ratio [OR], 2.77; 95% confidence interval [CI], 1.05-8.26) and role of physician-in-training (OR, 2.55; 95% CI, 1.08-6.43), including interns (OR, 4.22; 95% CI, 1.20-14.00) and resident physicians (OR, 3.14; 95% CI, 1.24-8.33). Odds were lower among staff confident in N95 use (OR, 0.55; 95% CI, 0.31-0.96) and decreased over the follow-up. CONCLUSIONS: Excess COVID-19 risk observed among physicians-in-training early in the COVID-19 pandemic was reduced with improved occupational health interventions before vaccinations.

Development and utilization of a surrogate SARS-CoV-2 viral neutralization assay to assess mRNA vaccine responses.

BACKGROUND: Tests for SARS-CoV-2 immunity are needed to help assess responses to vaccination, which can be heterogeneous and may wane over time. The plaque reduction neutralization test (PRNT) is considered the gold standard for measuring serum neutralizing antibodies but requires high level biosafety, live viral cultures and days to complete. We hypothesized that competitive enzyme linked immunoassays (ELISAs) based on SARS-CoV-2 spike protein's receptor binding domain (RBD) attachment to its host receptor, the angiotensin converting enzyme 2 receptor (ACE2r), would correlate with PRNT, given the central role of RBD-ACE2r interactions in infection and published studies to date, and enable evaluation of vaccine responses. METHODS AND RESULTS: Configuration and development of a competitive ELISA with plate-bound RBD and soluble biotinylated ACE2r was accomplished using pairs of pre/post vaccine serum. When the competitive ELISA was used to evaluate N = 32 samples from COVID-19 patients previously tested by PRNT, excellent correlation in IC50 results were observed (rs = .83, p < 0.0001). When the competitive ELISA was used to evaluate N = 42 vaccinated individuals and an additional N = 13 unvaccinated recovered COVID-19 patients, significant differences in RBD-ACE2r inhibitory activity were associated with prior history of COVID-19 and type of vaccine received. In longitudinal analyses pre and up to 200 days post vaccine, surrogate neutralizing activity increased markedly after primary and booster vaccine doses, but fell substantially, up to <12% maximal levels within 6 months. CONCLUSIONS: A competitive ELISA based on inhibition of RBD-ACE2r attachment correlates well with PRNT, quantifies significantly higher activity among vaccine recipients with prior COVID (vs. those without), and highlights marked declines in surrogate neutralizing activity over a 6 month period post vaccination. The findings raise concern about the duration of vaccine responses and potential need for booster shots.

Immunogenic amino acid motifs and linear epitopes of COVID-19 mRNA vaccines.

Reverse vaccinology is an evolving approach for improving vaccine effectiveness and minimizing adverse responses by limiting immunizations to critical epitopes. Towards this goal, we sought to identify immunogenic amino acid motifs and linear epitopes of the SARS-CoV-2 spike protein that elicit IgG in COVID-19 mRNA vaccine recipients. Paired pre/post vaccination samples from N = 20 healthy adults, and post-vaccine samples from an additional N = 13 individuals were used to immunoprecipitate IgG targets expressed by a bacterial display random peptide library, and preferentially recognized peptides were mapped to the spike primary sequence. The data identify several distinct amino acid motifs recognized by vaccine-induced IgG, a subset of those targeted by IgG from natural infection, which may mimic 3-dimensional conformation (mimotopes). Dominant linear epitopes were identified in the C-terminal domains of the S1 and S2 subunits (aa 558-569, 627-638, and 1148-1159) which have been previously associated with SARS-CoV-2 neutralization in vitro and demonstrate identity to bat coronavirus and SARS-CoV, but limited homology to non-pathogenic human coronavirus. The identified COVID-19 mRNA vaccine epitopes should be considered in the context of variants, immune escape and vaccine and therapy design moving forward.

Occupational lung diseases in the 21st century: the changing landscape and future challenges.

PURPOSE OF REVIEW: Occupational exposures remain an underrecognized and preventable cause of lung disease in high-income countries. The present review highlights the emergence of cleaning-related respiratory disease and the re-emergence of silicosis as examples of trends in occupational lung diseases in the 21st century. RECENT FINDINGS: Employment trends, such as the shift from large-scale manufacturing to a service economy, the growth of the healthcare sector, and changing consumer products have changed the spectrum of work-related lung diseases. Following decades of progress in reducing traditional hazards such as silica in U.S. workplaces, cases of advanced silicosis have recently re-emerged with the production of engineered stone countertops. With growth in the healthcare and service sectors in the United States, cleaning products have become an important cause of work-related asthma and have recently been associated with an increased risk of chronic obstructive pulmonary disease (COPD) in women. However, these occupational lung diseases largely go unrecognized by practicing clinicians. SUMMARY: The present article highlights how changes in the economy and work structure can lead to new patterns of inhalational workplace hazards and respiratory disease, including cleaning-related respiratory disease and silicosis. Pulmonary clinicians need to be able to recognize and diagnose these occupational lung diseases, which requires a high index of suspicion and a careful occupational history.

AccessMRS: integrating OpenMRS with smart forms on Android.

We present a new open-source Android application, AccessMRS, for interfacing with an electronic medical record system (OpenMRS) and loading 'Smart Forms' on a mobile device. AccessMRS functions as a patient-centered interface for viewing OpenMRS data; managing patient information in reminders, task lists, and previous encounters; and launching patient-specific 'Smart Forms' for electronic data collection and dissemination of health information. We present AccessMRS in the context of related software applications we developed to serve Community Health Workers, including AccessInfo, AccessAdmin, AccessMaps, and AccessForms. The specific features and design of AccessMRS are detailed in relationship to the requirements that drove development: the workflows of the Kenyan Ministry of Health Community Health Volunteers (CHVs) supported by the AMPATH Primary Health Care Program. Specifically, AccessMRS was designed to improve the quality of community-based Maternal and Child Health services delivered by CHVs in Kosirai Division. AccessMRS is currently in use by more than 80 CHVs in Kenya and undergoing formal assessment of acceptability, effectiveness, and cost.

MRI markers of small vessel disease in lobar and deep hemispheric intracerebral hemorrhage.

BACKGROUND AND PURPOSE: MRI evidence of small vessel disease is common in intracerebral hemorrhage (ICH). We hypothesized that ICH caused by cerebral amyloid angiopathy (CAA) or hypertensive vasculopathy would have different distributions of MRI T2 white matter hyperintensity (WMH) and microbleeds. METHODS: Data were analyzed from 133 consecutive patients with primary supratentorial ICH and adequate MRI sequences. CAA was diagnosed using the Boston criteria. WMH segmentation was performed using a validated semiautomated method. WMH and microbleeds were compared according to site of symptomatic hematoma origin (lobar versus deep) or by pattern of hemorrhages, including both hematomas and microbleeds, on MRI gradient recalled echo sequence (grouped as lobar only-probable CAA, lobar only-possible CAA, deep hemispheric only, or mixed lobar and deep hemorrhages). RESULTS: Patients with lobar and deep hemispheric hematoma had similar median normalized WMH volumes (19.5 cm versus 19.9 cm(3), P=0.74) and prevalence of >or=1 microbleed (54% versus 52%, P=0.99). The supratentorial WMH distribution was similar according to hemorrhage location category; however, the prevalence of brain stem T2 hyperintensity was lower in lobar hematoma versus deep hematoma (54% versus 70%, P=0.004). Mixed ICH was common (23%). Patients with mixed ICH had large normalized WMH volumes and a posterior distribution of cortical hemorrhages similar to that seen in CAA. CONCLUSIONS: WMH distribution is largely similar between CAA-related and non-CAA-related ICH. Mixed lobar and deep hemorrhages are seen on MRI gradient recalled echo sequence in up to one fourth of patients; in these patients, both hypertension and CAA may be contributing to the burden of WMH.

Risk of thromboembolism following acute intracerebral hemorrhage.

INTRODUCTION: Intracerebral hemorrhage (ICH) is the most feared complication of oral anticoagulant therapy (OAT). While anticoagulated patients have increased severity of bleeding following ICH, they may also be at increased risk for thromboembolic events (TEs) given that they had been prescribed OAT prior to their ICH. We hypothesized that TEs are relatively common following ICH, and that anticoagulated patients are at higher risk for these complications. METHODS: Consecutive patients with primary ICH presenting to a tertiary care hospital from 1994 to 2006 were prospectively characterized and followed. Hospital records were retrospectively reviewed for clinically relevant in-hospital TEs and patients were prospectively followed for 90 day mortality. RESULTS: For 988 patients of whom 218 (22%) were on OAT at presentation, median hospital length of stay was 7 (IQR 4-13) days and 90-day mortality was 36%. TEs were diagnosed in 71 patients (7.2%) including pulmonary embolism (1.8%), deep venous thrombosis (1.1%), myocardial ischemia (1.6%), and cerebrovascular ischemia (3.0%). Mean time to event was 8.4 +/- 7.0 days. Rates of TE were 5% among those with OAT-related ICH and 8% among those with non-OAT ICH (P = 0.2). After multivariable Cox regression, the only independent risk factor for developing a TE was external ventricular drain placement (HR 2.1, 95% CI 1.1-4.1, P = 0.03). TEs had no effect on 90-day mortality (HR 0.7, 95% CI 0.5-1.1, P = 0.1). CONCLUSIONS: The incidence of TEs in an unselected ICH population was 7.2%. Patients with OAT-related ICH were not at increased risk of TEs.