ABSTRACT
Faced with the COVID-19 pandemic, the US system for developing and testing technologies was challenged in unparalleled ways. This article describes the multi-institutional, transdisciplinary team of the "RADxSM Tech Test Verification Core" and its role in expediting evaluations of COVID-19 testing devices. Expertise related to aspects of diagnostic testing was coordinated to evaluate testing devices with the goal of significantly expanding the ability to mass screen Americans to preserve lives and facilitate the safe return to work and school. Focal points included: laboratory and clinical device evaluation of the limit of viral detection, sensitivity, and specificity of devices in controlled and community settings; regulatory expertise to provide focused attention to barriers to device approval and distribution; usability testing from the perspective of patients and those using the tests to identify and overcome device limitations, and engineering assessment to evaluate robustness of design including human factors, manufacturability, and scalability.
ABSTRACT
Secretory phospholipase 2 (sPLA2) acts as a mediator between proximal and distal events of the inflammatory cascade. Its role in SARS-CoV-2 infection is unknown, but could contribute to COVID-19 inflammasome activation and cellular damage. We present the first report of plasma sPLA2 levels in adults and children with COVID-19 compared with controls. Currently asymptomatic adults with a history of recent COVID-19 infection (≥4 weeks before) identified by SARS-CoV-2 IgG antibodies had sPLA2 levels similar to those who were seronegative (9 ± 6 vs.17 ± 28 ng/mL, P = 0.26). In contrast, children hospitalized with severe COVID-19 had significantly elevated sPLA2 compared with those with mild or asymptomatic SARS-CoV-2 infection (269 ± 137 vs. 2 ± 3 ng/mL, P = 0.01). Among children hospitalized with multisystem inflammatory syndrome in children (MIS-C), all had severe disease requiring pediatric intensive care unit (PICU) admission. sPLA2 levels were significantly higher in those with acute illness <10 days versus convalescent disease ≥10 days (540 ± 510 vs. 2 ± 1, P = 0.04). Thus, sPLA2 levels correlated with COVID-19 severity and acute MIS-C in children, implicating a role in inflammasome activation and disease pathogenesis. sPLA2 may be a useful biomarker to stratify risk and guide patient management for children with acute COVID-19 and MIS-C. Therapeutic compounds targeting sPLA2 and inflammasome activation warrant consideration.
Subject(s)
COVID-19/blood , Phospholipases A2, Secretory/blood , Systemic Inflammatory Response Syndrome/blood , Adolescent , Adult , Age Factors , Biomarkers/blood , COVID-19/complications , COVID-19/immunology , Child , Child, Preschool , Female , Humans , Infant , Male , Systemic Inflammatory Response Syndrome/pathology , Systemic Inflammatory Response Syndrome/virologyABSTRACT
OBJECTIVES: To determine SARS-CoV-2-antibody prevalence in pediatric healthcare workers (pHCWs). DESIGN: Baseline prevalence of anti-SARS-CoV-2-IgG was assessed in a prospective cohort study from a large pediatric healthcare facility. Prior SARS-CoV-2 testing history, potential risk factors and anxiety level about COVID-19 were determined. Prevalence difference between emergency department (ED)-based and non-ED-pHCWs was modeled controlling for those covariates. Chi-square test-for-trend was used to examine prevalence by month of enrollment. RESULTS: Most of 642 pHCWs enrolled were 31-40years, female and had no comorbidities. Half had children in their home, 49% had traveled, 42% reported an illness since January, 31% had a known COVID-19 exposure, and 8% had SARS-CoV-2 PCR testing. High COVID-19 pandemic anxiety was reported by 71%. Anti-SARS-CoV-2-IgG prevalence was 4.1%; 8.4% among ED versus 2.0% among non-ED pHCWs (p < 0.001). ED-work location and known COVID-19 exposure were independent risk factors. 31% of antibody-positive pHCWs reported no symptoms. Prevalence significantly (p < 0.001) increased from 3.0% in April-June to 12.7% in July-August. CONCLUSIONS: Anti-SARS-CoV-2-IgG prevalence was low in pHCWs but increased rapidly over time. Both working in the ED and exposure to a COVID-19-positive contact were associated with antibody-seropositivity. Ongoing universal PPE utilization is essential. These data may guide vaccination policies to protect front-line workers.