Effectiveness of an anti-fog polymer coating in protective eyewear: a blinded, randomised controlled cross-over trial with healthcare providers in an emergency department setting

BackgroundEye protection is a mandatory component of the personal protective equipment in healthcare settings, especially for suspected or confirmed cases of COVID-19 and during aerosolising procedures. Fogging of protective eyewear is a frequent problem experienced by providers. The hydrophilic property of a sulfonated polymer, BiaXam, may be able to decrease fogging through wicking moisture from the lens. In this study, we tested the anti-fogging properties of this polymer when applied to protective eyewear. MethodsAn investigator-initiated prospective, randomised, single-blinded cross-over study was conducted in an emergency department in a large, tertiary care hospital. Participants were blinded and randomised first to either a pair of anti-fog coated or uncoated eyewear, and then to the alternative pair after 2 hours. Study participants completed an identical survey at the end of each 2-hour period. Results50 emergency medicine healthcare providers were enrolled and 48 completed the study. Results demonstrated a significant difference in fogging between the coated and uncoated eyewear, as 81% of the participants reported fogging of the uncoated lenses and only 55% of the participants reported fogging in the coated pair (p=0.0029). Participants reported that the uncoated lenses fogged two times as frequently on a 10-point Likert scale (4.5 +/- 3.3 vs 2.1 +/- 2.5;p<0.0001). Subgroup analysis of participants who wore only a surgical mask demonstrated even more efficacious results with coated eyewear. ConclusionOverall, sulfonated polymer-coated eyewear improved provider visualisation, user experience and perceived mitigation of potential medical errors.

Longitudinal characterization of circulating neutrophils uncovers phenotypes associated with severity in hospitalized COVID-19 patients.

Mechanisms of neutrophil involvement in severe coronavirus disease 2019 (COVID-19) remain incompletely understood. Here, we collect longitudinal blood samples from 306 hospitalized COVID-19+ patients and 86 controls and perform bulk RNA sequencing of enriched neutrophils, plasma proteomics, and high-throughput antibody profiling to investigate relationships between neutrophil states and disease severity. We identify dynamic switches between six distinct neutrophil subtypes. At days 3 and 7 post-hospitalization, patients with severe disease display a granulocytic myeloid-derived suppressor cell-like gene expression signature, while patients with resolving disease show a neutrophil progenitor-like signature. Humoral responses are identified as potential drivers of neutrophil effector functions, with elevated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G1 (IgG1)-to-IgA1 ratios in plasma of severe patients who survived. In vitro experiments confirm that while patient-derived IgG antibodies induce phagocytosis in healthy donor neutrophils, IgA antibodies predominantly induce neutrophil cell death. Overall, our study demonstrates a dysregulated myelopoietic response in severe COVID-19 and a potential role for IgA-dominant responses contributing to mortality.

Longitudinal proteomic analysis of severe COVID-19 reveals survival-associated signatures, tissue-specific cell death, and cell-cell interactions.

Mechanisms underlying severe coronavirus disease 2019 (COVID-19) disease remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune and non-immune proteins linked to COVID-19. Deconvolution of our plasma proteome data using published scRNA-seq datasets reveals contributions from circulating immune and tissue cells. Sixteen percent of patients display reduced inflammation yet comparably poor outcomes. Comparison of patients who died to severely ill survivors identifies dynamic immune-cell-derived and tissue-associated proteins associated with survival, including exocrine pancreatic proteases. Using derived tissue-specific and cell-type-specific intracellular death signatures, cellular angiotensin-converting enzyme 2 (ACE2) expression, and our data, we infer whether organ damage resulted from direct or indirect effects of infection. We propose a model in which interactions among myeloid, epithelial, and T cells drive tissue damage. These datasets provide important insights and a rich resource for analysis of mechanisms of severe COVID-19 disease.

Alveolar, Endothelial, and Organ Injury Marker Dynamics in Severe COVID-19.

Rationale: Alveolar and endothelial injury may be differentially associated with coronavirus disease (COVID-19) severity over time. Objectives: To describe alveolar and endothelial injury dynamics and associations with COVID-19 severity, cardiorenovascular injury, and outcomes. Methods: This single-center observational study enrolled patients with COVID-19 requiring respiratory support at emergency department presentation. More than 40 markers of alveolar (including receptor for advanced glycation endproducts [RAGE]), endothelial (including angiopoietin-2), and cardiorenovascular injury (including renin, kidney injury molecule-1, and troponin-I) were serially compared between invasively and spontaneously ventilated patients using mixed-effects repeated-measures models. Ventilatory ratios were calculated for intubated patients. Associations of biomarkers with modified World Health Organization scale at Day 28 were determined with multivariable proportional-odds regression. Measurements and Main Results: Of 225 patients, 74 (33%) received invasive ventilation at Day 0. RAGE was 1.80-fold higher in invasive ventilation patients at Day 0 (95% confidence interval [CI], 1.50-2.17) versus spontaneous ventilation, but decreased over time in all patients. Changes in alveolar markers did not correlate with changes in endothelial, cardiac, or renal injury markers. In contrast, endothelial markers were similar to lower at Day 0 for invasive ventilation versus spontaneous ventilation, but then increased over time only among intubated patients. In intubated patients, angiopoietin-2 was similar (fold difference, 1.02; 95% CI, 0.89-1.17) to nonintubated patients at Day 0 but 1.80-fold higher (95% CI, 1.56-2.06) at Day 3; cardiorenovascular injury markers showed similar patterns. Endothelial markers were not consistently associated with ventilatory ratios. Endothelial markers were more often significantly associated with 28-day outcomes than alveolar markers. Conclusions: Alveolar injury markers increase early. Endothelial injury markers increase later and are associated with cardiorenovascular injury and 28-day outcome. Alveolar and endothelial injury likely contribute at different times to disease progression in severe COVID-19.

Early cross-coronavirus reactive signatures of humoral immunity against COVID-19.

The introduction of vaccines has inspired hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against SARS-CoV-2, thus we profiled the earliest humoral signatures in a large cohort of acutely ill (survivors and nonsurvivors) and mild or asymptomatic individuals with COVID-19. Although a SARS-CoV-2­specific immune response evolved rapidly in survivors of COVID-19, nonsurvivors exhibited blunted and delayed humoral immune evolution, particularly with respect to S2-specific antibodies. Given the conservation of S2 across ß-coronaviruses, we found that the early development of SARS-CoV-2­specific immunity occurred in tandem with preexisting common ß-coronavirus OC43 humoral immunity in survivors, which was also selectively expanded in individuals that develop a paucisymptomatic infection. These data point to the importance of cross-coronavirus immunity as a correlate of protection against COVID-19.

SARS-CoV-2 viremia is associated with distinct proteomic pathways and predicts COVID-19 outcomes.

BACKGROUNDSARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 in small-scale cohort studies. The mechanisms behind this association remain elusive.METHODSWe evaluated the relationship between SARS-CoV-2 viremia, disease outcome, and inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using a quantitative reverse transcription PCR-based platform. Proteomic data were generated with Proximity Extension Assay using the Olink platform.RESULTSThis study included 300 participants with nucleic acid test-confirmed COVID-19. Plasma SARS-CoV-2 viremia levels at the time of presentation predicted adverse disease outcomes, with an adjusted OR of 10.6 (95% CI 4.4-25.5, P < 0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and 3.9 (95% CI 1.5-10.1, P = 0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia, including upregulation of SARS-CoV-2 entry factors (ACE2, CTSL, FURIN), heightened markers of tissue damage to the lungs, gastrointestinal tract, and endothelium/vasculature, and alterations in coagulation pathways.CONCLUSIONThese results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia that underlies its ability to predict COVID-19 disease outcomes.FUNDINGMark and Lisa Schwartz; the National Institutes of Health (U19AI082630); the American Lung Association; the Executive Committee on Research at Massachusetts General Hospital; the Chan Zuckerberg Initiative; Arthur, Sandra, and Sarah Irving for the David P. Ryan, MD, Endowed Chair in Cancer Research; an EMBO Long-Term Fellowship (ALTF 486-2018); a Cancer Research Institute/Bristol Myers Squibb Fellowship (CRI2993); the Harvard Catalyst/Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH awards UL1TR001102 and UL1TR002541-01); and by the Harvard University Center for AIDS Research (National Institute of Allergy and Infectious Diseases, 5P30AI060354).

Delirium in Older Patients With COVID-19 Presenting to the Emergency Department.

Importance: Delirium is common among older emergency department (ED) patients, is associated with high morbidity and mortality, and frequently goes unrecognized. Anecdotal evidence has described atypical presentations of coronavirus disease 2019 (COVID-19) in older adults; however, the frequency of and outcomes associated with delirium in older ED patients with COVID-19 infection have not been well described. Objective: To determine how frequently older adults with COVID-19 present to the ED with delirium and their associated hospital outcomes. Design, Setting, and Participants: This multicenter cohort study was conducted at 7 sites in the US. Participants included consecutive older adults with COVID-19 presenting to the ED on or after March 13, 2020. Exposure: COVID-19 was diagnosed by positive nasal swab for severe acute respiratory syndrome coronavirus 2 (99% of cases) or classic radiological findings (1% of cases). Main Outcomes and Measures: The primary outcome was delirium as identified from the medical record according to a validated record review approach. Results: A total of 817 older patients with COVID-19 were included, of whom 386 (47%) were male, 493 (62%) were White, 215 (27%) were Black, and 54 (7%) were Hispanic or Latinx. The mean (SD) age of patients was 77.7 (8.2) years. Of included patients, 226 (28%) had delirium at presentation, and delirium was the sixth most common of all presenting symptoms and signs. Among the patients with delirium, 37 (16%) had delirium as a primary symptom and 84 (37%) had no typical COVID-19 symptoms or signs, such as fever or shortness of breath. Factors associated with delirium were age older than 75 years (adjusted relative risk [aRR], 1.51; 95% CI, 1.17-1.95), living in a nursing home or assisted living (aRR, 1.23; 95% CI, 0.98-1.55), prior use of psychoactive medication (aRR, 1.42; 95% CI, 1.11-1.81), vision impairment (aRR, 1.98; 95% CI, 1.54-2.54), hearing impairment (aRR, 1.10; 95% CI 0.78-1.55), stroke (aRR, 1.47; 95% CI, 1.15-1.88), and Parkinson disease (aRR, 1.88; 95% CI, 1.30-2.58). Delirium was associated with intensive care unit stay (aRR, 1.67; 95% CI, 1.30-2.15) and death (aRR, 1.24; 95% CI, 1.00-1.55). Conclusions and Relevance: In this cohort study of 817 older adults with COVID-19 presenting to US emergency departments, delirium was common and often was seen without other typical symptoms or signs. In addition, delirium was associated with poor hospital outcomes and death. These findings suggest the clinical importance of including delirium on checklists of presenting signs and symptoms of COVID-19 that guide screening, testing, and evaluation.