Association of SARS-CoV-2 nucleocapsid viral antigen and the receptor for advanced glycation end products with development of severe disease in patients presenting to the emergency department with COVID-19.

Introduction: There remains a need to better identify patients at highest risk for developing severe Coronavirus Disease 2019 (COVID-19) as additional waves of the pandemic continue to impact hospital systems. We sought to characterize the association of receptor for advanced glycation end products (RAGE), SARS-CoV-2 nucleocapsid viral antigen, and a panel of thromboinflammatory biomarkers with development of severe disease in patients presenting to the emergency department with symptomatic COVID-19. Methods: Blood samples were collected on arrival from 77 patients with symptomatic COVID-19, and plasma levels of thromboinflammatory biomarkers were measured. Results: Differences in biomarkers between those who did and did not develop severe disease or death 7 days after presentation were analyzed. After adjustment for multiple comparisons, RAGE, SARS-CoV-2 nucleocapsid viral antigen, interleukin (IL)-6, IL-10 and tumor necrosis factor receptor (TNFR)-1 were significantly elevated in the group who developed severe disease (all p<0.05). In a multivariable regression model, RAGE and SARS-CoV-2 nucleocapsid viral antigen remained significant risk factors for development of severe disease (both p<0.05), and each had sensitivity and specificity >80% on cut-point analysis. Discussion: Elevated RAGE and SARS-CoV-2 nucleocapsid viral antigen on emergency department presentation are strongly associated with development of severe disease at 7 days. These findings are of clinical relevance for patient prognostication and triage as hospital systems continue to be overwhelmed. Further studies are warranted to determine the feasibility and utility of point-of care measurements of these biomarkers in the emergency department setting to improve patient prognostication and triage.

Effects of the circulating environment of COVID-19 on platelet and neutrophil behavior.

Introduction: Thromboinflammatory complications are well described sequalae of Coronavirus Disease 2019 (COVID-19), and there is evidence of both hyperreactive platelet and inflammatory neutrophil biology that contributes to the thromoinflammatory milieu. It has been demonstrated in other thromboinflammatory diseases that the circulating environment may affect cellular behavior, but what role this environment exerts on platelets and neutrophils in COVID-19 remains unknown. We tested the hypotheses that 1) plasma from COVID-19 patients can induce a prothrombotic platelet functional phenotype, and 2) contents released from platelets (platelet releasate) from COVID-19 patients can induce a proinflammatory neutrophil phenotype. Methods: We treated platelets with COVID-19 patient and disease control plasma, and measured their aggregation response to collagen and adhesion in a microfluidic parallel plate flow chamber coated with collagen and thromboplastin. We exposed healthy neutrophils to platelet releasate from COVID-19 patients and disease controls and measured neutrophil extracellular trap formation and performed RNA sequencing. Results: We found that COVID-19 patient plasma promoted auto-aggregation, thereby reducing response to further stimulation ex-vivo. Neither disease condition increased the number of platelets adhered to a collagen and thromboplastin coated parallel plate flow chamber, but both markedly reduced platelet size. COVID-19 patient platelet releasate increased myeloperoxidasedeoxyribonucleic acid complexes and induced changes to neutrophil gene expression. Discussion: Together these results suggest aspects of the soluble environment circulating platelets, and that the contents released from those neutrophil behavior independent of direct cellular contact.

The DISTANCE study: Determining the impact of social distancing on trauma epidemiology during the COVID-19 epidemic-An interrupted time-series analysis.

BACKGROUND: The large-scale social distancing efforts to reduce SARS-CoV-2 transmission have dramatically changed human behaviors associated with traumatic injuries. Trauma centers have reported decreases in trauma volume, paralleled by changes in injury mechanisms. We aimed to quantify changes in trauma epidemiology at an urban Level I trauma center in a county that instituted one of the earliest shelter-in-place orders to inform trauma care during future pandemic responses. METHODS: A single-center interrupted time-series analysis was performed to identify associations of shelter-in-place with trauma volume, injury mechanisms, and patient demographics in San Francisco, California. To control for short-term trends in trauma epidemiology, weekly level data were analyzed 6 months before shelter-in-place. To control for long-term trends, monthly level data were analyzed 5 years before shelter-in-place. RESULTS: Trauma volume decreased by 50% in the week following shelter-in-place (p < 0.01), followed by a linear increase each successive week (p < 0.01). Despite this, trauma volume for each month (March-June 2020) remained lower compared with corresponding months for all previous 5 years (2015-2019). Pediatric trauma volume showed similar trends with initial decreases (p = 0.02) followed by steady increases (p = 0.05). Reductions in trauma volumes were due entirely to changes in nonviolent injury mechanisms, while violence-related injury mechanisms remained unchanged (p < 0.01). CONCLUSION: Although the shelter-in-place order was associated with an overall decline in trauma volume, violence-related injuries persisted. Delineating and addressing underlying factors driving persistent violence-related injuries during shelter-in-place orders should be a focus of public health efforts in preparation for future pandemic responses. LEVEL OF EVIDENCE: Epidemiological study, level III.