Association of Frailty with Adverse Outcomes in Patients with Suspected COVID-19 Infection

Older age and frailty are predictors of adverse outcomes in patients with COVID-19. In emergency medicine, patients do not present with the diagnosis, but with suspicion of COVID-19. The aim of this study was to assess the association of frailty and age with death or admission to intensive care in patients with suspected COVID-19. This single-centre prospective cohort study was performed in the Emergency Department of a tertiary care hospital. Patients, 65 years and older, with suspected COVID-19 presenting to the Emergency Department during the first wave of the pandemic were consecutively enrolled. All patients underwent nasopharyngeal SARS-CoV-2 PCR swab tests. Patients with a Clinical Frailty Scale (CFS) > 4, were considered to be frail. Associations between age, gender, frailty, and COVID-19 status with the composite adverse outcome of 30-day-intensive-care-admission and/or 30-day-mortality were tested. In the 372 patients analysed, the median age was 77 years, 154 (41.4%) were women, 44 (11.8%) were COVID-19-positive, and 125 (33.6%) were frail. The worst outcome was seen in frail COVID-19-patients with six (66.7%) adverse outcomes. Frailty (CFS > 4) and COVID-19-positivity were associated with an adverse outcome after adjustment for age and gender (frailty: OR 5.01, CI 2.56–10.17, p < 0.001; COVID-19: OR 3.47, CI 1.48–7.89, p = 0.003). Frailty was strongly associated with adverse outcomes and outperformed age as a predictor in emergency patients with suspected COVID-19

Direct Comparison of Clinical Characteristics, Outcomes, and Risk Prediction in Patients with COVID-19 and Controls—A Prospective Cohort Study

Most studies investigating early risk predictors in coronavirus disease 19 (COVID-19) lacked comparison with controls. We aimed to assess and directly compare outcomes and risk predictors at time of emergency department (ED) presentation in COVID-19 and controls. Consecutive patients presenting to the ED with suspected COVID-19 were prospectively enrolled. COVID-19-patients were compared with (i) patients tested negative (overall controls) and (ii) patients tested negative, who had a respiratory infection (respiratory controls). Primary outcome was the composite of intensive care unit (ICU) admission and death at 30 days. Among 1081 consecutive cases, 191 (18%) were tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 890 (82%) were tested negative (overall controls), of which 323 (30%) had a respiratory infection (respiratory controls). Incidence of the composite outcome was significantly higher in COVID-19 (23%) as compared with the overall control group (10%, adjusted-HR 2.45 (95%CI, 1.61–3.74), p < 0.001) or the respiratory control group (10%, adjusted-HR 2.93 (95%CI, 1.66–5.17), p < 0.001). Blood oxygen saturation, age, high-sensitivity troponin, c-reactive protein, and lactate dehydrogenase were identified as the strongest predictors of poor outcome available at time of ED presentation in COVID-19 with highly comparable prognostic utility in overall and respiratory controls. In conclusion, patients presenting to the ED with COVID-19 have a worse outcome than controls, even after adjustment for differences in baseline characteristics. Most predictors of poor outcome in COVID-19 were not restricted to COVID-19, but of comparable prognostic utility in controls and therefore generalizable to unselected patients with suspected COVID-19

Table_1_Complement and endothelial cell activation in COVID-19 patients compared to controls with suspected SARS-CoV-2 infection: A prospective cohort study.docx

BackgroundThromboinflammation may influence disease outcome in COVID-19. We aimed to evaluate complement and endothelial cell activation in patients with confirmed COVID-19 compared to controls with clinically suspected but excluded SARS-CoV-2 infection.MethodsIn a prospective, observational, single-center study, patients presenting with clinically suspected COVID-19 were recruited in the emergency department. Blood samples on presentation were obtained for analysis of C5a, sC5b-9, E-selectin, Galectin-3, ICAM-1 and VCAM-1.Results153 cases and 166 controls (suffering mainly from non-SARS-CoV-2 respiratory viral infections, non-infectious inflammatory conditions and bacterial pneumonia) were included. Hospital admission occurred in 62% and 45% of cases and controls, respectively. C5a and VCAM-1 concentrations were significantly elevated and E-selectin concentrations decreased in COVID-19 out- and inpatients compared to the respective controls. However, relative differences in outpatients vs. inpatients in most biomarkers were comparable between cases and controls. Elevated concentrations of C5a, Galectin-3, ICAM-1 and VCAM-1 on presentation were associated with the composite outcome of ICU- admission or 30-day mortality in COVID-19 and controls, yet more pronounced in COVID-19. C5a and sC5b-9 concentrations were significantly higher in COVID-19 males vs. females, which was not observed in the control group.ConclusionsOur data indicate an activation of the complement cascade and endothelium in COVID-19 beyond a nonspecific inflammatory trigger as observed in controls (i.e., “over”-activation).</p

Pulmonary Surfactant Proteins are Inhibited by IgA Autoantibodies in Severe COVID-19.

RATIONALE Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome with fatal outcomes. Evidence suggests that dysregulated immune responses, including autoimmunity, are key pathogenic factors. OBJECTIVES To assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity. METHODS We collected 147 blood, 9 lung tissue, and 36 bronchoalveolar lavage fluid samples from three tertiary hospitals in Switzerland and one in Germany. Severe COVID-19 was defined by the need to administer oxygen. We investigated the presence of IgA autoantibodies and their effects on pulmonary surfactant in COVID-19 using the following methods: immunofluorescence on tissue samples, immunoprecipitations followed by mass spectrometry on bronchoalveolar lavage fluid samples, enzyme-linked immunosorbent assays on blood samples, and surface tension measurements with medical surfactant. MEASUREMENTS AND MAIN RESULTS IgA autoantibodies targeting pulmonary surfactant proteins B and C were elevated in patients with severe COVID-19, but not in patients with influenza or bacterial pneumonia. Notably, pulmonary surfactant failed to reduce surface tension after incubation with either plasma or purified IgA from patients with severe COVID-19. CONCLUSIONS Our data suggest that patients with severe COVID-19 harbor IgA against pulmonary surfactant proteins B and C and that these antibodies block the function of lung surfactant, potentially contributing to alveolar collapse and poor oxygenation. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)