Objectives: Convalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. Design: Open-label, parallel-arm, phase II, multicentre, randomized controlled trial. Setting: Thirty-nine public and private hospitals across India. Participants: Hospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 ≤ 93% on room air). Intervention: Participants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome Measure: Composite of progression to severe disease (PaO2/FiO2<100) or all-cause mortality at 28 days post-enrolment. Results: Between 22 nd April to 14 th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: -0.61 to 1.83]. Interpretation: CP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19.

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BackgroundSepsis recognition in older emergency department (ED) patients is difficult due to atypical symptom presentation. We therefore investigated whether the prognostic and discriminative performance of the five most commonly used disease severity scores were appropriate for risk stratification of older ED sepsis patients (≥70 years) compared to a younger control group (<70 years).MethodsThis was an observational multi-centre study using an existing database in which ED patients who were hospitalized with a suspected infection were prospectively included. Patients were stratified by age < 70 and ≥70 years. We assessed the association with in-hospital mortality (primary outcome) and the area under the curve (AUC) with receiver operator characteristics of the Predisposition, Infection, Response, Organ dysfunction (PIRO), quick Sequential Organ Failure Assessment (qSOFA), Mortality in ED Sepsis (MEDS), and the Modified and National Early Warning (MEWS and NEWS) scores.ResultsIn-hospital mortality was 9.5% ((95%-CI); 7.4–11.5) in the 783 included older patients, and 4.6% (3.6–5.7) in the 1497 included younger patients. In contrast to younger patients, disease severity scores in older patients associated poorly with mortality. The AUCs of all disease severity scores were poor and ranged from 0.56 to 0.64 in older patients, significantly lower than the good AUC range from 0.72 to 0.86 in younger patients. The MEDS had the best AUC (0.64 (0.57–0.71)) in older patients. In older and younger patients, the newly proposed qSOFA score (Sepsis 3.0) had a lower AUC than the PIRO score (sepsis 2.0).ConclusionThe prognostic and discriminative performance of the five most commonly used disease severity scores was poor and less useful for risk stratification of older ED sepsis patients.Electronic supplementary materialThe online version of this article (10.1186/s13049-017-0436-3) contains supplementary material, which is available to authorized users.

Methods We conducted a multicenter, retrospective, observational, US-based study of COVID-19 patients undergoing hs-cTnT. Outcomes included short-term mortality (in-hospital and 30-days post-discharge) and a composite of major adverse events including respiratory failure requiring mechanical ventilation, cardiac arrest, and shock within the index presentation and/or mortality during the index hospitalization or within 30-days post-discharge. Results Among 367 COVID-19 patients undergoing hs-cTnT, myocardial injury was identified in 46%. They had a higher risk for mortality (20% vs. 12%, P&lt;0.0001; unadjusted HR 4.44, 95% CI 2.13-9.25, P&lt;0.001) and major adverse events (35% vs. 11%, P&lt;0.0001; unadjusted OR 4.29, 95% CI 2.50-7.40, P&lt;0.0001). Myocardial injury was associated with major adverse events (adjusted OR 3.84, 95% CI 2.00-7.36, P&lt;0.0001) but not mortality. Baseline (adjusted OR 1.003, 95% CI 1.00-1.007, P=0.047) and maximum (adjusted OR 1.005, 95% CI 1.001-1.009, P=0.0012) hs-cTnT were independent predictors of major adverse events. Most (95%) increases were due to myocardial injury, with 5% (n = 8) classified as type 1 or 2 myocardial infarction. A single hs-cTnT &lt;6 ng/L identified 26% of patients without mortality, with a 94.9% (95% CI 87.5-98.6) negative predictive value and 93.1% sensitivity (95% CI 83.3-98.1) for major adverse events in those presenting to the ED. Conclusions Myocardial injury is frequent and prognostic in COVID-19. While most hs-cTnT increases are modest and due to myocardial injury, they have important prognostic implications. A single hs-cTnT &lt;6 ng/L at presentation may facilitate the identification of patients with a favorable prognosis.

Binge drinking is widespread on American college campuses, but its effects on the cardiovascular system are poorly understood. This study sought evidence of preclinical cardiovascular changes in binge drinking young adults (n = 24) compared to nondrinking (n = 24) and social drinking (n = 23) peers during baseline, paced sighing (0.033 Hz), and paced breathing (0.1 Hz) tasks. Binge drinkers showed consistent but often statistically nonsignificant evidence of greater sympathetic activation and reduced baroreflex sensitivity. Interestingly, the structure of group-averaged baseline heart rate spectra was considerably different between groups in the low frequency range (0.05-0.15 Hz). In particular, the binge drinking group-averaged spectra showed several spectral peaks not evident in the other groups, possibly indicating two functionally distinct subranges (0.05-0.08 and 0.08-0.15 Hz) that reflect vascular tone baroreflex activity and heart rate baroreflex activity, respectively. Vascular tone baroreflex gain and power in two peaks in the 0.05-0.08 Hz range were associated with years of drinking in the binge drinking group. Vascular dysfunction may be an early indicator of drinking-related change in the cardiovascular system.