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Background: Convalescent plasma has been proposed as an early treatment to interrupt the progression of early COVID-19 to severe disease, but there is little definitive evidence. We aimed to assess whether early treatment with convalescent plasma reduces the risk of hospitalisation and reduces SARS-CoV-2 viral load among outpatients with COVID-19., Methods: We did a multicentre, double-blind, randomised, placebo-controlled trial in four health-care centres in Catalonia, Spain. Adult outpatients aged 50 years or older with the onset of mild COVID-19 symptoms 7 days or less before randomisation were eligible for enrolment. Participants were randomly assigned (1:1) to receive one intravenous infusion of either 250-300 mL of ABO-compatible high anti-SARS-CoV-2 IgG titres (EUROIMMUN ratio ≥6) methylene blue-treated convalescent plasma (experimental group) or 250 mL of sterile 0·9% saline solution (control). Randomisation was done with the use of a central web-based system with concealment of the trial group assignment and no stratification. To preserve masking, we used opaque tubular bags that covered the investigational product and the infusion catheter. The coprimary endpoints were the incidence of hospitalisation within 28 days from baseline and the mean change in viral load (in log 10 copies per mL) in nasopharyngeal swabs from baseline to day 7. The trial was stopped early following a data safety monitoring board recommendation because more than 85% of the target population had received a COVID-19 vaccine. Primary efficacy analyses were done in the intention-to-treat population, safety was assessed in all patients who received the investigational product. This study is registered with ClinicalTrials.gov, NCT04621123., Findings: Between Nov 10, 2020, and July 28, 2021, we assessed 909 patients with confirmed COVID-19 for inclusion in the trial, 376 of whom were eligible and were randomly assigned to treatment (convalescent plasma n=188 [serum antibody-negative n=160]; placebo n=188 [serum antibody-negative n=166]). Median age was 56 years (IQR 52-62) and the mean symptom duration was 4·4 days (SD 1·4) before random assignment. In the intention-to-treat population, hospitalisation within 28 days from baseline occurred in 22 (12%) participants who received convalescent plasma versus 21 (11%) who received placebo (relative risk 1·05 [95% CI 0·78 to 1·41]). The mean change in viral load from baseline to day 7 was -2·41 log 10 copies per mL (SD 1·32) with convalescent plasma and -2·32 log 10 copies per mL (1·43) with placebo (crude difference -0·10 log 10 copies per mL [95% CI -0·35 to 0·15]). One participant with mild COVID-19 developed a thromboembolic event 7 days after convalescent plasma infusion, which was reported as a serious adverse event possibly related to COVID-19 or to the experimental intervention., Interpretation: Methylene blue-treated convalescent plasma did not prevent progression from mild to severe illness and did not reduce viral load in outpatients with COVID-19. Therefore, formal recommendations to support the use of convalescent plasma in outpatients with COVID-19 cannot be concluded., Funding: Grifols, Crowdfunding campaign YoMeCorono., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Recent reports of patients with coronavirus disease 2019 (COVID-19) developing pneumothorax correspond mainly to case reports describing mechanically ventilated patients. The real incidence, clinical characteristics, and outcome of spontaneous pneumothorax (SP) as a form of COVID-19 presentation remain to be defined., Research Question: Do the incidence, risk factors, clinical characteristics, and outcomes of SP in patients with COVID-19 attending EDs differ compared with COVID-19 patients without SP and non-COVID-19 patients with SP?, Study Design and Methods: This case-control study retrospectively reviewed all patients with COVID-19 diagnosed with SP (case group) in 61 Spanish EDs (20% of Spanish EDs) and compared them with two control groups: COVID-19 patients without SP and non-COVID-19 patients with SP. The relative frequencies of SP were estimated in COVID-19 and non-COVID-19 patients in the ED, and annual standardized incidences were estimated for both populations. Comparisons between case subjects and control subjects included 52 clinical, analytical, and radiologic characteristics and four outcomes., Results: We identified 40 occurrences of SP in 71,904 patients with COVID-19 attending EDs (0.56‰; 95% CI, 0.40‰-0.76‰). This relative frequency was higher than that among non-COVID-19 patients (387 of 1,358,134, 0.28‰; 95% CI, 0.26‰-0.32‰; OR, 1.93; 95% CI, 1.41-2.71). The standardized incidence of SP was also higher in patients with COVID-19 (34.2 vs 8.2/100,000/year; OR, 4.19; 95% CI, 3.64-4.81). Compared with COVID-19 patients without SP, COVID-19 patients developing SP more frequently had dyspnea and chest pain, low pulse oximetry readings, tachypnea, and increased leukocyte count. Compared with non-COVID-19 patients with SP, case subjects differed in 19 clinical variables, the most prominent being a higher frequency of dysgeusia/anosmia, headache, diarrhea, fever, and lymphopenia (all with OR > 10). All the outcomes measured, including in-hospital death, were worse in case subjects than in both control groups., Interpretation: SP as a form of COVID-19 presentation at the ED is unusual (< 1‰ cases) but is more frequent than in the non-COVID-19 population and could be associated with worse outcomes than SP in non-COVID-19 patients and COVID-19 patients without SP., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)