High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial.

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 log10 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 log10 copies per mL (SD 1·32) with convalescent plasma and -2·32 log10 copies per mL (1·43) with placebo (crude difference -0·10 log10 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.

Heat stress assessment among workers in a Nicaraguan sugarcane farm.

BACKGROUND: Heat illness is a major cause of preventable morbidity worldwide. Workers exposed to intense heat can become unable to activate compensation mechanisms, putting their health at risk. Heat stress also has a direct impact on production by causing poor task performance and it increases the possibility of work-related morbidity and injuries. During the sugarcane harvest period, workers are exposed to excessive sunlight and heat from approximately 6 am to 3 pm. A first assessment of heat stress during the 2006/2007 harvesting season served to redesign the existing rehydration measures. In this project, sugarcane workers were provided with more rehydration solutions and water during their work schedule. OBJECTIVE: To assess heat stress preventive measures in order to improve existing rehydration strategies as a means of increasing productivity. METHODS: A small group of 22 workers were followed up for 15 days during working hours, from 6 am to 3 pm. Selection criteria were defined: to have worked more than 50% of the day's working schedule and to have worked for at least 10 days of the follow-up period. A simple data recollection sheet was used. Information regarding the amount of liquid intake was registered. Production output data was also registered. Temperature measurements were recorded by using a portable temperature monitoring device ('EasyLog', model EL-USB-2). RESULTS: The average temperature measurements were above the Nicaraguan Ministry of Labour thresholds. Seven workers drank 7-8 L of liquid, improving their production. Output production increased significantly (p=0.005) among those best hydrated, from 5.5 to 8 tons of cut sugarcane per worker per day. CONCLUSIONS: Productivity improved with the new rehydration measures. Awareness among workers concerning heat stress prevention was increased.

Cases from the Cleveland Clinic: cerebral venous sinus thrombosis presenting to the emergency department with worst headache of life.

A 31 year old woman presented with the worst headache of her life and was diagnosed with cerebral venous sinus thrombosis (CVST) by routine unenhanced computed tomography (CT) scan, subsequently confirmed with magnetic resonance imaging (MRI) and magnetic resonance venography (MRV). Awareness of this less common cause for acute neurological presentation in the Emergency setting is important; the imaging characteristics of CVST are reviewed.