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.

Factors associated with a low level of physical activity in patients with chronic obstructive pulmonary disease.

BACKGROUND: Physical activity such as walking is strongly recommended for patients with chronic obstructive pulmonary disease (COPD). METHODS: We undertook a multicenter observational study on COPD patients, collecting the daily walking time, COPD severity score (COPDSS), functional status [London Chest Activity of Daily Living (LCADL) questionnaire], health-related quality of life (QoL) rating [five-item EuroQL (EQ-5D) and Airways Questionnaire 20 (AQ20)], and anxiety and depression rating (Hospital Anxiety and Depression Scale). Multivariate logistic regression modeling was performed to identify the independent predictors of a low walking time (<30 min/day). RESULTS: We included 4,574 patients with a mean (±standard deviation) age of 67.1 ± 10.0 years, with a mean FEV1 (%) of 54.0 ± 23.7. The mean daily walking time was 73.6 ± 67.1 min (58.9 % at ≥60 min and 13.7 % at <30 min). A strong direct relationship was observed between daily walking time and better QoL (EQ-5D and AQ20) and functional status (LCADL; p < 0.001 in all cases). The independent predictors of a low walking time were a worse score in EQ-5D [odds ratio (OR) (95 % confidence interval per one-point increase of 0.23 (0.15-0.35)], a higher COPDSS [OR per one-point increase of 1.04 (1.02-1.07)], and the presence of depression [OR 1.58 (1.25-2.01)]. CONCLUSIONS: After adjustment for age and severity of symptoms, poor health status, severity of COPD, and depression are the main factors associated with a low walking time in COPD patients.

Impairment of quality of life in women with chronic obstructive pulmonary disease.

BACKGROUND: There is ample evidence of the differences between genders in chronic obstructive pulmonary disease (COPD). The purpose of this study was to identify the factors that contribute to these differences. METHODS: This was a multi-center, cross-sectional observational study including 4574 patients of 40 years of age and older who attended primary care and pulmonary clinics. Data were collected on COPD characteristics, comorbidities, quality of life as assessed by both the EuroQoL 5D questionnaire (EQ-5D) and the Airways Questionnaire 20 (AQ20), and prevalence of anxiety and depression. Data collected were compared between males and females. RESULTS: Mean age was 67 years and 740 patients (16.7%) were female. Women were significantly younger, had better pulmonary function, and smoked less; however, they showed poorer quality of life (EQ-5D: 0.6 [SD = 0.3] versus 0.7 [0.3]; p < 0.001; and AQ20: 10.4 [SD = 4.6] versus 9.2 [SD = 4.5]; p < 0.001) and a higher rate of anxiety (34.5% versus 20.6%; p < 0.001) and depression (31.7% versus 22.1%; p < 0.001). In a multivariate analysis, female gender was significantly associated to poorer quality of life (AQ20) but not to a higher rate of dyspnea. CONCLUSION: Women with COPD are younger and have lower rates of impaired lung function; however, they show poorer quality of life and more frequent COPD-associated anxiety and depression.

Socioeconomic status and health-related quality of life of patients with chronic obstructive pulmonary disease.

BACKGROUND: Socioeconomic status (SES) is an important determinant of health and premature death. However, the impact of poor SES on the health status of patients with chronic obstructive pulmonary disease (COPD) has not been well determined. OBJECTIVE: It was our aim to assess the impact of SES on the quality of life in COPD patients. METHODS: This was a cross-sectional, observational, multicenter study. A total of 4,574 patients completed the EuroQol 5-dimension questionnaire (EQ-5D) and the Airways Questionnaire 20 (AQ20). SES was based on the subject's occupation and educational level. Occupational categories were based on the major group classification of the International Standard Classification of Occupations. RESULTS: The mean age of the population was 67.1 years and the mean forced expiratory volume was 43.4%. There was a gradient of impairment in health-related quality of life (HRQoL) according to the educational level, with significantly worse scores for the EQ-5D and the AQ20 for medium and low educational levels compared with high education (p < 0.001). Similarly, HRQoL was also significantly impaired in more unskilled workers, with a gradient of the AQ20 from 8.6 units (SD 4.8) in class I to 10.1 units (4.6) in class V (p < 0.001) and from 0.75 units in class I to 0.63 units in class V for the EQ-5D index, as well as from 62.9 units in class I to 55.6 units in class V for the EQ-5D visual analogue scale (p < 0.001 for all comparisons). These differences remained significant after controlling for covariates. CONCLUSIONS: Patients with a lower educational level and belonging to the unskilled professional groups had a poorer HRQoL. This is evident even in a country where access to health care services is universal and free.