Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial.

We evaluated in this randomised, double-blind clinical trial the efficacy of melatonin as a prophylactic treatment for prevention of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and were randomised 1:1 to receive melatonin 2 mg administered orally for 12 weeks or placebo. The main outcome was the number of SARS-CoV-2 infections. A total of 344 volunteers were screened, and 314 were randomised: 151 to placebo and 163 to melatonin; 308 received the study treatment (148 placebo; 160 melatonin). We detected 13 SARS-CoV-2 infections, 2.6% in the placebo arm and 5.5% in the melatonin arm (p = 0.200). A total of 294 adverse events were detected in 127 participants (139 in placebo; 155 in melatonin). We found a statistically significant difference in the incidence of adverse events related to treatment: 43 in the placebo arm and 67 in the melatonin arm (p = 0.040), and in the number of participants suffering from somnolence related to treatment: 8.8% (n = 14) in the melatonin versus 1.4% (n = 2) in the placebo arm (p = 0.008). No severe adverse events related to treatment were reported. We cannot confirm our hypothesis that administration of melatonin prevents the development of SARS-CoV-2 infection in healthcare workers.

Health Care Workers' Reasons for Choosing Between Two Different COVID-19 Prophylaxis Trials in an Acute Pandemic Context: Single-Center Questionnaire Study.

BACKGROUND: In April 2020, two independent clinical trials to assess SARS-CoV-2 prophylaxis strategies among health care workers were initiated at our hospital: MeCOVID (melatonin vs placebo) and EPICOS (tenofovir disoproxil/emtricitabine vs hydroxychloroquine vs combination therapy vs placebo). OBJECTIVE: This study aimed to evaluate the reasons why health care workers chose to participate in the MeCOVID and EPICOS trials, as well as why they chose one over the other. METHODS: Both trials were offered to health care workers through an internal news bulletin. After an initial screening visit, all subjects were asked to respond to a web-based survey. RESULTS: In the first month, 206 health care workers were screened and 160 were randomized. The survey participation was high at 73.3%. Health care workers cited "to contribute to scientific knowledge" (n=80, 53.0%), followed by "to avoid SARS-CoV-2 infection" (n=33, 21.9%) and "the interest to be tested for SARS-CoV-2" (n=28, 18.5%), as their primary reasons to participate in the trials. We observed significant differences in the expected personal benefits across physicians and nurses (P=.01). The vast majority of volunteers (n=202, 98.0%) selected the MeCOVID trial, their primary reason being their concern regarding adverse reactions to treatments in the EPICOS trial (n=102, 69.4%). CONCLUSIONS: Health care workers' reasons to participate in prophylaxis trials in an acute pandemic context appear to be driven largely by their desire to contribute to science and to gain health benefits. Safety outweighed efficacy when choosing between the two clinical trials.

Age-Adjusted Endothelial Activation and Stress Index for Coronavirus Disease 2019 at Admission Is a Reliable Predictor for 28-Day Mortality in Hospitalized Patients With Coronavirus Disease 2019.

Background: Endothelial Activation and Stress Index (EASIX) predict death in patients undergoing allogeneic hematopoietic stem cell transplantation who develop endothelial complications. Because coronavirus disease 2019 (COVID-19) patients also have coagulopathy and endotheliitis, we aimed to assess whether EASIX predicts death within 28 days in hospitalized COVID-19 patients. Methods: We performed a retrospective study on COVID-19 patients from two different cohorts [derivation (n = 1,200 patients) and validation (n = 1,830 patients)]. The endpoint was death within 28 days. The main factors were EASIX [(lactate dehydrogenase * creatinine)/thrombocytes] and aEASIX-COVID (EASIX * age), which were log2-transformed for analysis. Results: Log2-EASIX and log2-aEASIX-COVID were independently associated with an increased risk of death in both cohorts (p < 0.001). Log2-aEASIX-COVID showed a good predictive performance for 28-day mortality both in the derivation cohort (area under the receiver-operating characteristic = 0.827) and in the validation cohort (area under the receiver-operating characteristic = 0.820), with better predictive performance than log2-EASIX (p < 0.001). For log2 aEASIX-COVID, patients with low/moderate risk (<6) had a 28-day mortality probability of 5.3% [95% confidence interval (95% CI) = 4-6.5%], high (6-7) of 17.2% (95% CI = 14.7-19.6%), and very high (>7) of 47.6% (95% CI = 44.2-50.9%). The cutoff of log2 aEASIX-COVID = 6 showed a positive predictive value of 31.7% and negative predictive value of 94.7%, and log2 aEASIX-COVID = 7 showed a positive predictive value of 47.6% and negative predictive value of 89.8%. Conclusion: Both EASIX and aEASIX-COVID were associated with death within 28 days in hospitalized COVID-19 patients. However, aEASIX-COVID had significantly better predictive performance than EASIX, particularly for discarding death. Thus, aEASIX-COVID could be a reliable predictor of death that could help to manage COVID-19 patients.

Transfusion support in COVID-19 patients: Impact on hospital blood component supply during the outbreak.

BACKGROUND: During the COVID-19 outbreak, most hospitals deferred elective surgical procedures to allow space for the overwhelming number of COVID-19 patient admissions, expecting a decrease in routine blood component requirements. However, because transfusion support needs of COVID-19 patients are not well known, its impact on hospital blood supply is uncertain. The objective of this study was to assess the effect of the COVID-19 pandemic on transfusion demand. STUDY DESIGN AND METHODS: Transfusion records during the peak of the COVID-19 pandemic (March 1-April 30, 2020) were reviewed in our center to assess changes in blood requirements. RESULTS: During this period 636 patients received a total of 2934 blood components, which reflects a 17.6% reduction in transfusion requirements with regard to the same period of 2019, and blood donations in Madrid dropped by 45%. The surgical blood demand decreased significantly during the outbreak (50.2%). Blood usage in the hematology and oncology departments remained unchanged, while the day ward demand halved, and intensive care unit transfusion needs increased by 116%. A total of 6.2% of all COVID inpatients required transfusion support. COVID-19 inpatients consumed 19% of all blood components, which counterbalanced the savings owed to the reduction in elective procedures. CONCLUSION: Although only a minority of COVID-19 inpatients required transfusion, the expected reduction in transfusion needs caused by the lack of elective surgical procedures is partially offset by the large number of admitted patients during the peak of the pandemic. This fact must be taken into account when planning hospital blood supply.

Risk factors and outcome of COVID-19 in patients with hematological malignancies.

BACKGROUND: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined. PATIENTS AND METHODS: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. RESULTS: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n = 58) or allogeneic stem cell transplantation (allo-SCT) (n = 65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p = 0.02). Prognostic factors identified for day 45 overall mortality (OM) by logistic regression multivariate analysis included age > 70 years [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.8, p = 0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p < 0.0001); ECOG 3-4 (OR, 2.56, 95% CI 1.4-4.7, p = 0.003); neutropenia (< 0.5 × 109/L) (OR 2.8, 95% CI 1.3-6.1, p = 0.01); and a C-reactive protein (CRP) > 20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p < 0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p = 0.02) whereas the use of hidroxycloroquine did not show significant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P = 0.1). CONCLUSIONS: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of inflammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19.