Reducing transmission of SARS-CoV-2
Kimberly A. Prather1, Chia C. Wang,2,3 Robert T. Schooley4
1Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92037, USA. 2Department of Chemistry, National Sun Yat-sen University, Kaohsiung, Taiwan 804, Republic of China. 3Aerosol Science Research Center, National Sun Yat-Sen University, Kaohsiung, Taiwan 804, Republic of China. 4Department of Medicine, Division of Infectious Diseases and Global Public Health, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA. Email: kprather@ucsd.edu
Masks and testing are necessary to combat asymptomatic spread in aerosols and droplets
Respiratory infections occur through the transmission of virus-containing droplets (>5 to 10 μm) and aerosols (≤5 μm) exhaled from infected individuals during breathing, speaking, coughing, and sneezing. Traditional respiratory disease control measures are designed to reduce transmis- sion by droplets produced in the sneezes and coughs of in- fected individuals. However, a large proportion of the spread of coronavirus disease 2019 (COVID-19) appears to be occurring through airborne transmission of aerosols pro- duced by asymptomatic individuals during breathing and speaking (1–3). Aerosols can accumulate, remain infectious in indoor air for hours, and be easily inhaled deep into the lungs. For society to resume, measures designed to reduce aerosol transmission must be implemented, including uni- versal masking and regular, widespread testing to identify and isolate infected asymptomatic individuals.
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Aerosol transmission of viruses must be acknowledged as a key factor leading to the spread of infectious respiratory diseases. Evidence suggests that SARS-CoV-2 is silently spreading in aerosols exhaled by highly contagious infected individuals with no symptoms. Owing to their smaller size, aerosols may lead to higher severity of COVID-19 because virus-containing aerosols penetrate more deeply into the lungs (10). It is essential that control measures be intro- duced to reduce aerosol transmission. A multidisciplinary approach is needed to address a wide range of factors that lead to the production and airborne transmission of respira- tory viruses, including the minimum virus titer required to cause COVID-19; viral load emitted as a function of droplet size before, during, and after infection; viability of the virus indoors and outdoors; mechanisms of transmission; air- borne concentrations; and spatial patterns. More studies of the filtering efficiency of different types of masks are also needed. COVID-19 has inspired research that is already lead- ing to a better understanding of the importance of airborne transmission of respiratory disease.
In summary, this multinational, observational, real- world study of patients with COVID-19 requiring hospitalisation found that the use of a regimen containing hydroxychloroquine or chloroquine (with or without a macrolide) was associated with no evidence of benefit, but instead was associated with an increase in the risk of ventricular arrhythmias and a greater hazard for in-hospital death with COVID-19. These findings suggest that these drug regimens should not be used outside of clinical trials and urgent confirmation from randomised clinical trials is needed...end
Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
In summary, this multinational, observational, real- world study of patients with COVID-19 requiring hospitalisation found that the use of a regimen containing hydroxychloroquine or chloroquine (with or without a macrolide) was associated with no evidence of benefit, but instead was associated with an increase in the risk of ventricular arrhythmias and a greater hazard for in-hospital death with COVID-19. These findings suggest that these drug regimens should not be used outside of clinical trials and urgent confirmation from randomised clinical trials is needed...end
Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
Mandeep R Mehra, Sapan S Desai, Frank Ruschitzka, Amit N Patel
Summary
Background Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19.
Methods We did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2. Patients who received one of the treatments of interest within 48 h of diagnosis were included in one of four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and patients who received none of these treatments formed the control group. Patients for whom one of the treatments of interest was initiated more than 48 h after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation).
Findings 96 032 patients (mean age 53·8 years, 46·3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10 698 (11·1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%; hazard ratio 1·335, 95% CI 1·223–1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368–1·531), chloroquine (16·4%; 1·365, 1·218–1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273–1·469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935–2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106–5·983), chloroquine (4·3%; 3·561, 2·760–4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344–4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation.
Interpretation We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.
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In summary, this multinational, observational, real- world study of patients with COVID-19 requiring hospitalisation found that the use of a regimen containing hydroxychloroquine or chloroquine (with or without a macrolide) was associated with no evidence of benefit, but instead was associated with an increase in the risk of ventricular arrhythmias and a greater hazard for in-hospital death with COVID-19. These findings suggest that these drug regimens should not be used outside of clinical trials and urgent confirmation from randomised clinical trials is needed.
Funding William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital. Copyright © 2020 Elsevier Ltd. All rights reserved. Published Online
May 22, 2020 https://doi.org/10.1016/ S0140-6736(20)31180-6
See Online/Comment https://doi.org/10.1016/ S0140-6736(20)31174-0
Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA, USA
(Prof M R Mehra MD); Surgisphere Corporation, Chicago, IL, USA (S S Desai MD); University Heart Center, University Hospital Zurich, Zurich, Switzerland (Prof F Ruschitzka MD); Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA (A N Patel MD); and HCA Research Institute, Nashville, TN, USA (A N Patel)
Correspondence to: Prof Mandeep R Mehra, Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA 02115, USA mmehra@bwh.harvard.edu
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