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      Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection

      review-article
      , MD, MPH 1 , 2 , 3 , * , , MD 1 , , MD 4 , , MD 5 , , MD 6 , , MD 1 , 2 , 3 , , MD 7 , , MD 8 , , MD 9 , , MD 10 , , MD 11 , , BS 12 , , MD 13 , , MD, PhD 14 , , MD, PhD 15 , , MD, MPH 1 , , MD, MPH 1 , , PhD 2 , , MD 16 , , MD 16 , , MD 16 , , MD 16 , , MD, PhD 17
      The American Journal of Medicine
      Published by Elsevier Inc.
      SARS-CoV-2, COVID-19, hospitalization, critical care, mortality, epidemiology, ambulatory treatment, antiviral, anti-inflammatory, anticoagulant

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          Abstract

          Approximately 9 months of the SARS-CoV-2 virus spreading across the globe has led to widespread COVID-19 acute hospitalizations and death. The rapidity and highly communicable nature of the SARS-CoV-2 outbreak has hampered the design and execution of definitive randomized, controlled trials of therapy outside of the clinic or hospital. In the absence of clinical trial results, physicians must use what has been learned about the pathophysiology of SARS-CoV-2 infection in determining early outpatient treatment of the illness with the aim of preventing hospitalization or death. This paper outlines key pathophysiological principles that relate to the patient with early infection treated at home. Therapeutic approaches based on these principles include: 1) reduction of reinoculation, 2) combination antiviral therapy, 3) immunomodulation, 4) antiplatelet/antithrombotic therapy 5) administration of oxygen, monitoring, and telemedicine. Future randomized trials testing the principles and agents discussed in this paper will undoubtedly refine and clarify their individual roles, however we emphasize the immediate need for management guidance in the setting of widespread hospital resource consumption, morbidity, and mortality.

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          Most cited references41

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          Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19

          Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19.
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            Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

            Background A relatively high mortality of severe coronavirus disease 2019 (COVID‐19) is worrying, and the application of heparin in COVID‐19 has been recommended by some expert consensus because of the risk of disseminated intravascular coagulation and venous thromboembolism. However, its efficacy remains to be validated. Methods Coagulation results, medications, and outcomes of consecutive patients being classified as having severe COVID‐19 in Tongji hospital were retrospectively analyzed. The 28‐day mortality between heparin users and nonusers were compared, as was a different risk of coagulopathy, which was stratified by the sepsis‐induced coagulopathy (SIC) score or D‐dimer result. Results There were 449 patients with severe COVID‐19 enrolled into the study, 99 of them received heparin (mainly with low molecular weight heparin) for 7 days or longer. D‐dimer, prothrombin time, and age were positively, and platelet count was negatively, correlated with 28‐day mortality in multivariate analysis. No difference in 28‐day mortality was found between heparin users and nonusers (30.3% vs 29.7%, P  = .910). But the 28‐day mortality of heparin users was lower than nonusers in patients with SIC score ≥4 (40.0% vs 64.2%, P  = .029), or D‐dimer >6‐fold of upper limit of normal (32.8% vs 52.4%, P  = .017). Conclusions Anticoagulant therapy mainly with low molecular weight heparin appears to be associated with better prognosis in severe COVID‐19 patients meeting SIC criteria or with markedly elevated D‐dimer.
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              The effect of large-scale anti-contagion policies on the COVID-19 pandemic

              Governments around the world are responding to the coronavirus disease 2019 (COVID-19) pandemic1, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with unprecedented policies designed to slow the growth rate of infections. Many policies, such as closing schools and restricting populations to their homes, impose large and visible costs on society; however, their benefits cannot be directly observed and are currently understood only through process-based simulations2-4. Here we compile data on 1,700 local, regional and national non-pharmaceutical interventions that were deployed in the ongoing pandemic across localities in China, South Korea, Italy, Iran, France and the United States. We then apply reduced-form econometric methods, commonly used to measure the effect of policies on economic growth5,6, to empirically evaluate the effect that these anti-contagion policies have had on the growth rate of infections. In the absence of policy actions, we estimate that early infections of COVID-19 exhibit exponential growth rates of approximately 38% per day. We find that anti-contagion policies have significantly and substantially slowed this growth. Some policies have different effects on different populations, but we obtain consistent evidence that the policy packages that were deployed to reduce the rate of transmission achieved large, beneficial and measurable health outcomes. We estimate that across these 6 countries, interventions prevented or delayed on the order of 61 million confirmed cases, corresponding to averting approximately 495 million total infections. These findings may help to inform decisions regarding whether or when these policies should be deployed, intensified or lifted, and they can support policy-making in the more than 180 other countries in which COVID-19 has been reported7.
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                Author and article information

                Contributors
                Journal
                Am J Med
                Am. J. Med
                The American Journal of Medicine
                Published by Elsevier Inc.
                0002-9343
                1555-7162
                7 August 2020
                7 August 2020
                Affiliations
                [1 ]Baylor University Medical Center
                [2 ]Baylor Heart and Vascular Institute
                [3 ]Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, TX
                [4 ]Cardiology Division, Regina Montis Regalis Hospital, Mondovì, Cuneo, Italy
                [5 ]Christ Advocate Medical Center, Chicago, IL
                [6 ]Emory University School of Medicine, Atlanta, GA
                [7 ]Johns Hopkins School of Medicine, Baltimore, MD
                [8 ]Cedars Sinai Medical Center, Los Angeles, CA
                [9 ]Abrazo Arizona Heart Hospital, Abrazo Health System, Phoenix, AZ
                [10 ]Carter Eye Center, Dallas, TX
                [11 ]Cardiorenal Society of America, Phoenix, AZ
                [12 ]University of Texas McGovern Medical School, Houston, TX
                [13 ]Bakersfield Heart Hospital, Bakersfield, CA
                [14 ]University of Siena, Le Scotte Hospital Viale Bracci Siena Italy
                [15 ]University of Torino, Torino, Italy
                [16 ]Henry Ford Hospital, Detroit MI
                [17 ]Yale University School of Public Health, New Haven, CT
                Author notes
                [* ]Address for Correspondence Peter A. McCullough, MD, MPH, Baylor Heart and Vascular Institute, 621 N. Hall St, H030, Dallas, TX USA 75226 peteramccullough@ 123456gmail.com
                Article
                S0002-9343(20)30673-2
                10.1016/j.amjmed.2020.07.003
                7410805
                32771461
                cc2a32a6-fff4-4182-90f9-211baf0a22ed
                © 2020 Published by Elsevier Inc.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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                sars-cov-2,covid-19,hospitalization,critical care,mortality,epidemiology,ambulatory treatment,antiviral,anti-inflammatory,anticoagulant

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