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All Studies   Meta Analysis    Recent:   

Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis

Risch, H., American Journal of Epidemiology, kwaa093, 27 May 2020, doi:10.1093/aje/kwaa093
May 2020  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
 
*, now with p < 0.00000000001 from 411 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 75 treatments. c19hcq.org
Five studies, including two controlled clinical trials, have demonstrated significant outpatient treatment efficacy.
8 meta analyses show significant improvements with hydroxychloroquine for mortality1-4, hospitalization1, recovery5, combined death/hospitalization/cases6, and cases7,8.
Currently there are 39 HCQ for COVID-19 early treatment studies, showing 76% lower mortality [61‑85%], 67% lower ventilation [-710‑99%], 31% lower ICU admission [1‑53%], and 41% lower hospitalization [28‑51%].
Risch et al., 27 May 2020, peer-reviewed, 1 author.
This PaperHCQAll
Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis
Dr Harvey A Risch
doi:10.1093/aje/kwaa093/5847586
More than 1.6 million Americans have been infected with SARS-CoV-2 and >10 times that number carry antibodies to it. High-risk patients presenting with progressing symptomatic disease have only hospitalization treatment with its high mortality. An outpatient treatment that prevents hospitalization is desperately needed. Two candidate medications have been widely discussed: remdesivir, and hydroxychloroquine+azithromycin. Remdesivir has shown mild effectiveness in hospitalized inpatients, but no trials have been registered in outpatients. Hydroxychloroquine+azithromycin has been widely misrepresented in both clinical reports and public media, and outpatient trials results are not expected until September. Early outpatient illness is very different than later hospitalized florid disease and the treatments differ. Evidence about use of hydroxychloroquine alone, or of hydroxychloroquine+azithromycin in inpatients, is irrelevant concerning efficacy of the pair in early high-risk outpatient disease. Five studies, including two controlled clinical trials, have demonstrated significant major outpatient treatment efficacy. Hydroxychloroquine+azithromycin has been used as standard-of-care in more than 300,000 older adults with multicomorbidities, with estimated proportion diagnosed with cardiac arrhythmias attributable to the medications 47/100,000 users, of which estimated mortality is <20%, 9/100,000 users, compared to the 10,000 Americans now dying each week. These medications need to be widely available and promoted immediately for physicians to prescribe.
References
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Bauchner, Fontanarosa, Randomized clinical trials and COVID-19: managing expectations, JAMA
Bendavid, Mulaney, Sood, COVID-19 antibody seroprevalence in Santa Clara County, doi:10.1101/2020.04.14.20062463
Bessière, Roccia, Delinière, Assessment of QT intervals in a case series of patients with coronavirus disease 2019 (COVID-19) infection treated with hydroxychloroquine alone or in combination with azithromycin in an intensive care unit, JAMA Cardiol
Bracken, Why are so many epidemiology associations inflated or wrong? Does poorly conducted animal research suggest implausible hypotheses?, Ann Epidemiol, doi:10.1016/j.annepidem.2008.11.006
Carlucci, Ahuja, Petrilli, Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients, doi:10.1101/2020.05.02.20080036
Catillon, Zeckhauser, Unleash the Data on COVID-19
Chorin, Dai, Shulman, The QT interval in patients with SARS-CoV-2 infection treated with hydroxychloroquine/azithromycin, doi:10.1101/2020.04.02.20047050
Derwand, Scholz, Does zinc supplementation enhance the clinical efficacy of chloroquine/hydroxychloroquine to win todays battle against COVID-19?, Med Hypotheses, doi:10.1016/j.mehy.2020.109815
Gautret, Lagier, Parola, Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int J Antimicrob Agent
Gendrot, Andreani, Jardot, In vitro antiviral activity of doxycycline against SARS-CoV-2
Giudicessi, Noseworthy, Friedman, Urgent guidance for navigating and circumventing the QTc prolonging and torsadogenic potential of possible pharmacotherapies for COVID-19. JMCP, Mayo Clin Proc, doi:10.1016/j.mayocp.2020.03.024
Grein, Ohmagari, Shin, Compassionate use of remdesivir for patients with severe Covid-19, N Engl J Med, doi:10.1056/NEJMoa2007016
Guerin, Lardenois, Levy, Covid-19: Etude rétrospective chez 88 sujets avec 3 approches thérapeutiques différentes
Hill, The environment and disease: association or causation?, Proc R Soc Med, doi:10.1177/003591576505800503
Lane, Weaver, Kostka, Safety of hydroxychloroquine, alone and in combination with azithromycin, doi:10.1101/2020.04.08.20054551v1
Lane, Weaver, Kostka, Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study, doi:10.1101/2020.04.08.20054551
Lover, Quantifying treatment effects of hydroxychloroquine and azithromycin for Covid-19: A secondary analysis of an open label non-randomized clinical trial, doi:10.1101/2020.03.22.20040949
Magagnoli, Narendran, Pereira, Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19, doi:10.1101/2020.04.16.20065920
Mercuro, Yen, Shim, Risk of QT interval prolongation associated with use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease 2019 (COVID-19), JAMA Cardiol May
Million, Lagier, Gautret, Early treatment of 1061 COVID-19 patients with hydroxychloroquine and azithromycin
Million, Roussel, Raoult, Response to Magagnoli, MedRxiv
Pharmaceuticals, Gilead announces results from phase 3 trial of investigational antiviral remdesivir in patients with severe COVID-19
Ramireddy, Chugh, Reinier, Experience with hydroxychloroquine and azithromycin in the COVID-19 pandemic: Implications for QT interval monitoring, doi:10.1101/2020.04.22.20075671
Roden, Harrington, Poppas, Considerations for drug interactions on QTc in exploratory COVID-19 (coronavirus disease 2019) treatment, Circulation, doi:10.1161/CIRCULATIONAHA.120.047521
Sermo, Breaking Results: Sermo's COVID-19 Real Time Barometer Study
Sterling, Dutch study suggests 3% of population may have coronavirus antibodies, Reuters
Sullum, Antibody tests in Colorado highlight the huge gap between confirmed COVID-19 cases and total infections
Tisdale, Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management, Can Pharm J (Ott, doi:10.1177/1715163516641136
Wang, Zhang, Du, Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Lancet, doi:10.1016/S0140-6736(20)31022-9
Williamson, Feldmann, Schwarz, Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2, doi:10.1101/2020.04.15.043166
Xu, Hussain, Wei, Associations of stay-at-home order and face-masking recommendation with trends in daily new cases and deaths of laboratory-confirmed COVID-19 in the United States, doi:10.1101/2020.05.01.20088237
Zelenko, To all medical professionals around the world
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HCQ + AZ has been used as the standard of ' 'care in more than 300,000 older adults with multiple comorbid conditions; the estimated ' 'proportion of such patients diagnosed with cardiac arrhythmia attributable to the medications ' 'is 47 per 100,000 users, among whom estimated mortality is less than 20% (9/100,000 users), ' 'as compared with the 10,000 Americans now dying each week. 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Estudio Nacional de ' 'Sero-Epidemiología de la Infección por SARS-COV-2 en España. Informe ' 'preliminar 13 de Mayo de 2020', 'author': 'Instituto de Salud Carlos III', 'year': '2020'}, { 'key': '2023101707254504300_ref7', 'article-title': 'Associations of stay-at-home order and face-masking recommendation with ' 'trends in daily new cases and deaths of laboratory-confirmed COVID-19 ' 'in the United States', 'author': 'Xu', 'year': '2020', 'journal-title': 'MedRXiv'}, { 'key': '2023101707254504300_ref8', 'article-title': 'Clinical benefit of remdesivir in rhesus macaques infected with ' 'SARS-CoV-2', 'author': 'Williamson', 'year': '2020', 'journal-title': 'BioRXiv'}, { 'issue': '24', 'key': '2023101707254504300_ref9', 'doi-asserted-by': 'crossref', 'first-page': '2327', 'DOI': '10.1056/NEJMoa2007016', 'article-title': 'Compassionate use of remdesivir for patients with severe Covid-19', 'volume': '382', 'author': 'Grein', 'year': '2020', 'journal-title': 'N Engl J Med'}, { 'issue': '10236', 'key': '2023101707254504300_ref10', 'doi-asserted-by': 'crossref', 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'author': 'COVID-19 Treatment Guidelines Panel', 'year': '2020'}, { 'issue': '24', 'key': '2023101707254504300_ref17', 'doi-asserted-by': 'crossref', 'first-page': 'e906', 'DOI': '10.1161/CIRCULATIONAHA.120.047521', 'article-title': 'Considerations for drug interactions on QTc in exploratory COVID-19 ' 'treatment', 'volume': '141', 'author': 'Roden', 'year': '2020', 'journal-title': 'Circulation'}, { 'key': '2023101707254504300_ref18', 'article-title': 'Outcomes of hydroxychloroquine usage in United States veterans ' 'hospitalized with Covid-19', 'author': 'Magagnoli', 'year': '2020', 'journal-title': 'MedRXiv'}, { 'key': '2023101707254504300_ref19', 'article-title': 'Response to Magagnoli, MedRxiv, 2020', 'author': 'Million', 'year': '2020'}, { 'key': '2023101707254504300_ref20', 'article-title': 'Covid-19: etude rétrospective chez 88 sujets avec 3 approches ' 'thérapeutiques différentes (traitement ' 'symptomatique/azithromycine/azithromycine + hydroxychloroquine)', 'author': 'Guerin', 'year': '2020'}, { 'key': '2023101707254504300_ref21', 'author': 'National Library of Medicine, National Institutes of Health', 'year': '2020'}, { 'key': '2023101707254504300_ref22', 'author': 'Centers for Disease Control and Prevention, US Department of Health and Human ' 'Services', 'year': '2020'}, {'key': '2023101707254504300_ref23', 'author': 'Catillon', 'year': '2020'}, { 'key': '2023101707254504300_ref24', 'article-title': 'Hydroxychloroquine and azithromycin as a treatment of COVID-19: results ' 'of an open-label non-randomized clinical trial', 'author': 'Gautret', 'journal-title': 'Int J Antimicrob Agents'}, { 'key': '2023101707254504300_ref25', 'article-title': 'Quantifying treatment effects of hydroxychloroquine and azithromycin ' 'for COVID-19: a secondary analysis of an open label non-randomized ' 'clinical trial (Gautret et al, 2020)', 'author': 'Lover', 'year': '2020', 'journal-title': 'MedRXiv'}, { 'issue': '5', 'key': '2023101707254504300_ref26', 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alone and in combination with ' 'azithromycin, in light of rapid wide-spread use for COVID-19: a ' 'multinational, network cohort and self-controlled case series study', 'author': 'Lane', 'year': '2020', 'journal-title': 'MedRXiv'}, { 'issue': '6', 'key': '2023101707254504300_ref42', 'doi-asserted-by': 'crossref', 'first-page': '1213', 'DOI': '10.1016/j.mayocp.2020.03.024', 'article-title': 'Urgent guidance for navigating and circumventing the QTc-prolonging and ' 'torsadogenic potential of possible pharmacotherapies for coronavirus ' 'disease 19 (COVID-19)', 'volume': '95', 'author': 'Giudicessi', 'year': '2020', 'journal-title': 'Mayo Clin Proc'}, { 'issue': '3', 'key': '2023101707254504300_ref43', 'doi-asserted-by': 'crossref', 'first-page': '220', 'DOI': '10.1016/j.annepidem.2008.11.006', 'article-title': 'Why are so many epidemiology associations inflated or wrong? 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