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

{ 'indexed': {'date-parts': [[2024, 3, 13]], 'date-time': '2024-03-13T12:22:23Z', 'timestamp': 1710332543725}, 'reference-count': 46, 'publisher': 'Oxford University Press (OUP)', 'issue': '11', 'license': [ { 'start': { 'date-parts': [[2020, 5, 27]], 'date-time': '2020-05-27T00:00:00Z', 'timestamp': 1590537600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'published-print': {'date-parts': [[2020, 11, 2]]}, 'abstract': '<jats:title>Abstract</jats:title>\n' ' <jats:p>More than 1.6 million Americans have been infected with severe acute ' 'respiratory syndrome coronavirus 2 (SARS-CoV-2), and\xa0more than 10 times that number carry ' 'antibodies to it. High-risk patients with progressing symptomatic disease currently have only ' 'hospitalization treatment, with its high mortality, available to them. An outpatient ' 'treatment that prevents hospitalization is desperately needed. Two candidate medications have ' 'been widely discussed: remdesivir and hydroxychloroquine (HCQ) + azithromycin (AZ). ' 'Remdesivir has shown mild effectiveness in hospitalized inpatients, but no trials in ' 'outpatients have been registered. HCQ + AZ has been widely misrepresented in both clinical ' 'reports and public media, and results of outpatient trials are not expected until September. ' 'Early outpatient illness is very different from later florid disease requiring ' 'hospitalization, and the treatments differ. Evidence about use of HCQ alone, or of HCQ + AZ ' 'in inpatients, is irrelevant with regard to the efficacy of HCQ + AZ in early high-risk ' 'outpatient disease. Five studies, including 2 controlled clinical trials, have demonstrated ' 'significant major outpatient treatment efficacy. 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. These medications need to be made ' 'widely available and promoted immediately for physicians to prescribe.</jats:p>', 'DOI': '10.1093/aje/kwaa093', 'type': 'journal-article', 'created': {'date-parts': [[2020, 5, 23]], 'date-time': '2020-05-23T04:21:36Z', 'timestamp': 1590207696000}, 'page': '1218-1226', 'source': 'Crossref', 'is-referenced-by-count': 53, 'title': 'Early Outpatient Treatment of Symptomatic, High-Risk COVID-19 Patients That Should Be Ramped Up ' 'Immediately as Key to the Pandemic Crisis', 'prefix': '10.1093', 'volume': '189', 'author': [{'given': 'Harvey A', 'family': 'Risch', 'sequence': 'first', 'affiliation': []}], 'member': '286', 'published-online': {'date-parts': [[2020, 5, 27]]}, 'reference': [ { 'key': '2023101707254504300_ref1', 'article-title': 'COVID-19 antibody seroprevalence in Santa Clara County, California', 'author': 'Bendavid', 'year': '2020', 'journal-title': 'MedRXiv'}, { 'key': '2023101707254504300_ref2', 'author': 'Los Angeles County Public Health', 'year': '2020'}, { 'key': '2023101707254504300_ref3', 'author': 'Sullum', 'year': '2020', 'journal-title': 'Reason'}, { 'key': '2023101707254504300_ref4', 'article-title': 'Amid ongoing COVID-19 pandemic, Governor Cuomo announces results of ' 'completed antibody testing study of 15,000 people showing 12.3 percent ' 'of population has COVID-19 antibodies', 'author': 'Office of the Governor, State of New York', 'year': '2020'}, { 'key': '2023101707254504300_ref5', 'article-title': 'Dutch study suggests 3% of population may have coronavirus antibodies', 'author': 'Sterling', 'year': '2020'}, { 'key': '2023101707254504300_ref6', 'article-title': 'Estudio ENE-COVID19: Primera Ronda. 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', 'first-page': '1569', 'DOI': '10.1016/S0140-6736(20)31022-9', 'article-title': 'Remdesivir in adults with severe COVID-19: a randomised, double-blind, ' 'placebo-controlled, multicentre trial', 'volume': '395', 'author': 'Wang', 'year': '2020', 'journal-title': 'Lancet'}, { 'key': '2023101707254504300_ref11', 'author': 'National Institute of Allergy and Infectious Diseases', 'year': '2020'}, { 'key': '2023101707254504300_ref12', 'author': 'Scientists to Stop COVID-19', 'year': '2020'}, { 'key': '2023101707254504300_ref13', 'first-page': '1', 'author': 'Food and Drug Administration, US Department of Health and Human Services', 'year': '2020'}, { 'key': '2023101707254504300_ref14', 'article-title': 'Randomized clinical trials and COVID-19: managing expectations', 'author': 'Bauchner', 'journal-title': 'JAMA'}, { 'key': '2023101707254504300_ref15', 'author': 'Food and Drug Administration, US Department of Health and Human Services', 'year': '2020'}, { 'key': '2023101707254504300_ref16', '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', 'first-page': '295', 'article-title': 'The environment and disease: association or causation?', 'volume': '58', 'author': 'Hill', 'year': '1965', 'journal-title': 'Proc R Soc Med'}, { 'key': '2023101707254504300_ref27', 'article-title': 'Early treatment of COVID-19 patients with hydroxychloroquine and ' 'azithromycin: a retrospective analysis of 1061 cases in Marseille, ' 'France', 'author': 'Million', 'journal-title': 'Travel Med Infect Dis'}, {'key': '2023101707254504300_ref28', 'author': 'Zelenko', 'year': '2020'}, {'key': '2023101707254504300_ref29', 'author': 'Barbosa Esper', 'year': '2020'}, {'key': '2023101707254504300_ref30', 'author': 'ABC Eyewitness News', 'year': '2020'}, { 'key': '2023101707254504300_ref31', 'doi-asserted-by': 'crossref', 'article-title': 'In vitro antiviral activity of doxycycline against SARS-CoV-2', 'author': 'Gendrot', 'year': '2020', 'DOI': '10.3390/molecules25215064'}, {'key': '2023101707254504300_ref32', 'author': 'State of Connecticut', 'year': '2020'}, {'key': '2023101707254504300_ref33', 'author': 'Gilead Sciences, Inc', 'year': '2020'}, { 'key': '2023101707254504300_ref34', 'author': 'Food and Drug Administration, US Department of Health and Human Services', 'year': '2020'}, { 'key': '2023101707254504300_ref35', 'article-title': 'Hydroxychloroquine sulfate—drug summary', 'author': 'PDR | Prescribers’ Digital Reference', 'year': '2020'}, { 'issue': '3', 'key': '2023101707254504300_ref36', 'doi-asserted-by': 'crossref', 'first-page': '139', 'DOI': '10.1177/1715163516641136', 'article-title': 'Drug-induced QT interval prolongation and torsades de pointes: role of ' 'the pharmacist in risk assessment, prevention and management', 'volume': '149', 'author': 'Tisdale', 'year': '2016', 'journal-title': 'Can Pharm J (Ott)'}, { 'key': '2023101707254504300_ref37', 'article-title': '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', 'author': 'Bessière', 'journal-title': 'JAMA Cardiol'}, { 'key': '2023101707254504300_ref38', 'article-title': 'The QT interval in patients with SARS-CoV-2 infection treated with ' 'hydroxychloroquine/azithromycin', 'author': 'Chorin', 'year': '2020', 'journal-title': 'MedRXiv'}, { 'key': '2023101707254504300_ref39', 'article-title': '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)', 'author': 'Mercuro', 'journal-title': 'JAMA Cardiol'}, { 'key': '2023101707254504300_ref40', 'article-title': 'Experience with hydroxychloroquine and azithromycin in the COVID-19 ' 'pandemic: implications for QT interval monitoring', 'author': 'Ramireddy', 'year': '2020', 'journal-title': 'MedRXiv'}, { 'key': '2023101707254504300_ref41', 'article-title': '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', '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? Does ' 'poorly conducted animal research suggest implausible hypotheses?', 'volume': '19', 'author': 'Bracken', 'year': '2009', 'journal-title': 'Ann Epidemiol'}, {'key': '2023101707254504300_ref44', 'author': 'SERMO'}, { 'key': '2023101707254504300_ref45', 'article-title': 'Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and ' 'azithromycin alone: outcomes in hospitalized COVID-19 patients', 'author': 'Carlucci', 'year': '2020', 'journal-title': 'MedRXiv'}, { 'key': '2023101707254504300_ref46', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.mehy.2020.109815', 'article-title': 'Does zinc supplementation enhance the clinical efficacy of ' "chloroquine/hydroxychloroquine to win today's battle against COVID-19?", 'volume': '142', 'author': 'Derwand', 'year': '2020', 'journal-title': 'Med Hypotheses'}], 'container-title': 'American Journal of Epidemiology', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'http://academic.oup.com/aje/advance-article-pdf/doi/10.1093/aje/kwaa093/33585862/kwaa093.pdf', 'content-type': 'application/pdf', 'content-version': 'am', 'intended-application': 'syndication'}, { 'URL': 'https://academic.oup.com/aje/article-pdf/189/11/1218/52186350/kwaa093.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'syndication'}, { 'URL': 'https://academic.oup.com/aje/article-pdf/189/11/1218/52186350/kwaa093.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 10, 17]], 'date-time': '2023-10-17T11:51:56Z', 'timestamp': 1697543516000}, 'score': 1, 'resource': {'primary': {'URL': 'https://academic.oup.com/aje/article/189/11/1218/5847586'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2020, 5, 27]]}, 'references-count': 46, 'journal-issue': { 'issue': '11', 'published-online': {'date-parts': [[2020, 5, 27]]}, 'published-print': {'date-parts': [[2020, 11, 2]]}}, 'URL': 'http://dx.doi.org/10.1093/aje/kwaa093', 'relation': {}, 'ISSN': ['0002-9262', '1476-6256'], 'subject': [], 'published-other': {'date-parts': [[2020, 11]]}, 'published': {'date-parts': [[2020, 5, 27]]}}