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All Studies   Meta Analysis    Recent:   

Double-blind, Randomized, Placebo-controlled Trial With N-acetylcysteine for Treatment of Severe Acute Respiratory Syndrome Caused by Coronavirus Disease 2019 (COVID-19)

de Alencar et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa1443
Sep 2020  
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Mortality -3% Improvement Relative Risk Ventilation -16% ICU admission 9% ICU time -12% Hospitalization time -10% N-acetylcysteine  de Alencar et al.  LATE TREATMENT  DB RCT Is late treatment with N-acetylcysteine beneficial for COVID-19? Double-blind RCT 135 patients in Brazil (April - May 2020) No significant difference in outcomes seen c19early.org de Alencar et al., Clinical Infectious.., Sep 2020 FavorsN-acetylcysteine Favorscontrol 0 0.5 1 1.5 2+
14th treatment shown to reduce risk in February 2021
 
*, now with p = 0.000027 from 24 studies, recognized in 3 countries.
Lower risk for mortality, hospitalization, and cases.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19early.org
RCT 135 severe stage patients in Brazil, showing no significant differences. NAC 21g (~300mg/kg) for 20 hours. U1111-1250-3561.
risk of death, 2.6% higher, RR 1.03, p = 0.94, treatment 9 of 67 (13.4%), control 9 of 68 (13.2%), odds ratio converted to relative risk.
risk of mechanical ventilation, 16.0% higher, RR 1.16, p = 0.64, treatment 16 of 67 (23.9%), control 14 of 68 (20.6%), odds ratio converted to relative risk.
risk of ICU admission, 8.5% lower, RR 0.91, p = 0.65, treatment 29 of 67 (43.3%), control 32 of 68 (47.1%), NNT 26, odds ratio converted to relative risk.
ICU time, 12.5% higher, relative time 1.12, p = 0.56, treatment 67, control 68.
hospitalization time, 10.0% higher, relative time 1.10, p = 0.87, treatment 67, control 68.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
de Alencar et al., 23 Sep 2020, Double Blind Randomized Controlled Trial, placebo-controlled, Brazil, peer-reviewed, median age 59.0, 65 authors, study period 10 April, 2020 - 25 May, 2020, average treatment delay 7.0 days.
This PaperN-acetylcys..All
Double-blind, Randomized, Placebo-controlled Trial With N-acetylcysteine for Treatment of Severe Acute Respiratory Syndrome Caused by Coronavirus Disease 2019 (COVID-19)
Julio Cesar Garcia De Alencar, Claudia De Lucena Moreira, Alicia Dudy Müller, Cleuber Esteves Chaves, Marina Akemi Fukuhara, Elizabeth Aparecida Da Silva, Maria De Fátima Silva Miyamoto, Vanusa Barbosa Pinto, Cauê Gasparotto Bueno, Felippe Lazar Neto, Luz Marina Gomez Gomez, Maria Clara Saad Menezes, Julio Flavio Meirelles Marchini, Lucas Oliveira Marino, Rodrigo Antônio Brandão Neto, Heraldo Possolo Souza, Fernando Salvetti Valente, Hassan Rahhal, Juliana Batista Rodrigues Pereira, Eduardo Messias Hirano Padrão, Annelise Passos Bispos Wanderley, Bruno Marques, Luz Marina Gomez Gomez, Edwin Albert D’souza, Arthur Petrillo Bellintani, Rodrigo Cezar Miléo, Rodrigo Werner Toccoli, Fernanda Máximo Fonseca E Silva, João Martelleto Baptista, Marcelo De Oliveira Silva, Giovanna Babikian Costa, Rafael Berenguer Luna, Henrique Tibucheski Dos Santos, Mariana Mendes Gonçalves Cimatti De Calasans, Marcelo Petrof Sanches, Diego Juniti Takamune, Luiza Boscolo, Pedro Antonio Araújo Simões, Manuela Cristina Adsuara Pandolfi, Beatriz Larios Fantinatti, Gabriel Travessini, Matheus Finardi Lima De Faria, Ligia Trombetta Lima, Bianca Ruiz Nicolao, Gabriel De Paula Maroni Escudeiro, João Pedro Afonso Nascimento, Bruna Tolentino Caldeira, Laura De Góes Campos, Vitor Macedo Brito Medeiros, Tales Cabral Monsalvarga, Isabela Harumi Omori, Diogo Visconti Guidotte, Alexandre Lemos Bortolotto, Rodrigo De Souza Abreu, Nilo Arthur Bezerra Martins, Carlos Eduardo Umehara Juck, Lucas De Oliveira Utiyama, Felipe Mouzo Bortoleto, Renan Dourado Tinel, Gabriel Martinez Andreola, Natalia Paula Cardoso, Osvaldo Santistevan Claure, João Vitor Ziroldo Lopes, Sabrina Correa Da Costa Ribeiro
Clinical Infectious Diseases, doi:10.1093/cid/ciaa1443
Background. A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce a redox imbalance in alveolar epithelium cells, causing apoptosis, increased inflammation and, consequently, impaired gas exchange. We hypothesized that N-acetylcysteine (NAC) administration could restore this redox homeostasis and suppress unfavorable evolution in patients with coronavirus disease 2019 . Methods. This was a double-blind, randomized, placebo-controlled, single-center trial conducted at the Emergency Department of Hospital das Clínicas, São Paulo, Brazil, to determine whether NAC in high doses can avoid respiratory failure in patients with COVID-19. We enrolled 135 patients with severe COVID-19 (confirmed or suspected), with an oxyhemoglobin saturation <94% or respiratory rate >24 breaths/minute. Patients were randomized to receive NAC 21 g (~300 mg/kg) for 20 hours or dextrose 5%. The primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), time in ICU, and mortality. Results. Baseline characteristics were similar between the 2 groups, with no significant differences in age, sex, comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest computed tomography scan findings. Sixteen patients (23.9%) in the placebo group received endotracheal intubation and mechanical ventilation, compared with 14 patients (20.6%) in the NAC group (P = .675). No difference was observed in secondary endpoints. Conclusions. Administration of NAC in high doses did not affect the evolution of severe COVID-19. clinical Trials Registration. Brazilian Registry of Clinical Trials (REBEC): U1111-1250-356 (http://www.ensaiosclinicos.gov. br/rg/RBR-8969zg/).
References
Alnahdi, John, Raza, N-acetyl cysteine attenuates oxidative stress and glutathione-dependent redox imbalance caused by high glucose/high palmitic acid treatment in pancreatic Rin-5F cells, PLoS One
Atkuri, Mantovani, Herzenberg, Herzenberg, N-Acetylcysteine-a safe antidote for cysteine/glutathione deficiency, Curr Opin Pharmacol
Bunyavanich, Do, Vicencio, Nasal gene expression of angiotensinconverting enzyme 2 in children and adults, JAMA
Cao, Wang, Wen, A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19, N Engl J Med
Cazzola, Calzetta, Page, Rogliani, Matera, Thiol-based drugs in pulmonary medicine: much more than mucolytics, Trends Pharmacol Sci
Diamond, The renin-angiotensin system: an integrated view of lung disease and coagulopathy in COVID-19 and therapeutic implications, J Exp Med
Dikalov, Nazarewicz, Angiotensin II-induced production of mitochondrial reactive oxygen species: potential mechanisms and relevance for cardiovascular disease, Antioxid Redox Signal
Docherty, Harrison, Green, Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study, BMJ
Ehre, Rushton, Wang, An improved inhaled mucolytic to treat airway muco-obstructive diseases, Am J Respir Crit Care Med
Ershad, Wermuth, Vearrier, N acetylcysteine
Felice, Nardin, Tanna, Use of RAAS inhibitors and risk of clinical deterioration in COVID-19: results from an Italian cohort of 133 hypertensives, Am J Hypertens, doi:10.1093/ajh/hpaa096
Fiorentini, Falzano, Rivabene, Fabbri, Malorni, N-acetylcysteine protects epithelial cells against the oxidative imbalance due to Clostridium difficile toxins, FEBS Lett
Fisher, Curry, Evaluation and treatment of acetaminophen toxicity, Adv Pharmacol
Grasselli, Zangrillo, Zanella, Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy, JAMA
Gurwitz, Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics, Drug Dev Res, doi:10.1002/ddr.21656
Harrison, Wendon, Gimson, Alexander, Williams, Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure, N Engl J Med
Hoffmann, Kleine-Weber, Schroeder, SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell
Lanza, Perez, Costa, Covid-19: the renin-angiotensin system imbalance hypothesis, Clin Sci
Laurindo, De Souza, Mde, Janiszewski, Redox aspects of vascular response to injury, Methods Enzymol
Lee, Hynan, Rossaro, Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure, Gastroenterology
Merad, Martin, Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages, Nat Rev Immunol
Oliveira, Laurindo, Implications of plasma thiol redox in disease, Clin Sci (Lond)
Pirola, Sookoian, Estimation of renin-angiotensin-aldosterone-system (RAAS)-inhibitor effect on COVID-19 outcome: a meta-analysis, J Infect
Redza-Dutordoir, Da, Activation of apoptosis signalling pathways by reactive oxygen species, Biochim Biophys Acta
Richardson, Hirsch, Narasimhan, Northwell COVID-19 Research Consortium. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York city area, JAMA
Smilkstein, Knapp, Kulig, Rumack, Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose: analysis of the national multicenter study (1976 to 1985), N Engl J Med
Souza, Frediani, Cobra, Angiotensin II modulates CD40 expression in vascular smooth muscle cells, Clin Sci (Lond)
Sturrock, Milne, Chevassut, The renin-angiotensin system -a therapeutic target in COVID-19?, Clin Med (Lond), doi:10.7861/clinmed.2020-0146
Tay, Poh, Rénia, Macary, Ng, The trinity of COVID-19: immunity, inflammation and intervention, Nat Rev Immunol
Touyz, Li, Delles, ACE2 the Janus-faced protein-from cardiovascular protection to severe acute respiratory syndrome-coronavirus and COVID-19, Clin Sci
Wang, Zhang, Bai, An anti-oxidative therapy for ameliorating cardiac injuries of critically ill COVID-19-infected patients, Int J Cardiol
Wong, Graudins, Simplification of the standard three-bag intravenous acetylcysteine regimen for paracetamol poisoning results in a lower incidence of adverse drug reactions, Clin Toxicol (Phila)
Wu, Hu, Zhang, Ren, Yu et al., Elevation of plasma angiotensin II level is a potential pathogenesis for the critically ill COVID-19 patients, Crit Care
Wu, Leung, Bushman, Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China, Nat Med
Zhang, Wang, Ni, COVID-19: melatonin as a potential adjuvant treatment, Life Sci
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We hypothesized that ' 'N-acetylcysteine (NAC) administration could restore this redox homeostasis and suppress ' 'unfavorable evolution in patients with coronavirus disease 2019 (COVID-19).</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Methods</jats:title>\n' ' <jats:p>This was a double-blind, randomized, placebo-controlled, ' 'single-center trial conducted at the Emergency Department of Hospital das Clínicas, São ' 'Paulo, Brazil, to determine whether NAC in high doses can avoid respiratory failure in ' 'patients with COVID-19. We enrolled 135 patients with severe COVID-19 (confirmed or ' 'suspected), with an oxyhemoglobin saturation &amp;lt;94% or respiratory rate &amp;gt;24 ' 'breaths/minute. Patients were randomized to receive NAC 21 g (~300 mg/kg) for 20 hours or ' 'dextrose 5%. The primary endpoint was the need for mechanical ventilation. Secondary ' 'endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), ' 'time in ICU, and mortality.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>Baseline characteristics were similar between the 2 groups, with no ' 'significant differences in age, sex, comorbidities, medicines taken, and disease severity. ' 'Also, groups were similar in laboratory tests and chest computed tomography scan findings. ' 'Sixteen patients (23.9%) in the placebo group received endotracheal intubation and mechanical ' 'ventilation, compared with 14 patients (20.6%) in the NAC group (P\u2005=\u2005.675). No ' 'difference was observed in secondary endpoints.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Conclusions</jats:title>\n' ' <jats:p>Administration of NAC in high doses did not affect the evolution of ' 'severe COVID-19.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Clinical Trials Registration</jats:title>\n' ' <jats:p>Brazilian Registry of Clinical Trials (REBEC): U1111-1250-356 ' '(http://www.ensaiosclinicos.gov.br/rg/RBR-8969zg/).</jats:p>\n' ' </jats:sec>', 'DOI': '10.1093/cid/ciaa1443', 'type': 'journal-article', 'created': {'date-parts': [[2020, 9, 21]], 'date-time': '2020-09-21T19:23:22Z', 'timestamp': 1600716202000}, 'page': 'e736-e741', 'source': 'Crossref', 'is-referenced-by-count': 20, 'title': [ 'Double-blind, Randomized, Placebo-controlled Trial With N-acetylcysteine for Treatment of ' 'Severe Acute Respiratory Syndrome Caused by Coronavirus Disease 2019 (COVID-19)'], 'prefix': '10.1093', 'volume': '72', 'author': [ { 'given': 'Julio Cesar 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'2021060106120827900_CIT0005', 'doi-asserted-by': 'crossref', 'first-page': '271', 'DOI': '10.1016/j.cell.2020.02.052', 'article-title': 'SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a ' 'clinically proven protease inhibitor', 'volume': '181', 'author': 'Hoffmann', 'year': '2020', 'journal-title': 'Cell'}, { 'key': '2021060106120827900_CIT0006', 'doi-asserted-by': 'crossref', 'first-page': '747', 'DOI': '10.1042/CS20200363', 'article-title': 'ACE2 the Janus-faced protein—from cardiovascular protection to severe ' 'acute respiratory syndrome-coronavirus and COVID-19', 'volume': '134', 'author': 'Touyz', 'year': '2020', 'journal-title': 'Clin Sci'}, { 'key': '2021060106120827900_CIT0007', 'doi-asserted-by': 'crossref', 'first-page': '290', 'DOI': '10.1186/s13054-020-03015-0', 'article-title': 'Elevation of plasma angiotensin II level is a potential pathogenesis ' 'for the critically ill COVID-19 patients', 'volume': '24', 'author': 'Wu', 'year': '2020', 'journal-title': 'Crit Care'}, { 'key': '2021060106120827900_CIT0008', 'doi-asserted-by': 'crossref', 'first-page': '2427', 'DOI': '10.1001/jama.2020.8707', 'article-title': 'Nasal gene expression of angiotensin-converting enzyme 2 in children ' 'and adults', 'volume': '323', 'author': 'Bunyavanich', 'year': '2020', 'journal-title': 'JAMA'}, { 'key': '2021060106120827900_CIT0009', 'doi-asserted-by': 'crossref', 'first-page': '432', 'DOI': '10.1016/S0076-6879(02)52039-5', 'article-title': 'Redox aspects of vascular response to injury', 'volume': '352', 'author': 'Laurindo', 'year': '2002', 'journal-title': 'Methods Enzymol'}, { 'key': '2021060106120827900_CIT0010', 'doi-asserted-by': 'crossref', 'first-page': '1085', 'DOI': '10.1089/ars.2012.4604', 'article-title': 'Angiotensin II-induced production of mitochondrial reactive oxygen ' 'species: potential mechanisms and relevance for cardiovascular disease', 'volume': '19', 'author': 'Dikalov', 'year': '2013', 'journal-title': 'Antioxid Redox Signal'}, { 'key': '2021060106120827900_CIT0011', 'doi-asserted-by': 'crossref', 'first-page': '2977', 'DOI': '10.1016/j.bbamcr.2016.09.012', 'article-title': 'Activation of apoptosis signalling pathways by reactive oxygen species', 'volume': '1863', 'author': 'Redza-Dutordoir', 'year': '2016', 'journal-title': 'Biochim Biophys Acta'}, { 'key': '2021060106120827900_CIT0012', 'doi-asserted-by': 'crossref', 'first-page': '423', 'DOI': '10.1042/CS20080155', 'article-title': 'Angiotensin II modulates CD40 expression in vascular smooth muscle ' 'cells', 'volume': '116', 'author': 'Souza', 'year': '2009', 'journal-title': 'Clin Sci (Lond)'}, { 'key': '2021060106120827900_CIT0013', 'doi-asserted-by': 'crossref', 'first-page': '171', 'DOI': '10.1164/rccm.201802-0245OC', 'article-title': 'An improved inhaled mucolytic to treat airway muco-obstructive diseases', 'volume': '199', 'author': 'Ehre', 'year': '2019', 'journal-title': 'Am J Respir Crit Care Med'}, { 'key': '2021060106120827900_CIT0014', 'doi-asserted-by': 'crossref', 'first-page': '856', 'DOI': '10.1053/j.gastro.2009.06.006', 'article-title': 'Intravenous N-acetylcysteine improves transplant-free survival in early ' 'stage non-acetaminophen acute liver failure', 'volume': '137', 'author': 'Lee', 'year': '2009', 'journal-title': 'Gastroenterology'}, { 'key': '2021060106120827900_CIT0015', 'doi-asserted-by': 'crossref', 'first-page': '263', 'DOI': '10.1016/bs.apha.2018.12.004', 'article-title': 'Evaluation and treatment of acetaminophen toxicity', 'volume': '85', 'author': 'Fisher', 'year': '2019', 'journal-title': 'Adv Pharmacol'}, { 'key': '2021060106120827900_CIT0016', 'doi-asserted-by': 'crossref', 'first-page': '452', 'DOI': '10.1016/j.tips.2019.04.015', 'article-title': 'Thiol-based drugs in pulmonary medicine: much more than mucolytics', 'volume': '40', 'author': 'Cazzola', 'year': '2019', 'journal-title': 'Trends Pharmacol Sci'}, { 'key': '2021060106120827900_CIT0017', 'volume-title': 'N acetylcysteine', 'author': 'Ershad', 'year': '2020'}, { 'key': '2021060106120827900_CIT0018', 'doi-asserted-by': 'crossref', 'first-page': '1257', 'DOI': '10.1042/CS20180157', 'article-title': 'Implications of plasma thiol redox in disease', 'volume': '132', 'author': 'Oliveira', 'year': '2018', 'journal-title': 'Clin Sci (Lond)'}, { 'key': '2021060106120827900_CIT0019', 'doi-asserted-by': 'crossref', 'first-page': '1259', 'DOI': '10.1042/CS20200492', 'article-title': 'Covid-19: the renin–angiotensin system imbalance hypothesis', 'volume': '134', 'author': 'Lanza', 'year': '2020', 'journal-title': 'Clin Sci'}, { 'key': '2021060106120827900_CIT0020', 'doi-asserted-by': 'crossref', 'first-page': '115', 'DOI': '10.3109/15563650.2015.1115055', 'article-title': 'Simplification of the standard three-bag intravenous acetylcysteine ' 'regimen for paracetamol poisoning results in a lower incidence of ' 'adverse drug reactions', 'volume': '54', 'author': 'Wong', 'year': '2016', 'journal-title': 'Clin Toxicol (Phila)'}, { 'key': '2021060106120827900_CIT0021', 'doi-asserted-by': 'crossref', 'first-page': '1787', 'DOI': '10.1056/NEJMoa2001282', 'article-title': 'A trial of lopinavir-ritonavir in adults hospitalized with severe ' 'Covid-19', 'volume': '382', 'author': 'Cao', 'year': '2020', 'journal-title': 'N Engl J Med'}, { 'key': '2021060106120827900_CIT0022', 'doi-asserted-by': 'crossref', 'first-page': 'e20201000', 'DOI': '10.1084/jem.20201000', 'article-title': 'The renin–angiotensin system: an integrated view of lung disease and ' 'coagulopathy in COVID-19 and therapeutic implications', 'volume': '217', 'author': 'Diamond', 'year': '2020', 'journal-title': 'J Exp Med'}, { 'key': '2021060106120827900_CIT0023', 'doi-asserted-by': 'crossref', 'first-page': 'e72', 'DOI': '10.7861/clinmed.2020-0146', 'article-title': 'The renin-angiotensin system - a therapeutic target in COVID-19?', 'volume': '20', 'author': 'Sturrock', 'year': '2020', 'journal-title': 'Clin Med (Lond)'}, { 'key': '2021060106120827900_CIT0024', 'doi-asserted-by': 'crossref', 'first-page': '355', 'DOI': '10.1016/j.coph.2007.04.005', 'article-title': 'N-Acetylcysteine–a safe antidote for cysteine/glutathione deficiency', 'volume': '7', 'author': 'Atkuri', 'year': '2007', 'journal-title': 'Curr Opin Pharmacol'}, { 'key': '2021060106120827900_CIT0025', 'doi-asserted-by': 'crossref', 'first-page': 'e0226696', 'DOI': '10.1371/journal.pone.0226696', 'article-title': 'N-acetyl cysteine attenuates oxidative stress and glutathione-dependent ' 'redox imbalance caused by high glucose/high palmitic acid treatment in ' 'pancreatic Rin-5F cells', 'volume': '14', 'author': 'Alnahdi', 'year': '2019', 'journal-title': 'PLoS One'}, { 'key': '2021060106120827900_CIT0026', 'doi-asserted-by': 'crossref', 'first-page': '124', 'DOI': '10.1016/S0014-5793(99)00706-1', 'article-title': 'N-acetylcysteine protects epithelial cells against the oxidative ' 'imbalance due to Clostridium difficile toxins', 'volume': '453', 'author': 'Fiorentini', 'year': '1999', 'journal-title': 'FEBS Lett'}, { 'key': '2021060106120827900_CIT0027', 'doi-asserted-by': 'crossref', 'first-page': '1852', 'DOI': '10.1056/NEJM199106273242604', 'article-title': 'Improvement by acetylcysteine of hemodynamics and oxygen transport in ' 'fulminant hepatic failure', 'volume': '324', 'author': 'Harrison', 'year': '1991', 'journal-title': 'N Engl J Med'}, { 'key': '2021060106120827900_CIT0028', 'first-page': '319', 'article-title': 'Efficacy of oral N-acetylcysteine in the treatment of acetaminophen ' 'overdose: analysis of the national multicenter study (1976 to 1985)', 'author': 'Smilkstein', 'year': '1988', 'journal-title': 'N Engl J Med'}, { 'key': '2021060106120827900_CIT0029', 'doi-asserted-by': 'crossref', 'first-page': '355', 'DOI': '10.1038/s41577-020-0331-4', 'article-title': 'Pathological inflammation in patients with COVID-19: a key role for ' 'monocytes and macrophages', 'volume': '20', 'author': 'Merad', 'year': '2020', 'journal-title': 'Nat Rev Immunol'}, { 'key': '2021060106120827900_CIT0030', 'doi-asserted-by': 'crossref', 'first-page': '506', 'DOI': '10.1038/s41591-020-0822-7', 'article-title': 'Estimating clinical severity of COVID-19 from the transmission dynamics ' 'in Wuhan, China', 'volume': '26', 'author': 'Wu', 'year': '2020', 'journal-title': 'Nat Med'}, { 'key': '2021060106120827900_CIT0031', 'doi-asserted-by': 'crossref', 'first-page': '276', 'DOI': '10.1016/j.jinf.2020.05.052', 'article-title': 'Estimation of renin-angiotensin-aldosterone-system (RAAS)-inhibitor ' 'effect on COVID-19 outcome: a meta-analysis', 'volume': '81', 'author': 'Pirola', 'year': '2020', 'journal-title': 'J Infect'}, { 'key': '2021060106120827900_CIT0032', 'doi-asserted-by': 'crossref', 'article-title': 'Use of RAAS inhibitors and risk of clinical deterioration in COVID-19: ' 'results from an Italian cohort of 133 hypertensives', 'author': 'Felice', 'year': '2020', 'journal-title': 'Am J 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Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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