Diretrizes Brasileiras para o tratamento farmacológico de pacientes hospitalizados com COVID-19

Diretriz conjunta da Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, da Sociedade Brasileira de Angiologia e Cirurgia Vascular, da Sociedade Brasileira de Infectologia, da Sociedade Brasileira de Pneumologia e Tisiologia e da Sociedade Brasileira de Reumatologia

Autores

  • Maicon Falavigna
  • Cinara Stein
  • José Luis Gomes do Amaral
  • Luciano Cesar Pontes de Azevedo
  • Karlyse Claudino Belli
  • Verônica Colpani
  • Clovis Arns da Cunha
  • Felipe Dal-Pizzol
  • Maria Beatriz Souza Dias
  • Juliana Carvalho Ferreira
  • Ana Paula da Rocha Freitas
  • Débora Dalmas Gräf
  • Hélio Penna Guimarães
  • Suzana Margareth Ajeje Lobo
  • José Tadeu Monteiro
  • Michelle Silva Nunes
  • Maura Salaroli de Oliveira
  • Clementina Corah Lucas Prado
  • Vania Cristina Canuto Santos
  • Rosemeri Maurici da Silva
  • Marcone Lima Sobreira
  • Viviane Cordeiro Veiga
  • Ávila Teixeira Vidal
  • Ricardo Machado Xavier
  • Alexandre Prehn Zavascki
  • Flávia Ribeiro Machado
  • Carlos Roberto Ribeiro de Carvalho

DOI:

https://doi.org/10.54143/jbmede.v2i1.69

Palavras-chave:

COVID-19, COVID-19/drug therapy, Health planning guidelines, SARS-CoV-2, Brazil

Resumo

Introduction: Several therapies are being used or proposed for COVID-19, and many lack appropriate evaluations of their effectiveness and safety. The purpose of this document is to develop recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil.


Methods: A group of 27 experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method.


Results: Sixteen recommendations were generated. They include strong recommendations for the use of corticosteroids in patients using supplemental oxygen, the use of anticoagulants at prophylactic doses to prevent thromboembolism and the nonuse of antibiotics in patients without suspected bacterial infection. It was not possible to make a recommendation regarding the use of tocilizumab in patients hospitalized with COVID-19 using oxygen due to uncertainties regarding the availability of and access to the drug. Strong recommendations against the use of hydroxychloroquine, convalescent plasma, colchicine, lopinavir + ritonavir and antibiotics in patients without suspected bacterial infection and also conditional recommendations against the use of casirivimab + imdevimab, ivermectin and rendesivir were made.


Conclusion: To date, few therapies have proven effective in the treatment of hospitalized patients with COVID-19, and only corticosteroids and prophylaxis for thromboembolism are recommended. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and promote economical resource use.

Referências

World Health Organization (WHO). Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV). Geneva: WHO; 2020. Available from: https://www.who.int/news/item/30-01-2020-statement-on-the-second-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-outbreak-of-novel-coronavirus-(2019-ncov)

World Health Organization (WHO). WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020. Geneva: WHO; 2020. Available from: https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020

World Health Organization (WHO). WHO Coronavirus (COVID-19) Dashboard. Geneva: WHO; 2020. Available from: https://covid19.who.int/

Brasil. Governo Federal. Ministério da Saúde. Boletins Epidemiológicos. Available from: https://www.gov.br/saude/pt-br/coronavirus/boletins-epidemiologicos-1/

Wu Z, McGoogan JM. Characteristics of and Important Lessons from the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-42.

World Health Organization (WHO). Therapeutics and COVID-19 2021: living guideline. 31 March 2021. Geneva: WHO; 2021. Available from: https://apps.who.int/iris/bitstream/handle/10665/340374/WHO-2019-nCoV-therapeutics-2021.1-eng.pdf?sequence=1&isAllowed=y

Kalil AC. Treating COVID-19-off-label drug use, compassionate use, and randomized clinical trials during pandemics. JAMA. 2020;323(19):1897-8.

Rennard SI, Kalil AC, Casaburi R. Chicken soup in the time of COVID. Chest. 2020;158(3):864-5.

Zagury-Orly I, Schwartzstein RM. Covid-19 - A Reminder to Reason. N Engl J Med. 2020;383(3):e12.

COVID-19 Recommendations - RecMap. 2021. COVID19 Recommendations and Gateway to Contextualization. [cited 2021 May 10]. Available from: https://covid19.recmap.org

Lotfi T, Stevens A, Akl EA, Falavigna M, Kredo T, Mathew JL, Schünemann HJ; eCOVID Collaborators. Getting trustworthy guidelines into the hands of decision-makers and supporting their consideration of contextual factors for implementation globally: recommendation mapping of COVID-19 guidelines. J Clin Epidemiol. 2021;135:182-6.

National COVID-19 Clinical Evidence Taskforce. Caring for people with COVID-19. Supporting Australia’s healthcare professionals with continually updated, evidence-based clinical guidelines. 2021. [cited 2021 May10]. Available from: https://covid19evidence.net.au/#living-guidelines

Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, Cheng VC, Edwards KM, Gandhi R, Gallagher J, Muller WJ, O'Horo JC, Shoham S, Murad MH, Mustafa RA, Sultan S, Falck-Ytter Y. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Infectious Diseases Society of America 2021; Version 5.6.0. [cited 2021 Mai 10]. Available from: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/

Falavigna M, Colpani V, Stein C, Azevedo LC, Bagattini AM, Brito GV, et al. Guidelines for the pharmacological treatment of COVID-19. The task-force/consensus guideline of the Brazilian Association of Intensive Care Medicine, the Brazilian Society of Infectious Diseases and the Brazilian Society of Pulmonology and Tisiology. Rev Bras Ter Intensiva. 2020;32(2):166-96.

National Institute for Health and Care Excellence (NICE). COVID-19 rapid guideline: managing COVID-19. 23 March 2021. [cited 2021 june 10]. Available from: https://www.nice.org.uk/guidance/ng191/chapter/Recommendations

National Institutes of Health (NIH). Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. 2021. [cited 2021 june 10]. Available from: https://www.covid19treatmentguidelines.nih.gov/whats-new/

Alhazzani W, Evans L, Alshamsi F, Møller MH, Ostermann M, Prescott HC, et al. Surviving Sepsis Campaign Guidelines on the Management of Adults with Coronavirus Disease 2019 (COVID-19) in the ICU: First Update. Crit Care Med. 2021;49(3):e219-e34.

Chalmers JD, Crichton ML, Goeminne PC, Cao B, Humbert M, Shteinberg M, et al. Management of hospitalised adults with coronavirus disease-19 (COVID-19): A European Respiratory Society living guideline. Eur Respir J. 2021;57(4):2100048.

Cuker A, Tseng EK, Nieuwlaat R, Angchaisuksiri P, Blair C, Dane K, et al. American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19. Blood Adv. 2021;5(3):872-88.

Alunno A, Najm A, Machado PM, Bertheussen H, Burmester GR, Carubbi F, et al. EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19. Ann Rheum Dis. 2021;80(6):698-706.

Schünemann H, Brozek J, Guyatt G, Oxman A, editors. GRADE Handbook. Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach. [Updated October 2013]. [cited 2021 June 10]. Available from: https://gdt.gradepro.org/app/handbook/handbook.html

The WHO Rapid Evidence Appraisal for COVID-19 Therapies Working Group, Sterne JA, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, et al. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients with COVID-19: A Meta-analysis. JAMA. 2020;324(13):1330-41.

RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021;384(8):693-704.

Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, Avezum A, Lopes RD, Bueno FR, Silva MVAO, Baldassare FP, Costa ELV, Moura RA, Honorato MO, Costa AN, Damiani LP, Lisboa T, Kawano-Dourado L, Zampieri FG, Olivato GB, Righy C, Amendola CP, Roepke RM, Freitas DH, Forte DN, Freitas FGR, Fernandes CC, Melro LM, Junior GF, Morais DC, Zung S, Machado FR, Azevedo LC; COALITION COVID-19 Brazil III Investigators. Effect of dexamethasone on days alive and Ventilator-Free in Patients with Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: the CoDEX randomized clinical trial. JAMA. 2020;324(13):1307-16.

Lopes RD, de Barros e Silva PG, Furtado RH, Macedo AV, Bronhara B, Damiani LP, Barbosa LM, de Aveiro Morata J, Ramacciotti E, de Aquino Martins P, de Oliveira AL, Nunes VS, Ritt LE, Rocha AT, Tramujas L, Santos SV, Diaz DR, Viana LS, Melro LM, de Alcântara Chaud MS, Figueiredo EL, Neuenschwander FC, Dracoulakis MD, Lima RG, de Souza Dantas VC, Fernandes AC, Gebara OC, Hernandes ME, Queiroz DA, Veiga VC, Canesin MF, de Faria LM, Feitosa-Filho GS, Gazzana MB, Liporace IL, de Oliveira Twardowsky A, Maia LN, Machado FR, de Matos Soeiro A, Conceição-Souza GE, Armaganijan L, Guimarães PO, Rosa RG, Azevedo LC, Alexander JH, Avezum A, Cavalcanti AB, Berwanger O; ACTION Coalition COVID-19 Brazil IV Investigators. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet. 2021;397(10291):2253-63.

Barbar S, Noventa F, Rossetto V, Ferrari A, Brandolin B, Perlati M, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450-7.

Spyropoulos AC, Anderson FAJ, FitzGerald G, Decousus H, Pini M, Chong BH, Zotz RB, Bergmann JF, Tapson V, Froehlich JB, Monreal M, Merli GJ, Pavanello R, Turpie AGG, Nakamura M, Piovella F, Kakkar AK, Spencer FA; IMPROVE Investigators. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140(3):706-14.

Spyropoulos AC, Cohen SL, Gianos E, Kohn N, Giannis D, Chatterjee S, Goldin M, Lesser M, Coppa K, Hirsch JS, McGinn T, Barish MA; COVID‐19 Consortium Group. Validation of the IMPROVE-DD risk assessment model for venous thromboembolism among hospitalized patients with COVID-19. Res Pract Thromb Haemost. 2021;5(2):296-300.

Raschke RA, Reilly BM, Guidry JR, Fontana JR, Srinivas S. The weight-based heparin dosing nomogram compared with a "standard care" nomogram. A randomized controlled trial. Ann Intern Med. 1993;119(9):874-81.

Sebaaly J, Covert K. Enoxaparin dosing at extremes of weight: literature review and dosing recommendations. Ann Pharmacother. 2018;52(9):898-909.

Duplaga BA, Rivers CW, Nutescu E. Dosing and monitoring of low-molecular-weight heparins in special populations. Pharmacotherapy. 2001;21(2):218-34.

Langford BJ, So M, Raybardhan S, Leung V, Westwood D, MacFadden DR, et al. Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis. Clin Microbiol Infect. 2020;26(12):1622-9.

RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397(10285):1637-45.

The REMAP-CAP Investigators, Gordon AC, Mouncey PR, Al-Beidh F, Rowan KM, Nichol AD, Arabi YM, et al. Interleukin-6 receptor antagonists in critically ill patients with Covid-19 - Preliminary report. medRxiv. 2021:2021.01.07.21249390.

Roche. Esclarecimento sobre o abastecimento e a demanda de tocilizumabe no mercado brasileiro. 2021 [Atualizado abril de 2021]. [citado 2021 junho 10]. Disponível em: https://www.roche.com.br/pt/por-dentro-da-roche/esclarecimento-sobre-o-abastecimento-e-a-demanda-de-tocilizumabe-no-mercado-brasileiro.html

Associação Médica Brasileira (AMB). Medicações para o tratamento da COVID-19. Comitê Extraordinário de Monitoramento COVID-19. [citado 2021 junho 10]. Disponível em: https://amb.org.br/noticias/medicacoes-para-o-tratamento-da-covid-19-cem-covid_amb/

Cavalcanti AB, Zampieri FG, Rosa RG, Azevedo LC, Veiga VC, Avezum A, Damiani LP, Marcadenti A, Kawano-Dourado L, Lisboa T, Junqueira DL, de Barros E Silva PG, Tramujas L, Abreu-Silva EO, Laranjeira LN, Soares AT, Echenique LS, Pereira AJ, Freitas FG, Gebara OC, Dantas VC, Furtado RH, Milan EP, Golin NA, Cardoso FF, Maia IS, Hoffmann Filho CR, Kormann AP, Amazonas RB, Bocchi de Oliveira MF, Serpa-Neto A, Falavigna M, Lopes RD, Machado FR, Berwanger O; Coalition Covid-19 Brazil I Investigators. Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19. N Engl J Med. 2020;383(21):2041-52.

Rosenberg ES, Dufort EM, Udo T, Wilberschied LA, Kumar J, Tesoriero J, et al. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State. JAMA. 2020;323(24):2493-502.

Magagnoli J, Narendran S, Pereira F, Cummings TH, Hardin JW, Sutton SS, et al. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. Med (N Y). 2020;1(1):114-127.e3.

Ip A, Berry DA, Hansen E, Goy AH, Pecora AL, Sinclaire BA, et al. Hydroxychloroquine and tocilizumab therapy in COVID-19 patients-An observational study. PLoS One. 2020;15(8):e0237693.

Furtado RH, Berwanger O, Fonseca HA, Corrêa TD, Ferraz LR, Lapa MG, Zampieri FG, Veiga VC, Azevedo LC, Rosa RG, Lopes RD, Avezum A, Manoel AL, Piza FM, Martins PA, Lisboa TC, Pereira AJ, Olivato GB, Dantas VC, Milan EP, Gebara OC, Amazonas RB, Oliveira MB, Soares RV, Moia DD, Piano LP, Castilho K, Momesso RG, Schettino GP, Rizzo LV, Neto AS, Machado FR, Cavalcanti AB; COALITION COVID-19 Brazil II Investigators. Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial. Lancet. 2020;396(10256):959-67.

Molina JM, Delaugerre C, Le Goff J, Mela-Lima B, Ponscarme D, Goldwirt L, et al. No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Med Mal Infect. 2020;50(4):384.

Chorin E, Dai M, Shulman E, Wadhwani L, Roi-Bar-Cohen, Barbhaiya C, et al. The QT interval in patients with SARS-CoV-2 Infection treated with hydroxychloroquine/azithromycin. medRxiv. 2020:2020.04.02.20047050.

Cipriani A, Zorzi A, Ceccato D, Capone F, Parolin M, Donato F, et al. Arrhythmic profile and 24-hour QT interval variability in COVID-19 patients treated with hydroxychloroquine and azithromycin. Int J Cardiol. 2020;316:280-4.

Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Musser BJ, Soo Y, Rofail D, Im J, Perry C, Pan C, Hosain R, Mahmood A, Davis JD, Turner KC, Hooper AT, Hamilton JD, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Kohli A, Sachdeva Y, Graber X, Kowal B, DiCioccio T, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD; Trial Investigators. REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N Engl J Med. 2021;384(3):238-51.

Roche. Report Results of Ab Cocktail (Casirivimab + Imdevimab) in P-III REGN-COV 2069 Trial for Symptomatic COVID 19 Infection. [updated 12 april 2021]. Available from: https://pharmashots.com/58368/roche-report-results-of-ab-cocktail-casirivimab-imdevimab-in-p-iii-regn-cov-2069-trial-for-symptomatic-covid-19-infection/

Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, Hohmann E, Chu HY, Luetkemeyer A, Kline S, Lopez de Castilla D, Finberg RW, Dierberg K, Tapson V, Hsieh L, Patterson TF, Paredes R, Sweeney DA, Short WR, Touloumi G, Lye DC, Ohmagari N, Oh MD, Ruiz-Palacios GM, Benfield T, Fätkenheuer G, Kortepeter MG, Atmar RL, Creech CB, Lundgren J, Babiker AG, Pett S, Neaton JD, Burgess TH, Bonnett T, Green M, Makowski M, Osinusi A, Nayak S, Lane HC; ACTT-1 Study Group Members. Remdesivir for the treatment of Covid-19 - Final report. N Engl J Med. 2020;383(19):1813-26.

Spinner CD, Gottlieb RL, Criner GJ, Arribas López JR, Cattelan AM, Soriano Viladomiu A, Ogbuagu O, Malhotra P, Mullane KM, Castagna A, Chai LY, Roestenberg M, Tsang OT, Bernasconi E, Le Turnier P, Chang SC, SenGupta D, Hyland RH, Osinusi AO, Cao H, Blair C, Wang H, Gaggar A, Brainard DM, McPhail MJ, Bhagani S, Ahn MY, Sanyal AJ, Huhn G, Marty FM; GS-US-540-5774 Investigators. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial. JAMA. 2020;324(11):1048-57.

WHO Solidarity Trial Consortium, Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, Abdool Karim Q, et al. Repurposed antiviral drugs for Covid-19 - interim WHO solidarity trial results. N Engl J Med. 2021;384(6):497-511.

Li L, Zhang W, Hu Y, Tong X, Zheng S, Yang J, et al. Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial. JAMA. 2020;324(5):460-70.

Gharbharan A, Jordans CC, Geurtsvankessel C, den Hollander JG, Karim F, Mollema FP, et al. Convalescent plasma for COVID-19. A randomized clinical trial. medRxiv. 2020:2020.07.01.20139857.

AlQahtani M, Abdulrahman A, Almadani A, Alali SY, Al Zamrooni AM, Hejab AH, et al. Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease. Sci Rep. 2021;11(1):9927.

Avendaño-Solà C, Ramos-Martínez A, Muñez-Rubio E, Ruiz-Antorán B, de Molina RM, Torres F, et al. Convalescent plasma for COVID-19: a multicenter, randomized clinical trial. medRxiv. 2020:2020.08.26.20182444.

Libster R, Pérez Marc GP, Wappner D, Coviello S, Bianchi A, Braem V, et al. Prevention of severe COVID-19 in the elderly by early high-titer plasma. medRxiv. 2020:2020.11.20.20234013.

RECOVERY Collaborative Group. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397(10289):2049-59.

Joyner MJ, Bruno KA, Klassen SA, Kunze KL, Johnson PW, Lesser ER, et al. Safety update: COVID-19 convalescent plasma in 20,000 hospitalized patients. Mayo Clin Proc. 2020;95(9):1888-97.

Simonovich VA, Burgos Pratx LD, Scibona P, Beruto MV, Vallone MG, Vázquez C, et al. A randomized trial of convalescent plasma in Covid-19 severe pneumonia. N Engl J Med. 2021;384(7):619-29.

O’Donnell MR, Grinsztejn B, Cummings MJ, Justman JE, Lamb MR, Eckhardt CM, et al. A randomized, double-blind controlled trial of convalescent plasma in adults with severe COVID-19. J Clin Invest. 2021;131(13):e150646.

Deftereos SG, Giannopoulos G, Vrachatis DA, Siasos GD, Giotaki SG, Gargalianos P, Metallidis S, Sianos G, Baltagiannis S, Panagopoulos P, Dolianitis K, Randou E, Syrigos K, Kotanidou A, Koulouris NG, Milionis H, Sipsas N, Gogos C, Tsoukalas G, Olympios CD, Tsagalou E, Migdalis I, Gerakari S, Angelidis C, Alexopoulos D, Davlouros P, Hahalis G, Kanonidis I, Katritsis D, Kolettis T, Manolis AS, Michalis L, Naka KK, Pyrgakis VN, Toutouzas KP, Triposkiadis F, Tsioufis K, Vavouranakis E, Martinèz-Dolz L, Reimers B, Stefanini GG, Cleman M, Goudevenos J, Tsiodras S, Tousoulis D, Iliodromitis E, Mehran R, Dangas G, Stefanadis C; GRECCO-19 investigators. Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019: the GRECCO-19 randomized clinical trial. JAMA Netw Open. 2020;3(6):e2013136.

Lopes MI, Bonjorno LP, Giannini MC, Amaral NB, Menezes PI, Dib SM, et al. Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo controlled clinical trial. RMD Open. 2021;7(1):e001455.

Randomised Evaluation of COVID-19 Therapy (RECOVERY). RECOVERY trial closes recruitment to colchicine treatment for patients hospitalised with COVID-19. [5 March 2021]. Available from: https://www.recoverytrial.net/news/recovery-trial-closes-recruitment-to-colchicine-treatment-for-patients-hospitalised-with-covid-19

Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382(19):1787-99.

RECOVERY Collaborative Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2020;396(10259):1345-52.

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11-05-2022

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Falavigna, M. ., Stein, C. ., Luis Gomes do Amaral, J. ., Cesar Pontes de Azevedo, L. ., Claudino Belli, K. ., Colpani, V. ., … Ribeiro de Carvalho, C. R. . (2022). Diretrizes Brasileiras para o tratamento farmacológico de pacientes hospitalizados com COVID-19: Diretriz conjunta da Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, da Sociedade Brasileira de Angiologia e Cirurgia Vascular, da Sociedade Brasileira de Infectologia, da Sociedade Brasileira de Pneumologia e Tisiologia e da Sociedade Brasileira de Reumatologia. JBMEDE - Jornal Brasileiro De Medicina De Emergência, 2(1), e22006. https://doi.org/10.54143/jbmede.v2i1.69

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