Estudo dos fármacos selecionados em ensaios clínicos na terapia farmacológica da COVID-19

Autores

DOI:

https://doi.org/10.33448/rsd-v11i1.24445

Palavras-chave:

COVID-19; SARS-CoV-2; Medicamentos; Ensaio Clínico; Terapêutica.

Resumo

A COVID-19 é uma infecção respiratória aguda causada pelo coronavírus SARS-CoV-2, potencialmente grave, de elevada transmissibilidade e de distribuição global. A busca por drogas que apresentam atividade sobre o SARS-CoV-2 é um desafio constante sem precedentes na validação de medicamentos eficazes no tratamento de pacientes acometidos pela COVID-19. Objetivo: Esta revisão integrativa teve como objetivo avaliar trabalhos na literatura científica, envolvendo ensaios clínicos que avaliam a eficácia de drogas já disponíveis no mercado para provável utilização no tratamento da COVID-19. Metodologia: A pesquisa foi realizada no período de abril de 2020 até junho de 2021 nas bases de dados PubMed, SciElo e Lilacs, utilizando os Descritores em Ciências da Saúde (DeCS) “COVID-19”, “SARS-CoV-2”, “Medicamentos”, “Ensaio Clínico”, “Terapêutica”. Os critérios para inclusão dos artigos na pesquisa foram os que apresentaram resumo e texto disponibilizados na íntegra eletronicamente, escritos em inglês, português e espanhol publicados no período de abril de 2020 a junho de 2021, em periódicos científicos e que avaliaram a eficácia de prováveis fármacos no tratamento da COVID-19 e ensaios clínicos em pacientes hospitalizados portadores da doença. Foram excluídos os artigos que não abordaram, em conjunto, o tema do estudo, artigos duplicados nas bases de dados, artigos de revisão, artigos baseados em ensaios in vitro / in vivo em animais, artigos baseados em medicina tradicional, estudos do tipo editorial e também os artigos reflexivos. Resultados: Dos 210 artigos identificados, 132 foram excluídos por não atenderem os critérios de inclusão, sendo selecionados para este estudo 78 artigos que objetivaram o estudo da eficácia de fármacos em ensaios clínicos internacionais. Destes, 67 estavam indexados na base de dados PubMed; 6 pelo SciELO; e, 5 na Lilacs. Foram analisados 49 fármacos, classificados em 22 classes farmacológicas. As principais classes de fármacos em estudos foram: antivirais de ação direta em monoterapia, 8 (16,32%); imunomoduladores, 7 (14,28%); imunomoduladores + associações, 2 (4,08%); e, imunoestimulantes + associações, 2 (4,08%). Conclusão: Os fármacos e suas associações em estudo não apresentaram eficácia terapêutica específica para o tratamento da COVID-19; porém, os ensaios clínicos indicaram melhora dos sintomas clínicos dos pacientes e do tempo de internamento hospitalar. Entretanto, alguns fármacos apresentaram significativas reações adversas, interferindo diretamente na segurança dos pacientes.

Referências

Abdelnabi, R., Foo, C., Jonghe, S., Maes, P., Weynand, B., Neyts, J. (2021). Molnupiravir Inhibits Replication of the Emerging SARS-CoV-2 Variants of Concern in a Hamster Infection Model. The Journal of Diseases, 224, 749 – 753. https://doi.org/10.1093/infdis/jiab361

Agarwal, A., Mukherjee, A., Kumar, G., Chatterjee, P., Bhatnagar, T., Malhotra, P., & PLACID Trial Collaborators (2020). Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial). Clinical research, 371, m3939. https://doi.org/10.1136/bmj.m3939

Agência Nacional de Vigilância Sanitária (ANVISA, 2021 a). Combate à pandemia. Anvisa autoriza uso emergencial de novo medicamento para Covid-19

https://www.gov.br/anvisa/pt-br/assuntos/noticias-anvisa/2021/anvisa-autoriza-uso-emergencial-de-novo-medicamento-para-Covid-19

Agência Nacional de Vigilância Sanitária (ANVISA, 2021 b). Leflunomida: Risco de aborto e malformações. http://antigo.anvisa.gov.br/informacoes-tecnicas13?p_p_id=101_INSTANCE_WvKKx2fhdjM2&p_p_col_id=column-1&p_p_col_pos=1&p_p_col_count=2&_101_INSTANCE_WvKKx2fhdjM2_groupId=33868&_101_INSTANCE_WvKKx2fhdjM2_urlTitle=leflunomida-risco-de-aborto-e-malformacoes-nos-fetos-e-associacao-com-o-surgimento-ou-reativacao-de-casos-de-tuberculose-e-outras-infeccoe-1&_101_INSTANCE_WvKKx2fhdjM2_struts_action=%2Fasset_publisher%2Fview_content&_101_INSTANCE_WvKKx2fhdjM2_assetEntryId=2891036&_101_INSTANCE_WvKKx2fhdjM2_type=content

Agência Nacional de Vigilância Sanitária (ANVISA,2021c). Aprovação REGN-CoV-2. https://www.gov.br/anvisa/pt-br/assuntos/noticias-anvisa/2021/aprovado-uso-emergencial-de-anticorpos-para-tratamento-de-covid-19/apresentacao-regn-cov2-ggmed.pdf/view

Agência Nacional de Vigilância Sanitária (ANVISA,2021d). Anvisa aprova o uso emergencial de mais uma associação de anticorpos contra o novo coronavírus. Banlanivimabe e Etesevimabe são indicados no tratamento das formas leve a moderada da Covid-19.Disponível em: https://www.gov.br/anvisa/pt-br/assuntos/noticias-anvisa/2021/anvisa-aprova-o-uso-emergencial-de-mais-uma-associacao-de-anticorpos-contra-o-novo-coronavirus

Agência Nacional de Vigilância Sanitária (ANVISA,2021e). Regkirona (Regdanvimabe). https://www.gov.br/anvisa/pt-br/assuntos/paf/coronavirus/medicamentos/regkirona

Agência Nacional de Vigilância Sanitária (ANVISA,2021f). Atualizada nota técnica sobre uso de plasma de doador convalescente. https://www.gov.br/anvisa/pt-br/assuntos/noticias-anvisa/2021/atualizada-nota-tecnica-sobre-uso-de-plasma-de-doador-convalescente

Amirian, E. S., & Levy, J. K. (2020). Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses. One health (Amsterdam, Netherlands), 9, 100 - 128. https://doi.org/10.1016/j.onehlt.2020.100128

Angus, D. C., Derde, L., Al-Beidh, F., Annane, D., Arabi, Y., Beane, A., van Bentum-Puijk, W., Berry, L., Bhimani, Z., Bonten, M., Bradbury, C., Brunkhorst, F., Buxton, M., Buzgau, A., Cheng, A. C., de Jong, M., Detry, M., Estcourt, L., Fitzgerald, M., Goossens, H.,Summers, C. (2020). Effect of Hydrocortisone on Mortality and Organ Support in Patients with Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. Jama, 324, 1317–1329. doi:10.1001/jama.2020.17022

Ansarin, K., Tolouian, R., Ardalan, M., Taghizadieh, A., Varshochi, M., Teimouri, S., Vaezi, T., Valizadeh, H., Saleh, P., Safiri, S., & Chapman, K. R. (2020). Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trial. BioImpacts, 10, 209–215. doi: 10.34172/bi.2020.27

Aquino, M.E., Silveira, H.I., Pescarini, M.J., Aquino, R., Souza, A.J., Rocha, S.A. (2020). Social distancing measures to control the COVID-19 pandemic: potential impacts and challenges in Brazil. Scielo Brazil. Ciência e Saúde Coletiva 25 (supl 1). https://doi.org/10.1590/1413-81232020256.1.10502020.

Bai, Y., Yao, L., Wei, T., Tian, F., Jin, D.-Y., Chen, L., & Wang, M. (2020). Presumed Asymptomatic Carrier Transmission of COVID-19. Jama, 323 (14), 1406-1407. doi: 10.1001 / jama.2020.2565

Barlow, A., Landolf, K.M, Barlow, B., Yeung, S., Heavner, J., Claassen C., Review of Emerging Pharmacotherapy for the Treatment of Coronavirus Disease 2019, Pharmacotherapy,40(5), 416-437. doi: 10.1002/phar.2398

Bengtson, C. D., Montgomery, R. N., Nazir, U., Satterwhite, L., Kim, M. D., Bahr, N. C., Castro, M., Baumlin, N., & Salathe, M. (2021). An Open Label Trial to Assess Safety of Losartan for Treating Worsening Respiratory Illness in COVID-19. Frontiers in Medicine, 8, article 630209. https://doi.org/10.3389/fmed.2021.630209

Bian, H., Zheng, Z., Wei, D., Zhang, Z., Kang, W., Hao, C. Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial. medRxiv; 2020. doi: https://doi.org/10.1101/2020.03.21.20040691

Blaising, J., Polyak, S. J & Pécheur, E. I. (2014). Arbidol as a broad-spectrum antiviral: an update. Antiviral Research,107, 84-94. https://doi.org/10.1016/j.antiviral.2014.04.006

Bronte, V., Ugel, S., Tinazzi, E., Vella, A., Sanctis, F., Cané, S. (2020). Baricitinib restrains the immune dysregulation in patients with severe COVID-19. The Journal of Clinical Investigation, 130, 6409-6416. doi: 10.1172 / JCI141772

Butler, C. C., Yu, L. M., Dorward, J., Gbinigie, O., Hayward, G., Saville, B. R., Van Hecke, O., Berry, N., Detry, M. A., Saunders, C., Fitzgerald, M., Harris, V., Djukanovic, R., Gadola, S., Kirkpatrick, J., de Lusignan, S., Ogburn, E., Evans, P. H., Thomas, N., Patel, M. G.,.Principal Trial Collaborative Group (2021). Doxycycline for community treatment of suspected COVID-19 in people at high risk of adverse outcomes in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. The Lancet. Respiratory Medicine, 9, 1010–1020. https://doi.org/10.1016/S2213-2600(21)00310-6

Caly, L., Druce, JD, Catton, MG, Jans, DA e Wagstaff, KM (2020). The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Research, 178 , 104787. https://doi.org/10.1016/j.antiviral.2020.104787

Cao, Y., Wei, J., Zou, L., Jiang, T., Wang, G., Chen, L., Huang, L., Meng, F., Huang, L., Wang, N., Zhou, X., Luo, H., Mao, Z., Chen, X., Xie, J., Liu, J., Cheng, H., Zhao, J., Huang, G., Wang, W., Zhou, J. (2020). Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial. The Journal of allergy and clinical immunology, 146, 137–146.e3. doi: 10.1016 / j.jaci.2020.05.019

Cavalli, G., & Dinarello, C. A. (2015). Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies. Rheumatology. Oxford England, 54, 2134–2144. https://doi.org/10.1093/rheumatology/kev269

Chan, J. F., Chan, K. H., Kao, R. Y., To, K. K., Zheng, B. J., Li, C. P., Li, P. T., Dai, J., Mok, F. K., Chen, H., Hayden, F. G., & Yuen, K. Y. (2013). Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. The Journal of infection, 67(6), 606–616. https://doi.org/10.1016/j.jinf.2013.09.029.

Chan, J. F.-W., Yuan, S., Kok, K.-H, To, K. K.-W., Chu, H., Yang, J., Poon, R. W. S. (2020). A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The Lancet, 395 Issue 10223, 514-523. https://doi.org/10.1016/S0140-6736(20)30154-9

Chen, C. P., Lin, Y. C., Chen, T. C., Tseng, T. Y., Wong, H. L., Kuo, C. Y., Lin, W. P., Huang, S. R., Wang, W. Y., Liao, J. H., Liao, C. S., Hung, Y. P., Lin, T. H., Chang, T. Y., Hsiao, C. F., Huang, Y. W., Chung, W. S., Cheng, C. Y., Cheng, S. H., & Taiwan HCQ Study Group (2020). A multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of Hydroxychloroquine and a retrospective study in adult patients with mild to moderate coronavirus disease 2019 (COVID-19). PloS one, 15(12), e0242763. https://doi.org/10.1371/journal.pone.0242763.

Chen, P., Nirula, A., Heller, B., Gottlieb, R. L., Boscia, J., Morris, J., Huhn, G., Cardona, J., Mocherla, B., Stosor, V., Shawa, I., Adams, A. C., Van Naarden, J., Custer, K. L., Shen, L., Durante, M., Oakley, G., Schade, A. E., Sabo, J., Patel, D. R., BLAZE-1 Investigators (2021). SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. The New England Journal of Medicine, 384(3), 229–237.

Chiba, S. (2020). Effect of early Oseltamivir on outpatients without hypoxia with suspected COVID-19. Wiener Klinische Wochenschrift, 133, 292 - 297. doi: 10.1007 / s00508-020-01780-0

Cohen J. (2020). Antibodies may curb pandemic before vaccines. Science (New York, N.Y.), 369(6505), 752–753. https://doi.org/10.1126/science.369.6505.752

CORIMUNO-19 Collaborative group (2021). Effect of Anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial. The Lancet. Respiratory Medicine, 9(3), 295–304.

Corral-Gudino, L., Bahamonde, A., Arnaiz-Revillas, F., Gómez-Barquero, J., Abadía-Otero, J., García-Ibarbia, C., Mora, V., Cerezo-Hernández, A., Hernández, J. L., López-Muñíz, G., Hernández-Blanco, F., Cifrián, J. M., Olmos, J. M., Carrascosa, M., Nieto, L., Fariñas, M. C., Riancho, J. A., & Glucocovid investigators (2021). Methylprednisolone in adults hospitalized with COVID-19 pneumonia : An open-label randomized trial (GLUCOCOVID). Wiener klinische Wochenschrift, 133(7-8), 303–311. https://doi.org/10.1007/s00508-020-01805-8

Dabbous, H. M., Abd-Elsalam, S., El-Sayed, M. H., Sherief, A. F., Ebeid, F., El Ghafar, M., Soliman, S., Elbahnasawy, M., Badawi, R., & Tageldin, M. A. (2021). Efficacy of Favipiravir in COVID-19 treatment: a multi-center randomized study. Archives of virology, 166(3), 949–954. https://doi.org/10.1007/s00705-021-04956-9

Das B. K. (2011). Azithromycin induced hepatocellular toxicity and hepatic encephalopathy in asymptomatic dilated cardiomyopathy. Indian Journal of Pharmacology, 43(6), 736–737. https://doi.org/10.4103/0253-7613.89841

Dastan, F., Nadji, S. A., Saffaei, A., Marjani, M., Moniri, A., Jamaati, H., Hashemian, S. M., Baghaei, P., Abedini, A., Varahram, M., Yousefian, S., & Tabarsi, P. (2020). Subcutaneous administration of Interferon beta-1a for COVID-19: A non-controlled prospective trial. International Immunopharmacology, 85, 106688. https://doi.org/10.1016/j.intimp.2020.106688

Davoodi, L., Abedi, SM, Salehifar, E., Alizadeh-Navaei, R., Rouhanizadeh, H., Khorasani, G., & Hosseinimehr, SJ (2020). Febuxostate therapy in ambulatory

patients with suspected COVID-19: a clinical trial. International Journal of Clinical Practice, 74 (11), e13600.

Davoudi-Monfared, E., Rahmani, H., Khalili, H., Hajiabdolbaghi, M., Salehi, M., Abbasian, L., Kazemzadeh, H., & Yekaninejad, M. S. (2020). A Randomized Clinical Trial of the Efficacy and Safety of Interferon β-1a in Treatment of Severe COVID-19. Antimicrobial agents and chemotherapy, 64(9), e01061-20. https://doi.org/10.1128/AAC.01061-20

De Clercq, E., & Li, G. (2016). Approved Antiviral Drugs over the Past 50 Years. Clinical Microbiology Reviews, 29(3), 695–747.

Deftereos, S. G., Giannopoulos, G., Vrachatis, D. A., Siasos, G. D., Giovani, S. G., Gargalianos, P., Metallidis, S., Cianos, G., Baltagiannis, S., Panagopoulos, P., Dolianitis, K., Randou, E., Syrigos, K., Kotanidou, A., Koulouris, N. G., Milionis, H., Sipsas, N., Gogos, C., Tsoukalas, G., Olímpios, C. D., GRECCO-19 investigators (2020). 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 network open, 3(6), e2013136. https://doi.org/10.1001/jamanetworkopen.2020.13136

Dequin, P. F., Heming, N., Meziani, F., Plantefève, G., Voiriot, G., Badié, J., François, B., Aubron, C., Ricard, J. D., Ehrmann, S., Jouan, Y., Guillon, A., Leclerc, M., Coffre, C., Bourgoin, H., Lengellé, C., Caille-Fénérol, C., Tavernier, E., Zohar, S., Giraudeau, B., … CAPE COVID Trial Group and the CRICS-TriGGERSep Network (2020). Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients with COVID-19: A Randomized Clinical Trial. JAMA, 324(13), 1298–1306.

Dhar, S. K., K, V., Damodar, S., Gujar, S., & Das, M. (2021). IL-6 and IL-10 as predictors of disease severity in COVID-19 patients: results from meta-analysis and regression. Heliyon, 7(2), e06155. https://doi.org/10.1016/j.heliyon.2021.e06155

Di Castelnuovo, A., Costanzo, S., Antinori, A., Berselli, N., Blandi, L., Bonaccio, M., Cauda, R., Guaraldi, G., Menicanti, L., Mennuni, M., Parruti, G., Patti, G., Santilli, F., Signorelli, C., Vergori, A., Abete, P., Ageno, W., Agodi, A., Agostoni, P., Aiello, L., Iacoviello, L. (2021). Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: The Multicenter Italian CORIST Study. Thrombosis and Haemostasis, 121(8), 1054–1065. https://doi.org/10.1055/a-1347-6070

Dubert, M., Visseaux, B., Isernia, V., Bouadma, L., Deconinck, L., Patrier, J., Wicky, P. H., Le Pluart, D., Kramer, L., Rioux, C., Le Hingrat, Q., Houhou-Fidouh, N., Yazdanpanah, Y., Ghosn, J., & Lescure, F. X. (2020). Case report study of the first five COVID-19 patients treated with remdesivir in France. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 98, 290–293. https://doi.org/10.1016/j.ijid.2020.06.093

Fahmi, A. N., Shehatou, G. S., Shebl, A. M., & Salem, H. A. (2016). Febuxostat protects rats against lipopolysaccharide-induced lung inflammation in a dose-dependent manner. Naunyn-Schmiedeberg's archives of pharmacology, 389(3), 269–278. https://doi.org/10.1007/s00210-015-1202-6

Fehr, A. R., & Perlman, S. (2015). Coronaviruses: an overview of their replication and pathogenesis. Methods in molecular biology (Clifton, N.J.), 1282, 1–23. https://doi.org/10.1007/978-1-4939-2438-7_1.

Galeotti, C., Kaveri, S. V., & Bayry, J. (2017). IVIG-mediated effector functions in autoimmune and inflammatory diseases. International immunology, 29(11), 491–498. https://doi.org/10.1093/intimm/dxx039

Gautret, P., Lagier, J. C., Parola, P., Hoang, V. T., Meddeb, L., Mailhe, M., Doudier, B., Courjon, J., Giordanengo, V., Vieira, V. E., Tissot Dupont, H., Honoré, S., Colson, P., Chabrière, E., La Scola, B., Rolain, J. M., Brouqui, P., & Raoult, D. (2020). Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International journal of antimicrobial agents, 56(1), 105949. https://doi.org/10.1016/j.ijantimicag.2020.105949

Geamănu Pancă, A., Popa-Cherecheanu, A., Marinescu, B., Geamănu, CD, & Voinea, LM (2014). Toxicidade retinal associada à exposição crônica à hidroxicloroquina e seu rastreio ocular. Análise. Journal of medicine and life , 7 (3), 322-326.

Gharebaghi, N., Nejadrahim, R., Mousavi, S. J., Sadat-Ebrahimi, S. R., & Hajizadeh, R. (2020). The use of intravenous immunoglobulin gamma for the treatment of severe coronavirus disease 2019: a randomized placebo-controlled double-blind clinical trial. BMC Infectious Diseases, 20(1), 786. https://doi.org/10.1186/s12879-020-05507-4

Goldman, J. D., Lye, D., Hui, D. S., Marks, K. M., Bruno, R., Montejano, R., Spinner, C. D., Galli, M., Ahn, M. Y., Nahass, R. G., Chen, Y. S., SenGupta, D., Hyland, R. H., Osinusi, A. O., Cao, H., Blair, C., Wei, X., Gaggar, A., Brainard, D. M., Towner, W. J., GS-US-540-5773 Investigators (2020). Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. The New England journal of medicine, 383(19), 1827–1837. https://doi.org/10.1056/NEJMoa2015301.

Gombart AF, Pierre A., Maggini S. A review of micronutrients and the immune system - working in harmony to reduce the risk of infection. Nutrients. 2020; 12 (1): 236.

Gottlieb, R. L., Nirula, A., Chen, P., Boscia, J., Heller, B., Morris, J., Huhn, G., Cardona, J., Mocherla, B., Stosor, V., Shawa, I., Kumar, P., Adams, A. C., Van Naarden, J., Custer, K. L., Durante, M., Oakley, G., Schade, A. E., Holzer, T. R., Ebert, P. J., Skovronsky, D. M. (2021). Effect of Bamlanivimabe as Monotherapy or in Combination with Etesevimabe on Viral Load in Patients with Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA, 325(7), 632–644.

Hasan, M. J., Rabbani, R., Anam, A. M., Huq, S., Polash, M., Nessa, S., & Bachar, S. C. (2021). Impact of high dose of Baricitinib in severe COVID-19 pneumonia: a prospective cohort study in Bangladesh. BMC Infectious Diseases, 21(1), 427. https://doi.org/10.1186/s12879-021-06119-2

Hinks, T., Cureton, L., Knight, R., Wang, A., Cane, J. L., Barber, V. S., Black, J., Dutton, S. J., Melhorn, J., Jabeen, M., Moss, P., Garlapati, R., Baron, T., Johnson, G., Cantle, F., Clarke, D., Elkhodair, S., Underwood, J., Lasserson, D., Pavord, I. D., Richards, D. (2021). Azithromycin versus standard care in patients with mild-to-moderate COVID-19 (ATOMIC2): an open-label, randomised trial. The Lancet. Respiratory Medicine, 9(10), 1130–1140.

Hosseini, F. S., Malektojari, A., Ghazizadeh, S., Hassaniazad, M., Davoodian, P., Dadvand, H., Nikpoor, A. R., Nikoofal-Sahlabadi, S., Kahoori, S., Sepandi, M., Hassanipour, S., & Fathalipour, M. (2021). The efficacy and safety of Ivermectin in patients with mild and moderate COVID-19: A structured summary of a study protocol for a randomized controlled trial. Trials, 22(1), 4. https://doi.org/10.1186/s13063-020-04988-7

Hou, L., & Huang, H. (2016). Immune suppressive properties of artemisinin family drugs. Pharmacology & Therapeutics, 166, 123–127. https://doi.org/10.1016/j.pharmthera.2016.07.002.

Hu, B., Guo, H., Zhou, P., & Shi, Z. L. (2021). Characteristics of SARS-CoV-2 and COVID-19. Nature reviews. Microbiology, 19(3), 141–154. https://doi.org/10.1038/s41579-020-00459-7.

Hu, K., Wang, M., Zhao, Y., Zhang, Y., Wang, T., Zheng, Z., Li, X., Zeng, S., Zhao, D., Li, H., Xu, K., & Lan, K. (2020). A Small-Scale Medication of Leflunomide as a Treatment of COVID-19 in an Open-Label Blank-Controlled Clinical Trial. Virologica Sínica, 35(6), 725–733.

Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., Cheng, Z., Yu, T., Xia, J., Wei, Y., Wu, W., Xie, X., Yin, W., Li, H., Liu, M., Xiao, Y., Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England), 395(10223), 497–506. https://doi.org/10.1016/S0140-6736(20)30183-5

Hung, I. F., Lung, K. C., Tso, E. Y., Liu, R., Chung, T. W., Chu, M. Y., Ng, Y. Y., Lo, J., Chan, J., Tam, A. R., Shum, H. P., Chan, V., Wu, A. K., Sin, K. M., Leung, W. S., Law, W. L., Lung, D. C., Sin, S., Yeung, P., Yip, C. C., Yuen, K. Y. (2020). Triple combination of Interferon beta-1b, Lopinavir-Ritonavir, and Ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet (London, England), 395(10238), 1695–1704.

Irie, K., Nakagawa, A., Fujita, H., Tamura, R., Eto, M., Ikesue, H., Muroi, N., Tomii, K., & Hashida, T. (2020). Pharmacokinetics of Favipiravir in Critically Ill Patients With COVID-19. Clinical and translational science, 13(5), 880–885.

JamaliMoghadamSiahkali, S., Zarezade, B., Koolaji, S., SeyedAlinaghi, S., Zendehdel, A., Tabarestani, M., Sekhavati Moghadam, E., Abbasian, L., Dehghan Manshadi, S. A., Salehi, M., Hasannezhad, M., Ghaderkhani, S., Meidani, M., Salahshour, F., Jafari, F., Manafi, N., & Ghiasvand, F. (2021). Safety and effectiveness of high-dose vitamin C in patients with COVID-19: a randomized open-label clinical trial. European journal of medical research, 26(1), 20. https://doi.org/10.1186/s40001-021-00490-1

Jung M, Schinazi R.F. Synthesis, and in vitro activity of human immunodeficiency virus of Artemisinin-related trioxanes (qinghaosu). Bioorg Med Chem Lett. 1994; 4 : 931-934. doi: 10.1016 / S0960-894X (01) 80266-3.

Kalil AC, Patterson TF, Mehta AK, Tomashek Km et al. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.The New England Journal of Medicine,384 ed.9, 795 – 807. doi: 10.1056/NEJMoa2031994.

Khalili, H., Nourian, A., Ahmadinejad, Z., Emadi Kouchak, H., Jafari, S., Dehghan Manshadi, S. A., Rasolinejad, M., & Kebriaeezadeh, A. (2020). Efficacy and safety of Sofosbuvir/ Ledipasvir in treatment of patients with COVID-19; A randomized clinical trial. Acta bio-medica : Atenei Parmensis, 91(4), e2020102.

Khamis, F., Al Naabi, H., Al Lawati, A., Ambusaidi, Z., Al Sharji, M., Al Barwani, U., Pandak, N., Al Balushi, Z., Al Bahrani, M., Al Salmi, I., & Al-Zakwani, I. (2021). Randomized controlled open label trial on the use of Favipiravir combined with inhaled Interferon beta-1b in hospitalized patients with moderate to severe COVID-19 pneumonia. International journal of infectious diseases : official publication of the International Society for Infectious Diseases, 102, 538–543. https://doi.org/10.1016/j.ijid.2020.11.008

Kochi, A. N., Tagliari, A. P., Forleo, G. B., Fassini, G. M., & Tondo, C. (2020). Cardiac and arrhythmic complications in patients with COVID-19. Journal of cardiovascular electrophysiology, 31(5), 1003–1008. https://doi.org/10.1111/jce.14479.

Kurtz, P., Righy, C., Gadelha, M, Bozza, F., Effect of Convalescent Plasma in Critically Ill Patients With COVID-19: An Observational Study. Frontiers in Medicine, 8, article 630982. https://doi.org/10.3389/fmed.2021.630982

Lai, C. C., Liu, Y. H., Wang, C. Y., Wang, Y. H., Hsueh, S. C., Yen, M. Y., Ko, W. C., & Hsueh, P. R. (2020). Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths. Journal of microbiology, immunology, and infection , 53(3), 404–412. https://doi.org/10.1016/j.jmii.2020.02.012

Lan, X., Shao, C., Zeng, X., Wu, Z., & Xu, Y. (2021). Lopinavir-Ritonavir alone or combined with Arbidol in the treatment of 73 hospitalized patients with COVID-19: A pilot retrospective study. International journal of clinical pharmacology and therapeutics, 59(5), 378–385. https://doi.org/10.5414/CP203861

Lee, J. S., & Shin, E. C. (2020). The type I interferon response in COVID-19: implications for treatment. Nature Reviews. Immunology, 20(10), 585–586. https://doi.org/10.1038/s41577-020-00429-3

Lemos, A.C., Do Espirito Santo, D., Salvetti, M., Girilio, R.N., Agra, L., Pazin, A. (2020) Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial. Thrombosis Research, 196, 359-366. https://www.thrombosisresearch.com/article/S0049-3848(20)30530-2/fulltext

Leneva, I., Kartashova, N., Poromov, A., Gracheva, A., Korchevaya, E., Glubokova, E., Borisova, O., Shtro, A., Loginova, S., Shchukina, V., Khamitov, R., & Faizuloev, E. (2021). Antiviral Activity of Umifenovir In Vitro against a Broad Spectrum of Coronaviruses, Including the Novel SARS-CoV-2 Virus. Viruses, 13(8), 1665. https://doi.org/10.3390/v13081665

Lenze, E. J., Mattar, C., Zorumski, C. F., Stevens, A., Schweiger, J., Nicol, G. E., Miller, J. P., Yang, L., Yingling, M., Avidan, M. S., & Reiersen, A. M. (2020). Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients with Symptomatic COVID-19: A Randomized Clinical Trial. JAMA, 324(22), 2292–2300.

Li, T., Sun, L., Zhang, W., Zheng, C., Jiang, C., Chen, M., Chen, D., Dai, Z., Bao, S., & Shen, X. (2020). Bromhexine Hydrochloride Tablets for the Treatment of Moderate COVID-19: An Open-Label Randomized Controlled Pilot Study. Clinical and Translational Science, 13(6), 1096–1102. https://doi.org/10.1111/cts.12881

Li, G., Yuan, M., Li, H., Deng, C., Wang, Q., Tang, Y., Zhang, H., Yu, W., Xu, Q., Zou, Y., Yuan, Y., Guo, J., Jin, C., Guan, X., Xie, F., & Song, J. (2021). Safety and efficacy of artemisinin-piperaquine for treatment of COVID-19: an open-label, non-randomised and controlled trial. International journal of antimicrobial agents, 57(1), 106216.

Li, L., Zhang, W., Hu, Y., Tong, X., Zheng, S., Yang, J., Kong, Y., Ren, L., Wei, Q., Mei, H., Hu, C., Tao, C., Yang, R., Wang, J., Yu, Y., Guo, Y., Wu, X., Xu, Z., Zeng, L., Xiong, N., … Liu, Z. (2020). Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients with Severe and Life-threatening COVID-19: A Randomized Clinical Trial. JAMA, 324(5), 460–470.

Libster, R., Pérez Marc, G., Wappner, D., Coviello, S., Bianchi, A., Braem, V., Esteban, I., Caballero, M. T., Wood, C., Berrueta, M., Rondan, A., Lescano, G., Cruz, P., Ritou, Y., Fernández Viña, V., Álvarez Paggi, D., Esperante, S., Ferreti, A., Ofman, G., Ciganda, Á., … Fundación INFANT–COVID-19 Group (2021). Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults. The New England journal of medicine, 384(7), 610–618.

Liu, Y., Yang, Y., Zhang, C., Huang, F., Wang, F., Yuan, J., Wang, Z., Li, J., Li, J., Feng, C., Zhang, Z., Wang, L., Peng, L., Chen, L., Qin, Y., Zhao, D., Tan, S., Yin, L., Xu, J., Zhou, C., … Liu, L. (2020). Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Science China. Life sciences, 63(3), 364–374.

Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., Zhu, N. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet, 395 (10224), 565-574.

Mahmud, R., Rahman, M. M., Alam, I., Ahmed, K., Kabir, A., Sayeed, S., Rassel, M. A., Monayem, F. B., Islam, M. S., Islam, M. M., Barshan, A. D., Hoque, M. M., Mallik, M. U., Yusuf, M. A., & Hossain, M. Z. (2021). Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial. The Journal of international medical research, 49(5), 1 - 14. https://doi.org/10.1177/03000605211013550

Manis, J.P. Overview of therapeutic monoclonal antibodies. Up To Date (2019). https://www.uptodate.com/contents/overview-of-therapeutic-monoclonal-antibodies

Meneses Calderón, J., Figueroa Flores, M., Paniagua Coria, L., Briones Garduño, J. C., Meneses Figueroa, J., Vargas Contretas, M. J., De la Cruz Ávila, L., Díaz Meza, S., Ramírez Chacón, R., Padmanabhan, S., & Mendieta Zerón, H. (2020). Nitazoxanide against COVID-19 in three explorative scenarios. Journal of infection in developing countries, 14(9), 982–986.

Mitjà, O., Corbacho-Monné, M., Ubals, M., Tebe, C., Peñafiel, J., Tobias, A., Ballana, E., Alemany, A., Riera-Martí, N., Pérez, C. A., Suñer, C., Laporte, P., Admella, P., Mitjà, J., Clua, M., Bertran, L., Sarquella, M., Gavilán, S., Ara, J., Argimon, J. M.,BCN PEP-CoV-2 RESEARCH GROUP (2020). Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciaa1009. Advance online publication. https://doi.org/10.1093/cid/ciaa1009

Mohamed Abdel-Salam Elgohary, MD 1Eman Medhat Hasan, MD 2Amany Ahmad Ibrahim, MD 3Mohamed Farouk Ahmed Abdelsalam, PhD4Raafat Zaher Abdel-Rahman, MD5Ashraf Ibrahim Zaki, MSc 1Mohamed Bakr Elaatar. Efficacy of Sofosbuvir plus Ledipasvir in Egyptian patients with COVID-19 compared to standard treatment: Randomized controlled trial . https://doi.org/10.1101/2021.05.19.21257429

Murai, Y., Kawasuji, H., Takegoshi, Y., Kaneda, M., Kimoto, K., Ueno, A., Miyajima, Y., Kawago, K., Fukui, Y., Ogami, C., Sakamaki, I., Tsuji, Y., Morinaga, Y., & Yamamoto, Y. (2021). A case of COVID-19 diagnosed with Favipiravir-induced drug fever based on a positive drug-induced lymphocyte stimulation test. International journal of infectious diseases , 106, 33–35.

Nojomi, M., Yassin, Z., Keyvani, H., Makiani, M. J., Roham, M., Laali, A., Dehghan, N., Navaei, M., & Ranjbar, M. (2020). Effect of Arbidol (Umifenovir) on COVID-19: a randomized controlled trial. BMC infectious diseases, 20(1), 954. https://doi.org/10.1186/s12879-020-05698-w

Obeid, S., Alen, J., Nguyen, V. H., Pham, V. C., Meuleman, P., Pannecouque, C., Le, T. N., Neyts, J., Dehaen, W., & Paeshuyse, J. (2013). Artemisinin analogues as potent inhibitors of in vitro hepatitis C virus replication. PloS one, 8(12), e81783. https://doi.org/10.1371/journal.pone.0081783

Organização Mundial da Saúde (OMS, 2021). Vacinas contra a COVID-19. https://www.paho.org/pt/vacinas-contra-covid-19

Organização Pan -Americana da Saúde (2020). OMS afirma que COVID-19 é agora caracterizada como pandemia. March 2020. https://www.paho.org/pt/news/11-3-2020-who-characterizes-covid-19-pandemic

Organização Pan -Americana da Saúde (2021 a). Folha informativa sobre a COVID-19. https://www.paho.org/pt/covid19

Organização Pan -Americana da Saúde (2021 b). Orientação Dinâmica da OMS. Medicamentos para prevenção da COVID-19. https://apps.who.int/iris/handle/10665/339877

Paeshuyse J, Coelmont L, Vliegen I, Hemel J Van, Vandenkerckhove J, Peys E. Hemin potentiates the anti-hepatitis C virus activity of the ntimalarial drug artemisinin. Biochem Biophys Res Commun. 2006; 348 : 139–144.

Pandey, S., Pathak, S. K., Pandey, A., Salunke, A. A., Chawla, J., Sharma, A., Sharma, S., Thivari, P., & Ratna, H. (2020). Ivermectin in COVID-19: What do we know? Diabetes & metabolic syndrome, 14(6), 1921–1922.

Pani, A., Lauriola, M., Romandini, A., & Scaglione, F. (2020). Macrolídeos e infecções virais: enfoque na azitromicina na patologia de COVID-19. International Journal of Antimicrobial Agents, 56, Issue 2. https://doi.org/10.1016/j.ijantimicag.2020.106053

Pasquini, Z., Montalti, R., Temperoni, C., Canovari, B., Mancini, M., Tempesta, M. (2020). Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU. Journal of Antimicrobial Chemotherapy, Volume 75, Issue 11, 3359–3365.

Piechotta V, Iannizzi C, Chai KL, Valk SJ, Kimber C, Dorando E, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Estcourt LJ, Skoetz N. Convalescent plasma or hyperimmune immunoglobulin for people with COVID‐19: a living systematic review. Cochrane Database of Systematic Reviews 2021, Issue 5. Art. No.: CD013600. DOI: 10.1002/14651858.CD013600

Rajendram, P., Sacha, G. L., Mehkri, O., Wang, X., Han, X., Vachharajani, V., & Duggal, A. (2021). Tocilizumab in Coronavirus Disease 2019-Related Critical Illness: A Propensity Matched Analysis. Critical care explorations, 3(1), e0327. https://doi.org/10.1097/CCE.0000000000000327

Rajter, J. C., Sherman, M. S., Fatteh, N., Vogel, F., Sacks, J., & Rajter, J. J. (2021). Use of Ivermectin Is Associated with Lower Mortality in Hospitalized Patients with Coronavirus Disease 2019: The Ivermectin in COVID Nineteen Study. Chest, 159(1), 85–92. https://doi.org/10.1016/j.chest.2020.10.009

Rakedzon, S., Neuberger, A., Domb, A. J., Petersiel, N., & Schwartz, E. (2021). From hydroxychloroquine to ivermectin: what are the anti-viral properties of anti-parasitic drugs to combat SARS-CoV-2? Journal of travel medicine, 28(2), taab005. https://doi.org/10.1093/jtm/taab005.

RECOVERY Collaborative Group (2021). Convalescent plasma in patients admitted to hospital with COVID-19 : a randomised controlled, open-label, platform trial. Lancet (London, England), 397(10289), 2049–2059. https://doi.org/10.1016/S0140-6736(21)00897-7

Rocco, P., Silva, P. L., Cruz, F. F., Melo-Junior, M., Tierno, P., Moura, M. A., De Oliveira, L., Lima, C. C., Dos Santos, E. A., Junior, W. F., Fernandes, A., Franchini, K. G., Magri, E., de Moraes, N. F., Gonçalves, J., Carbonieri, M. N., Dos Santos, I. S., Paes, N. F., Maciel, P., Rocha, R. P., SARITA-2 investigators (2021). Early use of nitazoxanide in mild COVID-19 disease: randomised, placebo-controlled trial. The European Respiratory Journal, 58(1), 2003725.

Romero, M.R., Efferth, T., Serrano, M.A., Castaño, B., Macias, R., Briz, O. Effect of Artemisinin / Artesunate as inhibitors of hepatitis B virus production in an "in vitro" replicative system”. Antiviral Research. 2005; 68 : 75–83. https://doi.org/10.1016/j.antiviral.2005.07.005

Rosa, S., & Santos, W. C. (2020). Clinical trials on drug repositioning for COVID-19 treatment. Revista panamericana de salud publica. Pan American journal of public health, 44, e40. https://doi.org/10.26633/RPSP.2020.40

Rossignol J. F. (2014). Nitazoxanide: a first-in-class broad-spectrum antiviral agent. Antiviral research, 110, 94–103. https://doi.org/10.1016/j.antiviral.2014.07.014

Ruiz-Antorán, B., Sancho-López, A., Torres, F., Moreno-Torres, V., de Pablo-López, I., García-López, P., Abad-Santos, F., Rosso-Fernández, C. M., Aldea-Perona, A., Montané, E., Aparicio-Hernández, R. M., Llop-Rius, R., Pedrós, C., Gijón, P., Hernández-Carballo, C., Pedrosa-Martínez, M. J., Rodríguez-Jiménez, C., Prada-Ramallal, G., Cabrera-García, L., Aguilar-García, J. A.,.TOCICOV-study group (2021). Combination of Tocilizumab and Steroids to Improve Mortality in Patients with Severe COVID-19 Infection: A Spanish, Multicenter, Cohort Study. Infectious diseases and therapy, 10(1), 347–362.

Salama, C., & Mohan, S. V. (2021). Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. Reply. The New England journal of medicine, 384(15), 1473–1474.

Salazar, E., Perez, K. K., Ashraf, M., Chen, J., Castillo, B., Christensen, P. A., Eubank, T., Bernard, D. W., Eagar, T. N., Long, S. W., Subedi, S., Olsen, R. J., Leveque, C., Schwartz, M. R., Dey, M., Chavez-East, C., Rogers, J., Shehabeldin, A., Joseph, D., Williams, G., … Musser, J. M. (2020). Treatment of Coronavirus Disease 2019 (COVID-19) Patients with Convalescent Plasma. The American journal of pathology, 190(8), 1680–1690.

Salvarani, C., Dolci, G., Massari, M., Merlo, D. F., Cavuto, S., Savoldi, L., Bruzzi, P., Boni, F., Braglia, L., Turrà, C., Ballerini, P. F., Sciascia, R., Zammarchi, L., Para, O., Scotton, P. G., Inojosa, W. O., Ravagnani, V., Salerno, N. D., Sainaghi, P. P., Brignone, A., … RCT-TCZ-COVID-19 Study Group (2021). Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial. JAMA internal medicine, 181(1), 24–31.

Sekhavati, E., Jafari, F., SeyedAlinaghi, S., Jamalimoghadamsiahkali, S., Sadr, S., Tabarestani, M., Pirhayati, M., Zendehdel, A., Manafi, N., Hajiabdolbaghi, M., Ahmadinejad, Z., Kouchak, H. E., Jafari, S., Khalili, H., Salehi, M., Seifi, A., Golestan, F. S., & Ghiasvand, F. (2020). Safety and effectiveness of azithromycin in patients with COVID-19: An open-label randomised trial. International journal of antimicrobial agents, 56(4), 106143.

Shakir L, Hussain M, Javeed A, Ashraf M, Riaz A. Artemisinins and immun system. Eur J Pharmacol. 2011; 668 : 6–14. doi: 10.1016 / j.ejphar.2011.06.044.

Shiraki, K., & Daikoku, T. (2020). Favipiravir, an anti-influenza drug against life-threatening RNA virus infections. Pharmacology & therapeutics, 209, 107512. https://doi.org/10.1016/j.pharmthera.2020.107512.

Simkin, J., Strange, T., Leblanc, N., & Rivera, J. C. (2021). What Is a Cytokine Storm, and Should It Matter to Me? The Journal of the American Academy of Orthopedic Surgeons, 29(7), 297–299. https://doi.org/10.5435/JAAOS-D-20-00805

Simonovich, V. A., Burgos Pratx, L. D., Scibona, P., Beruto, M. V., Vallone, M. G., Vázquez, C., Savoy, N., Giunta, D. H., Pérez, L. G., Sánchez, M., Gamarnik, A. V., Ojeda, D. S., Santoro, D. M., Camino, P. J., Antelo, S., Rainero, K., Vidiella, G. P., Miyazaki, E. A., Cornistein, W., Trabadelo, O. A., Plasm Study Group (2021). A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia. The New England journal of medicine, 384(7), 619–629

Strohbehn, G. W., Heiss, B. L., Rouhani, S. J., Trujillo, J. A., Yu, J., Kacew, A. J., Higgs, E. F., Bloodworth, J. C., Cabanov, A., Wright, R. C., Koziol, A., Weiss, A., Danahey, K., Karrison, T. G., Edens, C. C., Ventura, I. B., Pettit, N. N., Patel, B., Pisano, J., Strek, M. E., … Reid, P. D. (2020). COVIDOSE: Low-dose tocilizumab in the treatment of Covid-19. MedRxiv, 2020.07.20.20157503. https://doi.org/10.1101/2020.07.20.20157503.

Sukhatme, V., Reiersen, A., Vayttaden, S., Sukhatme, V. (2020). Fluvoxamine: A Review of Its Mechanism of Action and Its Role in COVID-19. Frontiers in Pharmacology. https://doi.org/10.3389/fphar.2021.652688

Tabarsi, P., Barati, S., Jamaati, H., Haseli, S., Marjani, M., Moniri, A., Abtahian, Z., Dastan, A., Yousefian, S., Eskandari, R., Saffaei, A., Monjazebi, F., Vahedi, A., & Dastan, F. (2021). Evaluating the effects of Intravenous Immunoglobulin (IVIg) on the management of severe COVID-19 cases: A randomized controlled trial. International immunopharmacology, 90, 107205.

Tang, W., Cao, Z., Han, M., Wang, Z., Chen, J., Sun, W., Wu, Y., Xiao, W., Liu, S., Chen, E., Chen, W., Wang, X., Yang, J., Lin, J., Zhao, Q., Yan, Y., Xie, Z., Li, D., Yang, Y., Liu, L., … Xie, Q. (2020). Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ (Clinical research ed.), 369, m1849. https://doi.org/10.1136/bmj.m1849

Thachil, J., Tang, N., Gando, S., Falanga, A., Levi, M., Clark, C., Iba, T. & Cattaneo, M. (2020b). Type and dose of heparin in Covid‐19: Reply. J Thromb Haemost, 18 (8), 2063–4.

Tomazini, B. M., Maia, I. S., Cavalcanti, A. B., Berwanger, O., Rosa, R. G., Veiga, V. C., Avezum, A., Lopes, R. D., Bueno, F. R., Silva, M., Baldassare, F. P., Costa, E., Moura, R., Honorato, M. O., Costa, A. N., Damiani, L. P., Lisboa, T., Kawano-Dourado, L., Zampieri, F. G., Olivato, G. B., COALITION COVID-19 Brazil III Investigators (2020). 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, 324(13), 1307–1316. https://doi.org/10.1001/jama.2020.17021

Varga, Z., Flammer, A. J., Steiger, P., Haberecker, M., Andermatt, R., Zinkernagel, A. S., Mehra, M. R., Schuepbach, R. A., Ruschitzka, F., & Moch, H. (2020). Endothelial cell infection and endotheliitis in COVID-19. Lancet (London, England), 395(10234), 1417–1418. https://doi.org/10.1016/S0140-6736(20)30937-5

Wang, M., Cao, R., Zhang, L., Yang, X., Liu, J., Xu, M., Xiao, G. (2020). Remdesivir and Chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research, 30 (3), 269-271.

Wang, M., Zhao, Y., Hu, W., Zhao, D., Zhang, Y., Wang, T., Zheng, Z., Li, X., Zeng, S., Liu, Z., Lu, L., Wan, Z., & Hu, K. (2020). Treatment of COVID-19 Patients with Prolonged Post-Symptomatic Viral Shedding with Leflunomide -- a Single-Center, Randomized, Controlled Clinical Trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 1417. Advance online publication. https://doi.org/10.1093/cid/ciaa1417

Weinreich, D. M., Sivapalasingam, S., Norton, T., Ali, S., Gao, H., Bhore, R., Musser, B. J., Soo, Y., Rofail, D., Im, J., Perry, C., Pan, C., Hosain, R., Mahmood, A., Davis, J. D., Turner, K. C., Hooper, A. T., Hamilton, J. D., Baum, A., Kyratsous, C. A., … Trial Investigators (2021). REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. The New England journal of medicine, 384(3), 238–251.

World Health Organization (2021a). WHO Coronavirus (COVID-19) Dashboard. Jun 2021. https://covid19.who.int/

WHO Collaborating Center of Drug Statistics Methodology (2021b). Lista ATC/DDD. https://www.whocc.no/atc_ddd_index/?code=L04AA37

World Health Organization (2021c). COVID-19 Manejo Clínico. https://iris.paho.org/handle/10665.2/53945?locale-attribute=pt

Yamazaki, S., Suzuki, T., Sayama, M., Nakada, T. A., Igari, H., & Ishii, I. (2021). Suspected cholestatic liver injury induced by favipiravir in a patient with COVID-19. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 27(2), 390–392. https://doi.org/10.1016/j.jiac.2020.12.021

Yao W, Wang F, Wang H. Immunomodulation of artemisinin e seus derivados. Sci Bull. 2016; 61 : 1399-1406. doi: 10.1007 / s11434-016-1105-z.

Yates, P., Newman, S., Oshry, L., Glassman, R., Leone, A., Reichel, E. (2020). Doxycycline treatment of high-risk COVID-19-positive patients with comorbid pulmonary disease. doi: 10.1177/1753466620951053.

Ye, Q., Wang, B., & Mao, J. (2020). The pathogenesis and treatment of the `Cytokine Storm' in COVID-19. The Journal of infection, 80(6), 607–613. https://doi.org/10.1016/j.jinf.2020.03.037.

Yuen, K.-S., Ye, Z.-W., Fung, S.-Y., Chan, C.-P., & Jin, D.-Y. (2020). SARS-CoV-2 and COVID-19: the most important research questions. Cell & Bioscience, 10 (1), 1-5. Doi: http://dx.doi.org/10.5694/mja2.50577.

Zhang, L., Lin, D., Sun, X., Curth, U., Drosten, C., Sauerhering, L. (2020), Crystal structure of SARS-CoV-2 main protease provides a basis for designof improved α-ketoamide inhibitors, 368, Issue 6489, 409-412.

Zhang, W., Zhao, Y., Zhang, F., Wang, Q., Li, T., Liu, Z., Wang, J., Qin, Y., Zhang, X., Yan, X., Zeng, X., & Zhang, S. (2020). The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clinical Immunology, 214, 108393. https://doi.org/10.1016/j.clim.2020.108393

Zhao, H., Zhu, Q., Zhang, C., Li, J., Wei, M., Qin, Y., Chen, G., Wang, K., Yu, J., Wu, Z., Chen, X., & Wang, G. (2021). Tocilizumab combined with favipiravir in the treatment of COVID-19: A multicenter trial in a small sample size. Biomedicine & pharmacotherapy 133, 110825. https://doi.org/10.1016/j.biopha.2020.110825

Zhou, Q., Chen, V., Shannon, C. P., Wei, X. S., Xiang, X., Wang, X., Wang, Z. H., Tebbutt, S. J., Kollmann, T. R., & Fish, E. N. (2020). Interferon-α2b Treatment for COVID-19. Frontiers in Immunology, 11, 1061. https://doi.org/10.3389/fimmu.2020.01061

Downloads

Publicado

03/01/2022

Como Citar

FURUZAWA, T. A. .; CARDIA, G. F. E. .; IWAKI, M. V. .; CREMER, E.; SPIRONELLO, R. A. .; COMAR, F. M. de S. S. .; CUMAN, R. K. N. . Estudo dos fármacos selecionados em ensaios clínicos na terapia farmacológica da COVID-19 . Research, Society and Development, [S. l.], v. 11, n. 1, p. e11611124445, 2022. DOI: 10.33448/rsd-v11i1.24445. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/24445. Acesso em: 23 nov. 2024.

Edição

v. 11 n. 1

Seção

Ciências da Saúde

Licença

Copyright (c) 2022 Tatiana Aparecida Furuzawa; Gabriel Fernando Esteves Cardia; Mariana Vessoni Iwaki; Edivaldo Cremer; Ricardo Alexandre Spironello; Francielli Maria de Souza Silva Comar; Roberto Kenji Nakamura Cuman

Creative Commons License
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.

Autores que publicam nesta revista concordam com os seguintes termos:

1) Autores mantém os direitos autorais e concedem à revista o direito de primeira publicação, com o trabalho simultaneamente licenciado sob a Licença Creative Commons Attribution que permite o compartilhamento do trabalho com reconhecimento da autoria e publicação inicial nesta revista.

2) Autores têm autorização para assumir contratos adicionais separadamente, para distribuição não-exclusiva da versão do trabalho publicada nesta revista (ex.: publicar em repositório institucional ou como capítulo de livro), com reconhecimento de autoria e publicação inicial nesta revista.

3) Autores têm permissão e são estimulados a publicar e distribuir seu trabalho online (ex.: em repositórios institucionais ou na sua página pessoal) a qualquer ponto antes ou durante o processo editorial, já que isso pode gerar alterações produtivas, bem como aumentar o impacto e a citação do trabalho publicado.