Investigational medications in 9,638 hospitalized patients with severe COVID-19: lessons from the “fail-and-learn” strategy during the first two waves of the pandemic in 2020

DOI record: { "DOI": "10.21203/rs.3.rs-2596201/v1", "URL": "http://dx.doi.org/10.21203/rs.3.rs-2596201/v1", "abstract": "<jats:title>Abstract</jats:title>\n <jats:p><jats:underline><jats:bold>Background:</jats:bold></jats:underline>\nThe early surge of the novel coronavirus disease 2019 (COVID-19) pandemic introduced a significant clinical challenge due to the high case-fatality rate in absence of evidence-based treatment recommendations. The empirical modalities were relegated to historical expertise from the traditional management of acute respiratory distress syndrome (ARDS) in conjunction with off-label pharmaceutical agents endorsed under the “emergency use authorization” paradigm by regulatory agencies. This study was designed to evaluate the insights from the “fail-and-learn” strategy in 2020 before the availability of COVID-19 vaccines and access to reliable insights from high-quality randomized controlled trials.\n<jats:underline><jats:bold>Methods:</jats:bold></jats:underline>\nA retrospective, multicenter, propensity-matched, case-control study was performed on a data registry comprising 186 hospitals from a national health care system in the United States, designed to investigate the efficacy of empirical treatment modalities during the early surge of the COVID-19 pandemic in 2020. Reflective of the time-windows of the initial two surges of the pandemic in 2020, patients were stratified into “early” (March 1–June 30) versus “late” (July 1–December 31) study cohorts. Logistic regression was applied to determine the efficacy of prevalent medications (remdesivir, azithromycin, hydroxychloroquine, corticosteroids, tocilizumab) and supplemental oxygen delivery modalities (invasive <jats:italic>vs.</jats:italic> non-invasive ventilation) on patient outcomes. The primary outcome measure was in-hospital mortality. Group comparisons were adjusted for covariates related to age, gender, ethnicity, body weight, comorbidities, and treatment modalities pertinent to organ failure replacement.\n<jats:underline><jats:bold>Results:</jats:bold></jats:underline>\nFrom a total of 87,788 patients in the multicenter data registry screened in this study, 9,638 patients were included who received 19,763 COVID-19 medications during the first two waves of the 2020 pandemic.The results showed inconclusive variable results pertinent to the impact of empirical medications on patient outcomes. In contrast, the necessity for oxygen supply showed significantly increased odds of mortality beyond the effect of the investigational medications. Of all the covariates associated with increased mortality, invasive mechanical ventilation had the highest odds ratios of 8.34 in the first surge and 9.46 in in the second surge of the pandemic (<jats:italic>P</jats:italic>&lt;0.01).\n<jats:underline><jats:bold>Conclusion:</jats:bold></jats:underline>\nThis retrospective multicenter observational cohort study on 9,638 hospitalized patients with severe COVID-19 during revealed that the necessity for invasive ventilation had the highest odds of mortality, beyond the variable effects observed by administration of the prevalent EUA-approved investigational drugs during the first two surges of the early 2020 pandemic in the United States.</jats:p>", "accepted": { "date-parts": [ [ 2023, 2, 16 ] ] }, "author": [ { "affiliation": [ { "name": "Sky Ridge Medical Center" } ], "family": "Delgado", "given": "Adam C.", "sequence": "first" }, { "affiliation": [ { "name": "HCA Healthcare Continental Division" } ], "family": "Cornett", "given": "Brendon", "sequence": "additional" }, { "affiliation": [ { "name": "HCA Healthcare Continental Division" } ], "family": "Choi", "given": "Ye Ji", "sequence": "additional" }, { "affiliation": [ { "name": "Sky Ridge Medical Center" } ], "family": "Colosimo", "given": "Christina", "sequence": "additional" }, { "affiliation": [ { "name": "University of Colorado" } ], "family": "Stahel", "given": "Vincent P.", "sequence": "additional" }, { "affiliation": [ { "name": "HCA Healthcare Continental Division" } ], "family": "Dziadkowiec", "given": "Oliwier", "sequence": "additional" }, { "affiliation": [ { "name": "East Carolina University" } ], "family": "Stahel", "given": "Philip F.", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2023, 2, 20 ] ], "date-time": "2023-02-20T18:36:25Z", "timestamp": 1676918185000 }, "deposited": { "date-parts": [ [ 2023, 2, 20 ] ], "date-time": "2023-02-20T18:36:50Z", "timestamp": 1676918210000 }, "group-title": "In Review", "indexed": { "date-parts": [ [ 2023, 2, 21 ] ], "date-time": "2023-02-21T05:38:12Z", "timestamp": 1676957892767 }, "institution": [ { "name": "Research Square" } ], "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2023, 2, 20 ] ] }, "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "unspecified", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 2, 20 ] ], "date-time": "2023-02-20T00:00:00Z", "timestamp": 1676851200000 } } ], "link": [ { "URL": "https://www.researchsquare.com/article/rs-2596201/v1", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://www.researchsquare.com/article/rs-2596201/v1.html", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "8761", "original-title": [], "posted": { "date-parts": [ [ 2023, 2, 20 ] ] }, "prefix": "10.21203", "published": { "date-parts": [ [ 2023, 2, 20 ] ] }, "publisher": "Research Square Platform LLC", "reference": [ { "DOI": "10.1001/jama.2020.2648", "article-title": "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", "author": "Wu Z", "doi-asserted-by": "crossref", "first-page": "1239", "issue": "13", "journal-title": "JAMA", "key": "ref1", "unstructured": "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.", "volume": "323", "year": "2020" }, { "DOI": "10.1093/jtm/taaa020", "article-title": "Isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus (2019-nCoV) outbreak", "author": "Wilder-Smith A", "doi-asserted-by": "crossref", "first-page": "taaa020", "issue": "2", "journal-title": "J Travel Med", "key": "ref2", "unstructured": "Wilder-Smith A, Freedman DO. Isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus (2019-nCoV) outbreak. J Travel Med. 2020;27(2):taaa020.", "volume": "27", "year": "2020" }, { "DOI": "10.1056/NEJMoa2001191", "article-title": "First case of 2019 novel coronavirus in the United States", "author": "Holshue ML", "doi-asserted-by": "crossref", "first-page": "929", "issue": "10", "journal-title": "N Engl J Med", "key": "ref3", "unstructured": "Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020;382(10):929–36.", "volume": "382", "year": "2020" }, { "DOI": "10.1186/s13037-020-00235-9", "article-title": "How to risk-stratify elective surgery during the COVID-19 pandemic?", "author": "Stahel PF", "doi-asserted-by": "crossref", "first-page": "8", "journal-title": "Patient Saf Surg", "key": "ref4", "unstructured": "Stahel PF. How to risk-stratify elective surgery during the COVID-19 pandemic? Patient Saf Surg. 2020;14:8.", "volume": "14", "year": "2020" }, { "article-title": "A new threat from an old enemy: Re–emergence of coronavirus", "author": "Docea AO", "first-page": "1631", "issue": "6", "journal-title": "Int J Mol Med", "key": "ref5", "unstructured": "Docea AO, Tsatsakis A, Albulescu D, et al. A new threat from an old enemy: Re–emergence of coronavirus. Int J Mol Med. 2020;45(6):1631–43.", "volume": "45", "year": "2020" }, { "author": "Khan S", "key": "ref6", "unstructured": "Khan S, Siddique R, Shereen MA et al. Emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2: Biology and therapeutic options.J. Clin. Microbiol.2020;58(5).", "year": "2020" }, { "DOI": "10.1615/CritRevImmunol.2020035633", "article-title": "COVID-19 and strategies for its therapeutics", "author": "Ma F", "doi-asserted-by": "crossref", "first-page": "513", "issue": "6", "journal-title": "Crit Rev Immunol", "key": "ref7", "unstructured": "Ma F, Gu T, Zhao S, Liu K, Dong Z. COVID-19 and strategies for its therapeutics. Crit Rev Immunol. 2020;40(6):513–26.", "volume": "40", "year": "2020" }, { "DOI": "10.1016/j.ejmech.2020.112527", "article-title": "A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir", "author": "Liang C", "doi-asserted-by": "crossref", "first-page": "112527", "journal-title": "Eur J Med Chem", "key": "ref8", "unstructured": "Liang C, Tian L, Liu Y, Hui N, Qiao G, Li H, et al. A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir. Eur J Med Chem. 2020;201:112527.", "volume": "201", "year": "2020" }, { "article-title": "Current evidence for directed and supportive investigational therapies against COVID-19", "author": "Rensburg R", "first-page": "10", "issue": "2", "journal-title": "Afr J Thorac Crit Care Med", "key": "ref9", "unstructured": "van Rensburg R, Pillay-Fuentes Lorente V, Decloedt EH. Current evidence for directed and supportive investigational therapies against COVID-19. Afr J Thorac Crit Care Med. 2020;26(2):10.", "volume": "26", "year": "2020" }, { "DOI": "10.1016/j.disamonth.2020.101058", "article-title": "COVID-19: Therapeutics and interventions currently under consideration", "author": "McFee RB", "doi-asserted-by": "crossref", "first-page": "101058", "issue": "9", "journal-title": "Dis Mon", "key": "ref10", "unstructured": "McFee RB. COVID-19: Therapeutics and interventions currently under consideration. Dis Mon. 2020;66(9):101058.", "volume": "66", "year": "2020" }, { "DOI": "10.3390/ph13080188", "article-title": "Emerging therapeutic modalities against COVID-19", "author": "Malik S", "doi-asserted-by": "crossref", "first-page": "188", "issue": "8", "journal-title": "Pharmaceuticals (Basel)", "key": "ref11", "unstructured": "Malik S, Gupta A, Zhong X, Rasmussen TP, Manautou JE, Bahal R. Emerging therapeutic modalities against COVID-19. Pharmaceuticals (Basel). 2020;13(8):188.", "volume": "13", "year": "2020" }, { "article-title": "Remdesivir use and outcomes during the FDA COVID-19 emergency use authorization period", "author": "Elshaboury RH", "first-page": "20499361211046669", "journal-title": "Ther Adv Infect Dis", "key": "ref12", "unstructured": "Elshaboury RH, Monk MM, Bebell LM, et al. Remdesivir use and outcomes during the FDA COVID-19 emergency use authorization period. Ther Adv Infect Dis. 2021;8:20499361211046669.", "volume": "8", "year": "2021" }, { "DOI": "10.14740/jocmr4201", "article-title": "Medical management of COVID-19: Evidence and experience", "author": "Bose S", "doi-asserted-by": "crossref", "first-page": "329", "issue": "6", "journal-title": "J Clin Med Res", "key": "ref13", "unstructured": "Bose S, Adapa S, Aeddula NR, et al. Medical management of COVID-19: Evidence and experience. J Clin Med Res. 2020;12(6):329–43.", "volume": "12", "year": "2020" }, { "DOI": "10.1002/art.41469", "article-title": "Antirheumatic disease therapies for the treatment of COVID-19: A systematic review and meta-analysis", "author": "Putman M", "doi-asserted-by": "crossref", "first-page": "36", "issue": "1", "journal-title": "Arthritis Rheumatol", "key": "ref14", "unstructured": "Putman M, Chock YPE, Tam H, et al. Antirheumatic disease therapies for the treatment of COVID-19: A systematic review and meta-analysis. Arthritis Rheumatol. 2021;73(1):36–47.", "volume": "73", "year": "2021" }, { "DOI": "10.1016/j.clim.2020.108450", "article-title": "The first case of COVID-19 treated with the complement C3 inhibitor AMY-101", "author": "Mastaglio S", "doi-asserted-by": "crossref", "first-page": "108450", "journal-title": "Clin Immunol", "key": "ref15", "unstructured": "Mastaglio S, Ruggeri A, Risitano AM, et al. The first case of COVID-19 treated with the complement C3 inhibitor AMY-101. Clin Immunol. 2020;215:108450.", "volume": "215", "year": "2020" }, { "DOI": "10.36401/JIPO-20-11", "article-title": "Repurposing interleukin-6 inhibitors to combat COVID-19", "author": "Kato S", "doi-asserted-by": "crossref", "first-page": "52", "issue": "2", "journal-title": "J Immunother Precis Oncol", "key": "ref16", "unstructured": "Kato S, Kurzrock R. Repurposing interleukin-6 inhibitors to combat COVID-19. J Immunother Precis Oncol. 2020;3(2):52–5.", "volume": "3", "year": "2020" }, { "DOI": "10.1080/14787210.2020.1799785", "article-title": "Hydroxychloroquine in the COVID-19 pandemic era: in pursuit of a rational use for prophylaxis of SARS-CoV-2 infection", "author": "Infante M", "doi-asserted-by": "crossref", "first-page": "5", "issue": "1", "journal-title": "Expert Rev Anti Infect Ther", "key": "ref17", "unstructured": "Infante M, Ricordi C, Alejandro R, Caprio M, Fabbri A. Hydroxychloroquine in the COVID-19 pandemic era: in pursuit of a rational use for prophylaxis of SARS-CoV-2 infection. Expert Rev Anti Infect Ther. 2021;19(1):5–16.", "volume": "19", "year": "2021" }, { "article-title": "Safety, tolerability, and pharmacokinetics of remdesivir, an antiviral for treatment of COVID-19, in healthy subjects", "author": "Humeniuk R", "first-page": "896", "issue": "5", "journal-title": "Clin Transl Sci", "key": "ref18", "unstructured": "Humeniuk R, Mathias A, Cao H, et al. Safety, tolerability, and pharmacokinetics of remdesivir, an antiviral for treatment of COVID-19, in healthy subjects. Clin Transl Sci. 2020;13(5):896–906.", "volume": "13", "year": "2020" }, { "author": "Sellitto C", "key": "ref19", "unstructured": "Sellitto C, Corbi G, Bertini N et al. Effect of remdesivir on mortality rate and clinical status of COVID-19 patients: a systematic review with meta-analysis.J. Chemother.2022:1–14.", "year": "2022" }, { "DOI": "10.1016/j.annonc.2020.03.300", "article-title": "Tocilizumab, an anti-IL-6 receptor antibody, to treat COVID-19-related respiratory failure: a case report", "author": "Michot JM", "doi-asserted-by": "crossref", "first-page": "961", "issue": "7", "journal-title": "Ann Oncol", "key": "ref20", "unstructured": "Michot JM, Albiges L, Chaput N, et al. Tocilizumab, an anti-IL-6 receptor antibody, to treat COVID-19-related respiratory failure: a case report. Ann Oncol. 2020;31(7):961–4.", "volume": "31", "year": "2020" }, { "DOI": "10.1002/rmv.2141", "article-title": "Interleukin-6 in Covid-19: A systematic review and meta-analysis", "author": "Coomes EA", "doi-asserted-by": "crossref", "first-page": "1", "issue": "6", "journal-title": "Rev Med Virol", "key": "ref21", "unstructured": "Coomes EA, Haghbayan H. Interleukin-6 in Covid-19: A systematic review and meta-analysis. Rev Med Virol. 2020;30(6):1–9.", "volume": "30", "year": "2020" }, { "DOI": "10.1002/jmv.26509", "article-title": "Efficacy of tocilizumab in COVID-19: A systematic review and meta-analysis", "author": "Aziz M", "doi-asserted-by": "crossref", "first-page": "1620", "issue": "3", "journal-title": "J Med Virol", "key": "ref22", "unstructured": "Aziz M, Haghbin H, Abu Sitta E, et al. Efficacy of tocilizumab in COVID-19: A systematic review and meta-analysis. J Med Virol. 2021;93(3):1620–30.", "volume": "93", "year": "2021" }, { "DOI": "10.1093/jac/dkab404", "article-title": "Azithromycin in patients with COVID-19: a systematic review and meta-analysis", "author": "Ayerbe L", "doi-asserted-by": "crossref", "first-page": "303", "issue": "2", "journal-title": "J Antimicrob Chemother", "key": "ref23", "unstructured": "Ayerbe L, Risco-Risco C, Forgnone I, Perez-Pinar M, Ayis S. Azithromycin in patients with COVID-19: a systematic review and meta-analysis. J Antimicrob Chemother. 2022;77(2):303–9.", "volume": "77", "year": "2022" }, { "DOI": "10.1007/s10654-022-00891-4", "article-title": "Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19", "author": "Garcia-Albeniz X", "doi-asserted-by": "crossref", "first-page": "789", "issue": "8", "journal-title": "Eur J Epidemiol", "key": "ref24", "unstructured": "Garcia-Albeniz X, Del Amo J, Polo R, Morales-Asencio JM, Hernan MA. Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19. Eur J Epidemiol. 2022;37(8):789–96.", "volume": "37", "year": "2022" }, { "article-title": "Efficacy and safety of chloroquine and hydroxychloroquine for treatment of COVID-19 patients-a systematic review and meta-analysis of randomized controlled trials", "author": "Eze P", "first-page": "93", "issue": "1", "journal-title": "Am J Cardiovasc Dis", "key": "ref25", "unstructured": "Eze P, Mezue KN, Nduka CU, Obianyo I, Egbuche O. Efficacy and safety of chloroquine and hydroxychloroquine for treatment of COVID-19 patients-a systematic review and meta-analysis of randomized controlled trials. Am J Cardiovasc Dis. 2021;11(1):93–107.", "volume": "11", "year": "2021" }, { "DOI": "10.31744/einstein_journal/2022RW0045", "article-title": "Hydroxychloroquine for treatment of COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials", "author": "Moraes VY", "doi-asserted-by": "crossref", "first-page": "eRW0045", "journal-title": "Einstein (Sao Paulo)", "key": "ref26", "unstructured": "Moraes VY, Marra AR, Matos LL, et al. Hydroxychloroquine for treatment of COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials. Einstein (Sao Paulo). 2022;20:eRW0045.", "volume": "20", "year": "2022" }, { "DOI": "10.1016/j.cca.2020.04.027", "article-title": "Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis", "author": "Henry BM", "doi-asserted-by": "crossref", "first-page": "167", "journal-title": "Clin Chim Acta", "key": "ref27", "unstructured": "Henry BM, Vikse J, Benoit S, Favaloro EJ, Lippi G. Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis. Clin Chim Acta. 2020;507:167–73.", "volume": "507", "year": "2020" }, { "DOI": "10.1016/j.cyto.2020.155151", "article-title": "COVID-19 cytokine storm: The anger of inflammation", "author": "Mahmudpour M", "doi-asserted-by": "crossref", "first-page": "155151", "journal-title": "Cytokine", "key": "ref28", "unstructured": "Mahmudpour M, Roozbeh J, Keshavarz M, Farrokhi S, Nabipour I. COVID-19 cytokine storm: The anger of inflammation. Cytokine. 2020;133:155151.", "volume": "133", "year": "2020" }, { "DOI": "10.3389/fimmu.2020.01661", "article-title": "Complement inhibition in coronavirus disease (COVID)-19: A neglected therapeutic option", "author": "Stahel PF", "doi-asserted-by": "crossref", "first-page": "1661", "journal-title": "Front Immunol", "key": "ref29", "unstructured": "Stahel PF, Barnum SR. Complement inhibition in coronavirus disease (COVID)-19: A neglected therapeutic option. Front Immunol. 2020;11:1661.", "volume": "11", "year": "2020" }, { "DOI": "10.1038/s41577-021-00665-1", "article-title": "The state of complement in COVID-19", "author": "Afzali B", "doi-asserted-by": "crossref", "first-page": "77", "issue": "2", "journal-title": "Nat Rev Immunol", "key": "ref30", "unstructured": "Afzali B, Noris M, Lambrecht BN, Kemper C. The state of complement in COVID-19. Nat Rev Immunol. 2022;22(2):77–84.", "volume": "22", "year": "2022" }, { "DOI": "10.1001/jama.2020.16761", "article-title": "Effect of hydrocortisone on 21-day mortality or respiratory support among critically ill patients with COVID-19: A randomized clinical trial", "author": "Dequin PF", "doi-asserted-by": "crossref", "first-page": "1298", "issue": "13", "journal-title": "JAMA", "key": "ref31", "unstructured": "Dequin PF, Heming N, Meziani F, et al. Effect of hydrocortisone on 21-day mortality or respiratory support among critically ill patients with COVID-19: A randomized clinical trial. JAMA. 2020;324(13):1298–306.", "volume": "324", "year": "2020" }, { "DOI": "10.1001/jama.2020.17021", "article-title": "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", "author": "Tomazini BM", "doi-asserted-by": "crossref", "first-page": "1307", "issue": "13", "journal-title": "JAMA", "key": "ref32", "unstructured": "Tomazini BM, Maia IS, Cavalcanti AB, et al. 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.", "volume": "324", "year": "2020" }, { "DOI": "10.1056/NEJMoa2021436", "article-title": "Dexamethasone in hospitalized patients with Covid-19", "author": "Group RC", "doi-asserted-by": "crossref", "first-page": "693", "issue": "8", "journal-title": "N Engl J Med", "key": "ref33", "unstructured": "Group RC, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693–704.", "volume": "384", "year": "2021" }, { "DOI": "10.1111/ijcp.14479", "article-title": "Impact of intermediate to high doses of methylprednisolone on mortality rate in patients with COVID-19 pneumonia-induced severe systemic inflammation", "author": "Climente-Marti M", "doi-asserted-by": "crossref", "first-page": "e14479", "issue": "9", "journal-title": "Int J Clin Pract", "key": "ref34", "unstructured": "Climente-Marti M, Ruiz-Millo O, Lopez-Cruz I, et al. Impact of intermediate to high doses of methylprednisolone on mortality rate in patients with COVID-19 pneumonia-induced severe systemic inflammation. Int J Clin Pract. 2021;75(9):e14479.", "volume": "75", "year": "2021" }, { "DOI": "10.1186/s43094-021-00217-3", "article-title": "Therapeutic role of corticosteroids in COVID-19: a systematic review of registered clinical trials", "author": "Raju R", "doi-asserted-by": "crossref", "first-page": "67", "issue": "1", "journal-title": "Fut J Pharm Sci", "key": "ref35", "unstructured": "Raju R, V P, Biatris PS. Therapeutic role of corticosteroids in COVID-19: a systematic review of registered clinical trials. Fut J Pharm Sci. 2021;7(1):67.", "volume": "7", "year": "2021" }, { "DOI": "10.1016/j.ijso.2020.11.008", "article-title": "Evaluation of invasive ventilation (intubation) prognosis in patients with Covid-19 symptoms", "author": "Farzan N", "doi-asserted-by": "crossref", "first-page": "149", "journal-title": "Int J Surg Open", "key": "ref36", "unstructured": "Farzan N, Vahabi S, Foroghi Ghomi SY, et al. Evaluation of invasive ventilation (intubation) prognosis in patients with Covid-19 symptoms. Int J Surg Open. 2020;27:149–53.", "volume": "27", "year": "2020" }, { "DOI": "10.1155/2022/9914081", "article-title": "Noninvasive ventilation in treatment of respiratory failure-related COVID-19 infection: Review of the literature", "author": "Mina B", "doi-asserted-by": "crossref", "first-page": "9914081", "journal-title": "Can Respir J", "key": "ref37", "unstructured": "Mina B, Newton A, Hadda V. Noninvasive ventilation in treatment of respiratory failure-related COVID-19 infection: Review of the literature. Can Respir J. 2022;2022:9914081.", "volume": "2022", "year": "2022" }, { "DOI": "10.1097/CCE.0000000000000727", "article-title": "Adoption and deadoption of medications to treat hospitalized patients with COVID-19", "author": "Barbash IJ", "doi-asserted-by": "crossref", "first-page": "e0727", "issue": "7", "journal-title": "Crit Care Explor", "key": "ref38", "unstructured": "Barbash IJ, Davis BS, Minturn JS, Kahn JM. Adoption and deadoption of medications to treat hospitalized patients with COVID-19. Crit Care Explor. 2022;4(7):e0727.", "volume": "4", "year": "2022" }, { "DOI": "10.1056/NEJMoa2021436", "article-title": "Dexamethasone in hospitalized patients with Covid-19", "author": "Horby P", "doi-asserted-by": "crossref", "first-page": "693", "issue": "8", "journal-title": "N Engl J Med", "key": "ref39", "unstructured": "Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693–704.", "volume": "384", "year": "2021" }, { "DOI": "10.3389/fmed.2020.596916", "article-title": "First Report of Tocilizumab Use in a Cohort of Latin American Patients Hospitalized for Severe COVID-19 Pneumonia", "author": "Valenzuela O", "doi-asserted-by": "crossref", "first-page": "596916", "journal-title": "Front Med (Lausanne)", "key": "ref40", "unstructured": "Valenzuela O, Ibanez S, Poli MC, et al. First Report of Tocilizumab Use in a Cohort of Latin American Patients Hospitalized for Severe COVID-19 Pneumonia. Front Med (Lausanne). 2020;7:596916.", "volume": "7", "year": "2020" }, { "DOI": "10.1056/NEJMoa2100433", "article-title": "Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19", "author": "Gordon AC", "doi-asserted-by": "crossref", "first-page": "1491", "issue": "16", "journal-title": "N Engl J Med", "key": "ref41", "unstructured": "Gordon AC, Mouncey PR, Al-Beidh F, et al. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. N Engl J Med. 2021;384(16):1491–502.", "volume": "384", "year": "2021" }, { "DOI": "10.1056/NEJMoa2028700", "article-title": "Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia", "author": "Rosas IO", "doi-asserted-by": "crossref", "first-page": "1503", "issue": "16", "journal-title": "N Engl J Med", "key": "ref42", "unstructured": "Rosas IO, Brau N, Waters M, et al. Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia. N Engl J Med. 2021;384(16):1503–16.", "volume": "384", "year": "2021" }, { "DOI": "10.1183/13993003.02523-2021", "article-title": "Effect of interleukin-6 receptor antagonists in critically ill adult patients with COVID-19 pneumonia: two randomised controlled trials of the CORIMUNO-19 Collaborative Group", "author": "Hermine O", "doi-asserted-by": "crossref", "first-page": "2102523", "issue": "2", "journal-title": "Eur Respir J", "key": "ref43", "unstructured": "Hermine O, Mariette X, Porcher R, et al. Effect of interleukin-6 receptor antagonists in critically ill adult patients with COVID-19 pneumonia: two randomised controlled trials of the CORIMUNO-19 Collaborative Group. Eur Respir J. 2022;60(2):2102523.", "volume": "60", "year": "2022" }, { "DOI": "10.1089/vim.2021.0111", "article-title": "Tocilizumab-induced unexpected increase of several inflammatory cytokines in critically ill COVID-19 patients: The anti-inflammatory side of IL-6", "author": "Ponthieux F", "doi-asserted-by": "crossref", "first-page": "60", "issue": "1", "journal-title": "Viral Immunol", "key": "ref44", "unstructured": "Ponthieux F, Dauby N, Maillart E, et al. Tocilizumab-induced unexpected increase of several inflammatory cytokines in critically ill COVID-19 patients: The anti-inflammatory side of IL-6. Viral Immunol. 2022;35(1):60–70.", "volume": "35", "year": "2022" }, { "DOI": "10.1371/journal.pone.0249349", "article-title": "What about tocilizumab? A retrospective study from a NYC Hospital during the COVID-19 outbreak", "author": "Mehta M", "doi-asserted-by": "crossref", "first-page": "e0249349", "issue": "4", "journal-title": "PLoS ONE", "key": "ref45", "unstructured": "Mehta M, Purpura LJ, McConville TH, et al. What about tocilizumab? A retrospective study from a NYC Hospital during the COVID-19 outbreak. PLoS ONE. 2021;16(4):e0249349.", "volume": "16", "year": "2021" }, { "article-title": "COVID-19 therapies for inpatients: a review and quality assessment of clinical guidelines", "author": "Wohl DA", "first-page": "00236", "issue": "4", "journal-title": "ERJ Open Res", "key": "ref46", "unstructured": "Wohl DA, Espinueva AA, Dau L, et al. COVID-19 therapies for inpatients: a review and quality assessment of clinical guidelines. ERJ Open Res. 2022;8(4):00236–2022.", "volume": "8", "year": "2022" }, { "DOI": "10.1186/s13613-020-00692-6", "article-title": "Caution about early intubation and mechanical ventilation in COVID-19", "author": "Tobin MJ", "doi-asserted-by": "crossref", "first-page": "78", "issue": "1", "journal-title": "Ann Intensive Care", "key": "ref47", "unstructured": "Tobin MJ, Laghi F, Jubran A. Caution about early intubation and mechanical ventilation in COVID-19. Ann Intensive Care. 2020;10(1):78.", "volume": "10", "year": "2020" }, { "DOI": "10.1186/s13037-020-00245-7", "article-title": "Successful COVID-19 rescue therapy by extra-corporeal membrane oxygenation (ECMO) for respiratory failure: a case report", "author": "Firstenberg MS", "doi-asserted-by": "crossref", "first-page": "20", "journal-title": "Patient Saf Surg", "key": "ref48", "unstructured": "Firstenberg MS, Stahel PF, Hanna J, Kotaru C, Crossno J Jr, Forrester J. Successful COVID-19 rescue therapy by extra-corporeal membrane oxygenation (ECMO) for respiratory failure: a case report. Patient Saf Surg. 2020;14:20.", "volume": "14", "year": "2020" }, { "DOI": "10.1016/j.athoracsur.2021.06.026", "article-title": "Multi-institutional analysis of 200 COVID-19 patients treated with extracorporeal membrane oxygenation: Outcomes and trends", "author": "Jacobs JP", "doi-asserted-by": "crossref", "first-page": "1452", "journal-title": "Ann Thorac Surg", "key": "ref49", "unstructured": "Jacobs JP, Stammers AH, St Louis JD, et al. Multi-institutional analysis of 200 COVID-19 patients treated with extracorporeal membrane oxygenation: Outcomes and trends. 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