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

{ 'institution': [{'name': 'Research Square'}], 'indexed': {'date-parts': [[2023, 2, 21]], 'date-time': '2023-02-21T05:38:12Z', 'timestamp': 1676957892767}, 'posted': {'date-parts': [[2023, 2, 20]]}, 'group-title': 'In Review', 'reference-count': 49, 'publisher': 'Research Square Platform LLC', 'license': [ { 'start': { 'date-parts': [[2023, 2, 20]], 'date-time': '2023-02-20T00:00:00Z', 'timestamp': 1676851200000}, 'content-version': 'unspecified', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'accepted': {'date-parts': [[2023, 2, 16]]}, 'abstract': '<jats:title>Abstract</jats:title>\n' ' <jats:p><jats:underline><jats:bold>Background:</jats:bold></jats:underline>\n' 'The 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>\n' 'A 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>\n' 'From 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>\n' 'This 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>', 'DOI': '10.21203/rs.3.rs-2596201/v1', 'type': 'posted-content', 'created': {'date-parts': [[2023, 2, 20]], 'date-time': '2023-02-20T18:36:25Z', 'timestamp': 1676918185000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': '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', 'prefix': '10.21203', 'author': [ { 'given': 'Adam C.', 'family': 'Delgado', 'sequence': 'first', 'affiliation': [{'name': 'Sky Ridge Medical Center'}]}, { 'given': 'Brendon', 'family': 'Cornett', 'sequence': 'additional', 'affiliation': [{'name': 'HCA Healthcare Continental Division'}]}, { 'given': 'Ye Ji', 'family': 'Choi', 'sequence': 'additional', 'affiliation': [{'name': 'HCA Healthcare Continental Division'}]}, { 'given': 'Christina', 'family': 'Colosimo', 'sequence': 'additional', 'affiliation': [{'name': 'Sky Ridge Medical Center'}]}, { 'given': 'Vincent P.', 'family': 'Stahel', 'sequence': 'additional', 'affiliation': [{'name': 'University of Colorado'}]}, { 'given': 'Oliwier', 'family': 'Dziadkowiec', 'sequence': 'additional', 'affiliation': [{'name': 'HCA Healthcare Continental Division'}]}, { 'given': 'Philip F.', 'family': 'Stahel', 'sequence': 'additional', 'affiliation': [{'name': 'East Carolina University'}]}], 'member': '8761', 'reference': [ { 'issue': '13', 'key': 'ref1', 'doi-asserted-by': 'crossref', 'first-page': '1239', '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', 'volume': '323', 'author': 'Wu Z', 'year': '2020', 'unstructured': 'Wu Z, McGoogan JM. 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