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We report here a further 333 cases of COVID\u201019 inpatients, treated with different doses of colchicine and its effect on mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>A case\u2010control comparison from two additional hospitals was conducted between increased doses of colchicine and added bromhexine to standard of care (SOC) versus current SOC. Risk and odds ratio, as well as subgroup analysis, was conducted with newly reported data, alongside aggregate data from all hospital centers to determine the extent of mortality reduction in COVID\u201019 inpatients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was a clear reduction in the mortality of inpatients with increasing doses of colchicine\u2014between twofold and sevenfold. Colchicine loading doses of 4\u2009mg are more effective than those with 2\u2009mg. Despite these doses being higher than the so\u2010called \u201cstandard doses,\u201d colchicine inpatients experienced lower mortality than SOC patients (5.7% vs. 19.53%). This mortality benefit was evident in different age subgroups, with a 4\u2010mg loading dose of colchicine proving slightly superior to a 2\u2010mg loading dose. Colchicine led to an overall relative risk reduction of 70.7%, with SOC patients having 3.91 higher odds of death. The safety of the doses was not different than the reported in the summary of product characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Inpatients in Bulgaria with added colchicine and bromhexine to SOC achieved better clinical and mortality outcomes than those on SOC alone. These results question the World Health Organization\u2014recommended strategy to inhibit viral replication. We posit that our treatment strategy to inhibit the Severe acute respiratory syndrome coronavirus 2 entry into the cell with inhaled bromhexine and the hyperactivated NLRP3 inflammasome with higher doses of colchicine, prevents the development of cytokine storm. The timing of the initiation of treatment seems critical.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.1273","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T06:54:06Z","timestamp":1716792846000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effect of increasing doses of colchicine on the treatment of 333 COVID\u201019 inpatients"],"prefix":"10.1002","volume":"12","author":[{"given":"Rumen","family":"Tiholov","sequence":"first","affiliation":[{"name":"Internal Medicine and Pulmology Department MHAT \u201cSv Ivan Rilsky\u201d Kozloduy Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander I.","family":"Lilov","sequence":"additional","affiliation":[{"name":"Department of Pneumology and Phthysiatrics SHATPPD \u201c Sofia district\u201d Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gergana","family":"Georgieva","sequence":"additional","affiliation":[{"name":"Rheumatology Department MHAT Sv Ivan Rilsky Kozloduy Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiril R.","family":"Palaveev","sequence":"additional","affiliation":[{"name":"Department of Pneumology and Phthysiatrics SHATPPD \u201c Sofia district\u201d Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Tashkov","sequence":"additional","affiliation":[{"name":"Department of Social Pharmacy and Pharmacoeconomics, Faculty of Pharmacy Medical University\u2014Sofia Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7528-590X","authenticated-orcid":false,"given":"Vanyo","family":"Mitev","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry and Biochemistry, Faculty of Medicine Medical University\u2014Sofia Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40744-022-00425-0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-022-01540-y"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2021.106322"},{"key":"e_1_2_8_5_1","unstructured":"c19early.org. 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