PDF(Pubmed)
Abstract：
BACKGROUND: Previous research done in Bulgaria demonstrated a fivefold reduction in mortality from COVID-19 with increased doses of colchicine from two hospitals in the country. We report here a further 333 cases of COVID-19 inpatients, treated with different doses of colchicine and its effect on mortality.
METHODS: A case-control 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-19 inpatients.
RESULTS: There was a clear reduction in the mortality of inpatients with increasing doses of colchicine-between twofold and sevenfold. Colchicine loading doses of 4 mg are more effective than those with 2 mg. Despite these doses being higher than the so-called \"standard doses,\" 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-mg loading dose of colchicine proving slightly superior to a 2-mg 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.
CONCLUSIONS: 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-recommended 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.
METHODS: A case-control 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-19 inpatients.
RESULTS: There was a clear reduction in the mortality of inpatients with increasing doses of colchicine-between twofold and sevenfold. Colchicine loading doses of 4 mg are more effective than those with 2 mg. Despite these doses being higher than the so-called \"standard doses,\" 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-mg loading dose of colchicine proving slightly superior to a 2-mg 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.
CONCLUSIONS: 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-recommended 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.
摘要：
背景：先前在保加利亚进行的研究表明，随着来自该国两家医院的秋水仙碱剂量的增加，COVID-19的死亡率降低了五倍。我们在这里报告了另外333例COVID-19住院患者，用不同剂量的秋水仙碱治疗及其对死亡率的影响。
方法：在增加剂量的秋水仙碱和添加溴己新治疗标准（SOC）与当前SOC之间进行了另外两家医院的病例对照比较。风险和赔率比，以及亚组分析，是用新报告的数据进行的，以及所有医院中心的汇总数据，以确定COVID-19住院患者死亡率降低的程度。
结果：秋水仙碱剂量增加后，住院患者的死亡率明显下降-在2倍至7倍之间。4mg的秋水仙碱负荷剂量比2mg的秋水仙碱负荷剂量更有效。尽管这些剂量高于所谓的“标准剂量”，“秋水仙碱住院患者的死亡率低于SOC患者(5.7%vs.19.53%）。这种死亡率益处在不同年龄的亚组中很明显，4-mg负荷剂量的秋水仙碱被证明略优于2-mg负荷剂量。秋水仙碱导致总体相对风险降低70.7%，SOC患者的死亡几率更高3.91。剂量的安全性与产品特性摘要中报告的没有差异。
结论：在SOC中添加秋水仙碱和溴己新的保加利亚住院患者比单独使用SOC的患者获得了更好的临床和死亡率结果。这些结果质疑世界卫生组织推荐的抑制病毒复制的策略。我们认为，我们的治疗策略是通过吸入溴己新和高剂量秋水仙碱的超活化NLRP3炎性体来抑制严重急性呼吸综合征冠状病毒2进入细胞，防止细胞因子风暴的发展。开始治疗的时机似乎很关键。
方法：在增加剂量的秋水仙碱和添加溴己新治疗标准（SOC）与当前SOC之间进行了另外两家医院的病例对照比较。风险和赔率比，以及亚组分析，是用新报告的数据进行的，以及所有医院中心的汇总数据，以确定COVID-19住院患者死亡率降低的程度。
结果：秋水仙碱剂量增加后，住院患者的死亡率明显下降-在2倍至7倍之间。4mg的秋水仙碱负荷剂量比2mg的秋水仙碱负荷剂量更有效。尽管这些剂量高于所谓的“标准剂量”，“秋水仙碱住院患者的死亡率低于SOC患者(5.7%vs.19.53%）。这种死亡率益处在不同年龄的亚组中很明显，4-mg负荷剂量的秋水仙碱被证明略优于2-mg负荷剂量。秋水仙碱导致总体相对风险降低70.7%，SOC患者的死亡几率更高3.91。剂量的安全性与产品特性摘要中报告的没有差异。
结论：在SOC中添加秋水仙碱和溴己新的保加利亚住院患者比单独使用SOC的患者获得了更好的临床和死亡率结果。这些结果质疑世界卫生组织推荐的抑制病毒复制的策略。我们认为，我们的治疗策略是通过吸入溴己新和高剂量秋水仙碱的超活化NLRP3炎性体来抑制严重急性呼吸综合征冠状病毒2进入细胞，防止细胞因子风暴的发展。开始治疗的时机似乎很关键。
