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早期对 SARS-CoV-2 感染(COVID-19)的多药物治疗以及降低疗养院(或门诊/流动)居民的死亡率。

Early multidrug treatment of SARS-CoV-2 infection (COVID-19) and reduced mortality among nursing home (or outpatient/ambulatory) residents.

机构信息

McMaster University and GUIDE Research Methods Group, Hamilton, Ontario, Canada.

The Resort at Texas City Nursing Home, Texas City, TX, USA.

出版信息

Med Hypotheses. 2021 Aug;153:110622. doi: 10.1016/j.mehy.2021.110622. Epub 2021 Jun 5.

Abstract

The outbreak of COVID-19 from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread all over the world with tremendous morbidity and mortality in the elderly. In-hospital treatment addresses the multifaceted nature of the illness including initial viral replication, cytokine storm, and endothelial injury with thrombosis. We identified nine reports of early treatment outcomes in COVID-19 nursing home patients. Multi-drug therapy including hydroxychloroquine with one or more anti-infectives, corticosteroids, and antithrombotic anti-blood clotting agents can be extended to seniors in the nursing home setting without hospitalization. Data from nine studies found hydroxychloroquine-based multidrug regimens were associated with a statistically significant > 60% reduction in mortality. Going forward, we conclude that early empiric treatment for the elderly with COVID-19 in the nursing home setting (or similar congregated settings with elderly residents/patients e.g. LTF or ALF) has a reasonable probability of success and acceptable safety. This group remains our highest at-risk group and warrants acute treatment focus prior to symptoms worsening. Given the rapidity and severity of SARS-CoV-2 outbreaks in nursing homes, in-center treatment of acute COVID-19 patients is a reasonable strategy to reduce the risks of hospitalization and death. If elderly high-risk patients in such congregated nursing home type settings are allowed to worsen with no early treatment, they may be too sick and fragile to benefit from in-hospital therapeutics and are at risk for pulmonary failure, life-ending micro-thrombi of the lungs, kidneys etc. The issue is timing of therapeutics, and we argue that early treatment before hospitalization, is the right time and can potentially save lives, especially among our higher-risk elderly populations hit hardest by severe illness and death from COVID-19. We must reiterate, we are talking about 'early' treatment before the disease is far along in the disease sequelae where the patient then needs hospitalization and aggressive interventions. We are referring to the initial days e.g. day one, post infection when symptoms emerge or there is strong clinical suspicion. This early therapeutic option deserves serious and urgent consideration by the medical establishment and respective decision-makers. Doctors must be allowed their clinical discretion in how they optimally treat their patients. Doctors must be brave and trust their skilled judgements and do all to save the lives of their patients. We therefore hypothesize that early outpatient ambulatory treatment, once initiated as soon as symptoms begin in high-risk positive persons, would significantly reduce hospitalizations and prevent deaths. Specifically, the provision of early multi-drug sequenced therapy with repurposed drugs will reduce hospitalization and death in elderly patients being cared for in long-term-care facilities. The most important implications of our hypothesis are: 1) hospitalizations and deaths would be reduced 2) transmission would be reduced due to the mitigation of symptoms and 3) recovery following infection and treatment provides for natural exposure immunity that is broad based, durable, and robust (helping towards natural immunity within the population). The end result is reduced strain on hospitals and systems that would allow for other non-COVID illnesses to receive care.

摘要

由严重急性呼吸系统综合症冠状病毒 2(SARS-CoV-2)引起的 COVID-19 爆发在全球范围内蔓延,老年人的发病率和死亡率极高。住院治疗针对疾病的多方面性质,包括初始病毒复制、细胞因子风暴和内皮损伤伴血栓形成。我们确定了 9 份关于 COVID-19 疗养院患者早期治疗结果的报告。多药物治疗包括羟氯喹加一种或多种抗感染药物、皮质类固醇和抗血栓抗凝血药物,可以扩展到疗养院的老年人,而无需住院。来自 9 项研究的数据发现,基于羟氯喹的多药物方案与死亡率显著降低 > 60%有关。展望未来,我们得出结论,对于疗养院(或类似的老年人居民/患者聚集环境,如 LTF 或 ALF)中的 COVID-19 老年患者进行早期经验性治疗具有合理的成功可能性和可接受的安全性。该群体仍然是我们风险最高的群体,需要在症状恶化之前进行急性治疗。鉴于 SARS-CoV-2 在疗养院中爆发的迅速性和严重性,对急性 COVID-19 患者进行中心治疗是减少住院和死亡风险的合理策略。如果允许此类聚集式疗养院类型环境中的高危老年患者病情恶化而不进行早期治疗,他们可能因病情严重而脆弱,无法从医院治疗中受益,并面临肺部衰竭、肺部、肾脏等微小血栓形成的生命威胁。问题是治疗的时机,我们认为,在疾病后遗症中,在患者需要住院和强化干预之前,在发病初期进行早期治疗,是正确的时间,并且可能挽救生命,尤其是在我们受 COVID-19 严重疾病和死亡影响最大的高风险老年人群中。我们必须重申,我们所说的是“早期”治疗,即在疾病进展到患者需要住院和积极干预的地步之前。我们指的是发病后的最初几天,例如感染后的第一天,出现症状或出现强烈的临床怀疑。这种早期治疗选择值得医疗保健机构和各自的决策者认真和紧急考虑。医生必须允许他们在如何为患者提供最佳治疗方面行使临床判断。医生必须勇敢并相信他们的专业判断,并尽一切努力挽救患者的生命。因此,我们假设一旦高危阳性患者出现症状,就开始进行早期门诊治疗,将显著减少住院治疗并预防死亡。具体而言,使用重新定位药物进行早期多药物序贯治疗将减少疗养院中接受护理的老年患者的住院治疗和死亡。我们假设的最重要意义是:1)减少住院治疗和死亡人数 2)由于症状缓解,减少传播 3)感染和治疗后的恢复提供了广泛、持久和强大的自然暴露免疫力(有助于人群中的自然免疫力)。结果是减轻了医院和系统的压力,使其他非 COVID 疾病能够得到治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8dd/8178530/a1d3b802c195/gr1_lrg.jpg

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