Precision Medicine for COVID-19 Based on the Inflammatory Response

A. D. Kothalkar, Dipali Jambhale, Vinayak Hingane, Satish Gore, Sudeep Deshpande
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Abstract

The threat due to the global pandemic of the coronavirus disease 2019 (COVID-19) demands a search for effective treatments to combat the severity of the infections and their associated morbidity and mortality in vulnerable populations. One of the medications with putative antiviral, anti-inflammatory, and immunomodulatory effects is fluvoxamine, a selective serotonin reuptake inhibitor and σ-1 receptor agonist. A few studies have reported doses of 100–300 mg/day to be effective. This retrospective study evaluates the outcomes of an individually tailored dosing strategy for fluvoxamine, based on measurements of inflammatory status, in treating COVID-19-positive individuals in India. This study included patients with severe acute respiratory syndrome coronavirus 2 infection visiting the outpatient department of a super speciality hospital in India from February to July 2021. Fluvoxamine was initiated at 50 mg or 100 mg twice daily based on their individual C-reactive protein (CRP) and D-dimer status. By day five, patients with rising or static levels of CRP and D-dimer were up-titrated. In a population of 104 individuals infected with COVID-19, 10 required up-titration of dose, and 94 patients did not need up-titration. Overall, there was very low mortality (N = 1) and hospitalization rate (8.7%). Those individuals who required an up-titration on day five had significantly elevated CRP and D-dimer levels compared to those who were maintained at the initial dose of 50 mg twice daily. In such patients, up-titration of the dose on day 5 appeared to offer better treatment benefits and outcomes. In our study population, there was only one mortality during the course of COVID-19. Given the individual variability in the host immune response to severe acute respiratory syndrome coronavirus 2 infection, tailoring the dose of a drug such as fluvoxamine based on the inflammatory status of the individual may be beneficial. Individually tailored dosing could combat disease progression while reducing side effects.
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基于炎症反应的 COVID-19 精准医疗
2019 年冠状病毒病(COVID-19)在全球大流行所带来的威胁要求人们寻找有效的治疗方法,以应对感染的严重性以及易感人群的相关发病率和死亡率。氟伏沙明是一种选择性5-羟色胺再摄取抑制剂和σ-1受体激动剂,是具有抗病毒、抗炎和免疫调节作用的药物之一。有几项研究报告称,100-300 毫克/天的剂量有效。 这项回顾性研究评估了根据炎症状态的测量结果单独定制氟伏沙明剂量策略在治疗印度 COVID-19 阳性患者方面的效果。 这项研究纳入了2021年2月至7月在印度一家超级专科医院门诊部就诊的严重急性呼吸综合征冠状病毒2感染患者。根据患者的C反应蛋白(CRP)和D-二聚体状况,氟伏沙明的剂量为50毫克或100毫克,每天两次。到了第五天,CRP 和 D-二聚体水平上升或保持不变的患者则需要增加剂量。 在感染 COVID-19 的 104 人中,有 10 人需要增加剂量,94 人不需要增加剂量。总体而言,死亡率(1 例)和住院率(8.7%)都非常低。与维持初始剂量(50 毫克,每天两次)的患者相比,需要在第五天增加剂量的患者的 CRP 和 D-二聚体水平明显升高。对于这些患者,在第 5 天加大剂量似乎能带来更好的治疗效果和结果。在我们的研究人群中,只有一人在 COVID-19 治疗期间死亡。 鉴于宿主对严重急性呼吸道综合征冠状病毒2感染的免疫反应存在个体差异,根据个体的炎症状态来调整氟伏沙明等药物的剂量可能会有所帮助。量身定制的药物剂量可以在减少副作用的同时遏制疾病进展。
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