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糖皮质激素和其他免疫抑制剂药物预先暴露与严重 COVID-19 结局之间的关联。

The association between pre-exposure to glucocorticoids and other immunosuppressant drugs with severe COVID-19 outcomes.

机构信息

Department of Medicine Solna, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden.

Department of Medicine Solna, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.

出版信息

Clin Microbiol Infect. 2022 Nov;28(11):1477-1485. doi: 10.1016/j.cmi.2022.05.014. Epub 2022 May 27.

Abstract

OBJECTIVES

Whether preinfection use of immunosuppressant drugs is associated with COVID-19 severity remains unclear. The study was aimed to determine the association between preinfection use of immunosuppressant drugs with COVID-19 outcomes within 1 month after COVID-19 diagnosis.

METHODS

This cohort study included individuals aged ≥18 years with underlying conditions associated with an immunocompromised state and diagnosed with COVID-19 between February 2020 and January 2021 at Karolinska University Hospital, Stockholm. Exposure to immunosuppressant drugs was defined based on dose and duration of drugs (glucocorticoids and drugs included in L01 or L04 chapter of Anatomical Therapeutic Chemical classification) before COVID-19 diagnosis. Outcomes included hospital admission, ICU admission, mechanical ventilation, mortality, renal failure, stroke, pulmonary embolism, and cardiac event. ORs were calculated using logistic regression and baseline covariate adjustment for confounding with inverse probability of treatment weights.

RESULTS

Of 1067 included individuals, 444 were pre-exposed to immunosuppressive treatments before COVID-19 diagnosis (72 high-dose glucocorticoids, 255 L01 drugs (antineoplastics), 198 L04 (other immunosuppressants) and 78 to multiple drugs). There was no association between pre-exposure and hospital admission (OR 0.83, 95% CI 0.64 to 1.09) because of COVID-19. Pre-exposure to L01 or L04 drugs were not associated with hospital admission (adjusted ORs (aORs): 1.23, 0.86 to 1.76 and 1.31, 0.77 to 2.21) or other outcomes. High-dose glucocorticoids (≥20 mg/day prednisolone equivalent) were associated with hospital admission (aOR 2.50, 1.26 to 4.96), cardiac events (aOR 1.93, 1.08 to 3.46), pulmonary embolism (aOR 2.78, 1.08 to 7.15), and mortality (aOR 3.48, 1.77 to 6.86) due to COVID-19.

DISCUSSION

Antineoplastic and other immunosuppressants drugs were not associated with COVID-19 severity whereas high-dose glucocorticoids were associated. Further studies should evaluate the effect of pre-exposure of different dose of glucocorticoids on COVID-19 prognosis.

摘要

目的

感染新冠病毒前使用免疫抑制剂是否与新冠病毒严重程度相关仍不清楚。本研究旨在确定新冠病毒诊断后 1 个月内,感染新冠病毒前使用免疫抑制剂与新冠病毒结局之间的关系。

方法

这项队列研究纳入了 2020 年 2 月至 2021 年 1 月期间在斯德哥尔摩卡罗林斯卡大学医院就诊、患有与免疫功能低下状态相关的基础疾病且被诊断为新冠病毒感染的年龄≥18 岁的患者。根据药物剂量和使用时间(皮质类固醇和解剖治疗化学分类 L01 或 L04 章中包含的药物)定义感染新冠病毒前使用免疫抑制剂的情况。结局包括住院、入住重症监护病房、机械通气、死亡、肾衰竭、中风、肺栓塞和心脏事件。使用 logistic 回归计算比值比(OR),并使用逆概率治疗加权法对混杂因素进行基线协变量调整。

结果

在纳入的 1067 名患者中,444 名在新冠病毒诊断前曾暴露于免疫抑制治疗(72 名使用高剂量皮质类固醇,255 名使用 L01 药物(抗肿瘤药),198 名使用 L04(其他免疫抑制剂),78 名使用多种药物)。感染新冠病毒前暴露于免疫抑制剂与住院(OR 0.83,95%CI 0.64 至 1.09)之间没有关联。暴露于 L01 或 L04 药物与住院(调整后比值比(aOR):1.23,0.86 至 1.76 和 1.31,0.77 至 2.21)或其他结局之间也没有关联。高剂量皮质类固醇(≥20 mg/天泼尼松龙当量)与住院(aOR 2.50,1.26 至 4.96)、心脏事件(aOR 1.93,1.08 至 3.46)、肺栓塞(aOR 2.78,1.08 至 7.15)和新冠病毒导致的死亡率(aOR 3.48,1.77 至 6.86)相关。

讨论

抗肿瘤药和其他免疫抑制剂与新冠病毒严重程度无关,而高剂量皮质类固醇则有关。应进一步研究不同剂量皮质类固醇暴露前对新冠病毒预后的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ab0/9135501/493bc66b45bb/gr1_lrg.jpg

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