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COVID-19 住院免疫功能低下患者的结局:世卫组织 ISARIC CCP-UK 前瞻性队列研究分析。

Outcome of COVID-19 in hospitalised immunocompromised patients: An analysis of the WHO ISARIC CCP-UK prospective cohort study.

机构信息

NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Department of Clinical Infection, Microbiology and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.

Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom.

出版信息

PLoS Med. 2023 Jan 31;20(1):e1004086. doi: 10.1371/journal.pmed.1004086. eCollection 2023 Jan.

Abstract

BACKGROUND

Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death and how this risk changed over the pandemic.

METHODS AND FINDINGS

We included patients > = 19 years with symptomatic community-acquired COVID-19 recruited to the ISARIC WHO Clinical Characterisation Protocol UK prospective cohort study. We defined immunocompromise as immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. We used logistic regression to compare the risk of death in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination, and comorbidities. We used Bayesian logistic regression to explore mortality over time. Between 17 January 2020 and 28 February 2022, we recruited 156,552 eligible patients, of whom 21,954 (14%) were immunocompromised. In total, 29% (n = 6,499) of immunocompromised and 21% (n = 28,608) of immunocompetent patients died in hospital. The odds of in-hospital mortality were elevated for immunocompromised patients (adjusted OR 1.44, 95% CI [1.39, 1.50], p < 0.001). Not all immunocompromising conditions had the same risk, for example, patients on active cancer treatment were less likely to have their care escalated to intensive care (adjusted OR 0.77, 95% CI [0.7, 0.85], p < 0.001) or ventilation (adjusted OR 0.65, 95% CI [0.56, 0.76], p < 0.001). However, cancer patients were more likely to die (adjusted OR 2.0, 95% CI [1.87, 2.15], p < 0.001). Analyses were adjusted for age, sex, socioeconomic deprivation, comorbidities, and vaccination status. As the pandemic progressed, in-hospital mortality reduced more slowly for immunocompromised patients than for immunocompetent patients. This was particularly evident with increasing age: the probability of the reduction in hospital mortality being less for immunocompromised patients aged 50 to 69 years was 88% for men and 83% for women, and for those >80 years was 99% for men and 98% for women. The study is limited by a lack of detailed drug data prior to admission, including steroid doses, meaning that we may have incorrectly categorised some immunocompromised patients as immunocompetent.

CONCLUSIONS

Immunocompromised patients remain at elevated risk of death from COVID-19. Targeted measures such as additional vaccine doses, monoclonal antibodies, and nonpharmaceutical preventive interventions should be continually encouraged for this patient group.

TRIAL REGISTRATION

ISRCTN 66726260.

摘要

背景

与免疫功能正常的患者相比,免疫功能低下的 COVID-19 患者住院的死亡率可能更高。然而,之前的研究结果相互矛盾。我们旨在确定免疫功能低下的患者是否面临更高的住院死亡风险,以及这种风险如何随着大流行而变化。

方法和发现

我们纳入了年龄大于等于 19 岁、因社区获得性 COVID-19 出现症状并招募到 ISARIC WHO 临床特征协议英国前瞻性队列研究中的患者。我们将免疫功能低下定义为入院前使用免疫抑制剂药物、癌症治疗、器官移植、HIV 或先天性免疫缺陷。我们使用逻辑回归比较两组患者的死亡风险,调整年龄、性别、贫困程度、种族、疫苗接种和合并症。我们使用贝叶斯逻辑回归来探索随时间推移的死亡率。2020 年 1 月 17 日至 2022 年 2 月 28 日期间,我们招募了 156552 名符合条件的患者,其中 21954 名(14%)为免疫功能低下。共有 29%(n=6499)的免疫功能低下患者和 21%(n=28608)的免疫功能正常患者在医院死亡。免疫功能低下患者的住院死亡率较高(调整后的 OR 1.44,95%CI [1.39,1.50],p<0.001)。并非所有免疫功能低下的情况都有相同的风险,例如,正在接受癌症治疗的患者不太可能将其治疗升级为重症监护(调整后的 OR 0.77,95%CI [0.7,0.85],p<0.001)或呼吸机治疗(调整后的 OR 0.65,95%CI [0.56,0.76],p<0.001)。然而,癌症患者更有可能死亡(调整后的 OR 2.0,95%CI [1.87,2.15],p<0.001)。分析调整了年龄、性别、社会经济剥夺、合并症和疫苗接种状况。随着大流行的进展,免疫功能低下患者的住院死亡率下降速度比免疫功能正常患者慢。对于年龄较大的患者,这种情况更为明显:50 至 69 岁的男性和女性免疫功能低下患者的医院死亡率降低的可能性分别为 88%和 83%,而 80 岁以上的患者的可能性分别为 99%和 98%。该研究受到缺乏入院前详细药物数据的限制,包括皮质类固醇剂量,这意味着我们可能错误地将一些免疫功能低下的患者归类为免疫功能正常。

结论

免疫功能低下的患者死于 COVID-19 的风险仍然较高。应持续鼓励为该患者群体提供额外的疫苗剂量、单克隆抗体和非药物预防干预等有针对性的措施。

试验注册

ISRCTN66726260。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e36/9928075/af69e7143283/pmed.1004086.g001.jpg

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