抽象
在一群严重asthma patients, a small number of COVID-19 cases was found; none resulted in death or a very severe disease course. Use of biologics for severe allergic or severe eosinophilic asthma was not associated with a higher risk of COVID-19.https://bit.ly/3ndzmyd.
To the Editor:
流行病学研究表明,哮喘患者不受2019年严重冠状病毒疾病(Covid-19)的风险增加(Covid-19)引起的冠状病毒严重急性呼吸综合征冠状病毒2(SARS-COV-2)造成的1–3]。最近的研究表明,哮喘患者的Covid-19严重程度可能取决于多种因素。A型低哮喘表型,使用口腔皮质类固醇和严重的哮喘可能是加重因子,而吸入皮质类固醇(ICS)和良好的哮喘控制的维持治疗可能是保护的[4]。然而,目前存在关于与具有严重哮喘和/或生物学使用的科目中与Covid-19相关的风险的稀缺信息。由于嗜血症缺乏是Covid-19严重程度的生物标志物[5], the eosinophil depletion induced by anti-IL5 and anti-IL5 receptor blocking monoclonal antibodies raises concern in patients and their treating physicians. The handful of case reports about patients using the monoclonal antibodies omalizumab [6],北大产7或者对于特应性皮炎的Dupilumab可以提供令人放心的图片,但迫切需要哮喘患者进行的更大的研究。在免疫介导的炎症疾病中,如类风湿性关节炎和牛皮癣,与生物学治疗无关与较差的Covid-19结果无关[8]。定位论文和指导方针推荐哮喘患者维持其定期治疗,包括哮喘生物学,适合那些有资格的人[9,10.[但流行病学或临床研究数据是稀缺的[1,11.]。
我们的观察研究的目的是根据来自比利时严重哮喘登记处(BSAR)的数据,评估成人严重哮喘患者的Covid-19的发生,并评估使用生物学的严重哮喘患者是否存在增加的风险与不使用这些药物的人相比,严重的Covid-19。
该BSAR是根据欧洲呼吸协会/美国胸科社会标准定义的严重哮喘患者的前瞻性队列,自2009年以来已注册1416名患者[188bet官网地址12.,13.]。在获得BSAR中央伦理委员会的修正案(UZ GENT; B67020084584)批准后,九个参与的哮喘中心联系了他们的患者。在777名严重哮喘患者中(68%的患者在BSAR中积极的后续行动,i.e.with registry visits during the past 2 years) that were contacted, 676 (87%) participated in this survey.
通过电话或在门诊病人期间进行标准化的问卷,并获得有关Covid-19的症状症状的信息,通过鼻咽拭子(PCR)或血清学(SARS-COV-2 IgG)的Covid-19和诊断测试的症状。4月30日至7月8日至4月8日之间联系了患者.2月24日,比利时政府政策是将PCR测试限制在医疗工作者或严重的Covid-19案件中,需要住院治疗。如果症状较温和,患者被检疫但未进行测试。从4月24日起,从症状和无症状的人口收集更大比例的样品,作为筛选计划的一部分,例如在干预或住院之前。可用于比利时严重哮喘临床应用的单克隆抗体是奥马拉姆,莫洛替珍珠,Benralizumab和Reslizumab,而Dupilumab尚未偿还哮喘。
676名参与者中的266名(39%)在调查前4个月内至少有一种暗示Covid-19的症状暗示。呼吸困难(n = 172; 25%),鼻窦(n = 116; 17%),生产咳嗽(n = 107; 16%),头痛(n = 105; 16%)和胸痛(n = 69; 10%),是最常见的报告症状。只有43名患者(6%)的发烧,只有35名(5%)的患者经历了突然的嗅觉和令人遗憾的功能障碍,症状被认为是Covid-19的特异性14.],表明研究人群中有症状Covid-19的低发生率。
在676名患者中,PCR对鼻咽吸气的PCR仅测试了66个,并对SARS-COV-2进行了阳性的九(14%)(表格1)。40 (61%) PCR tests were performed because the patients presented suggestive symptoms, whereas the remaining tests were done in the context of healthcare or contact screenings. All the patients that had a positive PCR test had presented with suggestive symptoms. As the national restrictions with regard to PCR testing might have led to an underestimation of the true incidence of SARS-CoV-2 infection in patients with severe asthma in Belgium, serology testing to determine SARS-CoV-2 IgG antibody levels was performed, at the discretion of the treating physician, in a subgroup of patients that had presented a combination of symptoms suggestive of COVID-19. Positive IgG serology was found in only eight out of 98 tested patients. Of note, three of these patients who showed positive SARS-CoV-2 IgG had also demonstrated a positive PCR test. Because serology testing for COVID-19 only became available for large-scale clinical use towards the end of our study period (June 2020), the number of cases identified by serology is probably also an underestimation of the true incidence. Overall, we identified 14 patients with COVID-19 infection confirmed by either PCR and/or specific IgG (表格1)。在这14名患者中,只有五个(所有PCR阳性)都住院(住院时间短,从2至8天间停留)。没有呈现严重的哮喘恶化或用全身皮质类固醇治疗,入场,重症监护单元,无侵入性通风,机械通气或体外膜氧合,没有死亡。只有三名患者接受补充氧疗法(3至8天)。胸部计算断层摄影扫描是在四名住院治疗严重的哮喘患者中进行的,并在三名患者中揭示了肺结核。患有确认的Covid-19患者报告了比研究人群的剩余时间更高的中位数(四分位数)症状数(6(3-10)与2(1-3);P <0.000001)。在呈现燃烧或嗅觉功能障碍的35名患者中,通过PCR和/或血清学测试24,并发现10(42%)阳性,这是一种与这些症状一致的发现,被认为是更具体的Covid-19 [14.]。重要的是,在生物学治疗的严重哮喘患者(抗IGE或抗IL5 /抗IL5R)和未接受任何哮喘生物学(P> 0.05)(P> 0.05)(P> 0.05)(P> 0.05)之间没有差异表格1)但随着确认案件的数量很小,这必须谨慎地解释。最近使用口腔皮质类固醇(OCS)已被确定为Covid-19相关死亡的危险因素[11.], but in our cohort none of the 58 patients treated with maintenance OCS (median prednisone dose of 5 mg) were diagnosed with COVID-19.
据我们所知,这项研究是第一个探讨Covid-19在大型患者严重哮喘患者中的Covid-19的风险和严重程度之一。调查结果表明,严重哮喘患者的Covid-19感染发生率低(676名患者中的14例; 2.1%)。尽管如此,很难将证实Covid-19案件的发病率与一般人群中的数字进行比较。比利时血液供体的血液样本分析显示出达到5.1%的血清透析[15.]。我们的研究表明,比利时中只有2.1%的哮喘患者对SARS-COV-2具有阳性PCR或特异性IgG,并且只有5%的Covid-19相关症状。这种相对较低的发病率是由于哮喘严重的人比一般人群更加谨慎,并遵守社会疏散和其他卫生措施,或者是否是由于(Patho)生理特征(2型炎症)或有益效果诸如IC的处理(后一种因素与血管紧张素转化酶2表达的较低诱导酶相关)[16.] remains to be elucidated.
Whereas viral respiratory tract infections are the most important cause of asthma exacerbations, none of the patients with confirmed COVID-19 in our BSAR cohort experienced an exacerbation. This is in line with the recent publication by Beurnier等。[1] reporting that, among hospitalised patients with severe pneumonia due to SARS-CoV-2 infection, patients with asthma were not overrepresented and did not present with an asthma exacerbation. The national restrictions with regard to PCR testing and the resulting possible underestimation of the true incidence of COVID-19 are a limitation of our study. Also, the participation in the survey of severe asthma patients already participating in a registry might have created some selection bias, limiting the generalisability of our data. On the other hand, the careful characterisation of the patients in our cohort is a strength of this research.
总之,在这种成年患者的严重哮喘患者中,发现了少数Covid-19案例,其中没有导致死亡或非常严重的疾病课程。用生物学治疗严重过敏或严重的嗜酸性哮喘的治疗与SARS-COV-2感染的风险较高,也没有更严重的Covid-19。这些数据支持目前在Covid-19大流行期间继续在严重的哮喘中继续治疗生物学治疗。
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脚注
作者贡献:S. Hanon,G. Brusselle和F. Schleich构思了这项研究。D. Schuermans和所有共同作者收集了数据。S. Hanon和F. Schleich分析了数据,并共同写了稿件。所有作者都提供了对数据的关键反馈,编辑了稿件并保证了数据和随后的稿件的准确性。
利益冲突:S. Hanon报告了GSK,Astrazeneca,Teva,Teva,Sanofi和Novartis的个人费用,在提交的工作之外,在Chiesi之外的补助和个人费用。
兴趣冲突:G. Brusselle报告了Astazeneca,Boehringer Ingelheim,Chiesi,GSK,诺华,赛诺菲和Teva的个人费用,在提交的工作之外。
Conflict of interest: M. Deschampheleire has nothing to disclose.
Conflict of interest: R. Louis reports grants and personal fees from GSK, AstraZeneca and Novartis, grants from Chiesi, outside the submitted work.
利益冲突:A. Michils从Astrazeneca和Chiesi的赠款,个人费用和非财政支持,从北方的北方的个人费用,在提交的工作之外,诺瓦斯的个人费用。
利益冲突:R.Peché无需披露。
利益冲突:C. Pilette没有什么可披露的。
利益冲突:P. Rummens没有什么可披露的。
利益冲突:D. Schuermans没有什么可披露的。
Conflict of interest: H. Simonis has nothing to disclose.
利益冲突:O. Vandenplas没有披露。
Conflict of interest: F. Schleich has nothing to disclose.
- 收到2020年7月21日。
- Accepted2020年9月27日。
- 版权所有©ers 2020
This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.