Boekel Laura, Atiqi Sadaf, Leeuw Maureen, Hooijberg Femke, Besten Yaëlle R, Wartena Rosa, Steenhuis Maurice, Vogelzang Erik, Webers Casper, Boonen Annelies, Gerritsen Martijn, Lems Willem F, Tas Sander W, van Vollenhoven Ronald F, Voskuyl Alexandre E, van der Horst-Bruinsma Irene, Nurmohamed Mike, Rispens Theo, Wolbink Gertjan
Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam University Medical Center, Amsterdam, Netherlands.
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Center, Amsterdam, Netherlands.
Lancet Rheumatol. 2023 Jul;5(7):e375-e385. doi: 10.1016/S2665-9913(23)00127-3. Epub 2023 May 31.
Studies on long-term consequences of COVID-19, commonly referred to as post-COVID condition, in patients with inflammatory rheumatic diseases are scarce and inconclusive. Furthermore, classifying patients with inflammatory rheumatic diseases as having post-COVID condition is complicated because of overlapping symptoms. Therefore, we investigated the risk of post-COVID condition and time until recovery, and compared the prevalence of symptoms seen in post-COVID condition, between patients with inflammatory rheumatic diseases and healthy controls, with and without a history of COVID-19.
In this substudy we used data from an ongoing prospective cohort study in the Netherlands. All adult patients with inflammatory rheumatic diseases from the Amsterdam Rheumatology and Immunology Center in Amsterdam, the Netherlands, were invited to participate in the study between April 26, 2020, and March 1, 2021. All patients were asked, but not obliged, to recruit their own control participant of the same sex, of comparable age (< 5 years), and without an inflammatory rheumatic disease. Demographic and clinical data, including data on the occurrence of SARS-CoV-2 infections, were collected via online questionnaires. On March 10, 2022, all study participants received a questionnaire on the occurrence, onset, severity, and duration of persistent symptoms during the first 2 years of the COVID-19 pandemic, independent of their history of SARS-CoV-2 infection. Additionally, we prospectively monitored a subset of participants who had a PCR or antigen confirmed SARS-CoV-2 infection in the 2-month period surrounding the questionnaire in order to assess COVID-19 sequelae. In line with WHO guidelines, post-COVID condition was defined as persistent symptoms that lasted at least 8 weeks, started after the onset and within 3 months of a PCR or antigen-confirmed SARS-CoV-2 infection, and could not be explained by an alternative diagnosis. Statistical analyses included descriptive statistics, logistic regression analyses, logistic-based causal mediation analyses, and Kaplan-Meier survival analyses for time until recovery from post-COVID condition. In exploratory analyses, E-values were calculated to investigate unmeasured confounding.
A total of 1974 patients with inflammatory rheumatic disease (1268 [64%] women and 706 [36%] men; mean age 59 years [SD 13]) and 733 healthy controls (495 [68%] women and 238 [32%] men; mean age 59 years [12]) participated. 468 (24%) of 1974 patients with inflammatory rheumatic disease and 218 (30%) of 733 healthy controls had a recent SARS-CoV-2 omicron infection. Of those, 365 (78%) of 468 patients with inflammatory rheumatic disease and 172 (79%) of 218 healthy controls completed the prospective follow-up COVID-19 sequelae questionnaires. More patients than controls fulfilled post-COVID condition criteria: 77 (21%) of 365 versus 23 (13%) of 172 (odds ratio [OR] 1·73 [95% CI 1·04-2·87]; p=0·033). The OR was attenuated after adjusting for potential confounders (adjusted OR 1·53 [95% CI 0·90-2·59]; p=0·12). Among those without a history of COVID-19, patients with inflammatory diseases were more likely to report persistent symptoms consistent with post-COVID condition than were healthy controls (OR 2·52 [95% CI 1·92-3·32]; p<0·0001). This OR exceeded the calculated E-values of 1·74 and 1·96. Recovery time from post-COVID condition was similar for patients and controls (p=0·17). Fatigue and loss of fitness were the most frequently reported symptoms in both patients with inflammatory rheumatic disease and healthy controls with post-COVID condition.
Post-COVID condition after SARS-CoV-2 omicron infections was higher in patients with inflammatory rheumatic disease than in healthy controls based on WHO classification guidelines. However, because more patients with inflammatory rheumatic disease than healthy controls without a history of COVID-19 reported symptoms that are commonly used to define a post-COVID condition during the first 2 years of the pandemic, it is likely that the observed difference in post-COVID condition between patients and controls might in part be explained by clinical manifestations in the context of underlying rheumatic diseases. This highlights the limitations of applying current criteria for post-COVID condition in patients with inflammatory rheumatic disease, and suggests it might be appropriate for physicians to keep a nuanced attitude when communicating the long-term consequences of COVID-19.
ZonMw (the Netherlands organization for Health Research and Development) and Reade foundation.
关于炎症性风湿性疾病患者中新冠病毒病（COVID-19）的长期后果（通常称为新冠后状况）的研究较少且结论不一。此外，由于症状重叠，将炎症性风湿性疾病患者归类为患有新冠后状况很复杂。因此，我们调查了新冠后状况的风险和恢复时间，并比较了有或没有COVID-19病史的炎症性风湿性疾病患者与健康对照者中新冠后状况所见症状的患病率。
在这项子研究中，我们使用了荷兰一项正在进行的前瞻性队列研究的数据。2020年4月26日至2021年3月1日期间，邀请了荷兰阿姆斯特丹风湿病和免疫学中心的所有成年炎症性风湿性疾病患者参与该研究。所有患者被要求（但无义务）招募一名年龄相仿（相差<5岁）、同性且无炎症性风湿性疾病的对照参与者。通过在线问卷收集人口统计学和临床数据，包括严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染发生的数据。2022年3月10日，所有研究参与者收到一份关于COVID-19大流行前两年持续症状的发生、发作、严重程度和持续时间的问卷，无论其SARS-CoV-2感染史如何。此外，我们前瞻性地监测了在问卷前后2个月内有PCR或抗原确诊的SARS-CoV-2感染的一部分参与者，以评估COVID-19后遗症。根据世界卫生组织（WHO）的指南，新冠后状况被定义为持续至少8周的持续症状，这些症状在PCR或抗原确诊的SARS-CoV-2感染发作后3个月内开始，且不能用其他诊断来解释。统计分析包括描述性统计、逻辑回归分析、基于逻辑的因果中介分析以及从新冠后状况恢复时间的Kaplan-Meier生存分析。在探索性分析中，计算E值以调查未测量的混杂因素。
共有1974例炎症性风湿性疾病患者（1268例[64%]女性和706例[36%]男性；平均年龄59岁[标准差13]）和733名健康对照者（495例[68%]女性和238例[32%]男性；平均年龄59岁[12]）参与。1974例炎症性风湿性疾病患者中有468例（24%），733名健康对照者中有218例（30%）近期感染了SARS-CoV-2奥密克戎毒株。其中，468例炎症性风湿性疾病患者中的365例（78%）和218名健康对照者中的172例（79%）完成了前瞻性随访的COVID-19后遗症问卷。满足新冠后状况标准的患者比对照者更多：365例中的77例（21%）对比172例中的23例（13%）（优势比[OR]1.73[95%置信区间1.04 - 2.87]；p = 0.033）。在调整潜在混杂因素后，OR值减弱（调整后OR 1.53[95%置信区间0.90 - 2.59]；p = 0.12）。在没有COVID-19病史的人群中，炎症性疾病患者比健康对照者更有可能报告与新冠后状况一致的持续症状（OR 2.52[95%置信区间1.92 - 3.32]；p<0.0001）。该OR值超过了计算出的1.74和1.96的E值。患者和对照者从新冠后状况恢复的时间相似（p = 0.17）。疲劳和体能下降是炎症性风湿性疾病患者和有新冠后状况的健康对照者中最常报告的症状。
根据WHO分类指南，炎症性风湿性疾病患者感染SARS-CoV-2奥密克戎毒株后的新冠后状况高于健康对照者。然而，由于在大流行的前两年中，有炎症性风湿性疾病的患者比没有COVID-19病史健康对照者报告了更多通常用于定义新冠后状况的症状，患者和对照者之间观察到的新冠后状况差异可能部分是由潜在风湿性疾病背景下的临床表现所解释。这凸显了在炎症性风湿性疾病患者中应用当前新冠后状况标准的局限性，并表明医生在告知COVID-19的长期后果时保持细致入微的态度可能是合适的。
荷兰卫生研究与发展组织（ZonMw）和里德基金会。
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