Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19.
Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19.
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长期COVID特征的发生率、共现率和演变：一项对273，618名COVID-19幸存者的6个月回顾性队列研究。
DOI：
10.1371/journal.pmed.1003773
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发表时间：
2021-09
期刊：
影响因子：
15.8
通讯作者：
Harrison PJ
中科院分区：
文献类型：
--
作者：
Taquet M;Dercon Q;Luciano S;Geddes JR;Husain M;Harrison PJ
长冠状病毒是指人们在感染新冠病毒后报告的影响不同器官的各种症状。迄今为止，还没有关于长冠状病毒特征的发生率和共现性、它们与年龄、性别或感染严重程度的关系以及它们对COVID-19的特异性程度的可靠估计。本研究的目的就是要解决这些问题。我们进行了一项基于相关电子健康记录（EHRs）数据的回顾性队列研究，这些数据来自8100万名患者，其中包括273,618名COVID-19幸存者。计算长covid的9个核心特征（呼吸困难/呼吸困难、疲劳/不适、胸/喉痛、头痛、腹部症状、肌痛、其他疼痛、认知症状、焦虑/抑郁）在6个月内和诊断后3 ~ 6个月内的发病率和共发生情况。并对其共现网络进行了分析。使用Kaplan-Meier分析和Cox比例风险模型与同一时期诊断为流感患者的倾向评分匹配队列进行比较。以特应性皮炎发生率为阴性对照。在COVID-19幸存者中（平均[SD]年龄：46.3[19.8]，55.6%为女性），57.00%在整个6个月期间（即包括急性期）记录了一个或多个长covid特征，36.55%在3至6个月期间记录。各特征的发生率分别为：呼吸异常（1 ~ 180天为18.71%，90 ~ 180天为7.94%）、疲劳/不适（12.82%,5.87%）、胸/喉痛（12.60%,5.71%）、头痛（8.67%,4.63%）、其他疼痛（11.60%,7.19%）、腹部症状（15.58%,8.29%）、肌痛（3.24%,1.54%）、认知症状（7.88%,3.95%）、焦虑/抑郁（22.82%,15.49%）。所有9个特征在COVID-19后比在流感后报告的频率更高（总超额发生率为16.60%，风险比在1.44 ~ 2.04之间，均p < 0.001），共同发生的频率更高，形成了一个更相互关联的网络。发病率和共发率的显著差异与性别、年龄和疾病严重程度有关。除了电子病历数据固有的局限性外，本研究的局限性还包括：(i)研究结果不能推广到患有COVID-19但未被诊断出来的患者，也不能推广到出现长期covid症状时未寻求或接受医疗护理的患者；（ii）研究结果没有说明临床特征的持久性；（iii）队列之间的差异可能会受到一个队列因其症状寻求或接受更多医疗护理的影响。长冠状病毒临床特征经常发生和共同发生，并对COVID-19表现出一定的特异性，尽管它们也在流感后观察到。根据人口统计学和疾病严重程度，观察到不同的长期covid临床特征。马克西姆·塔奎特（Maxime Taquet）及其同事调查了25多万人的长冠状病毒特征的发生率、共现性和演变。最近的研究描述了长冠状病毒。但我们不知道发展成这种情况的风险，也不知道它是如何受到年龄、性别或感染严重程度等因素的影响的。我们不知道2019冠状病毒病（COVID-19）后出现长冠状病毒特征的风险是否比流感后更大。我们不知道长期covid的不同特征在多大程度上同时发生。这项研究使用了273,618名被诊断为COVID-19的患者的电子健康记录数据，并估计了COVID-19诊断后6个月内出现长covid特征的风险。它比较了人群中不同群体的长covid特征的风险，并将其与流感后的风险进行了比较。研究发现，超过三分之一的患者在诊断出COVID-19后的3至6个月内具有一项或多项长期COVID-19特征。这明显高于流感后。在3到6个月的时间里有长冠状病毒特征的患者中，有五分之二的人在过去3个月里没有任何此类特征的记录。在患有更严重的COVID-19疾病的患者中，长covid特征的风险更高，在女性和年轻人中略高。白人和非白人患者同样受到影响。了解长covid特征的风险有助于规划相关的医疗保健服务提供。COVID-19后的风险高于流感后的风险，这一事实表明，它们的起源可能在一定程度上直接涉及SARS-CoV-2感染，而不仅仅是病毒感染的一般后果。这可能有助于开发针对长期covid的有效治疗方法。亚组的研究结果，以及大多数在3至6个月内具有长冠状病毒特征的患者在前3个月已经出现症状的事实，可能有助于识别风险最大的患者。
Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues. We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score–matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan–Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control. Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms. Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity. Maxime Taquet and colleagues investigate the incidence, co-occurrence and evolution of long-COVID features in more than a quarter of a million people. Long-COVID has been described in recent studies. But we do not know the risk of developing features of this condition and how it is affected by factors such as age, sex, or severity of infection. We do not know if the risk of having features of long-COVID is more likely after Coronavirus Disease 2019 (COVID-19) than after influenza. We do not know about the extent to which different features of long-COVID co-occur. This research used data from electronic health records of 273,618 patients diagnosed with COVID-19 and estimated the risk of having long-COVID features in the 6 months after a diagnosis of COVID-19. It compared the risk of long-COVID features in different groups within the population and also compared the risk to that after influenza. The research found that over 1 in 3 patients had one or more features of long-COVID recorded between 3 and 6 months after a diagnosis of COVID-19. This was significantly higher than after influenza. For 2 in 5 of the patients who had long-COVID features in the 3- to 6-month period, they had no record of any such feature in the previous 3 months. The risk of long-COVID features was higher in patients who had more severe COVID-19 illness, and slightly higher among females and young adults. White and non-white patients were equally affected. Knowing the risk of long-COVID features helps in planning the relevant healthcare service provision. The fact that the risk is higher after COVID-19 than after influenza suggests that their origin might, in part, directly involve infection with SARS-CoV-2 and is not just a general consequence of viral infection. This might help in developing effective treatments against long-COVID. The findings in the subgroups, and the fact that the majority of patients who have features of long-COVID in the 3- to 6-month period already had symptoms in the first 3 months, may help in identifying those at greatest risk.
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影响因子：
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