UCL MRC Unit for Lifelong Health and Ageing, 33 Bedford Place, London WC1B 5JU, UK; Institute of Cardiovascular Science, University College London, Gower Street, London WC1E 6BT, UK; The Royal Free Hospital, Center for Inherited Heart Muscle Conditions, Cardiology Department, Pond Street, Hampstead, London NW3 2QG, UK.
Institute of Cardiovascular Science, University College London, Gower Street, London WC1E 6BT, UK; Barts Heart Center, The Cardiovascular Magnetic Resonance Imaging Unit and The Inherited Cardiovascular Diseases Unit, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK.
EBioMedicine. 2022 Nov;85:104293. doi: 10.1016/j.ebiom.2022.104293. Epub 2022 Sep 28.
The majority of those infected by ancestral Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during the UK first wave (starting March 2020) did not require hospitalisation. Most had a short-lived mild or asymptomatic infection, while others had symptoms that persisted for weeks or months. We hypothesized that the plasma proteome at the time of first infection would reflect differences in the inflammatory response that linked to symptom severity and duration.
We performed a nested longitudinal case-control study and targeted analysis of the plasma proteome of 156 healthcare workers (HCW) with and without lab confirmed SARS-CoV-2 infection. Targeted proteomic multiple-reaction monitoring analysis of 91 pre-selected proteins was undertaken in uninfected healthcare workers at baseline, and in infected healthcare workers serially, from 1 week prior to 6 weeks after their first confirmed SARS-CoV-2 infection. Symptom severity and antibody responses were also tracked. Questionnaires at 6 and 12 months collected data on persistent symptoms.
Within this cohort (median age 39 years, interquartile range 30-47 years), 54 healthcare workers (44% male) had PCR or antibody confirmed infection, with the remaining 102 (38% male) serving as uninfected controls. Following the first confirmed SARS-CoV-2 infection, perturbation of the plasma proteome persisted for up to 6 weeks, tracking symptom severity and antibody responses. Differentially abundant proteins were mostly coordinated around lipid, atherosclerosis and cholesterol metabolism pathways, complement and coagulation cascades, autophagy, and lysosomal function. The proteomic profile at the time of seroconversion associated with persistent symptoms out to 12 months. Data are available via ProteomeXchange with identifier PXD036590.
Our findings show that non-severe SARS-CoV-2 infection perturbs the plasma proteome for at least 6 weeks. The plasma proteomic signature at the time of seroconversion has the potential to identify which individuals are more likely to suffer from persistent symptoms related to SARS-CoV-2 infection.
The COVIDsortium is supported by funding donated by individuals, charitable Trusts, and corporations including Goldman Sachs, Citadel and Citadel Securities, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from University College London Hospitals (UCLH) Charity. This work was additionally supported by the Translational Mass Spectrometry Research Group and the Biomedical Research Center (BRC) at Great Ormond Street Hospital.
在英国第一波疫情（始于 2020 年 3 月）中，大多数感染原始严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）的人无需住院治疗。大多数人经历了短暂的轻度或无症状感染，而其他人则出现了持续数周或数月的症状。我们假设首次感染时的血浆蛋白质组会反映出与症状严重程度和持续时间相关的炎症反应的差异。
我们进行了一项嵌套的纵向病例对照研究，并对 156 名有和没有实验室确认的 SARS-CoV-2 感染的医护人员（HCW）的血浆蛋白质组进行了靶向分析。在未感染的医护人员中，在基线时和感染后的医护人员中，对 91 种预先选择的蛋白质进行了靶向蛋白质组学多重反应监测分析，时间范围从首次确认的 SARS-CoV-2 感染前 1 周到 6 周后。还跟踪了症状严重程度和抗体反应。在 6 个月和 12 个月时，调查问卷收集了持续症状的数据。
在该队列中（中位年龄 39 岁，四分位间距 30-47 岁），54 名医护人员（44%为男性）经 PCR 或抗体确认为感染，其余 102 名（38%为男性）作为未感染对照。在首次确认的 SARS-CoV-2 感染后，血浆蛋白质组的紊乱持续了长达 6 周，与症状严重程度和抗体反应相关。差异丰富的蛋白质主要围绕脂质、动脉粥样硬化和胆固醇代谢途径、补体和凝血级联、自噬和溶酶体功能协调。血清转换时的蛋白质组谱与 12 个月时的持续症状相关。数据可通过 ProteomeXchange 以标识符 PXD036590 获得。
我们的发现表明，非严重的 SARS-CoV-2 感染会使血浆蛋白质组紊乱至少 6 周。血清转换时的血浆蛋白质组特征有可能识别出哪些个体更有可能出现与 SARS-CoV-2 感染相关的持续症状。
COVIDsortium 得到了个人、慈善信托和公司的捐款支持，包括高盛、城堡和城堡证券、盖伊基金会、GW 制药公司、库苏马信托、Jagclif 慈善信托，由巴茨慈善基金会通过伦敦大学学院医院（UCLH）慈善基金会提供支持。这项工作还得到了转化质谱研究小组和大奥蒙德街医院生物医学研究中心（BRC）的支持。
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