covid后疾病的综合分子特征：免疫球蛋白抑制和持续的SARS-CoV-2抗原是关键的病理生理驱动因素

IF 4.7 3区医学 Q1 INFECTIOUS DISEASES

Journal of Infection and Public Health Pub Date : 2025-06-06 DOI:10.1016/j.jiph.2025.102870

Alejandro Seco-Gonzalez , Paula Antelo-Riveiro , Susana B. Bravo , M.J. Domínguez-Santalla , E. Rodríguez-Ruiz , Ángel Piñeiro , Rebeca Garcia-Fandino

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引用次数: 0

摘要

COVID - 19后状态（PCC）或长COVID影响了很大一部分SARS-CoV-2感染后的个体，但其分子框架仍知之甚少。本研究旨在通过整合全理论质谱序列窗口获取（SWATH-MS）的广泛蛋白质组学分析和靶向质谱（MRM/SRM）的靶向抗原定量来确定PCC的分子特征。方法采用更新的SARS-CoV-2蛋白文库（v2022和v2024）的SWATH-MS对65例有症状或无症状的PCC患者的血浆和颗粒组分进行分析，从而全面分析免疫和病毒相关蛋白。病毒抗原的存在，特别是刺突和核衣壳蛋白，用MRM/SRM定量。采用聚类分析和降维方法，提出了一种基于蛋白质浓度的严重程度度量，以评估蛋白质组学改变与临床症状之间的相关性。结果PCC患者的一个关键发现，特别是在有症状的病例中，是免疫球蛋白的显著下调，包括kappa和lambda轻链。SWATH-MS分析鉴定出6个与疾病严重程度密切相关的蛋白（对应于UniProt条目Q8N5F4、LV147、KV311、KVD20、A0A5C2G1U0和KV315） (R²>；0.9)，强调了它们作为生物标志物的潜力。在颗粒样品中，蛋白质G1SG72 （ABCE1）作为与严重程度相关的标记物出现，表明抗病毒反应可能发生改变。提出的严重程度指标显示与临床症状有很强的相关性，提供了PCC严重程度的可量化测量，并实现了有效的患者分层。此外，MRM/SRM分析检测到症状性PCC患者中持续存在SARS-CoV-2抗原，特别是Spike和核衣壳蛋白。本研究确定了PCC的分子谱，其特征是免疫球蛋白下调和SARS-CoV-2抗原的持续存在，这可能有助于PCC持续的免疫改变。来自蛋白质组学分析的严重程度指标提供了一种基于症状严重程度对PCC患者进行分类的工具，可以支持未来针对有针对性干预措施的研究。

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Comprehensive molecular characterization of post-COVID condition: Immunoglobulin suppression and persistent SARS-CoV-2 antigens as key pathophysiological drivers

Background

Post-COVID condition (PCC), or long COVID, affects a significant proportion of individuals following SARS-CoV-2 infection, yet its molecular framework remains poorly understood. This study aimed to define the molecular profile of PCC by integrating broad proteomic analysis using Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS) with targeted antigen quantification through targeted mass spectrometry (MRM/SRM).

Methods

Plasma and pellet fractions from 65 PCC patients, classified as symptomatic or asymptomatic, were analyzed using SWATH-MS with updated SARS-CoV-2 protein libraries (v2022 and v2024), enabling a comprehensive profiling of immune- and viral-related proteins. The presence of viral antigens, specifically spike and nucleocapsid proteins, was quantified using MRM/SRM. A protein-concentration-based severity metric using clustering analysis and dimensionality reduction methods was proposed to assess correlations between proteomic alterations and clinical symptoms.

Results

A key finding in PCC patients, particularly in symptomatic cases, was a pronounced downregulation of immunoglobulins, including kappa and lambda light chains. SWATH-MS analysis identified six proteins (corresponding to UniProt entries Q8N5F4, LV147, KV311, KVD20, A0A5C2G1U0, and KV315) that strongly correlated with disease severity (R² > 0.9), highlighting their potential as biomarkers. In pellet samples, the protein G1SG72 (ABCE1) emerged as a marker associated with severity, suggesting possible alterations in antiviral responses. The severity metric proposed showed a strong correlation with clinical symptoms, providing a quantifiable measure of PCC severity and enabling effective patient stratification. Additionally, MRM/SRM analysis detected the persistent presence of SARS-CoV-2 antigens, specifically the Spike and Nucleocapsid proteins, in symptomatic PCC patients.

Conclusions

This study defines a molecular profile of PCC, marked by immunoglobulin downregulation and the persistence of SARS-CoV-2 antigens, which may contribute to ongoing immune alterations in PCC. The severity metric derived from proteomic profiling provides a tool for categorizing PCC patients based on symptom severity and could support future studies aimed at targeted interventions.

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来源期刊

Journal of Infection and Public Health PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH -INFECTIOUS DISEASES

CiteScore

13.10

自引率

1.50%

发文量

203

审稿时长

96 days

期刊介绍： The Journal of Infection and Public Health, first official journal of the Saudi Arabian Ministry of National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences and the Saudi Association for Public Health, aims to be the foremost scientific, peer-reviewed journal encompassing infection prevention and control, microbiology, infectious diseases, public health and the application of healthcare epidemiology to the evaluation of health outcomes. The point of view of the journal is that infection and public health are closely intertwined and that advances in one area will have positive consequences on the other. The journal will be useful to all health professionals who are partners in the management of patients with communicable diseases, keeping them up to date. The journal is proud to have an international and diverse editorial board that will assist and facilitate the publication of articles that reflect a global view on infection control and public health, as well as emphasizing our focus on supporting the needs of public health practitioners. It is our aim to improve healthcare by reducing risk of infection and related adverse outcomes by critical review, selection, and dissemination of new and relevant information in the field of infection control, public health and infectious diseases in all healthcare settings and the community.