Schmitz Timo, Freuer Dennis, Goßlau Yvonne, Warm Tobias Dominik, Hyhlik-Dürr Alexander, Linseisen Jakob, Meisinger Christa, Kirchberger Inge
Epidemiology, Medical Faculty, University of Augsburg, Augsburg, Germany.
Epidemiology, Medical Faculty, University of Augsburg, Augsburg, Germany.
Virus Res. 2024 Jun;344:199363. doi: 10.1016/j.virusres.2024.199363. Epub 2024 Mar 22.
To investigate whether specific immune response plasma proteins can predict an elevated risk of developing Long COVID symptoms or fatigue severity after SARS-CoV-2 infection.
This study was based on 257 outpatients with test-confirmed SARS-CoV-2 infection between February 2020 and January 2021. At least 12 weeks after the acute infection, 92 plasma proteins were measured using the Olink Target 96 immune response panel (median time between acute infection and venous blood sampling was 38.8 [IQR: 24.0-48.0] weeks). The presence of Long COVID symptoms and fatigue severity was assessed 115.8 [92.5-118.6] weeks after the acute infection by a follow-up postal survey. Long COVID (yes/no) was defined as having one or more of the following symptoms: fatigue, shortness of breath, concentration or memory problems. The severity of fatigue was assessed using the Fatigue Assessment Scale (FAS). In multivariable-adjusted logistic and linear regression models the associations between each plasma protein (exposure) and Long COVID (yes/no) or severity of fatigue were investigated.
Nine plasma proteins were significantly associated with Long COVID before, but not after adjusting for multiple testing (FDR-adjustment): DFFA, TRIM5, TRIM21, HEXIM1, SRPK2, PRDX5, PIK3AP1, IFNLR1 and HCLS1. Moreover, a total of 10 proteins were significantly associated with severity of fatigue before FDR-adjustment: SRPK2, ITGA6, CLEC4G, HEXIM1, PPP1R9B, PLXNA4, PRDX5, DAPP1, STC1 and HCLS1. Only SRPK2 and ITGA6 remained significantly associated after FDR-adjustment.
This study demonstrates that certain immune response plasma proteins might play an important role in the pathophysiology of Long COVID and severity of fatigue after SARS-CoV-2 infection.
研究特定免疫反应血浆蛋白是否能预测感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）后出现长期新冠症状或疲劳严重程度升高的风险。
本研究基于2020年2月至2021年1月期间257例经检测确诊感染SARS-CoV-2的门诊患者。在急性感染至少12周后，使用Olink Target 96免疫反应检测板检测92种血浆蛋白（急性感染与静脉血采样之间的中位时间为38.8[四分位间距：24.0 - 48.0]周）。通过后续邮寄调查在急性感染115.8[92.5 - 118.6]周后评估长期新冠症状的存在情况和疲劳严重程度。长期新冠（是/否）定义为出现以下一种或多种症状：疲劳、呼吸急促、注意力或记忆力问题。使用疲劳评估量表（FAS）评估疲劳严重程度。在多变量调整的逻辑回归和线性回归模型中，研究每种血浆蛋白（暴露因素）与长期新冠（是/否）或疲劳严重程度之间的关联。
在进行多重检验校正（错误发现率校正）之前，9种血浆蛋白与长期新冠显著相关，但校正后不再显著：DNA片段化因子亚基α（DFFA）、三聚体结构域蛋白5（TRIM5）、三聚体结构域蛋白21（TRIM21）、六聚体重复序列包含蛋白1（HEXIM1）、丝氨酸/苏氨酸蛋白激酶2（SRPK2）、过氧化物还原酶5（PRDX5）、磷脂酰肌醇-3激酶调节亚基相关蛋白1（PIK3AP1）、干扰素λ受体1（IFNLR1）和造血细胞特异性蛋白1（HCLS1）。此外，在错误发现率校正之前，共有10种蛋白与疲劳严重程度显著相关：SRPK2、整合素α6（ITGA6）、C型凝集素结构域家族4成员G（CLEC4G）、HEXIM1、蛋白磷酸酶1调节亚基9B（PPP1R9B）、血小板/内皮细胞黏附分子4（PLXNA4）、PRDX5、死亡相关蛋白磷酸酶1（DAPP1）、分泌型卷曲相关蛋白1（STC1）和HCLS1。错误发现率校正后，只有SRPK2和ITGA6仍显著相关。
本研究表明，某些免疫反应血浆蛋白可能在SARS-CoV-2感染后的长期新冠病理生理学和疲劳严重程度中起重要作用。
