Svobodová Barbora, Löfdahl Anna, Nybom Annika, Wigén Jenny, Hirdman Gabriel, Olm Franziska, Brunnström Hans, Lindstedt Sandra, Westergren-Thorsson Gunilla, Elowsson Linda
Lung Biology Unit, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden.
Department of Cardiothoracic Surgery and Transplantation, Skåne University Hospital, 222 42 Lund, Sweden.
Biomedicines. 2024 Dec 19;12(12):2893. doi: 10.3390/biomedicines12122893.
A novel patient group with chronic pulmonary fibrosis is emerging post COVID-19. To identify patients at risk of developing post-COVID-19 lung fibrosis, we here aimed to identify systemic proteins that overlap with fibrotic markers identified in patients with idiopathic pulmonary fibrosis (IPF) and may predict COVID-19-induced lung fibrosis. Ninety-two proteins were measured in plasma samples from hospitalized patients with moderate and severe COVID-19 in Sweden, before the introduction of the vaccination program, as well as from healthy individuals. These measurements were conducted using proximity extension assay (PEA) technology with a panel including inflammatory and remodeling proteins. Histopathological alterations were evaluated in explanted lung tissue. Connecting to IPF pathology, several proteins including decorin (DCN), tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) and chemokine (C-X-C motif) ligand 13 (CXCL13) were elevated in COVID-19 patients compared to healthy subjects. Moreover, we found incrementing expression of monocyte chemotactic protein-3 (MCP-3) and hepatocyte growth factor (HGF) when comparing moderate to severe COVID-19. Both extracellular matrix- and inflammation-associated proteins were identified as overlapping with pulmonary fibrosis, where we found DCN, TNFRSF12A, CXCL13, CXCL9, MCP-3 and HGF to be of particular interest to follow up on for the prediction of disease severity.
新型冠状病毒肺炎（COVID-19）后出现了一类患有慢性肺纤维化的新患者群体。为了识别有发生COVID-19后肺纤维化风险的患者，我们旨在识别与特发性肺纤维化（IPF）患者中确定的纤维化标志物重叠且可能预测COVID-19诱导的肺纤维化的全身蛋白。在瑞典引入疫苗接种计划之前，对中度和重度COVID-19住院患者以及健康个体的血浆样本中的92种蛋白进行了检测。这些检测使用了包含炎症和重塑蛋白的检测板的邻近延伸分析（PEA）技术。对切除的肺组织进行了组织病理学改变评估。与IPF病理学相关，与健康受试者相比，COVID-19患者中包括核心蛋白聚糖（DCN）、肿瘤坏死因子受体超家族成员12A（TNFRSF12A）和趋化因子（C-X-C基序）配体13（CXCL13）在内的几种蛋白升高。此外，在比较中度与重度COVID-19时，我们发现单核细胞趋化蛋白-3（MCP-3）和肝细胞生长因子（HGF）的表达增加。细胞外基质和炎症相关蛋白均被确定与肺纤维化重叠，我们发现DCN、TNFRSF12A、CXCL13、CXCL9、MCP-3和HGF对于预测疾病严重程度而言尤其值得后续关注。
