Respiratory Diseases Group, Respiratory Service, La Paz University Hospital, Instituto de Investigación Biomédica del Hospital Universitario la Paz (IdiPAZ), Madrid, Spain.
Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain.
Front Immunol. 2022 Jan 31;13:847894. doi: 10.3389/fimmu.2022.847894. eCollection 2022.
CD39/NTPDase1 has emerged as an important molecule that contributes to maintain inflammatory and coagulatory homeostasis. Various studies have hypothesized the possible role of CD39 in COVID-19 pathophysiology since no confirmatory data shed light in this regard. Therefore, we aimed to quantify CD39 expression on COVID-19 patients exploring its association with severity clinical parameters and ICU admission, while unraveling the role of purinergic signaling on thromboinflammation in COVID-19 patients. We selected a prospective cohort of patients hospitalized due to severe COVID-19 pneumonia (n=75), a historical cohort of Influenza A pneumonia patients (n=18) and sex/age-matched healthy controls (n=30). CD39 was overexpressed in COVID-19 patients' plasma and immune cell subsets and related to hypoxemia. Plasma soluble form of CD39 (sCD39) was related to length of hospital stay and independently associated with intensive care unit admission (adjusted odds ratio 1.04, 95%CI 1.0-1.08, p=0.038), with a net reclassification index of 0.229 (0.118-0.287; p=0.036). COVID-19 patients showed extracellular accumulation of adenosine nucleotides (ATP and ADP), resulting in systemic inflammation and pro-coagulant state, as a consequence of purinergic pathway dysregulation. Interestingly, we found that COVID-19 plasma caused platelet activation, which was successfully blocked by the P2Y receptor inhibitor, ticagrelor. Therefore, sCD39 is suggested as a promising biomarker for COVID-19 severity. As a conclusion, our study indicates that CD39 overexpression in COVID-19 patients could be indicating purinergic signaling dysregulation, which might be at the basis of COVID-19 thromboinflammation disorder.
CD39/NTPDase1 已成为维持炎症和凝血稳态的重要分子。由于没有明确的数据阐明这一点，因此各种研究假设 CD39 可能在 COVID-19 病理生理学中发挥作用。因此，我们旨在量化 COVID-19 患者中 CD39 的表达，探讨其与严重临床参数和 ICU 入院的关系，并揭示嘌呤能信号在 COVID-19 患者中的血栓炎症作用。我们选择了一组因严重 COVID-19 肺炎住院的患者（n=75）、一组流感 A 肺炎患者（n=18）和性别/年龄匹配的健康对照组（n=30）进行前瞻性队列研究。CD39 在 COVID-19 患者的血浆和免疫细胞亚群中过度表达，并与低氧血症有关。血浆可溶性 CD39（sCD39）与住院时间有关，与 ICU 入院独立相关（调整后优势比 1.04，95%CI 1.0-1.08，p=0.038），净再分类指数为 0.229（0.118-0.287；p=0.036）。COVID-19 患者表现出细胞外腺苷核苷酸（ATP 和 ADP）的积累，导致全身炎症和促凝状态，这是由于嘌呤能途径失调的结果。有趣的是，我们发现 COVID-19 血浆引起血小板激活，而 P2Y 受体抑制剂 ticagrelor 可成功阻断该激活。因此，sCD39 被认为是 COVID-19 严重程度的有前途的生物标志物。总之，我们的研究表明 COVID-19 患者中 CD39 的过度表达可能表明嘌呤能信号失调，这可能是 COVID-19 血栓炎症紊乱的基础。
