Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin.
Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin.
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DOI：
10.1186/s12933-021-01359-7
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发表时间：
2021-08-23
影响因子：
9.3
通讯作者：
Kell DB
中科院分区：
文献类型：
--
作者：
Pretorius E;Vlok M;Venter C;Bezuidenhout JA;Laubscher GJ;Steenkamp J;Kell DB
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)诱导的感染是冠状病毒病2019年(新冠肺炎)的原因，以急性临床病理为特征，包括可能伴有高凝和血小板过度激活的各种凝血疾病。最近，在表面上从急性新冠肺炎症状中恢复的患者中发现了一种新的新冠肺炎表型。这种新的综合征通常被称为新冠肺炎的长期冠状病毒感染/急性后遗症(PASC)。这里我们将其称为Long COVID/PASC。在急性感染后，挥之不去的症状会持续长达6个月(或更长时间)，新冠肺炎幸存者抱怨说，他们会复发疲劳或肌肉无力，呼吸困难，睡眠困难，以及焦虑或抑郁。鉴于血液凝块可以阻塞微血管，从而抑制氧交换，我们在这里调查长期COVID/PASC患者的挥之不去的症状是否可能是由于持续循环的血浆微凝块的存在，这些微凝块抵抗纤溶。我们使用包括蛋白质组学和荧光显微镜在内的技术来研究健康人、2型糖尿病(T2 DM)患者、急性新冠肺炎患者和那些有长期COVID/PASC症状的人的血浆样本。我们发现，Long COVID/PASC的血浆样本仍然含有大量异常(淀粉样蛋白)沉积(微凝块)。我们还表明，急性新冠肺炎和长期COVID/PASC血浆样本中的这些微凝块对纤溶具有抵抗力(与对照组和T2 DM的血浆相比)，即使在胰酶消化后也是如此。在第二次胰酶消化后，持续的小球沉积(微凝块)被溶解。我们检测到各种炎症分子在急性新冠肺炎和长COVID/PASC的上清液和溶解小球沉积物中均显著增加，而对照组和T2 DM的完全消化液的等量。尤其令人感兴趣的是，α(2)-抗纤溶酶(α2AP)、各种纤维蛋白原链以及困在溶解的抗纤溶颗粒沉积物中的血清淀粉样蛋白A(SAA)显著增加。急性新冠肺炎感染和慢性COVID/PASC患者的凝血病理可能受益于持续抗凝治疗以支持纤溶系统功能。
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by acute clinical pathologies, including various coagulopathies that may be accompanied by hypercoagulation and platelet hyperactivation. Recently, a new COVID-19 phenotype has been noted in patients after they have ostensibly recovered from acute COVID-19 symptoms. This new syndrome is commonly termed Long COVID/Post-Acute Sequelae of COVID-19 (PASC). Here we refer to it as Long COVID/PASC. Lingering symptoms persist for as much as 6 months (or longer) after acute infection, where COVID-19 survivors complain of recurring fatigue or muscle weakness, being out of breath, sleep difficulties, and anxiety or depression. Given that blood clots can block microcapillaries and thereby inhibit oxygen exchange, we here investigate if the lingering symptoms that individuals with Long COVID/PASC manifest might be due to the presence of persistent circulating plasma microclots that are resistant to fibrinolysis. We use techniques including proteomics and fluorescence microscopy to study plasma samples from healthy individuals, individuals with Type 2 Diabetes Mellitus (T2DM), with acute COVID-19, and those with Long COVID/PASC symptoms. We show that plasma samples from Long COVID/PASC still contain large anomalous (amyloid) deposits (microclots). We also show that these microclots in both acute COVID-19 and Long COVID/PASC plasma samples are resistant to fibrinolysis (compared to plasma from controls and T2DM), even after trypsinisation. After a second trypsinization, the persistent pellet deposits (microclots) were solubilized. We detected various inflammatory molecules that are substantially increased in both the supernatant and trapped in the solubilized pellet deposits of acute COVID-19 and Long COVID/PASC, versus the equivalent volume of fully digested fluid of the control samples and T2DM. Of particular interest was a substantial increase in α(2)-antiplasmin (α2AP), various fibrinogen chains, as well as Serum Amyloid A (SAA) that were trapped in the solubilized fibrinolytic-resistant pellet deposits. Clotting pathologies in both acute COVID-19 infection and in Long COVID/PASC might benefit from following a regime of continued anticlotting therapy to support the fibrinolytic system function.
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影响因子：
4
作者：
Grobbelaar LM;Venter C;Vlok M;Ngoepe M;Laubscher GJ;Lourens PJ;Steenkamp J;Kell DB;Pretorius E
通讯作者：
Pretorius E
影响因子：
2.4
作者：
Chen, JM;López, KA
通讯作者：
López, KA
影响因子：
20.3
作者：
Berzuini, Alessandra;Bianco, Cristiana;Prati, Daniele
通讯作者：
Prati, Daniele
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
DOI：
10.1016/j.ijid.2020.09.016
发表时间：
2020-11
期刊：
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
影响因子：
--
作者：
Afrin LB;Weinstock LB;Molderings GJ
通讯作者：
Molderings GJ