A disturbed balance between blood complement protective factors (FH, ApoE) and common pathway effectors (C5a, TCC) in acute COVID-19 and during convalesce.
A disturbed balance between blood complement protective factors (FH, ApoE) and common pathway effectors (C5a, TCC) in acute COVID-19 and during convalesce.
复制标题
DOI：
10.1038/s41598-022-17011-7
复制
发表时间：
2022-08-11
影响因子：
4.6
通讯作者：
Song, Wen-Chao
中科院分区：
文献类型：
--
作者：
Laudanski, Krzysztof;Okeke, Tony;Siddiq, Kumal;Hajj, Jihane;Restrepo, Mariana;Gullipalli, Damodar;Song, Wen-Chao
补体在感染期间对体内平衡的影响由细胞毒性(激活补体成分5(C5a)末端细胞毒复合体(TCC))和细胞保护元件(补体因子H(FH)和载脂蛋白E(ApoE))共同决定。在这里，我们调查了他们在感染SARS-CoV-2期间血液环境中关于病毒负荷、组织坏死程度和免疫反应方面的知识差距。101例因聚合酶链式反应确诊的新冠肺炎住院患者在H1(48小时)、H2(3-4天)、H3(5-7天)、H4(超过7天至93天)采集血液。使用电子病历收集既往疾病、治疗、脑血管事件(CVA)的发生率、深静脉血栓(DVT)和肺栓塞(PE)的病史以及死亡率。血浆C5a、TCC、FH、ApoE可作为补体环境。同时检测组织坏死(HMGB1，RAGE)、非特异性炎症反应(IL-6、C反应蛋白)、总病毒载量(SARS-CoV-2刺突蛋白)和特异性免疫应答(αS和N-蛋白)。C5a在所有时间点均保持升高，峰值出现在5-7天。研究了围绕三个簇结合的补体元素：#0(↑↑↑C5a，↑↑Tcc，↓↓ApoE)，#1↑C5a，↑Tcc，↑↑↑Fh)；#2(↑C5a，↑Tcc，↑Fh，↑↑↑ApoE)。FH和ApoE的下降是死亡的预测因子，而TCC和C5a与患者的住院时间、APACHE和CRP相关。C5a水平升高(Δ = 122.64；p = 0.0294；数据未显示)和FH水平降低(Δ = 836,969；p = 0.0285；数据未显示)与哮喘发病率共存。C5a与血凝和HMGB1显著相关，而与病毒载量和免疫应答无关。Remdevir对FH保存有积极影响，而恢复期血浆治疗可提高C5a水平。新冠肺炎患者ApoE和FH与C5a和TCC的三个补体激活簇表现出不同的环境。补体激活与坏死标志物的增加有关，但与病毒负担或免疫系统反应无关。
A complement effect on homeostasis during infection is determined by both cytotoxic (activate complement component 5 (C5a) terminal cytotoxic complex (TCC)), and cytoprotective elements (complement factor H (FH), as well as apolipoprotein E (ApoE)). Here, we investigated the gap in knowledge in their blood milieu during SARS-CoV-2 infection with respect to the viral burden, level of tissue necrosis, and immunological response. 101 patients hospitalized with a PCR-confirmed diagnosis of COVID-19 had blood collected at H1 (48 h), H2 (3–4 Days), H3 (5–7 days), H4 (more than 7 days up to 93 days). Pre-existing conditions, treatment, the incidence of cerebrovascular events (CVA), a history of deep venous thrombosis (DVT) and pulmonary embolism (PE), and mortality was collected using electronic medical records. Plasma C5a, TCC, FH, and ApoE were considered as a complement milieu. Tissue necrosis (HMGB1, RAGE), non-specific inflammatory responses (IL-6, C-reactive protein), overall viral burden (SARS-CoV-2 spike protein), and specific immune responses (IgG, IgA, IgM directed αS- & N-proteins) were assessed simultaneously. C5a remained elevated across all time points, with the peak at 5–7 days. Studied elements of complement coalesced around three clusters: #0 (↑↑↑C5a, ↑↑TCC, ↓↓ApoE), #1 ↑C5a, ↑TCC, ↑↑↑FH); #2 (↑C5a, ↑TCC, ↑FH, ↑↑↑ApoE). The decline in FH and ApoE was a predictor of death, while TCC and C5a correlated with patient length of stay, APACHE, and CRP. Increased levels of C5a (Δ = 122.64; p = 0.0294; data not shown) and diminished levels of FH (Δ = 836,969; p = 0.0285; data not shown) co-existed with CVA incidence. C5a correlated storngly with blood RAGE and HMGB1, but not with viral load and immunological responsiveness. Remdesivir positively affected FH preservation, while convalescent plasma treatment elevated C5a levels. Three clusters of complement activation demonstrated a various milieu of ApoE & FH vs C5a & TCC in COVID-19 patients. Complement activation is linked to increased necrosis markers but not to viral burden or immune system response.
登录
查看更多内容
影响因子：
7.3
作者：
Lipcsey M;Persson B;Eriksson O;Blom AM;Fromell K;Hultström M;Huber-Lang M;Ekdahl KN;Frithiof R;Nilsson B
通讯作者：
Nilsson B
影响因子：
158.5
作者：
Cavalcanti, A. B.;Zampieri, F. G.;Berwanger, O.
通讯作者：
Berwanger, O.
影响因子：
7.2
作者：
Buntinx, F;Niclaes, L;Van den Akker, M
通讯作者：
Van den Akker, M
影响因子：
12.7
作者：
Kolilekas, Lykourgos;Loverdos, Konstantinos;Gaga, Mina
通讯作者：
Gaga, Mina
影响因子：
8.8
作者：
Coopersmith, Craig M.;De Backer, Daniel;Rhodes, Andrew
通讯作者：
Rhodes, Andrew