Premortem Skin Biopsy Assessing Microthrombi, Interferon Type I Antiviral and Regulatory Proteins, and Complement Deposition Correlates with Coronavirus Disease 2019 Clinical Stage.
Premortem Skin Biopsy Assessing Microthrombi, Interferon Type I Antiviral and Regulatory Proteins, and Complement Deposition Correlates with Coronavirus Disease 2019 Clinical Stage.
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DOI：
10.1016/j.ajpath.2022.05.006
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发表时间：
2022-09
影响因子：
6
通讯作者：
Magro, Cynthia
中科院分区：
文献类型：
--
作者：
Laurence, Jeffrey;Nuovo, Gerard;Racine-Brzostek, Sabrina E.;Seshadri, Madhav;Elhadad, Sonia;Crowson, Neil;Mulvey, J. Justin;Harp, Joanna;Ahamed, Jasimuddin;Magro, Cynthia
除尸检外，缺乏2019冠状病毒病（COVID-19）临床阶段的组织相关性。在当前的研究中，检查了15名重度/危重COVID-19患者和6名轻度/中度COVID-19患者的皮肤穿刺活检标本。评估了动脉和静脉微血栓、C5 b-9和MASP 2沉积（分别代表替代和凝集素补体途径）以及I型干扰素驱动的抗病毒蛋白MxA（粘病毒抗性A）与SIN 3A（一种基于I型干扰素的促炎信号传导启动子）的差异表达的证据。对照受试者包括9名在COVID-19前患有脓毒症相关急性呼吸窘迫综合征（ARDS）和/或急性肾损伤（阿基）的患者。15例重度/危重COVID-19患者中有13例（87%）检测到微血栓，而6例轻度/中度COVID-19患者中无微血栓（P < 0.001），9例COVID-19前ARDS/阿基患者中无微血栓（P < 0.001）。对严重急性呼吸综合征冠状病毒2（COVID-19的病原体）的刺突蛋白染色的微血管内衬细胞也表达了组织因子。15例重度/危重COVID-19患者中有13例（87%）发生C5 b-9沉积，而6例轻度/中度COVID-19患者中无C5 b-9沉积（P < 0.001），9例COVID-19前ARDS/阿基患者中无C5 b-9沉积（P < 0.001）。MASP 2沉积也仅限于重度/危重COVID-19病例。所有6例轻度/中度COVID-19病例中均出现MxA表达，而13例重度/危重病例中有2例（15%）出现MxA表达（P < 0.001）。相比之下，SIN 3A仅限于与严重急性呼吸综合征冠状病毒2刺突蛋白共定位的重症/危重COVID-19病例。与对照受试者相比，重度/危重COVID-19患者血浆中的SIN 3A也升高（P ≤ 0.02）。总之，该研究使用皮肤确定了COVID-19临床阶段的死前组织相关性。如果在纵向队列中得到验证，这种方法可以识别有疾病进展风险的个体，并实现有针对性的干预。
Apart from autopsy, tissue correlates of coronavirus disease 2019 (COVID-19) clinical stage are lacking. In the current study, cutaneous punch biopsy specimens of 15 individuals with severe/critical COVID-19 and six with mild/moderate COVID-19 were examined. Evidence for arterial and venous microthrombi, deposition of C5b-9 and MASP2 (representative of alternative and lectin complement pathways, respectively), and differential expression of interferon type I–driven antiviral protein MxA (myxovirus resistance A) versus SIN3A, a promoter of interferon type I–based proinflammatory signaling, were assessed. Control subjects included nine patients with sepsis-related acute respiratory distress syndrome (ARDS) and/or acute kidney injury (AKI) pre–COVID-19. Microthrombi were detected in 13 (87%) of 15 patients with severe/critical COVID-19 versus zero of six patients with mild/moderate COVID-19 (P < 0.001) and none of the nine patients with pre–COVID-19 ARDS/AKI (P < 0.001). Cells lining the microvasculature staining for spike protein of severe acute respiratory syndrome coronavirus 2, the etiologic agent of COVID-19, also expressed tissue factor. C5b-9 deposition occurred in 13 (87%) of 15 patients with severe/critical COVID-19 versus zero of six patients with mild/moderate COVID-19 (P < 0.001) and none of the nine patients with pre–COVID-19 ARDS/AKI (P < 0.001). MASP2 deposition was also restricted to severe/critical COVID-19 cases. MxA expression occurred in all six mild/moderate versus two (15%) of 13 severe/critical cases (P < 0.001) of COVID-19. In contrast, SIN3A was restricted to severe/critical COVID-19 cases co-localizing with severe acute respiratory syndrome coronavirus 2 spike protein. SIN3A was also elevated in plasma of patients with severe/critical COVID-19 versus control subjects (P ≤ 0.02). In conclusion, the study identified premortem tissue correlates of COVID-19 clinical stage using skin. If validated in a longitudinal cohort, this approach could identify individuals at risk for disease progression and enable targeted interventions.
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影响因子：
64.5
作者：
Aid M;Busman-Sahay K;Vidal SJ;Maliga Z;Bondoc S;Starke C;Terry M;Jacobson CA;Wrijil L;Ducat S;Brook OR;Miller AD;Porto M;Pellegrini KL;Pino M;Hoang TN;Chandrashekar A;Patel S;Stephenson K;Bosinger SE;Andersen H;Lewis MG;Hecht JL;Sorger PK;Martinot AJ;Estes JD;Barouch DH
通讯作者：
Barouch DH
影响因子：
1.5
作者：
Andina, David;Noguera-Morel, Lucero;Torrelo, Antonio
通讯作者：
Torrelo, Antonio
影响因子：
64.8
作者：
Al-Aly, Ziyad;Xie, Yan;Bowe, Benjamin
通讯作者：
Bowe, Benjamin
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
人类肾脏是新型严重急性呼吸综合征冠状病毒2感染的目标
影响因子：
16.6
作者：
Diao B;Wang C;Wang R;Feng Z;Zhang J;Yang H;Tan Y;Wang H;Wang C;Liu L;Liu Y;Liu Y;Wang G;Yuan Z;Hou X;Ren L;Wu Y;Chen Y
通讯作者：
Chen Y