Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19.
Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19.
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DOI：
10.1186/s13054-020-03398-0
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发表时间：
2020-12-14
期刊：
影响因子：
--
通讯作者：
Kelvin DJ
中科院分区：
文献类型：
--
作者：
Bermejo-Martin JF;González-Rivera M;Almansa R;Micheloud D;Tedim AP;Domínguez-Gil M;Resino S;Martín-Fernández M;Ryan Murua P;Pérez-García F;Tamayo L;Lopez-Izquierdo R;Bustamante E;Aldecoa C;Gómez JM;Rico-Feijoo J;Orduña A;Méndez R;Fernández Natal I;Megías G;González-Estecha M;Carriedo D;Doncel C;Jorge N;Ortega A;de la Fuente A;Del Campo F;Fernández-Ratero JA;Trapiello W;González-Jiménez P;Ruiz G;Kelvin AA;Ostadgavahi AT;Oneizat R;Ruiz LM;Miguéns I;Gargallo E;Muñoz I;Pelegrin S;Martín S;García Olivares P;Cedeño JA;Ruiz Albi T;Puertas C;Berezo JÁ;Renedo G;Herrán R;Bustamante-Munguira J;Enríquez P;Cicuendez R;Blanco J;Abadia J;Gómez Barquero J;Mamolar N;Blanca-López N;Valdivia LJ;Fernández Caso B;Mantecón MÁ;Motos A;Fernandez-Barat L;Ferrer R;Barbé F;Torres A;Menéndez R;Eiros JM;Kelvin DJ
COVID-19 可与呼吸道和肺外疾病一起发展。 SARS-CoV-2 RNA 在呼吸道样本中检测到，也在血液、粪便和尿液中检测到。严重的 COVID-19 的特点是宿主对该病毒的反应失调。我们研究了血浆中病毒 RNA 血症或病毒 RNA 载量是否与严重的 COVID-19 以及这种失调反应有关。总共招募了 250 名 COVID-19 患者（50 名门诊患者、100 名住院病房患者和 100 名重症患者）。使用液滴数字 PCR 进行血浆中病毒 RNA 的检测和定量，针对 SARS-CoV-2 核蛋白基因的 N1 和 N2 区域。通过多变量逻辑回归评估了 SARS-CoV-2 RNA 血症和血浆中病毒 RNA 载量与严重程度之间的关联。通过计算 Spearman 相关系数来评估病毒 RNA 载量和证明宿主反应失调的生物标志物之间的相关性。与病房患者（27%）和门诊患者（2%）相比，危重患者（78%）病毒RNA血症的发生率较高（p<0.001）。危重患者血浆中的病毒RNA载量高于非危重患者，其中非幸存者的病毒RNA载量最高。当比较门诊患者和病房患者时，病毒RNA血症在多变量分析中并未显示出显着关联。相反，当病房患者与ICU患者进行比较时，病毒RNA血症和血浆病毒RNA载量均与危重症相关（OR [CI 95%]，p）：RNA血症（3.92 [1.183–12.968]，0.025），病毒RNA载量（N1）（1.962 [1.244–3.096]，0.004）；病毒 RNA 载量 (N2) (2.229 [1.382–3.595], 0.001)。血浆中病毒RNA载量与较高水平的趋化因子（CXCL10、CCL2）、指示全身炎症反应的生物标志物（IL-6、CRP、铁蛋白）、NK细胞活化（IL-15）、内皮功能障碍（VCAM-1、血管生成素-2、ICAM-1）、凝血激活（D-二聚体和INR）、组织损伤相关 （LDH、GPT）、中性粒细胞反应（中性粒细胞计数、髓过氧化物酶、GM-CSF）和免疫抑制（PD-L1、IL-10、淋巴细胞减少和单核细胞减少）。 SARS-CoV-2 RNA 血症和血浆中的病毒 RNA 载量与 COVID-19 的危重疾病相关。血浆中的病毒RNA载量与宿主反应失调的关键特征相关，表明不受控制的病毒复制在这种疾病的发病机制中发挥着重要作用。
COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%], p): RNAemia (3.92 [1.183–12.968], 0.025), viral RNA load (N1) (1.962 [1.244–3.096], 0.004); viral RNA load (N2) (2.229 [1.382–3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia). SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.
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影响因子：
5
作者：
Cameron MJ;Bermejo-Martin JF;Danesh A;Muller MP;Kelvin DJ
通讯作者：
Kelvin DJ
影响因子：
11.8
作者：
Veyer, David;Kerneis, Solen;Pere, Helene
通讯作者：
Pere, Helene
DOI：
10.1186/cc8208
发表时间：
2009
期刊：
Critical care (London, England)
影响因子：
--
作者：
Bermejo-Martin JF;Ortiz de Lejarazu R;Pumarola T;Rello J;Almansa R;Ramírez P;Martin-Loeches I;Varillas D;Gallegos MC;Serón C;Micheloud D;Gomez JM;Tenorio-Abreu A;Ramos MJ;Molina ML;Huidobro S;Sanchez E;Gordón M;Fernández V;Del Castillo A;Marcos MA;Villanueva B;López CJ;Rodríguez-Domínguez M;Galan JC;Cantón R;Lietor A;Rojo S;Eiros JM;Hinojosa C;Gonzalez I;Torner N;Banner D;Leon A;Cuesta P;Rowe T;Kelvin DJ
通讯作者：
Kelvin DJ
影响因子：
5
作者：
Bao, Jinfeng;Li, Chenxi;Gu, Bing
通讯作者：
Gu, Bing
影响因子：
11.8
作者：
Hagman, Karl;Hedenstierna, Magnus;Ursing, Johan
通讯作者：
Ursing, Johan