Virological Characterization of Critically Ill Patients With COVID-19 in the United Kingdom: Interactions of Viral Load, Antibody Status, and B.1.1.7 Infection.

Virological Characterization of Critically Ill Patients With COVID-19 in the United Kingdom: Interactions of Viral Load, Antibody Status, and B.1.1.7 Infection.
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DOI:
10.1093/infdis/jiab283
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发表时间:
2021-08-16
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
REMAP-CAP Immunoglobulin Domain UK Investigators
REMAP-CAP Immunoglobulin Domain UK Investigators
中科院分区:
其他
文献类型:
--
作者:
Ratcliff J;Nguyen D;Fish M;Rynne J;Jennings A;Williams S;Al-Beidh F;Bonsall D;Evans A;Golubchik T;Gordon AC;Lamikanra A;Tsang P;Ciccone NA;Leuscher U;Slack W;Laing E;Mouncey PR;Ziyenge S;Oliveira M;Ploeg R;Rowan KM;Shankar-Hari M;Roberts DJ;Menon DK;Estcourt L;Simmonds P;Harvala H;REMAP-CAP Immunoglobulin Domain UK Investigators

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含有严重急性呼吸综合征冠状病毒2(SARS-CoV-2)中和抗体的恢复期血浆正在研究用于2019冠状病毒病(COVID-19)治疗。我们报告了REMAP-CAP随机对照试验中免疫球蛋白领域入选的英国重症监护患者的不同病毒学特征,这些特征可能影响治疗结果。用PCR方法定量检测治疗前鼻咽拭子中SARS-CoV-2 RNA。通过加标蛋白ELISA测定抗体状态。使用针对D1118 H的等位基因特异性探针或限制性位点多态性(SfcI)将B.1.1.7与其他SARS-CoV-2毒株区分开来。在1274例受试者中,90%为PCR阳性,病毒载量为118-1.7 × 1011 IU/mL。  IgG血清阴性(n = 354; 28%)的中位病毒载量是血清阳性(n = 939; 72%)的40倍。    B.1.1.7的频率从2020年11月的<1%增加到2021年1月的82%。野生型SARS-CoV-2血清阴性个体的病毒载量显著高于血清阳性个体(中位数分别为5.8 × 106和2.0 × 105 IU/mL; P = 2 × 10−15)。        血清阳性B.1.1.7感染受试者的高病毒载量和对血清转化的抗性表明先天性和适应性免疫应答的清除效果较差。SARS-CoV-2毒株、病毒载量和抗体状态定义了用于分析治疗效果的亚组。参加恢复期血浆治疗试验的患者在病毒载量、感染SARS-CoV-2类型和抗体状态方面具有高度异质性,每种情况都可能影响治疗结果。B.1.1.7感染与较高的病毒载量和血清转换后清除率降低相关。
Convalescent plasma containing neutralizing antibody to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is under investigation for coronavirus disease 2019 (COVID-19) treatment. We report diverse virological characteristics of UK intensive care patients enrolled in the Immunoglobulin Domain of the REMAP-CAP randomized controlled trial that potentially influence treatment outcomes. SARS-CoV-2 RNA in nasopharyngeal swabs collected pretreatment was quantified by PCR. Antibody status was determined by spike-protein ELISA. B.1.1.7 was differentiated from other SARS-CoV-2 strains using allele-specific probes or restriction site polymorphism (SfcI) targeting D1118H. Of 1274 subjects, 90% were PCR positive with viral loads 118–1.7 × 1011IU/mL. Median viral loads were 40-fold higher in those IgG seronegative (n = 354; 28%) compared to seropositives (n = 939; 72%). Frequencies of B.1.1.7 increased from <1% in November 2020 to 82% of subjects in January 2021. Seronegative individuals with wild-type SARS-CoV-2 had significantly higher viral loads than seropositives (medians 5.8 × 106 and 2.0 × 105 IU/mL, respectively; P = 2 × 10−15). High viral loads in seropositive B.1.1.7-infected subjects and resistance to seroconversion indicate less effective clearance by innate and adaptive immune responses. SARS-CoV-2 strain, viral loads, and antibody status define subgroups for analysis of treatment efficacy. Patients enrolled in a trial for convalescent plasma treatment were highly heterogeneous in terms of viral loads, infecting SARS-CoV-2 types, and antibody status, each potentially influencing treatment outcomes. B.1.1.7 infections were associated with higher viral loads and reduced clearance postseroconversion.
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