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

被引：16

作者：

Ratcliff, Jeremy ^{[1
]}

Dung Nguyen ^{[1
]}

Fish, Matthew ^{[2
]}

Rynne, Jennifer ^{[2
]}

Jennings, Aislinn ^{[2
]}

Williams, Sarah ^{[1
]}

Al-Beidh, Farah ^{[3
]}

Bonsall, David ^{[4
,5
]}

Evans, Amy ^{[6
]}

Golubchik, Tanya ^{[5
]}

Gordon, Anthony C. ^{[3
,7
]}

Lamikanra, Abigail ^{[8
]}

Tsang, Pat ^{[8
]}

Ciccone, Nick A. ^{[9
,10
]}

Leuscher, Ullrich ^{[8
]}

Slack, Wendy ^{[8
]}

Laing, Emma ^{[6
]}

Mouncey, Paul R. ^{[11
]}

Ziyenge, Sheba ^{[12
,13
]}

Oliveira, Marta ^{[12
,13
,14
]}

Ploeg, Rutger ^{[12
,13
,14
]}

Rowan, Kathryn M. ^{[11
]}

Shankar-Hari, Manu ^{[2
,15
]}

Roberts, David J. ^{[8
,9
,10
]}

Menon, David K. ^{[16
]}

Estcourt, Lise ^{[6
,9
,10
]}

Simmonds, Peter ^{[1
]}

Harvala, Heli ^{[17
]}

机构：

[1] Univ Oxford, Nuffield Dept Med, Peter Medawar Bldg Pathogen Res, Oxford, England

[2] Kings Coll London, Sch Immunol & Microbial Sci, London, England

[3] Imperial Coll London, London, England

[4] Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Nuffield Dept Med, Oxford, England

[5] Univ Oxford, Wellcome Ctr Human Genet, Oxford, England

[6] NHS Blood & Transplant, Clin Trials Unit, Oxford, England

[7] Imperial Coll Healthcare NHS Trust, St Marys Hosp, London, England

[8] NHS Blood & Transplant, Clin Res & Dev, Oxford, England

[9] Univ Oxford, John Radcliffe Hosp, Haematol Theme, Radcliffe Dept Med, Oxford, England

[10] Univ Oxford, John Radcliffe Hosp, Haematol Theme, Biomed Res Ctr, Oxford, England

[11] Intens Care Natl Audit & Res Ctr, London, England

[12] Univ Oxford, Nuffield Dept Surg Sci, Surg Theme, Oxford, England

[13] Univ Oxford, Biomed Res Ctr, Surg Theme, Oxford, England

[14] NHS Blood & Transplant Res Lab, Oxford, England

[15] Guys & St Thomas NHS Fdn Trust, St Thomas Hosp, London, England

[16] Univ Cambridge, Univ Div Anaesthesia, Addenbrookes Hosp Cambridge, Cambridge, England

[17] NHS Blood & Transplant, Microbiol Serv, London, England

来源：

JOURNAL OF INFECTIOUS DISEASES | 2021年 / 224卷 / 04期

基金：

欧盟地平线“2020”;

关键词：

clade B.1.1.7; convalescent plasma; coronavirus; COVID-19; ELISA; polymerase chain reaction; randomized clinical trial; SARS-CoV-2; variant of concern; viral load;

D O I：

10.1093/infdis/jiab283

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background. 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. Methods. 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. Results. Of 1274 subjects, 90% were PCR positive with viral loads 118-1.7x10(11)IU/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 5.8x10(6) and 2.0x10(5) IU/mL, respectively; P=2x10(-15)). Conclusions. 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.

引用

页码：595 / 605

页数：11

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