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.


Journal

The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675

Informations de publication

Date de publication:
16 08 2021
Historique:
received: 04 03 2021
accepted: 20 05 2021
pubmed: 26 5 2021
medline: 29 9 2021
entrez: 25 5 2021
Statut: ppublish

Résumé

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.

Sections du résumé

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 118-1.7 × 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).
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.

Identifiants

pubmed: 34031695
pii: 6283590
doi: 10.1093/infdis/jiab283
pmc: PMC8241475
doi:

Substances chimiques

Antibodies, Neutralizing 0
Antibodies, Viral 0
Immunoglobulin G 0
RNA, Viral 0
Spike Glycoprotein, Coronavirus 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

595-605

Subventions

Organisme : NIH HHS
ID : COV19-RECPLAS
Pays : United States
Organisme : European Union
ID : 602525
Organisme : NIHR Imperial Biomedical Research Centre
Organisme : NIHR

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.

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Auteurs

Jeremy Ratcliff (J)

Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.

Dung Nguyen (D)

Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.

Matthew Fish (M)

School of Immunology and Microbial Sciences, Kings College London, London, United Kingdom.

Jennifer Rynne (J)

School of Immunology and Microbial Sciences, Kings College London, London, United Kingdom.

Aislinn Jennings (A)

School of Immunology and Microbial Sciences, Kings College London, London, United Kingdom.

Sarah Williams (S)

Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.

Farah Al-Beidh (F)

Imperial College London, London, United Kingdom.

David Bonsall (D)

Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.

Amy Evans (A)

Clinical Trials Unit, NHS Blood and Transplant, Oxford, United Kingdom.

Tanya Golubchik (T)

Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.

Anthony C Gordon (AC)

Imperial College London, London, United Kingdom.
Imperial College Healthcare NHS Trust, St Mary's Hospital, London, United Kingdom.

Abigail Lamikanra (A)

Clinical, Research, and Development, NHS Blood and Transplant, Oxford, United Kingdom.

Pat Tsang (P)

Clinical, Research, and Development, NHS Blood and Transplant, Oxford, United Kingdom.

Nick A Ciccone (NA)

Radcliffe Department of Medicine and Biomedical Research Centre, Haematology Theme, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.

Ullrich Leuscher (U)

Clinical, Research, and Development, NHS Blood and Transplant, Oxford, United Kingdom.

Wendy Slack (W)

Clinical, Research, and Development, NHS Blood and Transplant, Oxford, United Kingdom.

Emma Laing (E)

Clinical Trials Unit, NHS Blood and Transplant, Oxford, United Kingdom.

Paul R Mouncey (PR)

Intensive Care National Audit and Research Centre, London, United Kingdom.

Sheba Ziyenge (S)

Nuffield Department of Surgical Sciences and Biomedical Research Centre, Surgical Theme, University of Oxford, Oxford, United Kingdom.

Marta Oliveira (M)

Nuffield Department of Surgical Sciences and Biomedical Research Centre, Surgical Theme, University of Oxford, Oxford, United Kingdom.
NHS Blood and Transplant Research Laboratory, Oxford, United Kingdom.

Rutger Ploeg (R)

Nuffield Department of Surgical Sciences and Biomedical Research Centre, Surgical Theme, University of Oxford, Oxford, United Kingdom.
NHS Blood and Transplant Research Laboratory, Oxford, United Kingdom.

Kathryn M Rowan (KM)

Intensive Care National Audit and Research Centre, London, United Kingdom.

Manu Shankar-Hari (M)

School of Immunology and Microbial Sciences, Kings College London, London, United Kingdom.
Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London, United Kingdom.

David J Roberts (DJ)

Clinical, Research, and Development, NHS Blood and Transplant, Oxford, United Kingdom.
Radcliffe Department of Medicine and Biomedical Research Centre, Haematology Theme, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.

David K Menon (DK)

University Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital Cambridge, Cambridge, United Kingdom.

Lise Estcourt (L)

Clinical Trials Unit, NHS Blood and Transplant, Oxford, United Kingdom.
Radcliffe Department of Medicine and Biomedical Research Centre, Haematology Theme, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.

Peter Simmonds (P)

Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.

Heli Harvala (H)

Microbiology Services, NHS Blood and Transplant, London, United Kingdom.

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