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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.
Ratcliff, Jeremy; Nguyen, Dung; Fish, Matthew; Rynne, Jennifer; Jennings, Aislinn; Williams, Sarah; Al-Beidh, Farah; Bonsall, David; Evans, Amy; Golubchik, Tanya; Gordon, Anthony C; Lamikanra, Abigail; Tsang, Pat; Ciccone, Nick A; Leuscher, Ullrich; Slack, Wendy; Laing, Emma; Mouncey, Paul R; Ziyenge, Sheba; Oliveira, Marta; Ploeg, Rutger; Rowan, Kathryn M; Shankar-Hari, Manu; Roberts, David J; Menon, David K; Estcourt, Lise; Simmonds, Peter; Harvala, Heli.
  • Ratcliff J; Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
  • Nguyen D; Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
  • Fish M; School of Immunology and Microbial Sciences, Kings College London, London, United Kingdom.
  • Rynne J; School of Immunology and Microbial Sciences, Kings College London, London, United Kingdom.
  • Jennings A; School of Immunology and Microbial Sciences, Kings College London, London, United Kingdom.
  • Williams S; Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
  • Al-Beidh F; Imperial College London, London, United Kingdom.
  • Bonsall D; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
  • Evans A; Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
  • Golubchik T; Clinical Trials Unit, NHS Blood and Transplant, Oxford, United Kingdom.
  • Gordon AC; Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
  • Lamikanra A; Imperial College London, London, United Kingdom.
  • Tsang P; Imperial College Healthcare NHS Trust, St Mary's Hospital, London, United Kingdom.
  • Ciccone NA; Clinical, Research, and Development, NHS Blood and Transplant, Oxford, United Kingdom.
  • Leuscher U; Clinical, Research, and Development, NHS Blood and Transplant, Oxford, United Kingdom.
  • Slack W; Radcliffe Department of Medicine and Biomedical Research Centre, Haematology Theme, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
  • Laing E; Clinical, Research, and Development, NHS Blood and Transplant, Oxford, United Kingdom.
  • Mouncey PR; Clinical, Research, and Development, NHS Blood and Transplant, Oxford, United Kingdom.
  • Ziyenge S; Clinical Trials Unit, NHS Blood and Transplant, Oxford, United Kingdom.
  • Oliveira M; Intensive Care National Audit and Research Centre, London, United Kingdom.
  • Ploeg R; Nuffield Department of Surgical Sciences and Biomedical Research Centre, Surgical Theme, University of Oxford, Oxford, United Kingdom.
  • Rowan KM; Nuffield Department of Surgical Sciences and Biomedical Research Centre, Surgical Theme, University of Oxford, Oxford, United Kingdom.
  • Shankar-Hari M; NHS Blood and Transplant Research Laboratory, Oxford, United Kingdom.
  • Roberts DJ; Nuffield Department of Surgical Sciences and Biomedical Research Centre, Surgical Theme, University of Oxford, Oxford, United Kingdom.
  • Menon DK; NHS Blood and Transplant Research Laboratory, Oxford, United Kingdom.
  • Estcourt L; Intensive Care National Audit and Research Centre, London, United Kingdom.
  • Simmonds P; School of Immunology and Microbial Sciences, Kings College London, London, United Kingdom.
  • Harvala H; Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London, United Kingdom.
J Infect Dis ; 224(4): 595-605, 2021 08 16.
Article in English | MEDLINE | ID: covidwho-1367024
ABSTRACT

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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Load / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Diagnostic study / Experimental Studies / Randomized controlled trials Limits: Aged / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: English Journal: J Infect Dis Year: 2021 Document Type: Article Affiliation country: Infdis

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Load / SARS-CoV-2 / COVID-19 / Antibodies, Viral Type of study: Diagnostic study / Experimental Studies / Randomized controlled trials Limits: Aged / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: English Journal: J Infect Dis Year: 2021 Document Type: Article Affiliation country: Infdis