Virological and serological characterization of critically ill patients with COVID-19 in the UK: Interactions of viral load, antibody status and B.1.1.7 variant infection.
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Accepted version
Published version
Author(s)
Type
Journal Article
Abstract
BACKGROUND: Convalescent plasma containing neutralising antibody to SARS-CoV-2 is under investigation for COVID-19 treatment. We report diverse virological characteristics of UK intensive care patients enrolled in the Immunoglobulin Domain of the REMAP-CAP randomised controlled trial that potentially influence treatment outcomes. METHODS: SARS-CoV-2 RNA in nasopharyngeal swabs collected pre-treatment 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 seronegative for IgG antibodies (n=354; 28%) compared to seropositives (n=939; 72%). Frequencies of B.1.1.7 increased from <1% in early 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 2.0 x10 5 IU/ml respectively; p=2x10 -15). However, viral load distributions were elevated in both seronegative and seropositive subjects infected with B.1.1.7 (4.0x10 6 and 1.6x10 6 IU/ml respectively). 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.
Date Issued
2021-08-15
Date Acceptance
2021-05-20
Citation
Journal of Infectious Diseases, 2021, 224 (4), pp.595-605
ISSN
0022-1899
Publisher
Oxford University Press
Start Page
595
End Page
605
Journal / Book Title
Journal of Infectious Diseases
Volume
224
Issue
4
Copyright Statement
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of
America.
This is an Open Access article distributed under the terms of the Creative Commons AttributionNonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which
permits non-commercial reproduction and distribution of the work, in any medium, provided the
original work is not altered or transformed in any way, and that the work is properly cited. For
commercial re-use, please contact journals.permissions@oup.com
America.
This is an Open Access article distributed under the terms of the Creative Commons AttributionNonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which
permits non-commercial reproduction and distribution of the work, in any medium, provided the
original work is not altered or transformed in any way, and that the work is properly cited. For
commercial re-use, please contact journals.permissions@oup.com
Sponsor
NIHR
National Institute for Health Research
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/34031695
PII: 6283590
Grant Number
COVID-19-REMAP-CAP
Subjects
Coronavirus
Polymerase Chain Reaction
SARS-CoV-2 COVID-19
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2021-05-24