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

REMAP-CAP Immunoglobulin Domain UK Investigators

doi:10.1093/infdis/jiab283

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

REMAP-CAP Immunoglobulin Domain UK Investigators

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	595-605
Number of pages	11
Journal	The Journal of Infectious Diseases
Volume	224
Issue number	4
DOIs	https://doi.org/10.1093/infdis/jiab283
Publication status	Published - 24 May 2021

Keywords / Materials (for Non-textual outputs)

Aged
Antibodies, Neutralizing/immunology
Antibodies, Viral/immunology
COVID-19/immunology
Critical Illness
Female
Humans
Immunization, Passive
Immunoglobulin G/immunology
Male
Middle Aged
RNA, Viral/immunology
SARS-CoV-2/immunology
Serologic Tests/methods
Spike Glycoprotein, Coronavirus/immunology
United Kingdom
Viral Load/immunology

Access to Document

10.1093/infdis/jiab283

jiab283
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-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 [email protected] DOI: 10.1093/infdis/jiab283
Final published version, 1.75 MBLicence: Creative Commons: Attribution No Derivatives (CC-BY-ND)

https://academic.oup.com/jid/article/224/4/595/6283590

Cite this

@article{ccd272ccf61845a896493a16e8fe3d4f,

title = "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",

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.",

keywords = "Aged, Antibodies, Neutralizing/immunology, Antibodies, Viral/immunology, COVID-19/immunology, Critical Illness, Female, Humans, Immunization, Passive, Immunoglobulin G/immunology, Male, Middle Aged, RNA, Viral/immunology, SARS-CoV-2/immunology, Serologic Tests/methods, Spike Glycoprotein, Coronavirus/immunology, United Kingdom, Viral Load/immunology",

author = "{REMAP-CAP Immunoglobulin Domain UK Investigators} and Jeremy Ratcliff and Dung Nguyen and Matthew Fish and Jennifer Rynne and Aislinn Jennings and Sarah Williams and Farah Al-Beidh and David Bonsall and Amy Evans and Tanya Golubchik and Gordon, {Anthony C} and Abigail Lamikanra and Pat Tsang and Ciccone, {Nick A} and Ullrich Leuscher and Wendy Slack and Emma Laing and Mouncey, {Paul R} and Sheba Ziyenge and Marta Oliveira and Rutger Ploeg and Rowan, {Kathryn M} and Manu Shankar-Hari and Roberts, {David J} and Menon, {David K} and Lise Estcourt and Peter Simmonds and Heli Harvala",

note = "{\textcopyright} The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.",

year = "2021",

month = may,

day = "24",

doi = "10.1093/infdis/jiab283",

language = "English",

volume = "224",

pages = "595--605",

journal = "The Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "4",

}

TY - JOUR

T1 - Virological Characterization of Critically Ill Patients With COVID-19 in the United Kingdom

T2 - Interactions of Viral Load, Antibody Status, and B.1.1.7 Infection

AU - REMAP-CAP Immunoglobulin Domain UK Investigators

AU - Ratcliff, Jeremy

AU - Nguyen, Dung

AU - Fish, Matthew

AU - Rynne, Jennifer

AU - Jennings, Aislinn

AU - Williams, Sarah

AU - Al-Beidh, Farah

AU - Bonsall, David

AU - Evans, Amy

AU - Golubchik, Tanya

AU - Gordon, Anthony C

AU - Lamikanra, Abigail

AU - Tsang, Pat

AU - Ciccone, Nick A

AU - Leuscher, Ullrich

AU - Slack, Wendy

AU - Laing, Emma

AU - Mouncey, Paul R

AU - Ziyenge, Sheba

AU - Oliveira, Marta

AU - Ploeg, Rutger

AU - Rowan, Kathryn M

AU - Shankar-Hari, Manu

AU - Roberts, David J

AU - Menon, David K

AU - Estcourt, Lise

AU - Simmonds, Peter

AU - Harvala, Heli

N1 - © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.

PY - 2021/5/24

Y1 - 2021/5/24

N2 - 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.

AB - 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.

KW - Aged

KW - Antibodies, Neutralizing/immunology

KW - Antibodies, Viral/immunology

KW - COVID-19/immunology

KW - Critical Illness

KW - Female

KW - Humans

KW - Immunization, Passive

KW - Immunoglobulin G/immunology

KW - Male

KW - Middle Aged

KW - RNA, Viral/immunology

KW - SARS-CoV-2/immunology

KW - Serologic Tests/methods

KW - Spike Glycoprotein, Coronavirus/immunology

KW - United Kingdom

KW - Viral Load/immunology

U2 - 10.1093/infdis/jiab283

DO - 10.1093/infdis/jiab283

M3 - Article

C2 - 34031695

SN - 0022-1899

VL - 224

SP - 595

EP - 605

JO - The Journal of Infectious Diseases

JF - The Journal of Infectious Diseases

IS - 4

ER -

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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Keywords / Materials (for Non-textual outputs)

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