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

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

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

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

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

16 Citations (Scopus)

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.

Original language	English
Pages (from-to)	595-605
Number of pages	11
Journal	The Journal of infectious diseases
Volume	224
Issue number	4
Early online date	24 May 2021
DOIs	https://doi.org/10.1093/infdis/jiab283
Publication status	Published - 15 Aug 2021

Access to Document

10.1093/infdis/jiab283

Cite this

Ratcliff, J., Nguyen, D., Fish, M., Rynne, J., Jennings, A., Williams, S., Al-Beidh, F., Bonsall, D., Evans, A., Golubchik, T., Gordon, A. C., Lamikanra, A., Tsang, P., Ciccone, N. A., Leuscher, U., Slack, W., Laing, E., Mouncey, P. R., Ziyenge, S., ... Harvala, H. (2021). 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. The Journal of infectious diseases, 224(4), 595-605. https://doi.org/10.1093/infdis/jiab283

@article{6708b04084c84d308e3c0c93e7c4989a,

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.",

author = "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 = "Publisher Copyright: {\textcopyright} The Author(s) 2021.",

year = "2021",

month = aug,

day = "15",

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",

}

Ratcliff, J, Nguyen, D, Fish, M , Rynne, J , Jennings, A, Williams, S, Al-Beidh, F, Bonsall, D, Evans, A, Golubchik, T, Gordon, AC, Lamikanra, A, Tsang, P, Ciccone, NA, Leuscher, U, Slack, W, Laing, E, Mouncey, PR, Ziyenge, S, Oliveira, M, Ploeg, R, Rowan, KM, Shankar-Hari, M, Roberts, DJ, Menon, DK, Estcourt, L, Simmonds, P & Harvala, H 2021, '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', The Journal of infectious diseases, vol. 224, no. 4, pp. 595-605. https://doi.org/10.1093/infdis/jiab283

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 - 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

PY - 2021/8/15

Y1 - 2021/8/15

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.

UR - http://www.scopus.com/inward/record.url?scp=85116958347&partnerID=8YFLogxK

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this