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
<br><strong>Background<br></strong> 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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2021
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| _version_ | 1826286650879115264 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ratcliff, J |
| collection | OXFORD |
| description | <br><strong>Background<br></strong>
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.
<br><strong>Methods<br></strong>
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.
<br><strong>Results<br></strong>
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).
<br><strong>Conclusions<br></strong>
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. |
| first_indexed | 2024-03-07T01:46:54Z |
| format | Journal article |
| id | oxford-uuid:98b5fd00-9aa0-46a4-b01c-082a88cf836e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:46:54Z |
| publishDate | 2021 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:98b5fd00-9aa0-46a4-b01c-082a88cf836e2022-03-27T00:09:10ZVirological 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 infectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:98b5fd00-9aa0-46a4-b01c-082a88cf836eEnglishSymplectic ElementsOxford University Press2021Ratcliff, JNguyen, DFish, MRynne, JJennings, AWilliams, SAl-Beidh, FBonsall, DEvans, AGolubchik, TGordon, ACLamikanra, ATsang, PCiccone, NALeuscher, USlack, WLaing, EMouncey, PRZiyenge, SOliveira, MPloeg, RRowan, KMShankar-Hari, MRoberts, DJMenon, DKEstcourt, LSimmonds, PHarvala, H<br><strong>Background<br></strong> 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. <br><strong>Methods<br></strong> 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. <br><strong>Results<br></strong> 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). <br><strong>Conclusions<br></strong> 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. |
| spellingShingle | 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 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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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