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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 publication

DOI

10.1093/infdis/jiab283

Type

Journal article

Journal

J Infect Dis

Publication Date

16/08/2021

Volume

224

Pages

595 - 605

Keywords

COVID-19, ELISA, SARS-CoV-2, clade B.1.1.7, convalescent plasma, coronavirus, polymerase chain reaction, randomized clinical trial, variant of concern, viral load, Aged, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, Critical Illness, Female, Humans, Immunization, Passive, Immunoglobulin G, Male, Middle Aged, RNA, Viral, SARS-CoV-2, Serologic Tests, Spike Glycoprotein, Coronavirus, United Kingdom, Viral Load