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...

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Detalhes bibliográficos
Principais autores: 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
Formato: Journal article
Idioma:English
Publicado em: Oxford University Press 2021
Descrição
Resumo:<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.