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. (24th May 2021)

• Record Type: Journal Article
• Authors: Ratcliff, Jeremy; Nguyen, Dung; Fish, Matthew; Rynne, Jennifer; Jennings, Aislinn; Williams, Sarah; Al-Beidh, Farah; Bonsall, David; Evans, Amy; Golubchik, Tanya; Gordon, Anthony C; Lamikanra, Abigail; Tsang, Pat; Ciccone, Nick A; Leuscher, Ullrich; Slack, Wendy; Laing, Emma; Mouncey, Paul R; Ziyenge, Sheba; Oliveira, Marta; Ploeg, Rutger; Rowan, Kathryn M; Shankar-Hari, Manu; Roberts, David J; Menon, David K; Estcourt, Lise; Simmonds, Peter; Harvala, Heli
• Is Part Of: Journal of infectious diseases. Volume 224:Number 4(2021)
• Page Start: 595
• Page End: 605
• Publication Date: 2021-05-24
• Subjects: clade B.1.1.7 -- convalescent plasma -- coronavirus -- COVID-19 -- ELISA -- polymerase chain reaction -- randomized clinical trial -- SARS-CoV-2 -- variant of concern -- viral load; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiab283
• Languages: English
• ISSNs: 0022-1899

Abstract

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 ( Sfc I) targeting D1118H. Results: Of 1274 subjects, 90% were PCR positive with viral loads 118–1.7 × 10 11 IU/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 × 10 6 and 2.0 × 10 5 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. Abstract : Patients enrolled in a trial for convalescent plasma treatment were highly heterogeneous in terms of viral loads, infecting SARS-CoV-2 types, and antibody status, each potentially influencing treatment outcomes. B.1.1.7 infections were associated with higher viral loads and reduced clearance postseroconversion.