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

• Published in: The Journal of infectious diseases Vol. 224; no. 4; pp. 595 - 605
• Main 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
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 15.08.2021
• Subjects: Adaptive immunity; Antibodies; Coronaviruses; COVID-19; DNA probes; Enzyme-linked immunosorbent assay; Immune clearance; Immune response; Immunoglobulin G; Major and Brief Reports; Patients; Seroconversion; Severe acute respiratory syndrome coronavirus 2; United Kingdom > UK; COVID-19; SARS-CoV-2; viral load; clade B.1.1.7; coronavirus; randomized clinical trial; variant of concern; polymerase chain reaction; convalescent plasma; ELISA
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiab283

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. 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.