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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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Jeremy Ratcliff, Dung Nguyen, Matthew Fish, Jennifer Rynne, Aislinn Jennings, Sarah Williams, Farah Al-Beidh, David Bonsall, Amy Evans, Tanya Golubchik, Anthony C Gordon, Abigail Lamikanra, Pat Tsang, Nick A Ciccone, Ullrich Leuscher, Wendy Slack, Emma Laing, Paul R Mouncey, Sheba Ziyenge, Marta Oliveira & 8 more Rutger Ploeg, Kathryn M Rowan, Manu Shankar-Hari, David J Roberts, David K Menon, Lise Estcourt, Peter Simmonds, Heli Harvala

Original languageEnglish
JournalThe Journal of infectious diseases
E-pub ahead of print24 May 2021

King's Authors


BACKGROUND: Convalescent plasma containing neutralising antibody to SARS-CoV-2 is under investigation for COVID-19 treatment. We report diverse virological characteristics of UK intensive care patients enrolled in the Immunoglobulin Domain of the REMAP-CAP randomised controlled trial that potentially influence treatment outcomes.

METHODS: SARS-CoV-2 RNA in nasopharyngeal swabs collected pre-treatment 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 118-1.7x10 11 IU/ml. Median viral loads were 40-fold higher in those seronegative for IgG antibodies (n=354; 28%) compared to seropositives (n=939; 72%). Frequencies of B.1.1.7 increased from <1% in early 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 5.8x10 6 and 2.0 x10 5 IU/ml respectively; p=2x10 -15). However, viral load distributions were elevated in both seronegative and seropositive subjects infected with B.1.1.7 (4.0x10 6 and 1.6x10 6 IU/ml respectively).

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.

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