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.
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Ratcliff, J., Nguyen, D., Fish, M., Rynne, J., Jennings, A., Williams, S., Al-Beidh, F., Bonsall, D., Evans, A., Golubchik, T., Gordon, A., Lamikanra, A., Tsang, P., Ciccone, N., Leuschner, U., Laing, E., Slack, W., Mouncey, P., Ziyenge, S., Oliveira, M., Ploeg, R., Rowan, K., Shankar-Hari, M., Roberts, D., Menon, D., Estcourt, L., Simmonds, P., Harvala, H. & REMAP-CAP Immunoglobulin Domain UK Investigators 2021, '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', The Journal of Infectious Diseases, 224(4), pp. 595-605. https://doi.org/10.1093/infdis/jiab283