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.

Rights

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.

Cite as

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

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Last updated: 16 June 2022
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