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.
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.
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DOI:
10.1093/infdis/jiab283
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发表时间:
2021-08-16
期刊:
影响因子:
--
通讯作者:
REMAP-CAP Immunoglobulin Domain UK Investigators
中科院分区:
文献类型:
--
作者:
Ratcliff J;Nguyen D;Fish M;Rynne J;Jennings A;Williams S;Al-Beidh F;Bonsall D;Evans A;Golubchik T;Gordon AC;Lamikanra A;Tsang P;Ciccone NA;Leuscher U;Slack W;Laing E;Mouncey PR;Ziyenge S;Oliveira M;Ploeg R;Rowan KM;Shankar-Hari M;Roberts DJ;Menon DK;Estcourt L;Simmonds P;Harvala H;REMAP-CAP Immunoglobulin Domain UK Investigators
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. 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. 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). 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.
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