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

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.

Keywords: COVID-19; ELISA; SARS-CoV-2; clade B.1.1.7; convalescent plasma; coronavirus; polymerase chain reaction; randomized clinical trial; variant of concern; viral load.

Figure 1.

Comparison of viral loads in anti-SARS-CoV-2 seropositive and seronegative subjects. A, C, and D, Associations of anti-SARS-CoV-2 antibody status, invasive ventilation, and immunosuppression on viral load distributions as determined by RT-qPCR of pretreatment respiratory samples. Median values shown to the right of Tukey box plots. Distributions were compared by Mann-Whitney U test. B, Frequency of seropositivity in individuals with different viral loads quantified in respiratory samples. Abbreviations: IgG, immunoglobulin G; RT-qPCR, reverse transcription quantitative polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2.

Temporal emergence of the SARS-CoV-2 B.1.1.7 clade. Proportion of subjects with the B.1.1.7 clade virus enrolled to the REMAP-CAP trial in different weeks over the study period compared to proportions in the wider UK population from sequences deposited in GISAID. Numbers at the top of the graph indicate total enrolments/week. Abbreviations: GISAID, Global Influenza Surveillance and Response System REMAP-CAP, Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 3.

Viral loads of wild-type and B.1.1.7 strains in seronegative and seropositive subjects. Distributions of viral loads of in samples from patients infected with wild-type and B.1.1.7 strains, subdivided by serostatus. Distributions were compared by Mann-Whitney U test test. Abbreviation: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; WT, wild type.