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

REMAP-CAP Immunoglobulin Domain UK Investigators

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)595-605
Number of pages11
JournalThe Journal of Infectious Diseases
Volume224
Issue number4
DOIs
Publication statusPublished - 24 May 2021

Keywords

  • Aged
  • Antibodies, Neutralizing/immunology
  • Antibodies, Viral/immunology
  • COVID-19/immunology
  • Critical Illness
  • Female
  • Humans
  • Immunization, Passive
  • Immunoglobulin G/immunology
  • Male
  • Middle Aged
  • RNA, Viral/immunology
  • SARS-CoV-2/immunology
  • Serologic Tests/methods
  • Spike Glycoprotein, Coronavirus/immunology
  • United Kingdom
  • Viral Load/immunology

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