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.
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
COVID-19 Serotherapy
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
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
16 08 2021
16 08 2021
Historique:
received:
04
03
2021
accepted:
20
05
2021
pubmed:
26
5
2021
medline:
29
9
2021
entrez:
25
5
2021
Statut:
ppublish
Résumé
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.
Sections du résumé
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.
Identifiants
pubmed: 34031695
pii: 6283590
doi: 10.1093/infdis/jiab283
pmc: PMC8241475
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Immunoglobulin G
0
RNA, Viral
0
Spike Glycoprotein, Coronavirus
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
595-605Subventions
Organisme : NIH HHS
ID : COV19-RECPLAS
Pays : United States
Organisme : European Union
ID : 602525
Organisme : NIHR Imperial Biomedical Research Centre
Organisme : NIHR
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.
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