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 neutralising antibody to SARS-CoV-2 is under investigation for COVID-19 treatment. We report diverse virological characteristics of UK intensive care patients enrolled in the Immunoglobulin Domain of the REMAP-CAP randomised controlled trial that potentially influence treatment outcomes. Methods SARS-CoV-2 RNA in nasopharyngeal swabs collected pre-treatment 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 118-1.7x10 11 IU/ml. Median viral loads were 40-fold higher in those seronegative for IgG antibodies (n=354; 28%) compared to seropositives (n=939; 72%). Frequencies of B.1.1.7 increased from <1% in early 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 5.8x10 6 and 2.0 x10 5 IU/ml respectively; p=2x10 -15). However, viral load distributions were elevated in both seronegative and seropositive subjects infected with B.1.1.7 (4.0x10 6 and 1.6x10 6 IU/ml respectively). 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.

SARS-CoV-2 neutralising antibody testing in Europe: towards harmonisation of neutralising antibody titres for better use of convalescent plasma and comparability of trial data

“…These data are consistent with previously published observations that the spike mutations in Beta, and to a lesser extent also in Alpha, variants are associated with reduced susceptibility to neutralising antibodies [13][14][15]. Therefore, these must be considered in data analysis, especially when SARS-CoV-2 variants have emerged during the convalescent plasma trial periods [11,16,17]. Further international standards and harmonisations are required for each SARS-CoV-2 variant of concern.…”

Initial viral load and decay kinetics of SARS-CoV-2 lineage B.1.1.7 in the upper respiratory tract of adults and children

“…We found that SARS-CoV-2 B.1.1.7-infected individuals displayed initial NP viral loads around 1 log 10 higher than controls (median, 7.6 log 10 copies/ml; range, 3.3-12.1 vs. 6.8 log 10 copies/ml; range, 2.4-13.1; P <0.001), a figure that concurs remarkably with that observed by Jones et al [4] , and overall support previous observations 3 , 4 , 5 , 6 reported in studies involving large cohorts, that were nevertheless poorly defined regarding subject age, individual clinical condition at diagnosis, timing of URT specimen collection or all of the above. A subanalysis including only SARS-CoV-2 B.1.1.7-infected individuals as confirmed by whole-genome sequencing (n=108) yielded comparable results ( P <0.001) (not shown).…”

“…In this context, a novel SARS-CoV-2 variant lineage (B.1.1.7), first detected in the UK at the end of 2020 has transmission advantage over other lineages [2] . Increased transmissibility of the B.1.1.7 variant has been linked to enhanced ACE2 affinity [3] allegedly resulting in higher viral loads in URT, an observation that has been reported in some 3 , 4 , 5 , 6 , but not all [7] large series published to date. In addition, longer duration of SARS-CoV-2 RNA shedding in URT has been reported in individuals infected by the B.1.1.7 variant as compared to controls [8] ; if proven, this may have important implications regarding isolation policies.…”

Dominance of Alpha and Iota variants in SARS-CoV-2 vaccine breakthrough infections in New York City

“…During the time of our sample and data collection, there were two major variants arising in the New York City metro area constituting about two thirds of all cases, B.1.1.7, which was first reported in the UK 45 , and B.1.526, which arose in New York City around December of 2020 24,25 . B.1.1.7 was deemed a variant of concern by the WHO and CDC and was associated with higher viral loads in infected individuals 40,41 , enhanced epidemiological spread [45][46][47] , an extended window of acute infection 48 , less effective innate and adaptive immune clearance 49 , and increased death rates in elderly patients and/or individuals with comorbidities [50][51][52][53] . The B.1.1.7 variant, e.g., through the RBD N501Y mutation but also through NTD deletions, acquired an enhanced affinity to ACE2, higher infectivity and virulence [54][55][56][57] , while maintaining sensitivity to neutralization though with slightly impaired nAb titers 54,[58][59][60] .…”