S-Variant SARS-CoV-2 Lineage B1.1.7 Is Associated With Significantly Higher Viral Load in Samples Tested by TaqPath Polymerase Chain Reaction

Abstract

A SARS-CoV-2 variant B1.1.7 containing a mutation Δ69/70 has spread rapidly in the UK and shows an identifiable profile in ThermoFisher TaqPath RTqPCR (S-gene target failure; SGTF). We analysed recent test data for trends and significance. Linked Ct values for respiratory samples showed that a low Ct for ORF1ab and N were clearly associated with SGTF. Significantly more SGTF samples had higher inferred viral loads between 1x10 7 and 1x10 8. Our conclusion is that patients whose samples exhibit the SGTF profile are more likely to have high viral loads, which may explain higher infectivity and rapidity of spread.

Altered Subgenomic RNA Expression in SARS-CoV-2 B.1.1.7 Infections

“…Negligible differences were seen in other ORF sgRNA (Figure S2). Consistent with previous findings ( 6, 15 ), we also found significantly decreased E gene Ct (ECT; in house diagnostic assay ( 16 ); B.1.177 median=25, B.1.1.7 median=23) and significantly greater Relative Light Units (RLU; Hologic Panther platform; B.1.177 median=1121, B.1.1.7 median = 1177) in B.1.1.7 infections compared to B.1.177 infections (Figure 1E&F). Accordingly, total mapped reads and total genomic RNA reads (i.e.…”

“…These findings suggest a potential reason for enhanced transmissibility, though they did not account for potential confounders such as days since symptom onset at sampling. Many of these studies also use S gene target failure (SGTF) as a surrogate for the presence of B.1.1.7 ( 6 ) , which might misclassify samples, depending on the prevalence of B.1.1.7 ( 8 ) . Several analyses from community tested cases also suggest increased mortality associated with B.1.1.7 ( 8 ) .…”

“…Along with B.1.351, these variants of concern harbour functionally important mutations in the SARS-CoV-2 Spike protein, some of which demonstrate evidence of convergent evolution across all three lineages (Supplementary Table S1). Preliminary data ( 6, 7 ) shows that B.1.1.7 positive diagnostic respiratory samples may have lower cycle threshold (Ct) values, therefore higher viral loads, compared to other lineages. These findings suggest a potential reason for enhanced transmissibility, though they did not account for potential confounders such as days since symptom onset at sampling.…”

Interferon Resistance of Emerging SARS-CoV-2 Variants

“…As IFNs are critical in controlling early virus infection levels, IFN-resistant SARS-CoV-2 variants may produce higher viral loads that could in turn promote transmission and/or exacerbate pathogenesis. Consistent with this hypothesis, alarming preliminary reports linked B.1.1.7 with increased viral loads 34 and risk of death 35–37 . In addition to Spike, emerging variants exhibited mutations in nucleocapsid, membrane and nonstructural proteins NSP3, NSP6 and NSP12 (Supplementary Table 1).…”

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

“…They share the N501Y mutation in RBD besides the D614G mutation around the S1/S2 cleavage site (Table 2, Figure 6). Epidemiological studies suggest that the UK variant correlates with higher viral loads in patients [306], a >40% increased epidemiological growth [307,308], a longer duration of acute infection [309], and increased severity/death rate, particularly in patients of higher age and with comorbidities [310][311][312][313]. The UK variant acquired an enhanced affinity to ACE2 [314] while maintaining sensitivity to nAb responses though with 2-9 times reduced nAb titers in vaccinees and convalescent individuals [314][315][316].…”