Screening for the alpha variant of SARS-CoV-2 (B.1.1.7) the impact of this variant on circulating biomarkers in hospitalised patients
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Abstract
Control of SARS-CoV-2 transmission is complicated by the emergence of variants, especially those containing mutations in the spike protein. By enhancing infectivity and evading immunity, infection with these variants might result in more severe clinical outcomes as well as being more resistant to vaccines developed on the basis of the original prototypic virus variant. One such example is the alpha variant (B.1.1.7), which has been detected in more than 100 countries and rapidly become the dominant strain in the UK in late 2020 and early 2021. There is an urgent need to develop appropriate surveillance programmes to rapidly monitor the spread of variants and to better understand the role of variants in disease outcomes and immune evasion. The nucleotide sequencing method, the ‘gold standard’ of variant detection, is unsuitable as a fast-response surveillance tool by frontline diagnostic services which require detection methods with short turnaround times. We developed a screening protocol based of sequential allele-specific qPCR for detection of the N501Y mutation and H69/V70 deletion present in the alpha /B.1.1.7 variant. We tested this protocol in previously confirmed positive samples from the Pathology Dept, University Hospital Coventry and Warwickshire during the second wave period in the UK (December 2020-March 2021). In these samples variant identity was confirmed by NGS sequencing via COG-UK. Our results identified increased incidence of variants containing both N501Y and Δ69/70 HV mutations, especially in patients admitted during January and early February 2021. This approach, which yields results within 3 hours, can be used as an initial rapid screening step with NGS as confirmatory follow-up. We also report that the increased prevalence of alpha /B.1.1.7 variant in admitted patients since mid-January 2021, a period that characterised peaked mortality rates, was associated with a sharp 2.5-fold rise in the mean circulating IL-6 level and to a lesser extent Troponin-T. More detailed biomarker analysis of a small cohort of patients (n=83), where variant status and clinical outcomes were available, demonstrated that deceased patients infected with the alpha /B.1.1.7 variant had significantly higher levels of inflammation and cell injury markers, especially IL-6 and LDH, compared to deceased patients infected with a non- alpha /B.1.1.7 variant, pointing towards a more severe inflammatory disease phenotype. In contrast, both groups survivors most biomarker exhibited levels below the group average, with distinct patterns of modified z-scores present.
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SciScore for 10.1101/2021.06.18.21258699: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Nevertheless, this identifies a possible limitation of the assay that requires careful monitoring of specimen handling and storage. Application of this screening protocol in a random representative pool of positive samples tested in an NHS Pillar 1 …
SciScore for 10.1101/2021.06.18.21258699: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Nevertheless, this identifies a possible limitation of the assay that requires careful monitoring of specimen handling and storage. Application of this screening protocol in a random representative pool of positive samples tested in an NHS Pillar 1 laboratory during the SARS-CoV-2 second wave of winter 2020-2021 suggested that the alpha/B.1.1.7 VOC became the dominant variant early in January 2021 in our Pillar 1 laboratory. Earlier reports raised the possibility of this variant being associated with increased risk of death compared with other variants (15-17) as some of the mutation may increase ACE-2 receptor binding affinity. Although monthly death rates in hospitalised patients could not provide clear evidence of consistently and sustained increased mortality due to alpha/B.1.1.7 VOC, we did monitor levels of various biomarkers associated with COVID-19 severe disease (28, 29). During January-February of 2021, the period during which the prevalence of alpha/B.1.1.7 increased most notably, the mean levels of IL-6 were significantly higher compared to the previous 14-week mean. This unpredicted finding raises the possibility that hospitalised patients infected with the alpha/B.1.1.7 variant exhibited more severe disease. IL-6 has previously been proposed as a biomarker indicating excessive inflammation and disease severity (30, 31). Although the mortality rates during January-February of 2021 were not notably different, admitted patients during that period were generally you...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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