Recurrent SARS-CoV-2 mutations in immunodeficient patients
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Abstract
Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunodeficient patients are an important source of variation for the virus but are understudied. Many case studies have been published which describe one or a small number of long-term infected individuals but no study has combined these sequences into a cohesive dataset. This work aims to rectify this and study the genomics of this patient group through a combination of literature searches as well as identifying new case series directly from the COVID-19 Genomics UK (COG-UK) dataset. The spike gene receptor-binding domain and N-terminal domain (NTD) were identified as mutation hotspots. Numerous mutations associated with variants of concern were observed to emerge recurrently. Additionally a mutation in the envelope gene, T30I was determined to be the second most frequent recurrently occurring mutation arising in persistent infections. A high proportion of recurrent mutations in immunodeficient individuals are associated with ACE2 affinity, immune escape, or viral packaging optimisation.
There is an apparent selective pressure for mutations that aid cell–cell transmission within the host or persistence which are often different from mutations that aid inter-host transmission, although the fact that multiple recurrent de novo mutations are considered defining for variants of concern strongly indicates that this potential source of novel variants should not be discounted.
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SciScore for 10.1101/2022.03.02.22271697: (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
Software and Algorithms Sentences Resources De-novo Mutation Cumulative Occurrence Analysis Pipeline: Processing of the mutation calls was performed with a Python script (https://github.com/BioWilko/recurrent-sars-cov-2-mutations/blob/main/mutation_call_analysis.py) to investigate de novo mutations, which were defined as observed mutations within a genome series which were not present at day 0 of the genome series. Pythonsuggested: (IPython, RRID:SCR_001658)The resultant dataframe was finally formatted with an R script and figures generated using … SciScore for 10.1101/2022.03.02.22271697: (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
Software and Algorithms Sentences Resources De-novo Mutation Cumulative Occurrence Analysis Pipeline: Processing of the mutation calls was performed with a Python script (https://github.com/BioWilko/recurrent-sars-cov-2-mutations/blob/main/mutation_call_analysis.py) to investigate de novo mutations, which were defined as observed mutations within a genome series which were not present at day 0 of the genome series. Pythonsuggested: (IPython, RRID:SCR_001658)The resultant dataframe was finally formatted with an R script and figures generated using ggplot2 (Wickham, 2016). ggplot2suggested: (ggplot2, RRID:SCR_014601)Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.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.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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