Differences in innate Intracellular viral suppression competencies may explain variations in morbidity and mortality from SARS-CoV-2 infection
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Abstract
SARS-CoV-2 infection and COVID-19 ravage the world with wide variations in morbidity and mortality that have remained largely unexplained, even by mutations in protein coding regions. In this study, we analyzed available complete SARS-CoV-2 sequences using the CpG index as a signature of Zinc finger antiviral protein (ZAP) activity to examine population variations in innate intracellular antiviral competencies. The result suggests that differential ZAP activity may be a major determinant of the outcome of SARS-CoV-2 infection. SARS-CoV-2 sequences from Africa, Asia, and pools of asymptomatic patients had I_CpG signature evidence of high ZAP activity, while SARS-CoV-2 sequences from North America and Intensive Care Unit or Deceased patients had I_CpG signature of low ZAP activity. ZAP activity is linked to the interferon system. Low ZAP activity may be part of the explanation for the increased morbidity of SARS-CoV-2 in the elderly and with comorbidities like diabetes, obesity, and hypertension. It may also provide some insight into the discrepancies between invitro anti-SARS-CoV-2 activities of candidate therapies and performance in clinical trials. Furthermore, our results suggest that asymptomatic patients may paradoxically shed a more dangerous virus.
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SciScore for 10.1101/2020.09.13.20193524: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Sequences from GISAID were then matched to patient metadata on Microsoft excel sheet using ‘sequences name’ and ‘virus name’ respectively. Microsoft excelsuggested: (Microsoft Excel, RRID:SCR_016137)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:The limitations of this study are that database bias, group size bias and over-interpretation may result in spurious findings. …
SciScore for 10.1101/2020.09.13.20193524: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Sequences from GISAID were then matched to patient metadata on Microsoft excel sheet using ‘sequences name’ and ‘virus name’ respectively. Microsoft excelsuggested: (Microsoft Excel, RRID:SCR_016137)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:The limitations of this study are that database bias, group size bias and over-interpretation may result in spurious findings. Nonetheless, this study provides an additional explanation to the confounding observations in a disease of certain uncertainties: COVID-19. Prospective studies will be required to provide further validation of our findings.
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.
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