Acid pH Increases SARS-CoV-2 Infection and the Risk of Death by COVID-19
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Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect a broad range of human tissues by using the host receptor angiotensin-converting enzyme 2 (ACE2). Individuals with comorbidities associated with severe COVID-19 display higher levels of ACE2 in the lungs compared to those without comorbidities, and conditions such as cell stress, elevated glucose levels and hypoxia may also increase the expression of ACE2 . Here, we showed that patients with Barrett's esophagus (BE) have a higher expression of ACE2 in BE tissues compared to normal squamous esophagus, and that the lower pH associated with BE may drive this increase in expression. Human primary monocytes cultured in reduced pH displayed increased ACE2 expression and higher viral load upon SARS-CoV-2 infection. We also showed in two independent cohorts of 1,357 COVID-19 patients that previous use of proton pump inhibitors is associated with 2- to 3-fold higher risk of death compared to those not using the drugs. Our work suggests that pH has a great influence on SARS-CoV-2 Infection and COVID-19 severity.
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SciScore for 10.1101/2020.09.10.20179135: (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
Experimental Models: Cell Lines Sentences Resources Viral titers were obtained by plaque assays on Vero cells. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)Software and Algorithms Sentences Resources Acidosis and Barrett’s esophagus meta-analysis: We manually curated the Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/) to find esophagus transcriptome datasets related to “Barrett’s esophagus” and cell line transcriptome datasets related to “acidosis” and “pH reduction”. Gene Expression Omnibussuggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)We performed differential expression analyses … SciScore for 10.1101/2020.09.10.20179135: (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
Experimental Models: Cell Lines Sentences Resources Viral titers were obtained by plaque assays on Vero cells. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)Software and Algorithms Sentences Resources Acidosis and Barrett’s esophagus meta-analysis: We manually curated the Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/) to find esophagus transcriptome datasets related to “Barrett’s esophagus” and cell line transcriptome datasets related to “acidosis” and “pH reduction”. Gene Expression Omnibussuggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)We performed differential expression analyses using the limma package (12). limmasuggested: (LIMMA, RRID:SCR_010943)The MetaVolcanoR package (13) was used to combine the P values using the Fisher’s method. MetaVolcanoRsuggested: (MetaVolcanoR, RRID:SCR_018549)For enrichment analyses, we utilized the EnrichR tool (14) and fgsea R package (15) with gene sets from the Gene Ontology Biological Process database. EnrichRsuggested: (Enrichr, RRID:SCR_001575)Ontology Biologicalsuggested: NoneData were collected and managed using REDCap (v. 10.2.1) electronic data capture tools hosted at Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. REDCapsuggested: (REDCap, RRID:SCR_003445)(StataCorp LP, College Station, TX) StataCorpsuggested: (Stata, RRID:SCR_012763)Results from OddPub: Thank you for sharing your 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.
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