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Acid pH Increases SARS-CoV-2 Infection and the Risk of Death by COVID-19

Jimenez et al., Frontiers in Medicine, doi:10.3389/fmed.2021.637885
Aug 2021  
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28th treatment shown to reduce risk in November 2021, now with p = 0.0000000046 from 14 studies.
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5,000+ studies for 104 treatments. c19early.org
In Vitro study showing lower pH increased ACE2 expression and viral load on SARS-CoV-2 infection, and retrospective study showing proton pump inhibitor use, which is correlated with low gastric pH-related diseases, was associated with higher mortality.
3 preclinical studies support the efficacy of alkalinization for COVID-19:
Study covers PPIs and alkalinization.
Jimenez et al., 20 Aug 2021, Brazil, peer-reviewed, 21 authors. Contact: hnakaya@usp.br.
This PaperAlkalinizationAll
Acid pH Increases SARS-CoV-2 Infection and the Risk of Death by COVID-19
Leandro Jimenez, Ana Campos Codo, Vanderson De Souza Sampaio, Antonio E R Oliveira, Lucas Kaoru Kobo Ferreira, Gustavo Gastão Davanzo, Lauar De Brito Monteiro, João Victor Virgilio-Da-Silva, Mayla Gabriela Silva Borba, Gabriela Fabiano De Souza, Nathalia Zini, Flora De Andrade Gandolfi, Stéfanie Primon Muraro, José Luiz Proença-Modena, Fernando Almeida Val, Gisely Cardoso Melo, Wuelton Marcelo Monteiro, Maurício Lacerda Nogueira, Marcus Vinícius Guimarães Lacerda, Pedro M Moraes-Vieira, Helder I Nakaya
Frontiers in Medicine, doi:10.3389/fmed.2021.637885
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.
DATA AVAILABILITY STATEMENT The original contributions generated for this study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s. ETHICS STATEMENT The studies involving human participants were reviewed and approved by Brazilian Committee of Ethics in Human Research (CAAE: 30152620.1.0000.0005 and 30615920.2.0000.0005 for North region cohort, and 31588920.0.0000.5415 for Southeast region cohort). The patients/participants provided their written informed consent to participate in this study. AUTHOR CONTRIBUTIONS LJ, AO, LF, and HN performed the transcriptome analyses. AC, GD, LB, JV, GF, SM, JL, and PM-V performed the experimental work. VS, MB, NZ, FA, MN, FV, GC, WM, and ML performed the clinical analysis. HN coordinated the study. LJ and HN wrote the manuscript with inputs from all of the coauthors. All authors contributed to the article and approved the submitted version. SUPPLEMENTARY MATERIAL The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmed. 2021.637885/full#supplementary-material Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's Note: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations,..
References
Alexeyenko, Lee, Pernemalm, Guegan, Dessen et al., Network enrichment analysis: extension of gene-set enrichment analysis to gene networks, BMC Bioinformatics, doi:10.1186/1471-2105-13-226
Almario, Chey, Spiegel, Increased risk of COVID-19 among users of proton pump inhibitors, Am J Gastroenterol, doi:10.14309/ajg.0000000000000798
Bourgonje, Abdulle, Timens, Hillebrands, Navis et al., Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19), J Pathol, doi:10.1002/path.5471
Chen, Tan, Kou, Duan, Wang et al., Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool, BMC Bioinformatics, doi:10.1186/1471-2105-14-128
Chen, Wu, Chen, Yang, Chen, Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study, BMJ, doi:10.1136/bmj.m1091
Cheung, Hung, Chan, Lung, Tso et al., Gastrointestinal manifestations of SARS-CoV-2 infection and virus load in fecal samples from a Hong Kong Cohort: systematic review and meta-analysis, Gastroenterology, doi:10.1053/j.gastro.2020.03.065
Clarke, Belyaev, Lambert, Turner, Epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress, Clin Sci (Lond), doi:10.1042/CS20130291
Codo, Davanzo, Monteiro, De Souza, Muraro et al., Elevated glucose levels favor SARS-CoV-2 infection and monocyte response through a HIF-1α/glycolysis-dependent axis, Cell Metab, doi:10.2139/ssrn.3606770
Davis, Meltzer, GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductor, Bioinformatics, doi:10.1093/bioinformatics/btm254
Freedberg, Conigliaro, Wang, Tracey, Callahan et al., Famotidine use is associated with improved clinical outcomes in hospitalized COVID-19 patients: a propensity score matched retrospective cohort study, Gastroenterology, doi:10.1053/j.gastro.2020.05.053
Freedberg, Lebwohl, Abrams, The impact of proton pump inhibitors on the human gastrointestinal microbiome, Clin Lab Med, doi:10.1016/j.cll.2014.08.008
Henry, Aggarwal, Wong, Benoit, Vikse et al., Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: a pooled analysis, Am J Emerg Med, doi:10.1016/j.ajem.2020.05.073
Kiselev, Kirschner, Schaub, Andrews, Yiu et al., SC3: consensus clustering of single-cell RNA-seq data, Nat Methods, doi:10.1038/nmeth.4236
Li, Li, Zhang, Wang, Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues, Infect Dis Poverty, doi:10.1186/s40249-020-00662-x
Lin, Jiang, Zhang, Huang, Fang et al., Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection, Gut, doi:10.1136/gutjnl-2020-321013
Owen, White, Severson, Braden, Bailey et al., Single cell RNA-seq reveals profound transcriptional similarity between Barrett's oesophagus and oesophageal submucosal glands, Nat Commun, doi:10.1038/s41467-018-06796-9
Pedersen, Chodavarapu, Lazartigues, Forkhead box transcription factors of the FOXA class are required for basal transcription of angiotensinconverting enzyme 2, J Endocr Soc, doi:10.1210/js.2016-1071
Pinto, Oliveira, Singh, Jimenez, Gonçalves et al., ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19, J Infect Dis, doi:10.1093/infdis/jiaa332
Prada, Lima, Nakaya, MetaVolcanoR: Gene Expression Meta-analysis Visualization Tool
Ritchie, Phipson, Wu, Hu, Law et al., limma powers differential expression analyses for RNA-sequencing and microarray studies, Nucleic Acids Res, doi:10.1093/nar/gkv007
Senkel, Lucas, Klein-Hitpass, Ryffel, Identification of target genes of the transcription factor HNF1beta and HNF1alpha in a human embryonic kidney cell line, Biochim Biophys Acta, doi:10.1016/j.bbaexp.2005.10.003
Severson, Owen, White, Lu, Schuster-Böckler, BEARscc determines robustness of single-cell clusters using simulated technical replicates, Nat Commun, doi:10.1038/s41467-018-03608-y
Spechler, Souza, Barrett's esophagus, N Engl J Med, doi:10.1056/NEJMra1314704
Stuart, Butler, Hoffman, Hafemeister, Papalexi et al., Comprehensive integration of single-cell data, Cell, doi:10.1016/j.cell.2019.05.031
Sun, Chen, Hu, Wu, Liang et al., Does famotidine reduce the risk of progression to severe disease, death, and intubation for COVID-19 patients? A systemic review and meta-analysis, Dig Dis Sci, doi:10.1007/s10620-021-06872-z
Tariq, Saha, Furqan, Hassett, Pardi et al., Prevalence and mortality of COVID-19 patients with gastrointestinal symptoms: a systematic review and meta-analysis, Mayo Clin Proc, doi:10.1016/j.mayocp.2020.06.003
Won, Lee, Park, Kim, Park et al., Development of a laboratory-safe and low-cost detection protocol for SARS-CoV-2 of the coronavirus disease 2019 (COVID-19), Exp Neurobiol, doi:10.5607/en20009
Yan, Chen, Sun, Ahmed, Bhan et al., Will proton pump inhibitors lead to a higher risk of COVID-19 infection and progression to severe disease? A Meta-analysis, Jpn J Infect Dis, doi:10.7883/yoken.JJID.2021.074
Zhang, Han, Zhang, Duan, Shang et al., Diarrhea and altered inflammatory cytokine pattern in severe coronavirus disease 2019: impact on disease course and in-hospital mortality, J Gastroenterol Hepatol, doi:10.1111/jgh.15166
Zhang, Wu, Zhao, Liu, Zhou et al., Role of HIF-1alpha in the regulation ACE and ACE2 expression in hypoxic human pulmonary artery smooth muscle cells, Am J Physiol Lung Cell Mol Physiol, doi:10.1152/ajplung.90415.2008
Zou, Chen, Zou, Han, Hao et al., Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection, Front Med, doi:10.1007/s11684-020-0754-0
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A systemic review and ' 'meta-analysis', 'author': 'Sun', 'year': '2021', 'journal-title': 'Dig Dis Sci', 'DOI': '10.1007/s10620-021-06872-z'}, { 'key': 'B30', 'doi-asserted-by': 'publisher', 'article-title': 'Will proton pump inhibitors lead to a higher risk of COVID-19 infection ' 'and progression to severe disease? 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Med.', 'published': {'date-parts': [[2021, 8, 20]]}}
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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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