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Purinergic receptors dually control the inflammatory response: while adenosine A2A receptors (A2ARs) are anti-inflammatory, ATP P2X7 receptors (P2X7Rs) exert pro-inflammatory effects. The aim of this study was to assess if there were differences in allelic and genotypic frequencies of a loss-of-function SNP of ADORA2A (rs2298383) and a gain-of-function single nucleotide polymorphism (SNP) of P2RX7 (rs208294) in the severity of SARS-CoV-2-associated infection. Fifty-five individuals were enrolled and categorized according to the severity of the infection. Endpoint genotyping was performed in blood cells to screen for both SNPs. The TT genotype (vs. CT + CC) and the T allele (vs. C allele) of P2RX7 SNP were found to be associated with more severe forms of COVID-19, whereas the association between ADORA2A SNP and the severity of infection was not significantly different. The T allele of P2RX7 SNP was more frequent in people with more than one comorbidity and with cardiovascular conditions and was associated with colorectal cancer. Our findings suggest a more prominent role of P2X7R rather than of A2AR polymorphisms in SARS-CoV-2 infection, although larger population-based studies should be performed to validate our conclusions.<\/jats:p>","DOI":"10.3390\/ijms25116135","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T10:06:01Z","timestamp":1717409161000},"page":"6135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genetic Polymorphisms of P2RX7 but Not of ADORA2A Are Associated with the Severity of SARS-CoV-2 Infection"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1771-2349","authenticated-orcid":false,"given":"Jorge","family":"Lindo","sequence":"first","affiliation":[{"name":"FMUC\u2014Faculty of Medicine, University Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8464-0045","authenticated-orcid":false,"given":"C\u00e9lia","family":"Nogueira","sequence":"additional","affiliation":[{"name":"FMUC\u2014Faculty of Medicine, University Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5513-6664","authenticated-orcid":false,"given":"Rui","family":"Soares","sequence":"additional","affiliation":[{"name":"FMUC\u2014Faculty of Medicine, University Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Pathology Service, Portuguese Oncology Institute of Coimbra, 3004-011 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0726-7843","authenticated-orcid":false,"given":"Nuno","family":"Cunha","sequence":"additional","affiliation":[{"name":"Clinical Pathology Service, Portuguese Oncology Institute of Coimbra, 3004-011 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1889-5469","authenticated-orcid":false,"given":"Maria Ros\u00e1rio","family":"Almeida","sequence":"additional","affiliation":[{"name":"FMUC\u2014Faculty of Medicine, University Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9898-2409","authenticated-orcid":false,"given":"Lisa","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9862-0691","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Coelho","sequence":"additional","affiliation":[{"name":"IPCB\/ESALD\u2014Instituto Polit\u00e9cnico de Castelo Branco, Escola Superior de Sa\u00fade Dr. Lopes Dias, SPRINT-IPCB\u2014Sport Physical Activity and Health Research & Innovation Center, 6000-767 Castelo Branco, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8405-4249","authenticated-orcid":false,"given":"Francisco","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"IPCB\/ESALD\u2014Instituto Polit\u00e9cnico de Castelo Branco, Escola Superior de Sa\u00fade Dr. Lopes Dias, SPRINT-IPCB\u2014Sport Physical Activity and Health Research & Innovation Center, 6000-767 Castelo Branco, Portugal"}]},{"given":"Rodrigo A.","family":"Cunha","sequence":"additional","affiliation":[{"name":"FMUC\u2014Faculty of Medicine, University Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9347-0535","authenticated-orcid":false,"given":"Teresa","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"FMUC\u2014Faculty of Medicine, University Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CNC-UC\u2014Center for Neuroscience and Cell Biology, University Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University Coimbra, 3004-504 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.3389\/fimmu.2020.01441","article-title":"Immune response, inflammation, and the clinical spectrum of COVID-19","volume":"11","year":"2020","journal-title":"Front. 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