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The virus settles primarily on the nasal mucosa, and the infection and its course depend on individual susceptibility. Our aim was to investigate the nasopharynx composition\u2019s role in the individual susceptibility. During the first phase of SARS-CoV-2 pandemic, nasopharyngeal microbiome samples of close contact unvaccinated patients were investigated by 16S rRNA analysis and by culturing. The whole genome of cultured <jats:italic>Corynebacteria<\/jats:italic> was sequenced. The relative expression of ACE2, TMPRSS2, and cathepsin L on Caco-2 cells and the strength of S1-ACE2 binding were determined in the presence of <jats:italic>Corynebacteria<\/jats:italic>. From 55 close contacts exposed to identical SARS-CoV-2 exposure, 26 patients became infected and 29 remained uninfected. The nasopharyngeal microbiome analysis showed significantly higher abundance of <jats:italic>Corynebacteria<\/jats:italic> in uninfected group. <jats:italic>Corynebacterium accolens<\/jats:italic> could be cultivated only from uninfected individuals and<jats:italic> Corynebacterium propinquum<\/jats:italic> from both infected and uninfected. <jats:italic>Corynebacteria<\/jats:italic> from uninfected patient significantly reduced the ACE2 and cathepsin L expression. <jats:italic>C. accolens<\/jats:italic> significantly reduced the TMPRSS2 expression compared to other <jats:italic>Corynebacteria<\/jats:italic>. Furthermore, <jats:italic>Corynebacterium <\/jats:italic>spp. weakened the binding of the S1-ACE2. Most <jats:italic>C. accolens<\/jats:italic> isolates harbored the TAG lipase LipS1 gene. Based on these results, the presence of <jats:italic>Corynebacterium<\/jats:italic> spp. in the nasopharyngeal microbiota, especially <jats:italic>C. accolens<\/jats:italic> strains, could reduce the individual susceptibility to SARS-CoV-2 infection by several mechanisms: by downregulation the ACE2, the TMPRSS2 receptors, and cathepsin L in the host; through the inhibition of S1-ACE2 binding; and lipase production. These results suggest the use of <jats:italic>C. accolens<\/jats:italic> strains as probiotics in the nasopharynx in the future.<\/jats:p>","DOI":"10.1007\/s11357-023-00850-1","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T09:02:20Z","timestamp":1687251740000},"page":"2927-2938","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Specific nasopharyngeal Corynebacterium strains serve as gatekeepers against SARS-CoV-2 infection"],"prefix":"10.1007","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8601-3923","authenticated-orcid":false,"given":"Dora","family":"Szabo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Ostorhazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balazs","family":"Stercz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Makra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Penzes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Kristof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istvan","family":"Antal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janos M.","family":"Rethelyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reka I.","family":"Zsigmond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ede","family":"Birtalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bela","family":"Merkely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laszlo","family":"Tamas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,20]]},"reference":[{"issue":"11","key":"850_CR1","doi-asserted-by":"publisher","first-page":"e1009013","DOI":"10.1371\/journal.ppat.1009013","volume":"16","author":"A Pi\u0161lar","year":"2020","unstructured":"Pi\u0161lar A, Mitrovi\u0107 A, Saboti\u010d J, Pe\u010dar Fonovi\u0107 U, Peri\u0161i\u0107 Nanut M, Jako\u0161 T, et al. 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