biostudies-literatureMartino CEmil Aaltosen Säätiö (Emil Aaltonen Foundation)IBM | IBM ResearchNIEHS NIH HHSNHLBI NIH HHSNIHR | NIHR Cambridge Biomedical Research Centre (NIHR Cambridge BRC)French National Research AgencyAlfred Benzon FoundationNational Science Foundation (NSF)Alfred Benzon Foundation (The Alfred Benzon Foundation)Academy of FinlandEmerald FoundationNCCIH NIH HHSEmil Aaltosen SäätiöUC | University of California, San Diego (UCSD)Health Data Research UK (HDR UK)UC | University of California, San DiegoNational Science FoundationNovo Nordisk FoundationBritish Heart FoundationHHS | National Institutes of Health (NIH)NIAID NIH HHSUC San Diego Center for Microbiome InnovationHHS | National Institutes of HealthSydäntutkimussäätiöANID Becas Chile DoctoradoHealth Data Research UKMunz Chair of Cardiovascular Prediction and PreventionNIDDK NIH HHSSydäntutkimussäätiö (Finnish Foundation for Cardiovascular Research)Union's Horizon Europe Research and Innovation 459 ActionsNCI NIH HHSUnion's Horizon Europe Research and Innovation 459 ActionsNIHR | NIHR Cambridge Biomedical Research CentreWellcome TrustNIGMS NIH HHSe0401524https://www.ebi.ac.uk/biostudies/studies/S-EPMC11980591biostudies-literatureUnknown16(4)The gastrointestinal (GI) tract is a site of replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and GI symptoms are often reported by patients. SARS-CoV-2 cell entry depends upon heparan sulfate (HS) proteoglycans, which commensal bacteria that bathe the human mucosa are known to modify. To explore human gut HS-modifying bacterial abundances and how their presence may impact SARS-CoV-2 infection, we developed a task-based analysis of proteoglycan degradation on large-scale shotgun metagenomic data. We observed that gut bacteria with high predicted catabolic capacity for HS differ by age and sex, factors associated with coronavirus disease 2019 (COVID-19) severity, and directly by disease severity during/after infection, but do not vary between subjects with COVID-1mBioSARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx.PMC11980591U19 AI116497N/AR01ES027595UH2AI15302930221P30DK120515RG/18/13/33946R01 GM069811UM1-CA164917321351 and 354447BRC-1215-20014R01-CA077398RG/13/13/30194ANR-20-CE44-0005UH2 AI1530292031989P30-CA023100P30 CA023100R01 CA077398R35GM119850AI Horizons NetworkUM1 CA164917U01-CA199277P01 HL131474NNF20SA0066621P30 CA033572R01 ES027595101046041P30-CA033572335525U01 CA199277R00RG2503R01GM0698112018-721902702038509ANR-17-CE11-0014DP1 AT010885P30 DK120515R35 GM1198501DP1AT010885321356McDonald DZaramela LSCooper REsko JDMartino CRiva ALiang CInouye MSpielfogel ESLewis NEMarotz CASweeney DANiiranen TTaylor BHaiminen NSorrentino JTMartinez MEKim H-CPaulus MPJain MKosciolek TBroedlow CABerteau OAnderson CAMHasty JBelda-Ferre PSchifanella LLacey JVSalomaa VLai ADas PCarlin AFCheng SGarretson AFKlatt NRVazquez-Baeza YBasting CSwafford ADSoualmia FSalido RAClausen TMEstaki MBenjdia AAli FVictor TASavage KEKellman BPParida LArmingol ECovizzi ASong SJGilbert JAKuplicki RKnight RHuang SAllard SMBenbow JLZhang YJousilahti PSandoval DRZengler KHavulinna ASZhu QClark AEWandro SfalseSARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx.The gastrointestinal (GI) tract is a site of replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and GI symptoms are often reported by patients. SARS-CoV-2 cell entry depends upon heparan sulfate (HS) proteoglycans, which commensal bacteria that bathe the human mucosa are known to modify. To explore human gut HS-modifying bacterial abundances and how their presence may impact SARS-CoV-2 infection, we developed a task-based analysis of proteoglycan degradation on large-scale shotgun metagenomic data. We observed that gut bacteria with high predicted catabolic capacity for HS differ by age and sex, factors associated with coronavirus disease 2019 (COVID-19) severity, and directly by disease severity during/after infection, but do not vary between subjects with COVID-12025-01-01T00:00:00Z2025 Apr2026-06-02T19:08:59.459Z2025-07-13T03:04:39.863ZS-EPMC119805913999822610.1128/mbio.04015-24