Persistent and transient olfactory deficits in COVID-19 are associated to inflammation and zinc homeostasis

DOI record: { "DOI": "10.3389/fimmu.2023.1148595", "ISSN": [ "1664-3224" ], "URL": "http://dx.doi.org/10.3389/fimmu.2023.1148595", "abstract": "<jats:sec><jats:title>Introduction</jats:title><jats:p>The Coronavirus Disease 2019 (COVID-19) is mainly a respiratory syndrome that can affect multiple organ systems, causing a variety of symptoms. Among the most common and characteristic symptoms are deficits in smell and taste perception, which may last for weeks/months after COVID-19 diagnosis owing to mechanisms that are not fully elucidated.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In order to identify the determinants of olfactory symptom persistence, we obtained olfactory mucosa (OM) from 21 subjects, grouped according to clinical criteria: i) with persistent olfactory symptoms; ii) with transient olfactory symptoms; iii) without olfactory symptoms; and iv) non-COVID-19 controls. Cells from the olfactory mucosa were harvested for transcriptome analyses.</jats:p></jats:sec><jats:sec><jats:title>Results and discussion</jats:title><jats:p>RNA-Seq assays showed that gene expression levels are altered for a long time after infection. The expression profile of micro RNAs appeared significantly altered after infection, but no relationship with olfactory symptoms was found. On the other hand, patients with persistent olfactory deficits displayed increased levels of expression of genes involved in the inflammatory response and zinc homeostasis, suggesting an association with persistent or transient olfactory deficits in individuals who experienced <jats:italic>SARS-CoV-2</jats:italic> infection.</jats:p></jats:sec>", "alternative-id": [ "10.3389/fimmu.2023.1148595" ], "author": [ { "affiliation": [], "family": "Lupi", "given": "Lorenzo", "sequence": "first" }, { "affiliation": [], "family": "Bordin", "given": "Anna", "sequence": "additional" }, { "affiliation": [], "family": "Sales", "given": "Gabriele", "sequence": "additional" }, { "affiliation": [], "family": "Colaianni", "given": "Davide", "sequence": "additional" }, { "affiliation": [], "family": "Vitiello", "given": "Adriana", "sequence": "additional" }, { "affiliation": [], "family": "Biscontin", "given": "Alberto", "sequence": "additional" }, { "affiliation": [], "family": "Reale", "given": "Alberto", "sequence": "additional" }, { "affiliation": [], "family": "Garzino-Demo", "given": "Alfredo", "sequence": "additional" }, { "affiliation": [], "family": "Antonini", "given": "Angelo", "sequence": "additional" }, { "affiliation": [], "family": "Ottaviano", "given": "Giancarlo", "sequence": "additional" }, { "affiliation": [], "family": "Mucignat", "given": "Carla", "sequence": "additional" }, { "affiliation": [], "family": "Parolin", "given": "Cristina", "sequence": "additional" }, { "affiliation": [], "family": "Calistri", "given": "Arianna", "sequence": "additional" }, { "affiliation": [], "family": "De Pittà", "given": "Cristiano", "sequence": "additional" } ], "container-title": "Frontiers in Immunology", "container-title-short": "Front. Immunol.", "content-domain": { "crossmark-restriction": true, "domain": [ "frontiersin.org" ] }, "created": { "date-parts": [ [ 2023, 7, 15 ] ], "date-time": "2023-07-15T03:23:51Z", "timestamp": 1689391431000 }, "deposited": { "date-parts": [ [ 2023, 7, 15 ] ], "date-time": "2023-07-15T03:24:03Z", "timestamp": 1689391443000 }, "funder": [ { "DOI": "10.13039/100007479", "doi-asserted-by": "publisher", "name": "Fondazione Cassa di Risparmio di Padova e Rovigo" }, { "DOI": "10.13039/501100003500", "doi-asserted-by": "publisher", "name": "Università degli Studi di Padova" }, { "DOI": "10.13039/501100003500", "doi-asserted-by": "publisher", "name": "Università degli Studi di Padova" }, { "DOI": "10.13039/501100003407", "doi-asserted-by": "publisher", "name": "Ministero dell'Istruzione, dell'Università e della Ricerca" }, { "DOI": "10.13039/100019820", "doi-asserted-by": "publisher", "name": "Promega" } ], "indexed": { "date-parts": [ [ 2023, 7, 16 ] ], "date-time": "2023-07-16T04:15:03Z", 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"journal-title": "Pathog Dis", "key": "B2", "volume": "77", "year": "2019" }, { "DOI": "10.3389/FIMMU.2022.912336", "article-title": "Hallmarks of severe COVID-19 pathogenesis: a pas de deux between viral and host factors", "author": "Rovito", "doi-asserted-by": "publisher", "journal-title": "Front Immunol", "key": "B3", "year": "2022" }, { "DOI": "10.1371/JOURNAL.PONE.0270024", "article-title": "Genomic surveillance of SARS-CoV-2 in patients presenting neurological manifestations", "author": "Vicco", "doi-asserted-by": "publisher", "journal-title": "PloS One", "key": "B4", "volume": "17", "year": "2022" }, { "DOI": "10.1093/CID/CIAA330", "article-title": "Self-reported olfactory and taste disorders in patients with severe acute respiratory coronavirus 2 infection: a cross-sectional study", "author": "Giacomelli", "doi-asserted-by": "publisher", "journal-title": "Clin Infect Dis", "key": "B5", "volume": "71", "year": "2020" }, { "DOI": "10.1016/J.CMI.2020.05.017", "article-title": "Anosmia in COVID-19 patients", "author": "Hornuss", "doi-asserted-by": "publisher", "journal-title": "Clin Microbiol Infect", "key": "B6", "volume": "26", "year": "2020" }, { "DOI": "10.1038/S41467-020-19509-Y", "article-title": "Infection fatality rate of SARS-CoV2 in a super-spreading event in Germany", "author": "Streeck", "doi-asserted-by": "publisher", "first-page": "5829", "journal-title": "Nat Commun", "key": "B7", "volume": "11", "year": "2020" }, { "DOI": "10.3389/FNCIR.2022.862005", "article-title": "Not only COVID-19: involvement of multiple chemosensory systems in human diseases", "author": "Caretta", "doi-asserted-by": "publisher", "journal-title": "Front Neural Circuits", "key": "B8", "volume": "16", "year": "2022" }, { "DOI": "10.1016/J.MOLMED.2022.06.005", "article-title": "Olfactory dysfunction in COVID-19: pathology and long-term implications for brain health", "author": "Doty", "doi-asserted-by": "publisher", "journal-title": "Trends Mol Med", "key": "B9", "volume": "28", "year": "2022" }, { "DOI": "10.1007/S00408-021-00448-4", "article-title": "Post-viral anosmia (Loss of sensation of smell) did not begin with COVID-19", "author": "Dicpinigaitis", "doi-asserted-by": "publisher", "first-page": "237", "journal-title": "Lung", "key": "B10", "volume": "199", "year": "2021" }, { "DOI": "10.1002/LARY.28692", "article-title": "Anosmia and ageusia: common findings in COVID-19 patients", "author": "Vaira", "doi-asserted-by": "publisher", "first-page": "1787", "journal-title": "Laryngoscope", "key": "B11", "volume": "130", "year": "2020" }, { "DOI": "10.1016/J.NEULET.2021.135694", "article-title": "Smell and taste disorders in COVID-19: from pathogenesis to clinical features and outcomes", "author": "Mastrangelo", "doi-asserted-by": "publisher", "journal-title": "Neurosci Lett", "key": "B12", "volume": "748", "year": "2021" }, { "DOI": "10.1038/S41588-021-00986-W", "article-title": "The UGT2A1/UGT2A2 locus is associated with COVID-19-related loss of smell or taste", "author": "Shelton", "doi-asserted-by": "publisher", "journal-title": "Nat Genet", "key": "B13", "volume": "54", "year": "2022" }, { "DOI": "10.1016/B978-0-444-63855-7.00005-8", "article-title": "Olfactory receptor function", "author": "Glezer", "doi-asserted-by": "publisher", "first-page": "67", "journal-title": "Handb Clin Neurol", "key": "B14", "volume": "164", "year": "2019" }, { "DOI": "10.1038/S41419-019-1887-4", "article-title": "Direct neuronal reprogramming of olfactory ensheathing cells for CNS repair", "author": "Sun", "doi-asserted-by": "publisher", "first-page": "646", "journal-title": "Cell Death Dis", "key": "B15", "volume": "10", "year": "2019" }, { "DOI": "10.1016/J.ISCI.2020.101839", "article-title": "SARS-CoV-2 receptors and entry genes are expressed in the human olfactory neuroepithelium and brain", "author": "Fodoulian", "doi-asserted-by": "publisher", "first-page": "101839", "journal-title": "iScience", "key": "B16", "volume": "23", "year": "2020" }, { "DOI": "10.1093/CHEMSE/BJAA040", "article-title": "Anosmia in COVID-19: mechanisms and significance", "author": "Han", "doi-asserted-by": "publisher", "journal-title": "Chem Senses", "key": "B17", "volume": "45", "year": "2020" }, { "DOI": "10.1016/S1474-4422(21)00202-7", "article-title": "The mechanisms of smell loss after SARS-CoV-2 infection", "author": "Doty", "doi-asserted-by": "publisher", "journal-title": "Lancet Neurol", "key": "B18", "volume": "20", "year": "2021" }, { "DOI": "10.1177/1073858420956905", "article-title": "Anosmia in COVID-19: underlying mechanisms and assessment of an olfactory route to brain infection", "author": "Butowt", "doi-asserted-by": "publisher", "first-page": "582", "journal-title": "Neuroscientist", "key": "B19", "volume": "27", "year": "2021" }, { "DOI": "10.1016/J.CELL.2020.02.052", "article-title": "SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor", "author": "Hoffmann", "doi-asserted-by": "publisher", "first-page": "271", "journal-title": "Cell", "key": "B20", "volume": "181", "year": "2020" }, { "DOI": "10.1016/J.BBI.2020.06.032", "article-title": "Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters", "author": "Bryche", "doi-asserted-by": "publisher", "first-page": "579", "journal-title": "Brain Behav Immun", "key": "B21", "volume": "89", "year": "2020" }, { "DOI": "10.1126/science.abd2985", "article-title": "Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity", "author": "Cantuti-Castelvetri", "doi-asserted-by": "publisher", "journal-title": "Sci (1979)", "key": "B22", "volume": "370", "year": "2020" }, { "DOI": "10.1523/JNEUROSCI.20-20-07691.2000", "article-title": "Semaphorin 3A is required for guidance of olfactory axons in mice", "author": "Schwarting", "doi-asserted-by": "publisher", "journal-title": "J Neurosci", "key": "B23", "volume": "20", "year": "2000" }, { "DOI": "10.1111/J.1460-9568.2004.03304.X", "article-title": "Semaphorin 3A-mediated axon guidance regulates convergence and targeting of P2 odorant receptor axons", "author": "Schwarting", "doi-asserted-by": "publisher", "journal-title": "Eur J Neurosci", "key": "B24", "volume": "19", "year": "2004" }, { "DOI": "10.1016/J.CELL.2022.01.024", "article-title": "Non-cell-autonomous disruption of nuclear architecture as a potential cause of COVID-19-induced anosmia", "author": "Zazhytska", "doi-asserted-by": "publisher", "first-page": "1052", "journal-title": "Cell", "key": "B25", "volume": "185", "year": "2022" }, { "DOI": "10.4103/1673-5374.330625", "article-title": "Loss of smell in COVID-19: reasons for variable recovery patterns from anosmia", "author": "Baig", "doi-asserted-by": "publisher", "first-page": "1623", "journal-title": "Neural Regener Res", "key": "B26", "volume": "17", "year": "2022" }, { "DOI": "10.1126/SCITRANSLMED.ABF8396", "article-title": "COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters", "author": "de Melo", "doi-asserted-by": "publisher", "journal-title": "Sci Transl Med", "key": "B27", "volume": "13", "year": "2021" }, { "DOI": "10.1093/chemse/22.1.39", "article-title": "“Sniffin” sticks’. olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold", "author": "Hummel", "doi-asserted-by": "publisher", "first-page": "39", "journal-title": "Chem Senses", "key": "B28", "volume": "22", "year": "1997" }, { "DOI": "10.1261/RNA.234507", "article-title": "Direct and sensitive miRNA profiling from low-input total RNA", "author": "Wang", "doi-asserted-by": "publisher", "first-page": "151", "journal-title": "RNA", "key": "B29", "volume": "13", "year": "2007" }, { "DOI": "10.1038/nmeth.4197", "article-title": "Salmon provides fast and bias-aware quantification of transcript expression", "author": "Patro", "doi-asserted-by": "publisher", "journal-title": "Nat Methods", "key": "B30", "volume": "14", "year": "2017" }, { "DOI": "10.12688/F1000RESEARCH.7563.2", "article-title": "Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences", "author": "Soneson", "doi-asserted-by": "publisher", "first-page": "1521", "journal-title": "F1000Res", "key": "B31", "volume": "4", "year": "2015" }, { "DOI": "10.12688/f1000research.8987.2", "article-title": "From reads to genes to pathways: differential expression analysis of RNA-seq experiments using rsubread and the edgeR quasi-likelihood pipeline", "author": "Chen", "doi-asserted-by": "publisher", "first-page": "1438", "journal-title": "F1000Research", "key": "B32", "volume": "5", "year": "2016" }, { "DOI": "10.1093/BIOINFORMATICS/BTP443", "article-title": "A modified LOESS normalization applied to microRNA arrays: a comparative evaluation", "author": "Risso", "doi-asserted-by": "publisher", "journal-title": "Bioinformatics", "key": "B33", "volume": "25", "year": "2009" }, { "DOI": "10.1073/PNAS.082099299", "article-title": "Diagnosis of multiple cancer types by shrunken centroids of gene expression", "author": "Tibshirani", "doi-asserted-by": "publisher", "journal-title": "Proc Natl Acad Sci", "key": "B34", "volume": "99", "year": "2002" }, { "DOI": "10.1038/nbt.2931", "article-title": "Normalization of RNA-seq data using factor analysis of control genes or samples", "author": "Risso", "doi-asserted-by": "publisher", "first-page": "896", "journal-title": "Nat Biotechnol", "key": "B35", "volume": "32", "year": "2014" }, { "DOI": "10.1093/BIOINFORMATICS/BTP616", "article-title": "edgeR: a bioconductor package for differential expression analysis of digital gene expression data", "author": "Robinson", "doi-asserted-by": "publisher", "journal-title": "Bioinformatics", "key": "B36", "volume": "26", "year": "2010" }, { "DOI": "10.1101/315150", "article-title": "ShinyGO: a graphical enrichment tool for ani-mals and plants", "author": "Ge", "doi-asserted-by": "publisher", "journal-title": "bioRxiv", "key": "B37", "volume": "36", "year": "2018" }, { "DOI": "10.1007/s10517-018-4052-7", "article-title": "Variability of the expression of reference genes in samples of human olfactory epithelium", "author": "Kovalenko", "doi-asserted-by": "publisher", "journal-title": "Bull Exp Biol Med", "key": "B38", "volume": "164", "year": "2018" }, { "DOI": "10.1126/sciadv.abc5801", "article-title": "Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia", "author": "Brann", "doi-asserted-by": "publisher", "first-page": "1", "journal-title": "Sci Adv", "key": "B39", "volume": "6", "year": "2020" }, { "DOI": "10.1038/s41593-020-0587-9", "article-title": "Single-cell analysis of olfactory neurogenesis and differentiation in adult humans", "author": "Durante", "doi-asserted-by": "publisher", "journal-title": "Nat Neurosci", "key": "B40", "volume": "23", "year": "2020" }, { "DOI": "10.1007/s13238-015-0212-y", "article-title": "Biogenesis and regulation of the let-7 miRNAs and their functional implications", "author": "Lee", "doi-asserted-by": "publisher", "journal-title": "Protein Cell", "key": "B41", "volume": "7", "year": "2016" }, { "DOI": "10.1016/j.virusres.2018.11.001", "article-title": "MicroRNA-34/449 family and viral infections", "author": "Lv", "doi-asserted-by": "publisher", "first-page": "1", "journal-title": "Virus Res", "key": "B42", "volume": "260", "year": "2019" }, { "DOI": "10.1007/s00018-002-8454-2", "article-title": "Metallothionein: the multipurpose protein", "author": "Coyle", "doi-asserted-by": "publisher", "journal-title": "Cell Mol Life Sci", "key": "B43", "volume": "59", "year": "2002" }, { "DOI": "10.3389/fimmu.2015.00019", "article-title": "Turning 21: induction of miR-21 as a key switch in the inflammatory response", "author": "Sheedy", "doi-asserted-by": "publisher", "journal-title": "Front Immunol", "key": "B44", "volume": "6", "year": "2015" }, { "DOI": "10.1007/s00018-012-1124-0", "article-title": "MicroRNA-29 in the adaptive immune system: setting the threshold", "author": "Liston", "doi-asserted-by": "publisher", "journal-title": "Cell Mol Life Sci", "key": "B45", "volume": "69", "year": "2012" }, { "DOI": "10.3389/fimmu.2021.593473", "article-title": "miRNAs alter T helper 17 cell fate in the pathogenesis of autoimmune diseases", "author": "Huang", "doi-asserted-by": "publisher", "journal-title": "Front Immunol", "key": "B46", "volume": "12", "year": "2021" }, { "DOI": "10.1111/j.1365-2222.2006.02606.x", "article-title": "Regulation of the T cell response", "author": "Romagnani", "doi-asserted-by": "publisher", "journal-title": "Clin Exp Allergy", "key": "B47", "volume": "36", "year": "2006" }, { "DOI": "10.3389/fimmu.2019.01958", "article-title": "Expression, role, and regulation of neutrophil fcγ receptors", "author": "Wang", "doi-asserted-by": "publisher", "journal-title": "Front Immunol", "key": "B48", "volume": "10", "year": "2019" }, { "DOI": "10.1002/art.42486", "article-title": "Type-4 phosphodiesterase (PDE4) blockade reduces neutrophil activation in behçet’s disease", "author": "Le Joncour", "doi-asserted-by": "publisher", "journal-title": "Arthritis Rheumatol", "key": "B49", "year": "2023" }, { "DOI": "10.1016/j.medj.2020.07.002", "article-title": "Virus-host interactome and proteomic survey reveal potential virulence factors influencing SARS-CoV-2 pathogenesis", "author": "Li", "doi-asserted-by": "publisher", "first-page": "99", "journal-title": "Med", "key": "B50", "volume": "2", "year": "2021" }, { "DOI": "10.3390/ijms18102197", "article-title": "Metallothioneins: emerging modulators in immunity and infection", "author": "Vignesh", "doi-asserted-by": "publisher", "first-page": "2197", "journal-title": "Int J Mol Sci", "key": "B51", "volume": "18", "year": "2017" }, { "DOI": "10.15252/EMMM.202012421", "article-title": "The role of interleukin-6 in monitoring severe case of coronavirus disease 2019", "author": "Liu", "doi-asserted-by": "publisher", "journal-title": "EMBO Mol Med", "key": "B52", "volume": "12", "year": "2020" }, { "DOI": "10.3389/FIMMU.2021.613422/BIBTEX", "article-title": "Interleukin-6 is a biomarker for the development of fatal severe acute respiratory syndrome coronavirus 2 pneumonia", "author": "Santa Cruz", "doi-asserted-by": "publisher", "journal-title": "Front Immunol", "key": "B53", "volume": "12", "year": "2021" }, { "DOI": "10.1002/BIOF.5520120111", "article-title": "Zinc deficiency and taste dysfunction; contribution of carbonic anhydrase, a zinc-metalloenzyme, to normal taste sensation", "author": "Komai", "doi-asserted-by": "publisher", "first-page": "65", "journal-title": "Biofactors", "key": "B54", "volume": "12", "year": "2000" }, { "DOI": "10.2174/187153009788452390", "article-title": "T-Lymphocytes: a target for stimulatory and inhibitory effects of zinc ions", "author": "Honscheid", "doi-asserted-by": "publisher", "journal-title": "Endocr Metab Immune Disord Drug Targets", "key": "B55", "volume": "9", "year": "2009" }, { "DOI": "10.1016/J.JNUTBIO.2019.108240", "article-title": "Micronutrients in autoimmune diseases: possible therapeutic benefits of zinc and vitamin d", "author": "Wessels", "doi-asserted-by": "publisher", "first-page": "10240", "journal-title": "J Nutr Biochem", "key": "B56", "volume": "77", "year": "2020" }, { "DOI": "10.1083/JCB.200702081", "article-title": "Zinc is a novel intracellular second messenger", "author": "Yamasaki", "doi-asserted-by": "publisher", "journal-title": "J Cell Biol", "key": "B57", "volume": "177", "year": "2007" }, { "DOI": "10.4140/tcp.n.2010.756", "article-title": "Zinc and taste disturbances in older adults: a review of the literature", "author": "Williams", "doi-asserted-by": "publisher", "journal-title": "Consultant Pharmacist", "key": "B58", "volume": "31", "year": "2016" }, { "DOI": "10.3390/ijms21238941", "article-title": "Zinc in the brain: friend or foe", "author": "Choi", "doi-asserted-by": "publisher", "first-page": "1", "journal-title": "Int J Mol Sci", "key": "B59", "volume": "21", "year": "2020" }, { "DOI": "10.1002/lio2.513", "article-title": "Intra-nasal zinc level relationship to COVID-19 anosmia and type 1 interferon response: a proposal", "author": "Equils", "doi-asserted-by": "publisher", "journal-title": "Laryngoscope Investig Otolaryngol", "key": "B60", "volume": "6", "year": "2021" }, { "DOI": "10.1126/SCIENCE.ABD4585", "article-title": "Autoantibodies against type I IFNs in patients with life-threatening COVID-19", "author": "Bastard", "doi-asserted-by": "publisher", "journal-title": "Sci (1979)", "key": "B61", "volume": "370", "year": "2020" }, { "DOI": "10.1093/INFDIS/JIAA350", "article-title": "Interferon-β-1a inhibition of severe acute respiratory syndrome-coronavirus 2 In vitro when administered after virus infection", "author": "Clementi", "doi-asserted-by": "publisher", "journal-title": "J Infect Dis", "key": "B62", "volume": "222", "year": "2020" }, { "DOI": "10.1126/SCIENCE.2020.6500.369_125", "article-title": "Can interferons stop COVID-19 before it takes hold", "author": "Wadman", "doi-asserted-by": "publisher", "journal-title": "Science", "key": "B63", "volume": "369", "year": "2020" }, { "DOI": "10.1126/SCIENCE.ABD4570", "article-title": "Inborn errors of type I IFN immunity in patients with life-threatening COVID-19", "author": "Zhang", "doi-asserted-by": "publisher", "journal-title": "Science", "key": "B64", "volume": "370", "year": "2020" }, { "DOI": "10.5802/CRBIOL.36", "article-title": "Insufficient type I IFN immunity underlies life-threatening COVID-19 pneumonia", "author": "Bastard", "doi-asserted-by": "publisher", "first-page": "19", "journal-title": "C R Biol", "key": "B65", "volume": "344", "year": "2021" }, { "DOI": "10.3389/FIMMU.2020.01712", 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"publisher", "journal-title": "Clin Nutr Open Sci", "key": "B69", "volume": "44", "year": "2022" }, { "DOI": "10.1007/S12011-021-02946-1", "article-title": "Evaluation of serum trace element levels and biochemical parameters of COVID-19 patients according to disease severity", "author": "Kocak", "doi-asserted-by": "publisher", "journal-title": "Biol Trace Elem Res", "key": "B70", "volume": "200", "year": "2022" }, { "DOI": "10.3389/FIMMU.2022.906551", "article-title": "Serum free zinc is associated with vaccination response to SARS-CoV-2", "author": "Chillon", "doi-asserted-by": "publisher", "journal-title": "Front Immunol", "key": "B71", "volume": "13", "year": "2022" }, { "DOI": "10.1016/J.IJID.2022.06.016", "article-title": "COVID-19 prophylaxis with doxycycline and zinc in health care workers: a prospective, randomized, double-blind clinical trial", "author": "Stambouli", "doi-asserted-by": "publisher", "journal-title": "Int J Infect Dis", "key": "B72", "volume": "122", "year": "2022" }, { "DOI": "10.1016/j.ijid.2012.06.006", "article-title": "Understanding the roles of cytokines and neutrophil activity and neutrophil apoptosis in the protective versus deleterious inflammatory response in pneumonia", "author": "Bordon", "doi-asserted-by": "publisher", "journal-title": "Int J Infect Dis", "key": "B73", "volume": "17", "year": "2013" }, { "DOI": "10.1038/nri3399", "article-title": "Neutrophil recruitment and function in health and inflammation", "author": "Kolaczkowska", "doi-asserted-by": "publisher", "journal-title": "Nat Rev Immunol", "key": "B74", "volume": "13", "year": "2013" }, { "DOI": "10.1111/bjd.17339", "article-title": "The epithelial zinc transporter ZIP10 epigenetically regulates human epidermal homeostasis by modulating histone acetyltransferase activity", "author": "Bin", "doi-asserted-by": "publisher", "journal-title": "Br J Dermatol", "key": "B75", "volume": "180", "year": "2019" }, { "DOI": "10.3390/life11030186", "article-title": "Zinc metalloproteins in epigenetics and their crosstalk", "author": "Yusuf", "doi-asserted-by": "publisher", "first-page": "1", "journal-title": "Life", "key": "B76", "volume": "11", "year": "2021" } ], "reference-count": 76, "references-count": 76, "relation": {}, "resource": { "primary": { "URL": "https://www.frontiersin.org/articles/10.3389/fimmu.2023.1148595/full" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [ "Immunology", "Immunology and Allergy" ], "subtitle": [], "title": "Persistent and transient olfactory deficits in COVID-19 are associated to inflammation and zinc homeostasis", "type": "journal-article", "update-policy": "http://dx.doi.org/10.3389/crossmark-policy", "volume": "14" }