{"doi":"10.1016/j.ijid.2021.02.019","title":"The unbalanced p53/SIRT1 axis may impact lymphocyte homeostasis in COVID-19 patients","abstract":"BACKGROUND/OBJECTIVES: A dysregulated inflammatory profile plays an important role in coronavirus disease-2019 (COVID-19) pathogenesis. Moreover, the depletion of lymphocytes is typically associated with an unfavourable disease course. We studied the role and impact of p53 and deacetylase Sirtuin 1 (SIRT1) on lymph-monocyte homeostasis and their possible effect on T and B cell signalling. METHODS: Gene expression analysis and flow cytometry were performed on peripheral blood mononuclear cells (PBMC) of 35 COVID-19 patients and 10 healthy donors (HD). Inflammatory cytokines, the frequency of Annexin+ cells among CD3+ T cells and CD19+ B cell subsets were quantified. RESULTS: PBMC from COVID-19 patients had a higher p53 expression, and higher concentrations of plasma proinflammatory cytokines (IL1β, TNF-α, IL8, and IL6) than HD. Deacetylase Sirtuin 1 (SIRT1) expression was significantly decreased in COVID-19 patients and was negatively correlated with p53 (p = 0.003 and r = -0.48). A lower expression of IL-7R and B Cell linker (BLNK), key genes for lymphocyte homeostasis and function, was observed in COVID-19 than in HD. The reduction of IgK and IgL chains was seen in lymphopenic COVID-19 patients. A significant increase in both apoptotic B and T cells were observed. Inflammatory cytokines correlated positively with p53 (IL-1β: r = 0.5 and p = 0.05; IL-8: r = 0.5 and p = 0.05) and negatively with SIRT1 (IL1-β: r = -0.5 and p = 0.04; TNF-α: r = -0.4 and p = 0.04). CONCLUSIONS: Collectively, our data indicate that the inflammatory environment, the dysregulated p53/SIRT1 axis and low expression of IL7R and BLNK may impact cell survival, B cell signalling and antibody production in COVID-19 patients. Further studies are required to define the functional impact of low BLNK/IL7R expression during severe acute respiratory syndrome coronavirus-2 infection.","journal":"International Journal of Infectious Diseases","year":2021,"id":157366,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":50,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9281,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":240142,"name":"Eleonora Tartaglia","orcid":"0000-0001-5773-7781","position":1,"is_corresponding":false},{"id":240137,"name":"Alessandra Sacchi","orcid":"0000-0003-4964-386X","position":2,"is_corresponding":false},{"id":240147,"name":"Gian María Fimia","orcid":"0000-0003-4438-3325","position":3,"is_corresponding":false},{"id":240139,"name":"Eleonora Cimini","orcid":"0000-0002-2659-0868","position":4,"is_corresponding":false},{"id":240141,"name":"Rita Casetti","orcid":"0000-0002-7574-8780","position":5,"is_corresponding":false},{"id":243517,"name":"Stefania Notari","orcid":null,"position":6,"is_corresponding":false},{"id":240140,"name":"Germana Grassi","orcid":"0000-0001-8168-8721","position":7,"is_corresponding":false},{"id":243518,"name":"Luisa Marchioni","orcid":null,"position":8,"is_corresponding":false},{"id":663905,"name":"Michele Bibas","orcid":"0000-0001-5689-7759","position":9,"is_corresponding":false},{"id":85541,"name":"Maria Rosaria Capobianchi","orcid":"0000-0003-3465-0071","position":10,"is_corresponding":false},{"id":228967,"name":"Franco Locatelli","orcid":"0000-0002-7976-3654","position":11,"is_corresponding":false},{"id":228081,"name":"Markus Maeurer","orcid":"0000-0002-8436-8077","position":12,"is_corresponding":false},{"id":85550,"name":"Alimuddin Zumla","orcid":"0000-0002-5111-5735","position":13,"is_corresponding":false},{"id":240149,"name":"Andrea Antinori","orcid":"0000-0003-2121-4684","position":14,"is_corresponding":false},{"id":240150,"name":"Emanuele Nicastri","orcid":"0000-0002-5606-8712","position":15,"is_corresponding":false},{"id":85534,"name":"Giuseppe Ippolito","orcid":"0000-0002-1076-2979","position":16,"is_corresponding":false},{"id":228459,"name":"Chiara Agrati","orcid":"0000-0002-5252-0927","position":17,"is_corresponding":false},{"id":240138,"name":"Veronica Bordoni","orcid":"0000-0002-1747-2245","position":0,"is_corresponding":true}],"reference_count":15,"raw_metadata":null,"created_at":"2026-07-18T23:44:17.471040Z","pmid":"33578018","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}