Management of immunosuppression in lung transplant recipients and COVID-19 outcomes: an observational retrospective cohort-study

DOI record: { "DOI": "10.1186/s12879-024-09269-1", "ISSN": [ "1471-2334" ], "URL": "http://dx.doi.org/10.1186/s12879-024-09269-1", "abstract": "<jats:title>Abstract</jats:title><jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>The aim of this study was to assess the impact of immunosuppression management on coronavirus disease 2019 (COVID-19) outcomes.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>We performed a single-center retrospective study in a cohort of 358 lung transplant recipients (LTx) over the period from March 2020 to April 2022. All included symptomatic patients had at least one positive SARS-CoV-2 rt-PCR. We used a composite primary outcome for COVID-19 including increased need for oxygen since the hospital admission, ICU transfer, and in-hospital mortality. We assessed by univariate and multivariate analyses the risk factors for poor outcomes.</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>Overall, we included 91 LTx who contracted COVID-19. The COVID-19 in-hospital mortality rate reached 4.4%. By hierarchical clustering, we found a strong and independent association between the composite poor outcome and the discontinuation of at least one immunosuppressive molecule among tacrolimus, cyclosporine, mycophenolate mofetil, and everolimus. Obesity (OR = 16, 95%CI (1.96; 167), <jats:italic>p</jats:italic> = 0.01) and chronic renal failure (OR = 4.6, 95%CI (1.4; 18), <jats:italic>p</jats:italic> = 0.01) were also independently associated with the composite poor outcome. Conversely, full vaccination was protective (OR = 0.23, 95%CI (0.046; 0.89), <jats:italic>p</jats:italic> = 0.047).</jats:p>\n </jats:sec><jats:sec>\n <jats:title>Conclusion</jats:title>\n <jats:p>The administration of immunosuppressive drugs such as tacrolimus, cyclocporine or everolimus can have a protective effect in LTx with COVID-19, probably related to their intrinsic antiviral capacity.</jats:p>\n </jats:sec>", "alternative-id": [ "9269" ], "article-number": "536", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "28 January 2024" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "28 March 2024" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "28 May 2024" }, { "group": { "label": "Declarations", "name": "EthicsHeading" }, "name": "Ethics", "order": 1 }, { "group": { "label": "Ethics approval and consent to participate", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "Due to the retrospective nature of the study, the need for informed consent was waived by the Ethics Committee of the Société de Pneumologie de Langue Française (CEPRO) (number CEPRO2023-036)" }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 3, "value": "The authors declare no competing interests." } ], "author": [ { "affiliation": [], "family": "Bes-Berlandier", "given": "Hugo", "sequence": "first" }, { "affiliation": [], "family": "Coiffard", "given": "Benjamin", "sequence": "additional" }, { "affiliation": [], "family": "Bermudez", "given": "Julien", "sequence": "additional" }, { "affiliation": [], "family": "Demazes-dufeu", "given": "Nadine", "sequence": "additional" }, { "affiliation": [], "family": "Coltey", "given": "Bérengère", "sequence": "additional" }, { "affiliation": [], "family": "Boschi", "given": "Céline", "sequence": "additional" }, { "affiliation": [], "family": "Colson", "given": "Philippe", "sequence": "additional" }, { "affiliation": [], "family": "Hraiech", "given": "Sami", "sequence": "additional" }, { "affiliation": [], "family": "Reynaud-Gaubert", "given": "Martine", "sequence": "additional" }, { "affiliation": [], "family": "Cassir", "given": "Nadim", "sequence": "additional" } ], "container-title": "BMC Infectious Diseases", "container-title-short": "BMC Infect Dis", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2024, 5, 28 ] ], "date-time": "2024-05-28T15:08:55Z", "timestamp": 1716908935000 }, "deposited": { "date-parts": [ [ 2024, 5, 28 ] ], "date-time": "2024-05-28T15:09:06Z", "timestamp": 1716908946000 }, "indexed": { "date-parts": [ [ 2024, 5, 28 ] ], "date-time": "2024-05-28T17:40:18Z", "timestamp": 1716918018350 }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2024, 5, 28 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2024, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 5, 28 ] ], "date-time": "2024-05-28T00:00:00Z", "timestamp": 1716854400000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 5, 28 ] ], "date-time": "2024-05-28T00:00:00Z", "timestamp": 1716854400000 } } ], "link": [ { "URL": "https://link.springer.com/content/pdf/10.1186/s12879-024-09269-1.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/article/10.1186/s12879-024-09269-1/fulltext.html", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/content/pdf/10.1186/s12879-024-09269-1.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1186", "published": { "date-parts": [ [ 2024, 5, 28 ] ] }, "published-online": { "date-parts": [ [ 2024, 5, 28 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1371/journal.pone.0258154", "author": "E Ge", "doi-asserted-by": "publisher", "first-page": "e0258154", "journal-title": "PLoS ONE", "key": "9269_CR1", "unstructured": "Ge E, Li Y, Wu S, Candido E, Wei X. Association of pre-existing comorbidities with mortality and disease severity among 167,500 individuals with COVID-19 in Canada: a population-based cohort study. PLoS ONE. 2021;16:e0258154.", "volume": "16", "year": "2021" }, { "DOI": "10.1111/ajt.16428", "author": "S Trapani", "doi-asserted-by": "publisher", "first-page": "2509", "journal-title": "Am J Transpl", "key": "9269_CR2", "unstructured": "Trapani S, Masiero L, Puoti F, et al. Incidence and outcome of SARS-CoV-2 infection on solid organ transplantation recipients: a nationwide population-based study. Am J Transpl. 2021;21:2509–21.", "volume": "21", "year": "2021" }, { "DOI": "10.1016/j.cmi.2022.02.039", "author": "M Gatti", "doi-asserted-by": "publisher", "first-page": "1057", "journal-title": "Clin Microbiol Infect", "key": "9269_CR3", "unstructured": "Gatti M, Rinaldi M, Bussini L, et al. Clinical outcome in solid organ transplant recipients affected by COVID-19 compared to general population: a systematic review and meta-analysis. Clin Microbiol Infect. 2022;28:1057–65.", "volume": "28", "year": "2022" }, { "DOI": "10.1111/tid.13967", "author": "AJ Trindade", "doi-asserted-by": "publisher", "first-page": "e13967", "journal-title": "Transpl Infect Dis", "key": "9269_CR4", "unstructured": "Trindade AJ, Chapin KC, Gannon WD, et al. Clinical course of SARS-CoV-2 infection and recovery in lung transplant recipients. Transpl Infect Dis. 2022;24:e13967.", "volume": "24", "year": "2022" }, { "DOI": "10.1111/ajt.16241", "author": "M Aversa", "doi-asserted-by": "publisher", "first-page": "3072", "journal-title": "Am J Transpl", "key": "9269_CR5", "unstructured": "Aversa M, Benvenuto L, Anderson M, et al. COVID-19 in lung transplant recipients: a single center case series from New York City. Am J Transpl. 2020;20:3072–80.", "volume": "20", "year": "2020" }, { "DOI": "10.1016/j.healun.2022.06.011", "author": "E Roosma", "doi-asserted-by": "publisher", "first-page": "1237", "journal-title": "J Heart Lung Transpl", "key": "9269_CR6", "unstructured": "Roosma E, van Gemert JP, de Zwart AES, et al. The effect of COVID-19 on transplant function and development of CLAD in lung transplant patients: a multicenter experience. J Heart Lung Transpl. 2022;41:1237–47.", "volume": "41", "year": "2022" }, { "DOI": "10.1111/ctr.13511", "author": "O Manuel", "doi-asserted-by": "publisher", "first-page": "e13511", "journal-title": "Clin Transpl", "key": "9269_CR7", "unstructured": "Manuel O, Estabrook M, American Society of Transplantation Infectious Diseases Community of Practice. RNA respiratory viral infections in solid organ transplant recipients: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transpl. 2019;33:e13511.", "volume": "33", "year": "2019" }, { "DOI": "10.1111/tid.13556", "author": "M Ringer", "doi-asserted-by": "publisher", "first-page": "e13556", "journal-title": "Transpl Infect Dis", "key": "9269_CR8", "unstructured": "Ringer M, Azmy V, Kaman K, et al. A retrospective matched cohort single-center study evaluating outcomes of COVID-19 and the impact of immunomodulation on COVID-19-related cytokine release syndrome in solid organ transplant recipients. Transpl Infect Dis. 2021;23:e13556.", "volume": "23", "year": "2021" }, { "DOI": "10.1111/ajt.16431", "author": "RK Avery", "doi-asserted-by": "publisher", "first-page": "2498", "journal-title": "Am J Transpl", "key": "9269_CR9", "unstructured": "Avery RK, Chiang TP-Y, Marr KA, et al. Inpatient COVID-19 outcomes in solid organ transplant recipients compared to non-solid organ transplant patients: a retrospective cohort. Am J Transpl. 2021;21:2498–508.", "volume": "21", "year": "2021" }, { "DOI": "10.3389/fphar.2020.00856", "author": "G Terrazzano", "doi-asserted-by": "publisher", "first-page": "856", "journal-title": "Front Pharmacol", "key": "9269_CR10", "unstructured": "Terrazzano G, Rubino V, Palatucci AT, Giovazzino A, Carriero F, Ruggiero G. An Open question: is it rational to inhibit the mtor-dependent pathway as COVID-19 therapy? Front Pharmacol. 2020;11:856.", "volume": "11", "year": "2020" }, { "DOI": "10.1016/j.antiviral.2020.104878", "author": "A Pizzorno", "doi-asserted-by": "publisher", "first-page": "104878", "journal-title": "Antiviral Res", "key": "9269_CR11", "unstructured": "Pizzorno A, Padey B, Dubois J, et al. In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2. Antiviral Res. 2020;181:104878.", "volume": "181", "year": "2020" }, { "DOI": "10.1111/ctr.14027", "author": "F Bösch", "doi-asserted-by": "publisher", "first-page": "e14027", "journal-title": "Clin Transpl", "key": "9269_CR12", "unstructured": "Bösch F, Börner N, Kemmner S, et al. Attenuated early inflammatory response in solid organ recipients with COVID-19. Clin Transpl. 2020;34:e14027.", "volume": "34", "year": "2020" }, { "key": "9269_CR13", "unstructured": "Clinical Spectrum. https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/. Accessed 18 August 2023." }, { "DOI": "10.1016/j.healun.2019.03.009", "author": "GM Verleden", "doi-asserted-by": "publisher", "first-page": "493", "journal-title": "J Heart Lung Transpl", "key": "9269_CR14", "unstructured": "Verleden GM, Glanville AR, Lease ED, et al. Chronic lung allograft dysfunction: definition, diagnostic criteria, and approaches to treatment-A consensus report from the Pulmonary Council of the ISHLT. J Heart Lung Transpl. 2019;38:493–503.", "volume": "38", "year": "2019" }, { "DOI": "10.3389/fmicb.2021.786233", "author": "P Colson", "doi-asserted-by": "publisher", "first-page": "786233", "journal-title": "Front Microbiol", "key": "9269_CR15", "unstructured": "Colson P, Fournier P-E, Chaudet H, et al. Analysis of SARS-CoV-2 variants from 24,181 patients exemplifies the role of globalization and zoonosis in Pandemics. Front Microbiol. 2021;12:786233.", "volume": "12", "year": "2021" }, { "DOI": "10.1002/jmv.29033", "author": "NN Nguyen", "doi-asserted-by": "publisher", "first-page": "e29033", "journal-title": "J Med Virol", "key": "9269_CR16", "unstructured": "Nguyen NN, Houhamdi L, Meddeb L, Colson P, Gautret P. Reinfection with SARS-CoV-2 Omicron BA.4 and BA.5 variants. J Med Virol. 2023;95:e29033.", "volume": "95", "year": "2023" }, { "key": "9269_CR17", "unstructured": "Polack FP, Thomas SJ, Kitchin N et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;:NEJMoa2034577." }, { "key": "9269_CR18", "unstructured": "Coronavirus Disease 2019 (COVID-19)| CDC. https://www.cdc.gov/coronavirus/2019-nCoV/index.html. Accessed 18 August 2023." }, { "key": "9269_CR19", "unstructured": "R: The R Project for Statistical Computing. https://www.r-project.org/. Accessed 23 September 2023." }, { "DOI": "10.18637/jss.v025.i01", "doi-asserted-by": "crossref", "key": "9269_CR20", "unstructured": "Husson F, Josse J, Lê S. FactoMineR: an R Package for Multivariate Analysis. J Stat Softw 2008; 25." }, { "DOI": "10.1111/ajt.16368", "author": "B Coiffard", "doi-asserted-by": "publisher", "first-page": "1586", "journal-title": "Am J Transpl", "key": "9269_CR21", "unstructured": "Coiffard B, Lepper PM, Prud’Homme E, et al. Management of lung transplantation in the COVID-19 era-An international survey. Am J Transpl. 2021;21:1586–96.", "volume": "21", "year": "2021" }, { "DOI": "10.1111/ajt.16692", "author": "MR Heldman", "doi-asserted-by": "publisher", "first-page": "2774", "journal-title": "Am J Transpl", "key": "9269_CR22", "unstructured": "Heldman MR, Kates OS, Safa K, et al. COVID-19 in hospitalized lung and non-lung solid organ transplant recipients: a comparative analysis from a multicenter study. Am J Transpl. 2021;21:2774–84.", "volume": "21", "year": "2021" }, { "DOI": "10.3389/fmed.2022.852973", "doi-asserted-by": "publisher", "key": "9269_CR23", "unstructured": "Pinchera B, Spirito L, Buonomo AR et al. mTOR Inhibitor Use Is Associated With a Favorable Outcome of COVID-19 in Patients of Kidney Transplant: Results of a Retrospective Study. Frontiers in Medicine. 2022; 9. https://www.frontiersin.org/articles/https://doi.org/10.3389/fmed.2022.852973. Accessed 14 July 2022." }, { "DOI": "10.1053/j.gastro.2020.11.045", "author": "LS Belli", "doi-asserted-by": "publisher", "first-page": "1151", "journal-title": "Gastroenterology", "key": "9269_CR24", "unstructured": "Belli LS, Fondevila C, Cortesi PA, et al. Protective role of Tacrolimus, Deleterious Role of Age and comorbidities in Liver Transplant recipients with Covid-19: results from the ELITA/ELTR multi-center European study. Gastroenterology. 2021;160:1151–e11633.", "volume": "160", "year": "2021" }, { "DOI": "10.1111/tid.13410", "doi-asserted-by": "crossref", "key": "9269_CR25", "unstructured": "Desmazes-Dufeu N, Coltey B, Amari L et al. Discordant courses of COVID-19 in a cohabiting couple of lung transplant recipients. Transpl Infect Dis 2020;:e13410." }, { "DOI": "10.1016/j.celrep.2021.108940", "author": "G Garcia", "doi-asserted-by": "publisher", "first-page": "108940", "journal-title": "Cell Rep", "key": "9269_CR26", "unstructured": "Garcia G, Sharma A, Ramaiah A, et al. Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication. Cell Rep. 2021;35:108940.", "volume": "35", "year": "2021" }, { "DOI": "10.1111/cei.12669", "author": "M Sabbatini", "doi-asserted-by": "publisher", "first-page": "230", "journal-title": "Clin Exp Immunol", "key": "9269_CR27", "unstructured": "Sabbatini M, Ruggiero G, Palatucci AT, et al. Oscillatory mTOR inhibition and Treg increase in kidney transplantation. Clin Exp Immunol. 2015;182:230–40.", "volume": "182", "year": "2015" }, { "DOI": "10.1681/ASN.2020030348", "author": "M Willicombe", "doi-asserted-by": "publisher", "first-page": "1145", "journal-title": "J Am Soc Nephrol", "key": "9269_CR28", "unstructured": "Willicombe M, Thomas D, McAdoo S. COVID-19 and calcineurin inhibitors: should they get left out in the storm? J Am Soc Nephrol. 2020;31:1145–6.", "volume": "31", "year": "2020" }, { "DOI": "10.1016/j.virusres.2014.02.010", "author": "J Carbajo-Lozoya", "doi-asserted-by": "publisher", "first-page": "44", "journal-title": "Virus Res", "key": "9269_CR29", "unstructured": "Carbajo-Lozoya J, Ma-Lauer Y, Malešević M, et al. Human coronavirus NL63 replication is cyclophilin A-dependent and inhibited by non-immunosuppressive cyclosporine A-derivatives including Alisporivir. Virus Res. 2014;184:44–53.", "volume": "184", "year": "2014" }, { "DOI": "10.3389/ti.2022.10369", "author": "NS Ogando", "doi-asserted-by": "publisher", "first-page": "10369", "journal-title": "Transpl Int", "key": "9269_CR30", "unstructured": "Ogando NS, Metscher E, Moes DJAR, et al. The cyclophilin-dependent calcineurin inhibitor voclosporin inhibits SARS-CoV-2 replication in Cell Culture. Transpl Int. 2022;35:10369.", "volume": "35", "year": "2022" }, { "DOI": "10.1016/j.bcp.2019.03.022", "author": "AM Liddicoat", "doi-asserted-by": "publisher", "first-page": "472", "journal-title": "Biochem Pharmacol", "key": "9269_CR31", "unstructured": "Liddicoat AM, Lavelle EC. Modulation of innate immunity by cyclosporine A. Biochem Pharmacol. 2019;163:472–80.", "volume": "163", "year": "2019" }, { "DOI": "10.1111/tid.13595", "author": "A Karruli", "doi-asserted-by": "publisher", "first-page": "e13595", "journal-title": "Transpl Infect Dis", "key": "9269_CR32", "unstructured": "Karruli A, Spiezia S, Boccia F, et al. Effect of immunosuppression maintenance in solid organ transplant recipients with COVID-19: systematic review and meta-analysis. Transpl Infect Dis. 2021;23:e13595.", "volume": "23", "year": "2021" }, { "DOI": "10.1016/j.jinf.2020.10.024", "author": "M Merli", "doi-asserted-by": "publisher", "first-page": "414", "journal-title": "J Infect", "key": "9269_CR33", "unstructured": "Merli M, Pasulo L, Perricone G, et al. Impact of immunosuppressive therapy on the severity of COVID-19 in solid organ transplant recipients. J Infect. 2021;82:414–51.", "volume": "82", "year": "2021" }, { "DOI": "10.1111/ajt.16807", "author": "LG Modelli de Andrade", "doi-asserted-by": "publisher", "first-page": "610", "journal-title": "Am J Transpl", "key": "9269_CR34", "unstructured": "Modelli de Andrade LG, de Sandes-Freitas TV, Requião-Moura LR, et al. Development and validation of a simple web-based tool for early prediction of COVID-19-associated death in kidney transplant recipients. Am J Transpl. 2022;22:610–25.", "volume": "22", "year": "2022" }, { "DOI": "10.1002/iid3.1128", "author": "UW Choi", "doi-asserted-by": "publisher", "first-page": "e1128", "journal-title": "Immun Inflamm Dis", "key": "9269_CR35", "unstructured": "Choi UW, Ai X, Li H, Hao Y, Yao X, Guan Y. Immunosuppressive therapy and COVID-19 infection in patients with NMOSD. Immun Inflamm Dis. 2024;12:e1128.", "volume": "12", "year": "2024" }, { "DOI": "10.1111/tid.14131", "doi-asserted-by": "crossref", "key": "9269_CR36", "unstructured": "Weder MM, Kadl A. Longitudinal impact of COVID-19 on lung function in lung transplant recipients: time to stop worrying? Transpl Infect Dis 2023;:e14131." }, { "DOI": "10.1007/s15010-021-01734-2", "author": "V Thakur", "doi-asserted-by": "publisher", "first-page": "309", "journal-title": "Infection", "key": "9269_CR37", "unstructured": "Thakur V, Bhola S, Thakur P, et al. Waves and variants of SARS-CoV-2: understanding the causes and effect of the COVID-19 catastrophe. Infection. 2022;50:309–25.", "volume": "50", "year": "2022" }, { "DOI": "10.1007/s11596-021-2395-1", "author": "L Forchette", "doi-asserted-by": "publisher", "first-page": "1037", "journal-title": "Curr Med Sci", "key": "9269_CR38", "unstructured": "Forchette L, Sebastian W, Liu T. A Comprehensive Review of COVID-19 Virology, vaccines, variants, and therapeutics. Curr Med Sci. 2021;41:1037–51.", "volume": "41", "year": "2021" }, { "DOI": "10.1016/j.transproceed.2021.12.014", "author": "J Zimmermann", "doi-asserted-by": "publisher", "first-page": "1504", "journal-title": "Transpl Proc", "key": "9269_CR39", "unstructured": "Zimmermann J, Glueck OM, Fertmann JM, et al. COVID-19 in recent lung transplant recipients: clinical outcomes and management strategies. Transpl Proc. 2022;54:1504–16.", "volume": "54", "year": "2022" }, { "DOI": "10.1097/TP.0000000000003508", "author": "J Messika", "doi-asserted-by": "publisher", "first-page": "177", "journal-title": "Transplantation", "key": "9269_CR40", "unstructured": "Messika J, Eloy P, Roux A, et al. COVID-19 in lung transplant recipients. Transplantation. 2021;105:177–86.", "volume": "105", "year": "2021" }, { "DOI": "10.1371/journal.pone.0257807", "author": "JC Kamp", "doi-asserted-by": "publisher", "first-page": "e0257807", "journal-title": "PLoS ONE", "key": "9269_CR41", "unstructured": "Kamp JC, Hinrichs JB, Fuge J, Ewen R, Gottlieb J. COVID-19 in lung transplant recipients-risk prediction and outcomes. PLoS ONE. 2021;16:e0257807.", "volume": "16", "year": "2021" } ], "reference-count": 41, "references-count": 41, "relation": {}, "resource": { "primary": { "URL": "https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09269-1" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Management of immunosuppression in lung transplant recipients and COVID-19 outcomes: an observational retrospective cohort-study", "type": "journal-article", "update-policy": "http://dx.doi.org/10.1007/springer_crossmark_policy", "volume": "24" }