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Severe COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotype

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dc.contributor.authorTrombetta, Amelia Chiara
dc.contributor.authorFarias, Guilherme B.
dc.contributor.authorGomes, André
dc.contributor.authorGodinho-Santos, Ana
dc.contributor.authorRosmaninho, Pedro
dc.contributor.authorConceição, Carolina M.
dc.contributor.authorLaia, Joel
dc.contributor.authorSantos, Diana F.
dc.contributor.authorAlmeida, Afonso
dc.contributor.authorMota, Catarina
dc.contributor.authorGomes, Andreia
dc.contributor.authorMontesinos Serrano, Marta
dc.contributor.authorVeldhoen, Marc
dc.contributor.authorSousa, Ana E.
dc.contributor.authorFernandes, Susana M.
dc.date.accessioned2023-05-26T13:57:03Z
dc.date.available2023-05-26T13:57:03Z
dc.date.issued2021
dc.descriptionCopyright © 2021 Trombetta, Farias, Gomes, Godinho-Santos, Rosmaninho, Conceição, Laia, Santos, Almeida, Mota, Gomes, Serrano, Veldhoen, Sousa and Fernandes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.pt_PT
dc.description.abstractAfter more than one year since the COVID-19 outbreak, patients with severe disease still constitute the bottleneck of the pandemic management. Aberrant inflammatory responses, ranging from cytokine storm to immune-suppression, were described in COVID-19 and no treatment was demonstrated to change the prognosis significantly. Therefore, there is an urgent need for understanding the underlying pathogenic mechanisms to guide therapeutic interventions. This study was designed to assess myeloid cell activation and phenotype leading to recovery in patients surviving severe COVID-19. We evaluated longitudinally patients with COVID-19 related respiratory insufficiency, stratified according to the need of intensive care unit admission (ICU, n = 11, and No-ICU, n = 9), and age and sex matched healthy controls (HCs, n = 11), by flow cytometry and a wide array of serum inflammatory/immune-regulatory mediators. All patients featured systemic immune-regulatory myeloid cell phenotype as assessed by both unsupervised and supervised analysis of circulating monocyte and dendritic cell subsets. Specifically, we observed a reduction of CD14lowCD16+ monocytes, and reduced expression of CD80, CD86, and Slan. Moreover, mDCs, pDCs, and basophils were significantly reduced, in comparison to healthy subjects. Contemporaneously, both monocytes and DCs showed increased expression of CD163, CD204, CD206, and PD-L1 immune-regulatory markers. The expansion of M2-like monocytes was significantly higher at admission in patients featuring detectable SARS-CoV-2 plasma viral load and it was positively correlated with the levels of specific antibodies. In No-ICU patients, we observed a peak of the alterations at admission and a progressive regression to a phenotype similar to HCs at discharge. Interestingly, in ICU patients, the expression of immuno-suppressive markers progressively increased until discharge. Notably, an increase of M2-like HLA-DRhighPD-L1+ cells in CD14++CD16- monocytes and in dendritic cell subsets was observed at ICU discharge. Furthermore, IFN-γ and IL-12p40 showed a decline over time in ICU patients, while high values of IL1RA and IL-10 were maintained. In conclusion, these results support that timely acquisition of a myeloid cell immune-regulatory phenotype might contribute to recovery in severe systemic SARS-CoV-2 infection and suggest that therapeutic agents favoring an innate immune system regulatory shift may represent the best strategy to be implemented at this stage.pt_PT
dc.description.sponsorshipThe Research was funded by Fundação para a Ciência e Tecnologia (FCT), “APOIO ESPECIAL RESEARCH 4COVID-19” projects 803, 125, 231_596873172, and 729. AMCG and GF received fellowships funded by FCT (DOCTORATES4COVID-19, 2020.10202.BD), and JANSSEN- CILAG FARMACÊUTICA, respectively. The funder was not involved in the study design, collection, analysis, interpretation of data, writing of the article or decision to submit it for publication. MV was supported by the European Union H2020 ERA project (No 667824 – EXCELLtoINNOV). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 667824.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFront Immunol. 2021 Jun 23;12:691725pt_PT
dc.identifier.doi10.3389/fimmu.2021.691725pt_PT
dc.identifier.eissn1664-3224
dc.identifier.urihttp://hdl.handle.net/10451/57629
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontierspt_PT
dc.relationDOCTORATES4COVID-19, 2020.10202.BDpt_PT
dc.relationLeverage research EXCELLence and INNOVation potential of Instituto de Medicina Molecular (IMM) through translational biomedical research in immunity and infection.
dc.relation.publisherversionhttps://www.frontiersin.org/journals/immunologypt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectCOVID-19pt_PT
dc.subjectM2-like differentiationpt_PT
dc.subjectSARS-CoV-2pt_PT
dc.subjectImmune-regulationpt_PT
dc.subjectInnate immunitypt_PT
dc.titleSevere COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotypept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumber667824
oaire.awardTitleLeverage research EXCELLence and INNOVation potential of Instituto de Medicina Molecular (IMM) through translational biomedical research in immunity and infection.
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/667824/EU
oaire.citation.titleFrontiers in Immunologypt_PT
oaire.citation.volume12pt_PT
oaire.fundingStreamH2020
person.familyNameTrombetta
person.familyNameBorlido Farias
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person.familyNameM Conceição
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person.familyNameFeliciano dos Santos
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person.familyNamedos Santos Gomes
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person.givenNameDiana Isabel
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person.givenNameMaria Catarina
person.givenNameAndreia Filipa
person.givenNameMarta
person.givenNameMarc
person.givenNameAna E.
person.givenNameSusana
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project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
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