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  1. Article ; Online: Temporal patterns of cytokine and injury biomarkers in hospitalized COVID-19 patients treated with methylprednisolone.

    Mwangi, Victor Irungu / Netto, Rebeca Linhares Abreu / de Morais, Carlos Eduardo Padron / Silva, Arineia Soares / Silva, Bernardo Maia / Lima, Amanda Barros / Neves, Juliana Costa Ferreira / Borba, Mayla Gabriela Silva / Val, Fernando Fonseca de Almeida E / de Almeida, Anne Cristine Gomes / Costa, Allyson Guimarães / Sampaio, Vanderson de Souza / Gardinassi, Luiz Gustavo / de Lacerda, Marcus Vinicius Guimarães / Monteiro, Wuelton Marcelo / de Melo, Gisely Cardoso

    Frontiers in immunology

    2023  Volume 14, Page(s) 1229611

    Abstract: Background: The novel coronavirus disease 2019 (COVID-19) presents with complex pathophysiological effects in various organ systems. Following the COVID-19, there are shifts in biomarker and cytokine equilibrium associated with altered physiological ... ...

    Abstract Background: The novel coronavirus disease 2019 (COVID-19) presents with complex pathophysiological effects in various organ systems. Following the COVID-19, there are shifts in biomarker and cytokine equilibrium associated with altered physiological processes arising from viral damage or aggressive immunological response. We hypothesized that high daily dose methylprednisolone improved the injury biomarkers and serum cytokine profiles in COVID-19 patients.
    Methods: Injury biomarker and cytokine analysis was performed on 50 SARS-Cov-2 negative controls and 101 hospitalized severe COVID-19 patients: 49 methylprednisolone-treated (MP group) and 52 placebo-treated serum samples. Samples from the treated groups collected on days D1 (pre-treatment) all the groups, D7 (2 days after ending therapy) and D14 were analyzed. Luminex assay quantified the biomarkers HMGB1, FABP3, myoglobin, troponin I and NTproBNP. Immune mediators (CXCL8, CCL2, CXCL9, CXCL10, TNF, IFN-γ, IL-17A, IL-12p70, IL-10, IL-6, IL-4, IL-2, and IL-1β) were quantified using cytometric bead array.
    Results: At pretreatment, the two treatment groups were comparable demographically. At pre-treatment (D1), injury biomarkers (HMGB1, TnI, myoglobin and FABP3) were distinctly elevated. At D7, HMGB1 was significantly higher in the MP group (p=0.0448) compared to the placebo group, while HMGB1 in the placebo group diminished significantly by D14 (p=0.0115). Compared to healthy control samples, several immune mediators (IL-17A, IL-6, IL-10, MIG, MCP-1, and IP-10) were considerably elevated at baseline (all p≤0.05). At D7, MIG and IP-10 of the MP-group were significantly lower than in the placebo-group (p=0.0431, p=0.0069, respectively). Longitudinally, IL-2 (MP-group) and IL-17A (placebo-group) had increased significantly by D14. In placebo group, IL-2 and IL-17A continuously increased, as IL-12p70, IL-10 and IP-10 steadily decreased during follow-up. The MP treated group had IL-2, IFN-γ, IL-17A and IL-12p70 progressively increase while IL-1β and IL-10 gradually decreased towards D14. Moderate to strong positive correlations between chemokines and cytokines were observed on D7 and D14.
    Conclusion: These findings suggest MP treatment could ameliorate levels of myoglobin and FABP3, but appeared to have no impact on HMGB1, TnI and NTproBNP. In addition, methylprednisolone relieves the COVID-19 induced inflammatory response by diminishing MIG and IP-10 levels. Overall, corticosteroid (methylprednisolone) use in COVID-19 management influences the immunological molecule and injury biomarker profile in COVID-19 patients.
    MeSH term(s) Humans ; Cytokines ; Interleukin-10 ; HMGB1 Protein ; Interleukin-17 ; Methylprednisolone/therapeutic use ; Chemokine CXCL10 ; Interleukin-2 ; Interleukin-6 ; Myoglobin ; COVID-19 ; SARS-CoV-2 ; Interleukin-12
    Chemical Substances Cytokines ; Interleukin-10 (130068-27-8) ; HMGB1 Protein ; Interleukin-17 ; Methylprednisolone (X4W7ZR7023) ; Chemokine CXCL10 ; Interleukin-2 ; Interleukin-6 ; Myoglobin ; Interleukin-12 (187348-17-0)
    Language English
    Publishing date 2023-08-16
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1229611
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid)

    Jeronimo, Christiane Maria Prado / Farias, Maria Eduarda Leão / Val, Fernando Fonseca Almeida / Sampaio, Vanderson Souza / Alexandre, Marcia Almeida Araújo / Melo, Gisely Cardoso / Safe, Izabella Picinin / Borba, Mayla Gabriela Silva / Netto, Rebeca Linhares Abreu / Maciel, Alex Bezerra Silva / Neto, João Ricardo Silva / Oliveira, Lucas Barbosa / Figueiredo, Erick Frota Gomes / Oliveira Dinelly, Kelry Mazurega / de Almeida Rodrigues, Maria Gabriela / Brito, Marcelo / Mourão, Maria Paula Gomes / Pivoto João, Guilherme Augusto / Hajjar, Ludhmila Abrahão /
    Bassat, Quique / Romero, Gustavo Adolfo Sierra / Naveca, Felipe Gomes / Vasconcelos, Heline Lira / de Araújo Tavares, Michel / Brito-Sousa, José Diego / Costa, Fabio Trindade Maranhão / Nogueira, Maurício Lacerda / Baía-da-Silva, Djane Clarys / Xavier, Mariana Simão / Monteiro, Wuelton Marcelo / Lacerda, Marcus Vinícius Guimarães / de Lemos Vasconcelos, Adria / Praia Marins, Adriana Ferreira / de Oliveira Trindade, Alexandre / Mendes Záu, Aline Sales / de Oliveira, Amanda Carvalho / Azevedo Furtado, Ana Carolina / Coelho Rocha, Ana Paula / da Silva Souza, Anderson / de Souza Dias, Andiana / Belém, Aníbal / dos Santos, Anna Gabriela Rezende / da Silva Sousa, Antonny Michael / da Silva, Beatriz França / Franco, Beatriz Leitão / da Silva, Bernardo Maia / da Costa, Bleno Leonam Gonçalves / Sato Barros do Amaral, Camila Miriam Suemi / Judice, Carla C / de Morais, Carlos Eduardo Padron / Camilo, Cecília Cunha / Sena da Silva, Danielle Severino / Gomes Duarte, Debora Camila / da Silva, Ejandre Garcia Negreiros / da Silva Lemos, Elias / de Fátima Ponte Frota, Elisângela / do Nascimento, Elizandra Freitas / de Almeida, Elson Silva / Marques, Elyana Almeida / de Almeida, Emanuel Medeiros Marinho / da Silva, Emanuelle Lira / dos Santos, Ester Galvão / da Silva Oliveira, Ezequiel / Martins Shimizu, Fábio Manabu / de Souza, Fabíola Ramalho Ferreira / da Silva do Vale, Felipe / dos Santos de Almeida Lima, Fernanda / da Fonseca, Fernando Hugo Jesus / Fontenelle, Flávia Alencar / de Azevedo Furtado, Francielen / Da Silva Pereira, Gabrielle / Bezerra, Geísa Aleixo / Maciel Salazar, Guilherme Kemeron / da Silva Pereira, Handerson / de Melo, Hilda Ferreira / Oliveira, Ingrid Nascimento / Pereira Filho, Ivanildo Vieira / Gomes, Jacimara Vasques / e Silva Rosa, Jaily / Lemos, Jonas Mota / Brutus, Josué Nélio / Pessoa, Karina Pinheiro / Costa Rodrigues, Laleyska Deucylane / Barros Cirino, Larissa Esthefani / Mourão Filho, Lauro Fragata / Moura, Leandro / Barbosa, Lisiane Rísia Pinto / de Souza, Lorenna Pereira / de Lima Ferreira, Luiz Carlos / dos Santos, Marcela Menezes / da Silva, Marcus Vinicius Ramos / Rodrigues, Mauro Pereira / de Menezes, Mayara Tavares / dos Santos Mota, Micaela Maciel / Freire, Monique / Corrêa, Nadya Fonseca / Rocha, Nagila Morais / Bittencourt, Najara / de Melo Silva, Natália Guedes / de Oliveira Saraiva, Priscilla / de Sousa Monteiro, Quézia / dos Santos, Rafael Theodoro / Freire, Raíssa Soares / de Araújo Pinto, Rebecca Augusta / Ferreira, Reinan Brotas / de Lima, Rodrigo Saboia / de Melo, Rosângela Francisca Tanantas / Saenz, Sabrina Teixeira / Alvarez Fernandes, Salete Sara / Vítor-Silva, Sheila / de Oliveira, Tânia Maria Rodrigues / Tavella, Tatyana A / Câmara, Thais Tavares / Santos, Thalie Cavalcante / Pinto, Thiago Serrão / dos Santos, Tilza Waleska Rocha / do Nascimento, Valdinete Alves / Sousa Barbosa, Wanessa Pessoa / de Melo, Wellinthon Ferreira / Salgado Sobrinho, Wlademir Braga

    Clinical Infectious Diseases ; ISSN 1058-4838 1537-6591

    A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial

    2020  

    Abstract: Abstract Background Steroid use for coronavirus disease 2019 (COVID-19) is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ... ...

    Abstract Abstract Background Steroid use for coronavirus disease 2019 (COVID-19) is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19. Methods A parallel, double-blind, placebo-controlled, randomized, Phase IIb clinical trial was performed with hospitalized patients aged ≥18 years with clinical, epidemiological, and/or radiological suspected COVID-19 at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution) twice daily for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality. Results From 18 April to 16 June 2020, 647 patients were screened, 416 were randomized, and 393 were analyzed as mITT, with 194 individuals assigned to MP and 199 to placebo. SARS-CoV-2 infection was confirmed by reverse transcriptase polymerase chain reaction in 81.3%. The mortality rates at Day 28 were not different between groups. A subgroup analysis showed that patients over 60 years old in the MP group had a lower mortality rate at Day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until Day 7. Conclusions The findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population. Clinical Trials Registration NCT04343729.
    Keywords Microbiology (medical) ; Infectious Diseases ; covid19
    Language English
    Publisher Oxford University Press (OUP)
    Publishing country uk
    Document type Article ; Online
    DOI 10.1093/cid/ciaa1177
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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