Timeline Kinetics of Systemic and Airway Immune Mediator Storm for Comprehensive Analysis of Disease Outcome in Critically Ill COVID-19 Patients

Gonçalves, Juan Jonathan; Mata, Camila Pacheco Silveira Martins da; Lourenço, Alice Aparecida; Ribeiro, Ágata Lopes; Ferreira, Geovane Marques; Fraga-Silva, Thais Fernanda de Campos; Souza, Fernanda Mesquita de; Almeida, Vanessa Egídio Silveira; Batista, Iara Antunes; D`Avila-Mesquita, Carolina; Couto, Ariel E. S.; Campos, Ligia C. B.; Paim, Adriana Alves Oliveira; Ferreira, Linziane Lopes; Oliveira, Patrícia de; Teixeira, Lorena de Almeida; Marques, Daisymara Priscila de Almeida; Moraes, Henrique Retes de; Pereira, Samille Henriques; Brito-de-Sousa, Joaquim Pedro; Campi-Azevedo, Ana Carolina; Peruhype-Magalhães, Vanessa; Araújo, Márcio Sobreira Silva; Teixeira-Carvalho, Andréa; Fonseca, Flávio Guimarães da; Bonato, Vânia Luiza Deperon; Becari, Christiane; Ferro, Denise; Menegüeti, Mayra Gonçalves; Mazzoni, Amanda Alves Silva; Auxiliadora‐Martins, Maria; Coelho-dos-Reis, Jordana Grazziela Alves; Martins‐Filho, Olindo Assis

doi:10.3389/fimmu.2022.903903

Cited by 5 publications

(12 citation statements)

References 35 publications

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“…The decreasing levels of inflammatory cytokines TNFα, IL-1β on the 28th day of follow-up in COVID-19 patients are consistent with the results of the study by Perpiñan et al, except in the case of IL-1β, which was increased at four–six weeks after admission in that study [ 37 ]. Different shifts in IL-1β have also been reported in a study by Goncalves et al [ 38 ]. Moreover, we observed that, compared with non-severe COVID-19, severe infection was associated not only with significant baseline up-regulation of inflammatory biomarkers levels (TNFα, IL-1β, PTX3), which is consistent with the results of our previous study [ 39 ], but also with elevated resistin and decreased adiponectin.…”

Section: Discussionsupporting

confidence: 69%

Chemerin as a Potential Marker of Resolution of Inflammation in COVID-19 Infection

et al. 2022

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Chemerin is one of the specialized pro-resolving mediators that participate in the early phase of inflammation and contribute to the initiation of the pro-resolving response. There is a paucity of data regarding the time course of chemerin during acute infections. We aimed to evaluate the sequence of inflammatory responses in the acute COVID-19 phase throughout onset and resolution of inflammation. We evaluated changes in selected biomarkers in COVID-19 survivors on the 7-day and 28-day follow up. Chemerin was lower in patients with baseline moderate/severe disease at day 7 compared with asymptomatic patients and individuals with mild illness (7265 [5526–9448] vs. 8730 [6888–11,058] pg/mL; p = 0.03). Only in patients with moderate/severe disease, but not in those with mild symptoms, were chemerin concentrations decreased one week after infection onset compared with baseline (7265 [5526–9448] vs. 8866 [6383–10,690] pg/mL; p < 0.05) with a subsequent increase on the 28-day follow up (9313 [7353–11,033] pg/mL; p < 0.05). Resolution of inflammation in the group of moderate/severe SARS-CoV2 infection was associated with increasing serum concentrations of chemerin, contrary to pro-inflammatory cytokines and adipokines (pentraxin 3, TNFα, resistin, leptin). A similar pattern of angiopoietin-2 dynamics may suggest signs of enhanced vascularization as a consequence of acute SARS-CoV2 infection.

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Section: Discussionsupporting

confidence: 69%

Chemerin as a Potential Marker of Resolution of Inflammation in COVID-19 Infection

et al. 2022

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“…The innate immune system is of great importance in viral infections, especially in respiratory infections, in which the lung is the target organ. A differential and divergent cytokine storm both systemic and in the airways will also be crucial to define immune responses and outcome of critically ill COVID-19 patients ( 47 ). This inflamed milieu also allows for improved binding to surface antigens and can influence the secretion of other cytokines as interferons and interleukins, as well as regulatory factors.…”

Section: Discussionmentioning

confidence: 99%

Algorithms for predicting COVID outcome using ready-to-use laboratorial and clinical data

Lourenço,

Amaral,

Paim

et al. 2024

Front. Public Health

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The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging crisis affecting the public health system. The clinical features of COVID-19 can range from an asymptomatic state to acute respiratory syndrome and multiple organ dysfunction. Although some hematological and biochemical parameters are altered during moderate and severe COVID-19, there is still a lack of tools to combine these parameters to predict the clinical outcome of a patient with COVID-19. Thus, this study aimed at employing hematological and biochemical parameters of patients diagnosed with COVID-19 in order to build machine learning algorithms for predicting COVID mortality or survival. Patients included in the study had a diagnosis of SARS-CoV-2 infection confirmed by RT-PCR and biochemical and hematological measurements were performed in three different time points upon hospital admission. Among the parameters evaluated, the ones that stand out the most are the important features of the T1 time point (urea, lymphocytes, glucose, basophils and age), which could be possible biomarkers for the severity of COVID-19 patients. This study shows that urea is the parameter that best classifies patient severity and rises over time, making it a crucial analyte to be used in machine learning algorithms to predict patient outcome. In this study optimal and medically interpretable machine learning algorithms for outcome prediction are presented for each time point. It was found that urea is the most paramount variable for outcome prediction over all three time points. However, the order of importance of other variables changes for each time point, demonstrating the importance of a dynamic approach for an effective patient’s outcome prediction. All in all, the use of machine learning algorithms can be a defining tool for laboratory monitoring and clinical outcome prediction, which may bring benefits to public health in future pandemics with newly emerging and reemerging SARS-CoV-2 variants of concern.

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“…The activity of BromAc ® was observed on regulatory cytokines such as IL-10. IL-10 has been shown to be augmented in tracheal aspirate samples from critically ill COVID patients that progress to death ( 18 ). Not only proinflammatory but also increased regulatory factors need to be addressed during a modulatory response, considering that IL-10 and other regulatory cytokines may contribute to impaired resolutive mechanisms during tissue repair and convalescence associated with long COVID ( 19 , 20 ).…”

Section: Discussionmentioning

confidence: 99%

Taming the SARS-CoV-2-mediated proinflammatory response with BromAc®

Ferreira,

Clarindo,

Ribeiro

et al. 2023

Front. Immunol.

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IntroductionIn the present study, the impact of BromAc®, a specific combination of bromelain and acetylcysteine, on the SARS-CoV-2-specific inflammatory response was evaluated.MethodsAn in vitro stimulation system was standardized using blood samples from 9 healthy donors, luminex assays and flow cytometry were performed. Results and discussionBromAc® demonstrated robust anti-inflammatory activity in human peripheral blood cells upon SARS-CoV-2 viral stimuli, reducing the cytokine storm, composed of chemokines, growth factors, and proinflammatory and regulatory cytokines produced after short-term in vitro culture with the inactivated virus (iSARS-CoV-2). A combined reduction in vascular endothelial growth factor (VEGF) induced by SARS-CoV-2, in addition to steady-state levels of platelet recruitment-associated growth factor-PDGFbb, was observed, indicating that BromAc® may be important to reduce thromboembolism in COVID-19. The immunophenotypic analysis of the impact of BromAc® on leukocytes upon viral stimuli showed that BromAc® was able to downmodulate the populations of CD16+ neutrophils and CD14+ monocytes observed after stimulation with iSARS-CoV-2. Conversely, BromAc® treatment increased steady-state HLA-DR expression in CD14+ monocytes and preserved this activation marker in this subset upon iSARS-CoV-2 stimuli, indicating improved monocyte activation upon BromAc® treatment. Additionally, BromAc® downmodulated the iSARS-CoV-2-induced production of TNF-a by the CD19+ B-cells. System biology approaches, utilizing comprehensive correlation matrices and networks, showed distinct patterns of connectivity in groups treated with BromAc®, suggesting loss of connections promoted by the compound and by iSARS-CoV-2 stimuli. Negative correlations amongst proinflammatory axis and other soluble and cellular factors were observed in the iSARS-CoV-2 group treated with BromAc® as compared to the untreated group, demonstrating that BromAc® disengages proinflammatory responses and their interactions with other soluble factors and the axis orchestrated by SARS-CoV-2.ConclusionThese results give new insights into the mechanisms for the robust anti-inflammatory effect of BromAc® in the steady state and SARS-CoV-2-specific immune leukocyte responses, indicating its potential as a therapeutic strategy for COVID-19.

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Timeline Kinetics of Systemic and Airway Immune Mediator Storm for Comprehensive Analysis of Disease Outcome in Critically Ill COVID-19 Patients

Cited by 5 publications

References 35 publications

Chemerin as a Potential Marker of Resolution of Inflammation in COVID-19 Infection

Chemerin as a Potential Marker of Resolution of Inflammation in COVID-19 Infection

Algorithms for predicting COVID outcome using ready-to-use laboratorial and clinical data

Taming the SARS-CoV-2-mediated proinflammatory response with BromAc®

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