High mobility group box 1, <scp>ATP</scp>, lipid mediators, and tissue factor are elevated in <scp>COVID</scp>‐19 patients: <scp>HMGB1</scp> as a biomarker of worst prognosis

Vicentino, Amanda Roberta Revoredo; Fraga-Junior, Vanderlei da Silva; Palazzo, Matheus; Tasmo, Natália Recardo Amorim; Rodrigues, Danielle A. S.; Barroso, Shana Priscila Coutinho; Ferreira, Samila Natiane; Borges, Anna Cristina Neves; Allonso, Diego; Fantappíé, Marcelo Rosado; Scharfstein, Júlio; Oliveira, Ana Carolina; Vianna‐Jorge, Rosane; Vale, Andre M.; Coutinho‐Silva, Robson; Savio, Luiz Eduardo Baggio; Canetti, Cláudio; Benjamim, Cláudia F.

doi:10.1111/cts.13475

Cited by 8 publications

(4 citation statements)

References 50 publications

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“…For example, the mean HMGB1 value of 487.6 pg/mL (315.5-721.8) measured in our study correlated with the value determined by Boley et al [16] in COVID-19 patients with moderate symptoms (514.7 ± 248.9 pg/mL). These HMGB1 values are significantly lower than the 933.2 pg/mL detected in critically ill patients by Sivakorn et al [14] or 125.4 ng/mL, which were established as cut-off values to distinguish patients at higher risk of death [42]. According to Vicentino et al [42], measuring serum HMGB1 levels up to day 12 after hospital admission can help guide pharmacological and medical interventions in early phases of COVID-19 recovery with ongoing inflammation or immune dysfunction.…”

Section: Discussionmentioning

confidence: 80%

Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission

Grigorov,

Pejić,

Todorović

et al. 2023

IJMS

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The careful monitoring of patients with mild/moderate COVID-19 is of particular importance because of the rapid progression of complications associated with COVID-19. For prognostic reasons and for the economic management of health care resources, additional biomarkers need to be identified, and their monitoring can conceivably be performed in the early stages of the disease. In this retrospective cross-sectional study, we found that serum concentrations of high-mobility group box 1 (HMGB1) and heme oxygenase-1 (HO-1), at the time of hospital admission, could be useful biomarkers for COVID-19 management. The study included 160 randomly selected recovered patients with mild to moderate COVID-19 on admission. Compared with healthy controls, serum HMGB1 and HO-1 levels increased by 487.6 pg/mL versus 43.1 pg/mL and 1497.7 pg/mL versus 756.1 pg/mL, respectively. Serum HO-1 correlated significantly with serum HMGB1, oxidative stress parameters (malondialdehyde (MDA), the phosphatidylcholine/lysophosphatidylcholine ratio (PC/LPC), the ratio of reduced and oxidative glutathione (GSH/GSSG)), and anti-inflammatory acute phase proteins (ferritin, haptoglobin). Increased heme catabolism/hemolysis were not detected. We hypothesize that the increase in HO-1 in the early phase of COVID-19 disease is likely to have a survival benefit by providing protection against oxidative stress and inflammation, whereas the level of HMGB1 increase reflects the activity of the innate immune system and represents levels within which the disease can be kept under control.

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Section: Discussionmentioning

confidence: 80%

Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission

Grigorov,

Pejić,

Todorović

et al. 2023

IJMS

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“…HMGB-1 has been implicated in several studies demonstrating its utility as both a biomarker of COVID-19 prognosis and risk factor of developing long COVID symptoms [ 14 , 40 , 41 ]. This study further adds to this body of knowledge by highlighting HMGB-1 as a promising biomarker that may assist in predicting SARS-CoV-2 vaccine outcomes.…”

Section: Discussionmentioning

confidence: 99%

Immuno-Microbial Signature of Vaccine-Induced Immunity against SARS-CoV-2

Umeda,

Torres,

Kunihiro

et al. 2024

Vaccines

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Although vaccines address critical public health needs, inter-individual differences in responses are not always considered in their development. Understanding the underlying basis for these differences is needed to optimize vaccine effectiveness and ultimately improve disease control. In this pilot study, pre- and post-antiviral immunological and gut microbiota features were characterized to examine inter-individual differences in SARS-CoV-2 mRNA vaccine response. Blood and stool samples were collected before administration of the vaccine and at 2-to-4-week intervals after the first dose. A cohort of 14 adults was separated post hoc into two groups based on neutralizing antibody levels (high [HN] or low [LN]) at 10 weeks following vaccination. Bivariate correlation analysis was performed to examine associations between gut microbiota, inflammation, and neutralization capacity at that timepoint. These analyses revealed significant differences in gut microbiome composition and inflammation states pre-vaccination, which predicted later viral neutralization capacity, with certain bacterial taxa, such as those in the genus Prevotella, found at higher abundance in the LN vs HN group that were also negatively correlated with a panel of inflammatory factors such as IL-17, yet positively correlated with plasma levels of the high mobility group box 1 (HMGB-1) protein at pre-vaccination. In particular, we observed a significant inverse relationship (Pearson = −0.54, p = 0.03) between HMGB-1 pre-vaccination and neutralization capacity at 10 weeks post-vaccination. Consistent with known roles as mediators of inflammation, our results altogether implicate HMGB-1 and related gut microbial signatures as potential biomarkers in predicting SARS-CoV-2 mRNA vaccine effectiveness measured by the production of viral neutralization antibodies.

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“…Interestingly, in lung tissues of SARS-CoV2-infected humans and mice, hyperactivated MCs were found [19][20][21]. Thereby, the presence of hyperactivated MCs correlated with the strongly elevated levels of IL-33 [22,23], ATP [24] and MC proteases [19] in the serum of COVID-19 patients. Therefore, ATP/IL-33 co-sensing in infected lung tissues might be a potential mechanism explaining the hyperactivated MC phenotype in SARS-CoV2-infected individuals [14].…”

Section: Introductionmentioning

confidence: 89%

ATP/IL-33-Co-Sensing by Mast Cells (MCs) Requires Activated c-Kit to Ensure Effective Cytokine Responses

Seifert,

Küchler,

Drube

2023

Cells

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Mast cells (MCs) are sentinel cells which represent an important part of the first line of defense of the immune system. MCs highly express receptors for danger-associated molecular patterns (DAMPs) such as the IL-33R and P2X7, making MCs to potentially effective sensors for IL-33 and adenosine-triphosphate (ATP), two alarmins which are released upon necrosis-induced cell damage in peripheral tissues. Besides receptors for alarmins, MCs also express the stem cell factor (SCF) receptor c-Kit, which typically mediates MC differentiation, proliferation and survival. By using bone marrow-derived MCs (BMMCs), ELISA and flow cytometry experiments, as well as p65/RelA and NFAT reporter MCs, we aimed to investigate the influence of SCF on alarmin-induced signaling pathways and the resulting cytokine production and degranulation. We found that the presence of SCF boosted the cytokine production but not degranulation in MCs which simultaneously sense ATP and IL-33 (ATP/IL-33 co-sensing). Therefore, we conclude that SCF maintains the functionality of MCs in peripheral tissues to ensure appropriate MC reactions upon cell damage, induced by pathogens or allergens.

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High mobility group box 1, ATP, lipid mediators, and tissue factor are elevated in COVID‐19 patients: HMGB1 as a biomarker of worst prognosis

Cited by 8 publications

References 50 publications

Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission

Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission

Immuno-Microbial Signature of Vaccine-Induced Immunity against SARS-CoV-2

ATP/IL-33-Co-Sensing by Mast Cells (MCs) Requires Activated c-Kit to Ensure Effective Cytokine Responses

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