Interferon gamma-induced protein 10 (IP-10) for the early prognosis of the risk for severe respiratory failure and death in COVID-19 pneumonia

Samaras, Charilaos; Kyriazopoulou, Evdoxia; Poulakou, Garyfallia; Reiner, Eran; Kosmidou, Maria; Karanika, Ioanna; Petrakis, Vasileios; Adamis, George; Gatselis, Nikolaos; Fragkou, Archontoula; Rapti, Aggeliki; Taddei, Eleonora; Kalomenidis, Ioannis; Chrysos, George; Bertoli, Giulia; Kainis, Ilias; Alexiou, Zoi; Castelli, Francesco; Serino, Francesco Saverio; Bakakos, Petros; Nicastri, Emanuele; Tzavara, Vassiliki; Kostis, Evangelos; Dagna, Lorenzo; Koukidou, Sofia; Tzatzagou, Glykeria; Chini, Maria; Bassetti, Matteo; Trakatelli, Christina; Tsoukalas, George; Selmi, Carlo; Samarkos, Michael; Pyrpasopoulou, Athina; Masgala, Aikaterini; Antonakis, Emmanouil; Argyraki, Aikaterini; Akinosoglou, Karolina; Sympardi, Styliani; Panagopoulos, Periklis; Milionis, Haralampos; Metallidis, Simeon; Syrigos, Konstantinos; Angel, Alon; Dalekos, George Ν.; Netea, Mihai G.; Giamarellos‐Bourboulis, Evangelos J.

doi:10.1016/j.cyto.2022.156111

Cited by 8 publications

(3 citation statements)

References 25 publications

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“…We have shown that IP10 measurements combined with routinely employed clinical laboratory blood tests at or very close to the point of hospital admission offer a simple and improved means to prognosticate subsequent clinical deterioration from COVID-19 over a 30-day window in independent Discovery and Validation cohorts in the U.K. At a threshold of 0.25, IP10-plus-laboratory tests showed values of 0.8 for sensivity and specificity. Our findings are supported by other reports appearing after our COVID-IP study that independently attested to the value of IP10 measurements in predicting clinical deterioration in COVID-19 [29][30][31][32][33] . In this regard, IP10 measurements seemingly offer insights into the pathology of COVID-19 that are less likely to be offered by physiologic measurements that are often generic across very many disease settings.…”

Section: Discussionsupporting

confidence: 92%

“…Moreover, within the IP10, IL-6, and IL-10 triad, the most significant discriminator of ward to ICU was IP10 (Fig. 2b), seemingly consistent with several other, independent reports published following our initial COVID-IP study that likewise claimed that IP10 levels were predictive of subsequent deterioration in COVID-19 [29][30][31][32][33] .…”

Section: Parameters Anticipating Clinical Deteriorationsupporting

confidence: 88%

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IP10 levels refine severity prognostication in COVID-19 and implicate causes of clinical deterioration: lessons for pandemic preparedness

Das,

Wei,

McKenzie

et al. 2024

Preprint

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SummaryBackgroundEmerging pandemics place immense strains on healthcare systems that may be ameliorated by rapid development of biomarkers whose measurements may predict disease severity and additionally inform about disease causation. Conspicuously, such routine measures rarely include immunological cytokines or chemokines, despite their contributions to host protection and immunopathology.MethodsMultiplex bead-array and ELISA-based serum cytokine and chemokine measurements, routinely employed clinical laboratory measures, and clinical outcomes were collectively fed into predictive model development for prognostication of COVID-19 severity in an unvaccinated UK cohort (Discovery; early-to-mid 2020), with subsequent external validation among a pauci-vaccinated UK cohort (early 2021) and part-vaccinated India cohort (early 2022 to early 2023). Correlates of disease severity were assessed by high-content spectral flow cytometry.FindingsIncorporating a practical test for the chemokine IP10 (a.k.a. CXCL10) alongside routine clinical laboratory assays increased at-admission test accuracy to prognosticate intensive care requirements or in-hospital mortality at 30 days in the Discovery and Validation cohorts. In the India cohort, high IP10 levels predicted terminal deterioration among unvaccinated persons. High-resolution immune-profiling within subsets of the Discovery and India cohorts associated a T cell-centric signature with disease severity and with high IP10 levels, thereby identifying candidate drivers of COVID-19 deterioration.ConclusionsIP10 levels measured at or around hospital admission offer a practical biomarker enhancing COVID-19 patient outcome prognostication, particluarly in unvaccinated individuals, and offer mechanistic insights into pathogenesis. Thus, prompt application of systems immune-profiling in future pandemics might rapidly identify prognostic and mechanistic biomarkers of patient deterioration, aiding clinical decision-making at a time of severe healthcare strain.FundingMedical Research Council grant, CARDINNATE.

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Section: Discussionsupporting

confidence: 92%

Section: Parameters Anticipating Clinical Deteriorationsupporting

confidence: 88%

IP10 levels refine severity prognostication in COVID-19 and implicate causes of clinical deterioration: lessons for pandemic preparedness

Das,

Wei,

McKenzie

et al. 2024

Preprint

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“…Increased IL-18 levels have been observed in patients with HIV and pneumonia, suggesting an exacerbated inflammatory response [51,54,55]. IP10 (interferon gamma-inducible protein 10), also known as CXCL10, is a chemoattractive cytokine that attracts inflammatory cells, especially T lymphocytes, to the site of infection [56,57]. Increased IP10 levels have been associated with lung inflammation and an altered immune response in patients with HIV and pneumonia [23,27].…”

Section: Discussionmentioning

confidence: 99%

Markers of Inflammation, Tissue Damage, and Fibrosis in Individuals Diagnosed with Human Immunodeficiency Virus and Pneumonia: A Cohort Study

Peña-Valencia,

Riaño,

Herrera-Diaz

et al. 2024

Pathogens

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Previous studies have noted that persons living with human immunodeficiency virus (HIV) experience persistent lung dysfunction after an episode of community-acquired pneumonia (CAP), although the underlying mechanisms remain unclear. We hypothesized that inflammation during pneumonia triggers increased tissue damage and accelerated pulmonary fibrosis, resulting in a gradual loss of lung function. We carried out a prospective cohort study of people diagnosed with CAP and/or HIV between 2016 and 2018 in three clinical institutions in Medellín, Colombia. Clinical data, blood samples, and pulmonary function tests (PFTs) were collected at baseline. Forty-one patients were included, divided into two groups: HIV and CAP (n = 17) and HIV alone (n = 24). We compared the concentrations of 17 molecules and PFT values between the groups. Patients with HIV and pneumonia presented elevated levels of cytokines and chemokines (IL-6, IL-8, IL-18, IL-1RA, IL-10, IP-10, MCP-1, and MIP-1β) compared to those with only HIV. A marked pulmonary dysfunction was evidenced by significant reductions in FEF25, FEF25-75, and FEV1. The correlation between these immune mediators and lung function parameters supports the connection between pneumonia-associated inflammation and end organ lung dysfunction. A low CD4 cell count (<200 cells/μL) predicted inflammation and lung dysfunction. These results underscore the need for targeted clinical approaches to mitigate the adverse impacts of CAP on lung function in this population.

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Divergent autoantibody and cytokine levels in COVID‐19 sepsis patients influence survival

Kühn,

Heinen,

Sutter

et al. 2024

Journal of Medical Virology

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Studies have pointed to a decisive role of autoantibodies in the context of sepsis and severe Coronavirus disease 2019 (COVID‐19), which itself often fulfills the criteria for sepsis, including dysregulated immune responses and organ dysfunction. To directly compare and further analyze the autoantibody profiles of sepsis patients with and without COVID‐19, the luciferase immunoprecipitation systems (LIPS) assay was used to measure the levels of autoantibodies against a variety of clinically relevant cytokines, lung‐associated proteins, other autoantigens, and antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). In addition, cytokine titers were measured with the LEGENDplex™ Human Antivirus Response Panel. We observed significantly increased levels of autoantibodies in 59% of the COVID‐19‐Sepsis group compared to 48% of the Sepsis group. Significant differences were identified between the groups for the levels of autoantibodies against gATPase. The cytokine levels of interferon (IFN)‐λ1 and IP‐10 were higher in the COVID‐19‐Sepsis group compared to the Sepsis group. Additional correlations between autoantibodies, cytokines and 30‐day survival could be demonstrated, suggesting varied underlying pathological mechanisms. Elevated levels of cytokines and autoantibodies may serve as prognostic indicators for the survival probability of sepsis patients, highlighting the intricate relationship between immune responses and patient outcomes in the context of both sepsis and COVID‐19.

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Interferon gamma-induced protein 10 (IP-10) for the early prognosis of the risk for severe respiratory failure and death in COVID-19 pneumonia

Cited by 8 publications

References 25 publications

IP10 levels refine severity prognostication in COVID-19 and implicate causes of clinical deterioration: lessons for pandemic preparedness

IP10 levels refine severity prognostication in COVID-19 and implicate causes of clinical deterioration: lessons for pandemic preparedness

Markers of Inflammation, Tissue Damage, and Fibrosis in Individuals Diagnosed with Human Immunodeficiency Virus and Pneumonia: A Cohort Study

Divergent autoantibody and cytokine levels in COVID‐19 sepsis patients influence survival

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