Circulating Interleukin-8 Dynamics Parallels Disease Course and Is Linked to Clinical Outcomes in Severe COVID-19

D’Rozario, Ranit; Raychaudhuri, Deblina; Bandopadhyay, Purbita; Sarif, Jafar; Mehta, Priyanka; Liu, Chinky Shiu Chen; Sinha, Bishnu Prasad; Roy, Jayasree; Bhaduri, Ritwik; Das, Monidipa; Bandyopadhyay, Sanghamitra; Paul, Shekhar Ranjan; Chatterjee, Shilpak; Pandey, Rajesh; Ray, Yogiraj; Ganguly, Dipyaman

doi:10.3390/v15020549

Cited by 5 publications

(3 citation statements)

References 44 publications

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“…This might suggest that inhibition of C5a can reduce endotheliopathy caused by COVID-19 and thereby protects against thrombotic complications in severely ill COVID-19 patients [ 7 , 16 ]. Vilobelimab also appeared to reduce levels of the proinflammatory chemokine interleukin-8 (IL-8) in the phase 2 PANAMO trial [ 7 ], which plays a significant role in the pathogenesis of ARDS and likely COVID-19 as well [ 7 , 17 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic analysis of vilobelimab, anaphylatoxin C5a and antidrug antibodies in PANAMO: a phase 3 study in critically ill, invasively mechanically ventilated COVID-19 patients

Lim¹,

Vlaar²,

Bruin³

et al. 2023

ICMx

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Background Vilobelimab, a complement 5a (C5a)-specific monoclonal antibody, reduced mortality in critically ill COVID-19 patients in a phase 3 multicentre, randomized, double-blind, placebo-controlled study. As part of the study, vilobelimab concentrations and C5a levels as well as antidrug antibodies (ADAs) to vilobelimab were analysed. Results From Oct 1, 2020 to Oct 4, 2021, 368 invasively mechanically ventilated COVID-19 patients were randomized: 177 patients were randomly assigned to receive vilobelimab while 191 patients received placebo. Pharmacokinetic sampling was only performed at sites in Western Europe. Blood samples for vilobelimab measurements were available for 93 of 177 (53%) patients in the vilobelimab group and 99 of 191 (52%) patients in the placebo group. On day 8, after three infusions, mean vilobelimab (trough) concentrations ranged from 21,799.3 to 302,972.1 ng/mL (geometric mean 137,881.3 ng/mL). Blood samples for C5a measurements were available for 94 of 177 (53%) patients in the vilobelimab group and 99 of 191 (52%) patients in the placebo group. At screening, C5a levels were highly elevated and comparable between groups. In the vilobelimab group, median C5a levels were 118.3 ng/mL [IQR 71.2–168.2 ng/mL] and in the placebo group, median C5a levels were 104.6 ng/mL [IQR 77.5–156.6 ng/mL]. By day 8, median C5a levels were reduced by 87% in the vilobelimab group (median 14.5 ng/mL [IQR 9.5–21.0 ng/mL], p < 0.001) versus an 11% increase in the placebo group (median 119.2 ng/mL [IQR 85.9–152.1 ng/mL]). Beyond day 8, though plasma sampling was sparse, C5a levels did not reach screening levels in the vilobelimab group while C5a levels remained elevated in the placebo group. Treatment-emergent ADAs were observed in one patient in the vilobelimab group at hospital discharge on day 40 and in one patient in the placebo group at hospital discharge on day 25. Conclusions This analysis shows that vilobelimab efficiently inhibits C5a in critically ill COVID-19 patients. There was no evidence of immunogenicity associated with vilobelimab treatment. Trialregistration ClinicalTrials.gov, NCT04333420. Registered 3 April 2020, https://clinicaltrials.gov/ct2/show/NCT04333420

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic analysis of vilobelimab, anaphylatoxin C5a and antidrug antibodies in PANAMO: a phase 3 study in critically ill, invasively mechanically ventilated COVID-19 patients

Lim¹,

Vlaar²,

Bruin³

et al. 2023

ICMx

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“…These new data are crucial for the development of management pathways. Novel biomarkers, both on a cellular level, such as markers of lymphocyte apoptosis [356], and on a molecular level, such as interleukin 8 [357], interleukin-17, plasminogen activator inhibitors [356], microRNA [87] and gene expression tests [358], could enrich the repertoire of tests available to clinicians in the future.…”

Section: Transition In Evidencementioning

confidence: 99%

Effective prognostic and clinical risk stratification in COVID‐19 using multimodality biomarkers

et al. 2023

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In acute coronavirus disease 19 (COVID‐19) patients, effective clinical risk stratification has important implications on treatment and therapeutic resource distribution. This article reviews the evidence behind a wide range of biomarkers with prognostic value in COVID‐19. Patient characteristics and co‐morbidities, such as cardiovascular and respiratory diseases, are associated with increased mortality risk. Peripheral oxygen saturation and arterial oxygenation are predictive of severe respiratory compromise, whereas risk scores such as the 4C‐score enable multi‐factorial prognostic risk estimation. Blood tests such as markers of inflammation, cardiac injury and d‐dimer and abnormalities on electrocardiogram are linked to inpatient prognosis. Of the imaging modalities, lung ultrasound and echocardiography enable the bedside assessment of prognostic abnormalities in COVID‐19. Chest radiograph (CXR) and computed tomography (CT) can inform about prognostic pulmonary pathologies, whereas cardiovascular CT detects high‐risk features such as coronary artery and aortic calcification. Dynamic changes in biomarkers, such as blood tests, CXR, CT and electrocardiogram findings, can further inform about disease severity and prognosis. Despite the vast volumes of existing evidence, several gaps exist in our understanding of COVID‐19 biomarkers. First, the pathophysiological basis on which these markers can foretell prognosis in COVID‐19 remains poorly understood. Second, certain under‐explored tests such as thoracic impedance assessment and cardiovascular magnetic resonance imaging deserve further investigation. Lastly, the prognostic values of most biomarkers in COVID‐19 are derived from retrospective analyses. Prospective studies are required to validate these markers for guiding clinical decision‐making and to facilitate their translation into clinical management pathways.

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“…We speculate that this may be due to the rise in IL-8 levels, which promotes mitochondrial energy utilization disorders and exacerbates the abnormal transmission of oxidative respiratory chains; it may also be that the increase in IL-8 levels affects oxidative metabolic stress damage and promotes the destruction of alveolar cell integrity (22). In previous studies, D'Rozario R et al also mentioned that IL-8 can enhance the inflammatory process by regulating the negative feedback of the body's immune function (23). Considering that LP is an inflammatory disease with immune dysfunction caused by pathogen infection, the mechanism of IL-8 may also be related to the changes in immune metabolism.…”

Section: Il-8 Was Higher In Children With Poor Prognosismentioning

confidence: 99%

Association of IL-8 levels in serum and bronchoalveolar lavage fluid with sputum emboli in children with lobar pneumonia

Qingqing Chen,

Na Lv,

Xue Wang

et al. 2023

Cell Mol Biol (Noisy-le-grand)

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Materials and Methods Research timeThis study was conducted in the Department of Respiratory Medicine of our hospital from January 2022 to June 2023. Study participantsA retrospective analysis was performed on 69 LP children (observation group, OG) and 60 healthy control children (control group, CG) who visited our hospital from January 2022 to November 2022. The study was conducted in strict accordance with the Declaration of Helsinki and

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Circulating Interleukin-8 Dynamics Parallels Disease Course and Is Linked to Clinical Outcomes in Severe COVID-19

Cited by 5 publications

References 44 publications

Pharmacokinetic analysis of vilobelimab, anaphylatoxin C5a and antidrug antibodies in PANAMO: a phase 3 study in critically ill, invasively mechanically ventilated COVID-19 patients

Pharmacokinetic analysis of vilobelimab, anaphylatoxin C5a and antidrug antibodies in PANAMO: a phase 3 study in critically ill, invasively mechanically ventilated COVID-19 patients

Effective prognostic and clinical risk stratification in COVID‐19 using multimodality biomarkers

Association of IL-8 levels in serum and bronchoalveolar lavage fluid with sputum emboli in children with lobar pneumonia

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