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33 results on '"Maes, Bastiaan"'

2. Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial

Author

De Leeuw, Elisabeth, Van Damme, Karel F. A., Declercq, Jozefien, Bosteels, Cedric, Maes, Bastiaan, Tavernier, Simon J., Detalle, Laurent, Smart, Trevor, Glatt, Sophie, Debeuf, Nincy, Deckers, Julie, Lameire, Sahine, Vandecasteele, Stefaan J., De Neve, Nikolaas, Demedts, Ingel K., Govaerts, Elke, Knoop, Christiane, Vanhove, Karolien, Moutschen, Michel, Terryn, Wim, Depuydt, Pieter, Van Braeckel, Eva, Haerynck, Filomeen, Hendrickx, Tine C. J., Parrein, Vanessa, Lalla, Marianna, Brittain, Claire, and Lambrecht, Bart N.

Published
2022
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3. Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial

Author

Declercq, Jozefien, Van Damme, Karel F A, De Leeuw, Elisabeth, Maes, Bastiaan, Bosteels, Cedric, Tavernier, Simon J, De Buyser, Stefanie, Colman, Roos, Hites, Maya, Verschelden, Gil, Fivez, Tom, Moerman, Filip, Demedts, Ingel K, Dauby, Nicolas, De Schryver, Nicolas, Govaerts, Elke, Vandecasteele, Stefaan J, Van Laethem, Johan, Anguille, Sebastien, van der Hilst, Jeroen, Misset, Benoit, Slabbynck, Hans, Wittebole, Xavier, Liénart, Fabienne, Legrand, Catherine, Buyse, Marc, Stevens, Dieter, Bauters, Fre, Seys, Leen J M, Aegerter, Helena, Smole, Ursula, Bosteels, Victor, Hoste, Levi, Naesens, Leslie, Haerynck, Filomeen, Vandekerckhove, Linos, Depuydt, Pieter, van Braeckel, Eva, Rottey, Sylvie, Peene, Isabelle, Van Der Straeten, Catherine, Hulstaert, Frank, and Lambrecht, Bart N

Published
2021
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5. A20 deficiency in myeloid cells protects mice from diet-induced obesity and insulin resistance due to increased fatty acid metabolism

Author

Catrysse, Leen, Maes, Bastiaan, Mehrotra, Parul, Martens, Arne, Hoste, Esther, Martens, Liesbet, Maueröder, Christian, Remmerie, Anneleen, Bujko, Anna, Slowicka, Karolina, Sze, Mozes, Vikkula, Hanna, Ghesquière, Bart, Scott, Charlotte L., Saeys, Yvan, van de Sluis, Bart, Ravichandran, Kodi, Janssens, Sophie, and van Loo, Geert

Published
2021
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6. Epithelial HMGB1 Delays Skin Wound Healing and Drives Tumor Initiation by Priming Neutrophils for NET Formation

Author

Hoste, Esther, Maueröder, Christian, van Hove, Lisette, Catrysse, Leen, Vikkula, Hanna-Kaisa, Sze, Mozes, Maes, Bastiaan, Karjosukarso, Dyah, Martens, Liesbet, Gonçalves, Amanda, Parthoens, Eef, Roelandt, Ria, Declercq, Wim, Fuentes, Ignacia, Palisson, Francis, Gonzalez, Sergio, Salas-Alanis, Julio C., Boon, Louis, Huebener, Peter, Mulder, Klaas Willem, Ravichandran, Kodi, Saeys, Yvan, Schwabe, Robert Felix, and van Loo, Geert

Published
2019
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7. Zilucoplan in patients with acute hypoxic respiratory failure due to COVID-19 (ZILU-COV): A structured summary of a study protocol for a randomised controlled trial

Author

Declercq, Jozefien, Bosteels, Cedric, Van Damme, Karel, De Leeuw, Elisabeth, Maes, Bastiaan, Vandecauter, Ans, Vermeersch, Stefanie, Delporte, Anja, Demeyere, Bénédicte, Vuylsteke, Marnik, Lalla, Marianna, Smart, Trevor, Detalle, Laurent, Bouw, René, Streffer, Johannes, Degeeter, Thibo, Vergotte, Marie, Guisez, Tanguy, Van Braeckel, Eva, Van Der Straeten, Catherine, and Lambrecht, Bart N.

Published
2020
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8. Correction to: Treatment of severely ill COVID-19 patients with anti-interleukin drugs (COV-AID): A structured summary of a study protocol for a randomised controlled trial

Author

Maes, Bastiaan, Bosteels, Cedric, De Leeuw, Elisabeth, Declercq, Jozefien, Van Damme, Karel, Delporte, Anja, Demeyere, Bénédicte, Vermeersch, Stéfanie, Vuylsteke, Marnik, Willaert, Joren, Bollé, Laura, Vanbiervliet, Yuri, Decuypere, Jana, Libeer, Frederick, Vandecasteele, Stefaan, Peene, Isabelle, and Lambrecht, Bart N.

Published
2020
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9. Correction to: Sargramostim to treat patients with acute hypoxic respiratory failure due to COVID-19 (SARPAC): A structured summary of a study protocol for a randomised controlled trial

Author

Bosteels, Cedric, Maes, Bastiaan, Van Damme, Karel, De Leeuw, Elisabeth, Declercq, Jozefien, Delporte, Anja, Demeyere, Bénédicte, Vermeersch, Stéfanie, Vuylsteke, Marnik, Willaert, Joren, Bollé, Laura, Vanbiervliet, Yuri, Decuypere, Jana, Libeer, Frederick, Vandecasteele, Stefaan, Peene, Isabelle, and Lambrecht, Bart N.

Published
2020
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10. Sargramostim to treat patients with acute hypoxic respiratory failure due to COVID-19 (SARPAC): A structured summary of a study protocol for a randomised controlled trial

Author

Bosteels, Cedric, Maes, Bastiaan, Van Damme, Karel, De Leeuw, Elisabeth, Declercq, Jozefien, Delporte, Anja, Demeyere, Bénédicte, Vermeersch, Stéfanie, Vuylsteke, Marnik, Willaert, Joren, Bollé, Laura, Vanbiervliet, Yuri, Decuypere, Jana, Libeer, Frederick, Vandecasteele, Stefaan, Peene, Isabelle, and Lambrecht, Bart

Published
2020
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11. Treatment of severely ill COVID-19 patients with anti-interleukin drugs (COV-AID): A structured summary of a study protocol for a randomised controlled trial

Author

Maes, Bastiaan, Bosteels, Cedric, De Leeuw, Elisabeth, Declercq, Jozefien, Van Damme, Karel, Delporte, Anja, Demeyere, Bénédicte, Vermeersch, Stéfanie, Vuylsteke, Marnik, Willaert, Joren, Bollé, Laura, Vanbiervliet, Yuri, Decuypere, Jana, Libeer, Frederick, Vandecasteele, Stefaan, Peene, Isabelle, and Lambrecht, Bart

Published
2020
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12. A complement atlas identifies interleukin-6–dependent alternative pathway dysregulation as a key druggable feature of COVID-19

Author

Van Damme, Karel F. A., primary, Hoste, Levi, additional, Declercq, Jozefien, additional, De Leeuw, Elisabeth, additional, Maes, Bastiaan, additional, Martens, Liesbet, additional, Colman, Roos, additional, Browaeys, Robin, additional, Bosteels, Cédric, additional, Verwaerde, Stijn, additional, Vermeulen, Nicky, additional, Lameire, Sahine, additional, Debeuf, Nincy, additional, Deckers, Julie, additional, Stordeur, Patrick, additional, Depuydt, Pieter, additional, Van Braeckel, Eva, additional, Vandekerckhove, Linos, additional, Guilliams, Martin, additional, Schetters, Sjoerd T. T., additional, Haerynck, Filomeen, additional, Tavernier, Simon J., additional, and Lambrecht, Bart N., additional

Published
2023
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13. STE20 kinase TAOK3 regulates type 2 immunity and metabolism in obesity

Author

Maes, Bastiaan, primary, Fayazpour, Farzaneh, additional, Catrysse, Leen, additional, Lornet, Guillaume, additional, Van De Velde, Evelien, additional, De Wolf, Caroline, additional, De Prijck, Sofie, additional, Van Moorleghem, Justine, additional, Vanheerswynghels, Manon, additional, Deswarte, Kim, additional, Descamps, Benedicte, additional, Vanhove, Christian, additional, Van der Schueren, Bart, additional, Vangoitsenhoven, Roman, additional, Hammad, Hamida, additional, Janssens, Sophie, additional, and Lambrecht, Bart N., additional

Published
2023
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14. A complement atlas identifies interleukin-6–dependent alternative pathway dysregulation as a key druggable feature of COVID-19

Author

Van Damme, Karel F.A., Hoste, Levi, Declercq, Jozefien, De Leeuw, Elisabeth, Maes, Bastiaan, Martens, Liesbet, Colman, Roos, Browaeys, Robin, Bosteels, Cédric, Verwaerde, Stijn, Vermeulen, Nicky, Lameire, Sahine, Debeuf, Nincy, Deckers, Julie, Stordeur, Patrick, Depuydt, Pieter, Van Braeckel, Eva, Vandekerckhove, Linos, Guilliams, Martin, Schetters, Sjoerd T.T., Haerynck, Filomeen, Tavernier, Simon J., Lambrecht, Bart N., Van Damme, Karel F.A., Hoste, Levi, Declercq, Jozefien, De Leeuw, Elisabeth, Maes, Bastiaan, Martens, Liesbet, Colman, Roos, Browaeys, Robin, Bosteels, Cédric, Verwaerde, Stijn, Vermeulen, Nicky, Lameire, Sahine, Debeuf, Nincy, Deckers, Julie, Stordeur, Patrick, Depuydt, Pieter, Van Braeckel, Eva, Vandekerckhove, Linos, Guilliams, Martin, Schetters, Sjoerd T.T., Haerynck, Filomeen, Tavernier, Simon J., and Lambrecht, Bart N.

Abstract

Improvements in COVID-19 treatments, especially for the critically ill, require deeper understanding of the mechanisms driving disease pathology. The complement system is not only a crucial component of innate host defense but can also contribute to tissue injury. Although all complement pathways have been implicated in COVID-19 pathogenesis, the upstream drivers and downstream effects on tissue injury remain poorly defined. We demonstrate that complement activation is primarily mediated by the alternative pathway, and we provide a comprehensive atlas of the complement alterations around the time of respiratory deterioration. Proteomic and single-cell sequencing mapping across cell types and tissues reveals a division of labor between lung epithelial, stromal, and myeloid cells in complement production, in addition to liver-derived factors. We identify IL-6 and STAT1/3 signaling as an upstream driver of complement responses, linking complement dysregulation to approved COVID-19 therapies. Furthermore, an exploratory proteomic study indicates that inhibition of complement C5 decreases epithelial damage and markers of disease severity. Collectively, these results support complement dysregulation as a key druggable feature of COVID-19.

Published
2023

15. A Complement Atlas identifies interleukin 6 dependent alternative pathway dysregulation as a key druggable feature of COVID-19

Author

Van Damme, Karel F.A., primary, Hoste, Levi, additional, Declercq, Jozefien, additional, Leeuw, Elisabeth De, additional, Maes, Bastiaan, additional, Martens, Liesbet, additional, Colman, Roos, additional, Browaeys, Robin, additional, Bosteels, Cédric, additional, Verwaerde, Stijn, additional, Vermeulen, Nicky, additional, Lameire, Sahine, additional, Debeuf, Nincy, additional, Deckers, Julie, additional, Stordeur, Patrick, additional, Guilliams, Martin, additional, Schetters, Sjoerd T.T., additional, Haerynck, Filomeen, additional, Tavernier, Simon J., additional, and Lambrecht, Bart N., additional

Published
2023
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16. Loss of GM-CSF-dependent instruction of alveolar macrophages in COVID-19 provides a rationale for inhaled GM-CSF treatment

Author

Bosteels, Cedric, primary, Van Damme, Karel F.A., additional, De Leeuw, Elisabeth, additional, Declercq, Jozefien, additional, Maes, Bastiaan, additional, Bosteels, Victor, additional, Hoste, Levi, additional, Naesens, Leslie, additional, Debeuf, Nincy, additional, Deckers, Julie, additional, Cole, Basiel, additional, Pardons, Marion, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Weygaerde, Yannick Vande, additional, Malfait, Thomas, additional, Vandecasteele, Stefaan J., additional, Demedts, Ingel K., additional, Slabbynck, Hans, additional, Allard, Sabine, additional, Depuydt, Pieter, additional, Van Braeckel, Eva, additional, De Clercq, Jozefien, additional, Martens, Liesbet, additional, Dupont, Sam, additional, Seurinck, Ruth, additional, Vandamme, Niels, additional, Haerynck, Filomeen, additional, Roychowdhury, Debasish F., additional, Vandekerckhove, Linos, additional, Guilliams, Martin, additional, Tavernier, Simon J., additional, and Lambrecht, Bart N., additional

Published
2022
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17. Adverse outcomes of frailty in the elderly: the Rotterdam Study

Author

Lahousse, Lies, Maes, Bastiaan, Ziere, Gijsbertus, Loth, Daan W., Verlinden, Vincentius J. A., Zillikens, M. Carola, Uitterlinden, André G., Rivadeneira, Fernando, Tiemeier, Henning, Franco, Oscar H., Ikram, M. Arfan, Hofman, Albert, Brusselle, Guy G., and Stricker, Bruno H.

Published
2014

18. Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with Covid-19: an open-label randomized controlled trial

Author

De Leeuw, Elisabeth, primary, Damme, Karel F.A. Van, additional, Declercq, Jozefien, additional, Bosteels, Cedric, additional, Maes, Bastiaan, additional, Tavernier, Simon J., additional, Detalle, Laurent, additional, Smart, Trevor, additional, Glatt, Sophie, additional, Debeuf, Nincy, additional, Deckers, Julie, additional, Lameire, Sahine, additional, Vandecasteele, Stefaan J, additional, De Neve, Nikolaas, additional, Demedts, Ingel K., additional, Govaerts, Elke, additional, Knoop, Christiane, additional, Vanhove, Karolien, additional, Moutschen, Michel, additional, Terryn, Wim, additional, Depuydt, Pieter, additional, Braeckel, Eva Van, additional, Haerynck, Filomeen, additional, Hendrickx, Tine C.J., additional, Parrein, Vanessa, additional, Lalla, Marianna, additional, Brittain, Claire, additional, and Lambrecht, Bart N., additional

Published
2022
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19. Additional file 5 of Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial

Author

De Leeuw, Elisabeth, Van Damme, Karel F. A., Declercq, Jozefien, Bosteels, Cedric, Maes, Bastiaan, Tavernier, Simon J., Detalle, Laurent, Smart, Trevor, Glatt, Sophie, Debeuf, Nincy, Deckers, Julie, Lameire, Sahine, Vandecasteele, Stefaan J., De Neve, Nikolaas, Demedts, Ingel K., Govaerts, Elke, Knoop, Christiane, Vanhove, Karolien, Moutschen, Michel, Terryn, Wim, Depuydt, Pieter, Van Braeckel, Eva, Haerynck, Filomeen, Hendrickx, Tine C. J., Parrein, Vanessa, Lalla, Marianna, Brittain, Claire, and Lambrecht, Bart N.

Abstract

Additional file 5: Figure S1. Primary Outcome. GeoMean, Geometric Mean; LSGeoMean, Least Square Geometric Means; LSMean, Least Square Means.

Published
2022
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20. Additional file 4 of Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial

Author

De Leeuw, Elisabeth, Van Damme, Karel F. A., Declercq, Jozefien, Bosteels, Cedric, Maes, Bastiaan, Tavernier, Simon J., Detalle, Laurent, Smart, Trevor, Glatt, Sophie, Debeuf, Nincy, Deckers, Julie, Lameire, Sahine, Vandecasteele, Stefaan J., De Neve, Nikolaas, Demedts, Ingel K., Govaerts, Elke, Knoop, Christiane, Vanhove, Karolien, Moutschen, Michel, Terryn, Wim, Depuydt, Pieter, Van Braeckel, Eva, Haerynck, Filomeen, Hendrickx, Tine C. J., Parrein, Vanessa, Lalla, Marianna, Brittain, Claire, and Lambrecht, Bart N.

Abstract

Additional file 4. Additional statistical explanation.

Published
2022
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21. Additional file 2 of Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial

Author

De Leeuw, Elisabeth, Van Damme, Karel F. A., Declercq, Jozefien, Bosteels, Cedric, Maes, Bastiaan, Tavernier, Simon J., Detalle, Laurent, Smart, Trevor, Glatt, Sophie, Debeuf, Nincy, Deckers, Julie, Lameire, Sahine, Vandecasteele, Stefaan J., De Neve, Nikolaas, Demedts, Ingel K., Govaerts, Elke, Knoop, Christiane, Vanhove, Karolien, Moutschen, Michel, Terryn, Wim, Depuydt, Pieter, Van Braeckel, Eva, Haerynck, Filomeen, Hendrickx, Tine C. J., Parrein, Vanessa, Lalla, Marianna, Brittain, Claire, and Lambrecht, Bart N.

Abstract

Additional file 2. Statistical analysis plan.

Published
2022
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22. Additional file 6 of Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial

Author

De Leeuw, Elisabeth, Van Damme, Karel F. A., Declercq, Jozefien, Bosteels, Cedric, Maes, Bastiaan, Tavernier, Simon J., Detalle, Laurent, Smart, Trevor, Glatt, Sophie, Debeuf, Nincy, Deckers, Julie, Lameire, Sahine, Vandecasteele, Stefaan J., De Neve, Nikolaas, Demedts, Ingel K., Govaerts, Elke, Knoop, Christiane, Vanhove, Karolien, Moutschen, Michel, Terryn, Wim, Depuydt, Pieter, Van Braeckel, Eva, Haerynck, Filomeen, Hendrickx, Tine C. J., Parrein, Vanessa, Lalla, Marianna, Brittain, Claire, and Lambrecht, Bart N.

Abstract

Additional file 6: Figure S2. Laboratory Values. Medians are represented by triangles, with an upward point for Zilucoplan and a downward point for Control, respectively. CRP, C-reactive protein; LDH, lactate dehydrogenase.

Published
2022
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23. Additional file 1 of Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial

Author

De Leeuw, Elisabeth, Van Damme, Karel F. A., Declercq, Jozefien, Bosteels, Cedric, Maes, Bastiaan, Tavernier, Simon J., Detalle, Laurent, Smart, Trevor, Glatt, Sophie, Debeuf, Nincy, Deckers, Julie, Lameire, Sahine, Vandecasteele, Stefaan J., De Neve, Nikolaas, Demedts, Ingel K., Govaerts, Elke, Knoop, Christiane, Vanhove, Karolien, Moutschen, Michel, Terryn, Wim, Depuydt, Pieter, Van Braeckel, Eva, Haerynck, Filomeen, Hendrickx, Tine C. J., Parrein, Vanessa, Lalla, Marianna, Brittain, Claire, and Lambrecht, Bart N.

Abstract

Additional file 1. Study protocol.

Published
2022
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24. Additional file 7 of Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial

Author

De Leeuw, Elisabeth, Van Damme, Karel F. A., Declercq, Jozefien, Bosteels, Cedric, Maes, Bastiaan, Tavernier, Simon J., Detalle, Laurent, Smart, Trevor, Glatt, Sophie, Debeuf, Nincy, Deckers, Julie, Lameire, Sahine, Vandecasteele, Stefaan J., De Neve, Nikolaas, Demedts, Ingel K., Govaerts, Elke, Knoop, Christiane, Vanhove, Karolien, Moutschen, Michel, Terryn, Wim, Depuydt, Pieter, Van Braeckel, Eva, Haerynck, Filomeen, Hendrickx, Tine C. J., Parrein, Vanessa, Lalla, Marianna, Brittain, Claire, and Lambrecht, Bart N.

Abstract

Additional file 7: Table S1. Primary and supportive endpoints in the full analysis data set. LSMean, least square mean; PaO2, arterial partial pressure of oxygen; FiO2, fraction of inspired oxygen; PaO2, partial pressure of arterial oxygen; ARDS, acute respiratory distress syndrome; CRP, C-reactive protein; CI, confidence interval; SD, standard deviation. *Based on the highest temperature in 24 h. Table S2. Follow-up endpoints. SD, standard deviation; DLCO, diffusing capacity of lung for carbon monoxide; HRCT, high-resolution computed tomography; WHO, world health organisation. 6-point ordinal scale: 2 on invasive mechanical ventilation; 3 on non-invasive ventilation or high flow oxygen devices; 4 hospitalized, requiring supplemental oxygen; 5 hospitalized, not requiring supplemental oxygen, 6 not hospitalized.

Published
2022
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25. Additional file 3 of Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial

Author

De Leeuw, Elisabeth, Van Damme, Karel F. A., Declercq, Jozefien, Bosteels, Cedric, Maes, Bastiaan, Tavernier, Simon J., Detalle, Laurent, Smart, Trevor, Glatt, Sophie, Debeuf, Nincy, Deckers, Julie, Lameire, Sahine, Vandecasteele, Stefaan J., De Neve, Nikolaas, Demedts, Ingel K., Govaerts, Elke, Knoop, Christiane, Vanhove, Karolien, Moutschen, Michel, Terryn, Wim, Depuydt, Pieter, Van Braeckel, Eva, Haerynck, Filomeen, Hendrickx, Tine C. J., Parrein, Vanessa, Lalla, Marianna, Brittain, Claire, and Lambrecht, Bart N.

Abstract

Additional file 3. Overview secondary and exploratory endpoints.

Published
2022
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26. TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C

Author

MIS-C Clinicians, Hoste, Levi, Roels, Lisa, Naesens, Leslie, Bosteels, Victor, Vanhee, Stijn, Dupont, Sam, Bosteels, Cedric, Browaeys, Robin, Vandamme, Niels, Verstaen, Kevin, Roels, Jana, Van Damme, Karel F A, Maes, Bastiaan, De Leeuw, Elisabeth, Declercq, Jozefien, Aegerter, Helena, Seys, Leen, Smole, Ursula, De Prijck, Sofie, Vanheerswynghels, Manon, Claes, Karlien, Debacker, Veronique, Van Isterdael, Gert, Backers, Lynn, Claes, Kathleen B M, Bastard, Paul, Jouanguy, Emmanuelle, Zhang, Shen-Ying, Mets, Gilles, Dehoorne, Joke, Vandekerckhove, Kristof, Schelstraete, Petra, Willems, Jef, Stordeur, Patrick, Janssens, Sophie, Beyaert, Rudi, Saeys, Yvan, Casanova, Jean-Laurent, Lambrecht, Bart N, Haerynck, Filomeen, Tavernier, Simon J, Daelemans, Siel, Pulmonary Medicine, Clinical sciences, Growth and Development, and Pediatrics

Subjects
Male, T-Lymphocytes, CHILDREN, LIPOPOLYSACCHARIDE, infectious diseases, Lymphocyte Activation, HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, DISEASE, pediatric SARS-CoV-2 infection, Monocytes, Cohort Studies, IFNγ signature, TIM3+ TRBV11-2 T cells, Medicine and Health Sciences, Immunology and Allergy, immunodysregulation syndrome, Child, Complement Activation, Hepatitis A Virus Cellular Receptor 2, Interleukin-15, B-Lymphocytes, Superantigens, Patrolling, hemic and immune systems, Systemic Inflammatory Response Syndrome, Cell biology, Killer Cells, Natural, Interferon Type I, SHOCK, Cytokines, Female, Adolescent, MULTISYSTEM INFLAMMATORY SYNDROME, Immunology, Receptors, Antigen, T-Cell, CD16+ NK cells, MIS-C, SARS-COV-2, CD16, Biology, Article, Infectious Disease and Host Defense, Interferon-gamma, Humans, Pediatrics, Perinatology, and Child Health, Cell Proliferation, Inflammation, INTERFERON-GAMMA, SARS-CoV-2, Receptors, IgG, Biology and Life Sciences, COVID-19, Immunity, Humoral, Enterocytes, patrolling monocytes, BARRIER FUNCTION, Alveolar Epithelial Cells, Blood Vessels, Signature (topology)
Abstract

MIS-C is a novel immunodysregulation syndrome in children with a history of SARS-CoV-2 infection. This study employs a multi-omics approach to explore its immunopathogenesis. The authors show that IFNγ-mediated interactions between T cells, monocytes, and NK cells reside at the heart of the disease., In rare instances, pediatric SARS-CoV-2 infection results in a novel immunodysregulation syndrome termed multisystem inflammatory syndrome in children (MIS-C). We compared MIS-C immunopathology with severe COVID-19 in adults. MIS-C does not result in pneumocyte damage but is associated with vascular endotheliitis and gastrointestinal epithelial injury. In MIS-C, the cytokine release syndrome is characterized by IFNγ and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFNγ levels correlate with granzyme B production in CD16+ NK cells and TIM3 expression on CD38+/HLA-DR+ T cells. Single-cell TCR profiling reveals a skewed TCRβ repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3+/CD38+/HLA-DR+ T cells. Using NicheNet, we confirm IFNγ as a central cytokine in the communication between TIM3+/CD38+/HLA-DR+ T cells, CD16+ NK cells, and patrolling monocytes. Normalization of IFNγ, loss of TIM3, quiescence of CD16+ NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis., Graphical Abstract

Published
2021
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27. The STE-20 kinase TAOK3 regulates obesity-associated metabolism and type 2 immunity in murine adipose tissue

Author

Hammad Hamida, Descamps Benedicte, Vanhove Christian, Lornet Guillaume, Van Moorleghem Justine, De Wolf Caroline, De Prijck Sofie, Vanheerswynghels Manon, Catrysse Leen, Velde Evelien Van De, Deswarte Kim, Maes Bastiaan, Janssens Sophie, N Lambrecht Bart, and Fayazpour Farzaneh

Subjects
Kinase, medicine, Adipose tissue, Metabolism, Type 2 immunity, Biology, medicine.disease, Obesity, Cell biology
Published
2021
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28. Early treatment with inhaled GM-CSF improves oxygenation and anti-viral immunity in COVID-19 induced lung injury – a randomized clinical trial

Author

Lambrecht, Bart, primary, Damme, Karel Van, additional, De Leeuw, Elisabeth, additional, Declercq, Jozefien, additional, Maes, Bastiaan, additional, Bosteels, Victor, additional, Hoste, Levi, additional, Naesens, Leslie, additional, Debeuf, Nincy, additional, Deckers, Julie, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Weygaerde, Yannick Vande, additional, Malfait, Thomas, additional, Vandecasteele, Stefaan, additional, Demedts, Ingel, additional, Slabbynck, Hans, additional, Allard, Sabine, additional, Depuydt, Pieter, additional, Braeckel, Eva Van, additional, De Clercq, Jozefien, additional, Martens, Liesbet, additional, Dupont, Sam, additional, Seurinck, Ruth, additional, Vandamme, Niels, additional, Haerynck, Filomeen, additional, Roychowdhury, Debasish, additional, Vandekerckhove, Linos, additional, Guilliams, Martin, additional, Tavernier, Simon, additional, and Bosteels, Cedric, additional

Published
2021
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29. Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19 : a meta-analysis

Author

The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, [missing], Domingo, Pere, Mur, Isabel, Mateo, Gracia María, Gutierrez, Maria del Mar, Pomar, Virginia, de Benito, Natividad, Corbacho, Noemí, Herrera, Silvia, Millan, Lucia, Muñoz, Jessica, Malouf, Jorge, Molas, Maria Ema, Asensi, Victor, Horcajada, Juan Pablo, Estrada, Vicente, Gutierrez, Felix, Torres, Ferran, Perez-Molina, Jose A, Fortun, Jesús, Villar, Luisa M, Hohenthal, Ulla, Marttila, Harri, Vuorinen, Tytti, Nordberg, Marika, Valtonen, Mika, Frigault, Matthew J, Mansour, Michael K, Patel, Naomi J, Fernandes, Ana, Harvey, Liam, Foulkes, Andrea S, Healy, Brian C, Shah, Ruta, Bensaci, Ana Maria, Woolley, Ann E., Nikiforow, Sarah, Lin, Nina, Sagar, Manish, Shrager, Harry, Huckins, David S., Axelrod, Matthew, Pincus, Michael D, Fleisher, Jorge, Lampa, Jon, Nowak, Piotr, Vesterbacka, Jan C., Rasmuson, Johan, Skorup, Paul, Janols, Helena, Niward, Katarina F, Chatzidionysiou, Katerina, Asgeirsson, Hilmir, Parke, Åsa, Blennow, Ola, Svensson, Anna-Karin, Aleman, Soo, Sönnerborg, Anders, Henter, Jan-Inge, Horne, Anna Carin, Al-Beidh, Farah, Angus, Derek, Annane, Djillali, Arabi, Yaseen, Beane, Abigail, Berry, Scott, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Buxton, Meredith, Cheng, Allen, Cove, Matt, De Jong, Menno, Derde, Lennie, Estcourt, Lise, Goossens, Herman, Gordon, Anthony, Green, Cameron, Haniffa, Rashan, Ichihara, Nao, Lamontagne, Francois, Lawler, Patrick, Litton, Ed, Marshall, John, McArthur, Colin, McAuley, Daniel, McGuinness, Shay, McVerry, Bryan, Montgommery, Stephanie, Mouncey, Paul, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane, Reyes, Felipe, Rowan, Kathryn, Saito, Hiroki, Santos, Marlene, Seymour, Chris, Shankar-Hari, Manu, Turgeon, Alexis, Turner, Anne, van Bentum-Puijk, Wilma, van de Veerdonk, Frank, Webb, Steve, Zarychanski, Ryan, Baillie, J Kenneth, Beasley, Richard, Cooper, Nichola, Fowler, Robert, Galea, James, Hills, Thomas, King, Andrew, Morpeth, Susan, Netea, Mihai, Ogungbenro, Kayode, Pettila, Ville, Tong, Steve, Uyeki, Tim, Youngstein, Taryn, Higgins, Alisa, Lorenzi, Elizabeth, Berry, Lindsay, Salama, Carlos, Rosas, Ivan O., Ruiz-Antorán, Belén, Muñez Rubio, Elena, Ramos Martínez, Antonio, Campos Esteban, José, Avendaño Solá, Cristina, Pizov, Reuven, Sanz Sanz, Jesus, Abad-Santos, Francisco, Bautista-Hernández, Azucena, García-Fraile, Lucio, Barrios, Ana, Gutiérrez Liarte, Ángela, Alonso Pérez, Tamara, Rodríguez-García, Sebastian C, Mejía-Abril, Gina, Prieto, Jose Carlos, Leon, Rafael, VEIGA, VIVIANE C., SCHEINBERG, PHILLIP, FARIAS, DANIELLE L.C., PRATS, JOÃO G., CAVALCANTI, ALEXANDRE B., MACHADO, FLAVIA R., ROSA, REGIS G., BERWANGER, OTÁVIO, AZEVEDO, LUCIANO C.P., LOPES, RENATO D., DOURADO, LETICIA K., CASTRO, CLAUDIO G., ZAMPIERI, FERNANDO G., AVEZUM, ALVARO, LISBOA, THIAGO C., ROJAS, SALOMÓN S.O., COELHO, JULIANA C., LEITE, RODRIGO T., CARVALHO, JULIO CESAR, ANDRADE, LUIS E.C., SANDES, ALEX R., PINTÃO, MARIA CAROLINA T., SANTOS, SUELI V., ALMEIDA, THIAGO M.L., COSTA, ANDRÉ N., GEBARA, OTAVIO C.E., FREITAS, FLAVIO G.R., PACHECO, EDUARDO S., MACHADO, DAVID J.B., MARTIN, JOSIANE, CONCEIÇÃO, FABIO G., SIQUEIRA, SUELLEN R.R., DAMIANI, LUCAS P., ISHIHARA, LUCIANA M., SCHNEIDER, DANIEL, DE SOUZA, DENISE, Hermine, Olivier, Mariette, Xavier, Tharaux, Pierre Louis, Resche Rigon, Matthieu, Porcher, Raphael, Ravaud, Philippe, Azoulay, Elie, Cadranel, Jacques, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Lacombe, Karine, Mahevas, Matthieu, Pene, Frédéric, Pourchet-Martinez, Valérie, Schlemmer, Frédéric, Tibi, Annick, Yazdanpanah, Yazdan, Dougados, Maxime, Bureau, Serge, Horby, Peter W, Landray, Martin J, Baillie, Kenneth J, Buch, Maya H, Chappell, Lucy C, Day, Jeremy N, Faust, Saul N, Haynes, Richard, Jaki, Thomas, Jeffery, Katie, Juszczak, Edmund, Lim, Wei Shen, Mafham, Marion, Montgomery, Alan, Mumford, Andrew, Thwaites, Guy, Kamarulzaman, Adeeba, Syed Omar, Sharifah Faridah, Ponnampalavanar, Sasheela, Raja Azwa, Raja Iskandar Syah, Wong, Pui Li, Kukreja, Anjanna, Ong, Hang Cheng, Sulaiman, Helmi, Basri, Sazali, Ng, Rong Xiang, Megat Johari, Bushra, Rajasuriar, Reena, Chong, Meng Li, Neelamegam, Malinee, Syed Mansor, Syed Mukhtar, Zulhaimi, Nurul Syuhada, Lee, Cheng Siang, Altice, Frederick, Price, Christina, Malinis, Maricar, Hasan, Mohd Shahnaz, Wong, Chee Kuan, Chidambaram, Suresh, Misnan, Nor Arisah, Mohd Thabit, Alif Adlan, Sim, Benedict, Bidin, Farah Nadiah, Mohd Abd Rahim, Mohd Abd Hafiz, Saravanamuttu, Sujana, Tuang, Wei Xuan, Mohamed Gani, Yasmin, Thangavelu, Suvintheran, Tay, Kim Heng, Ibrahim, Nur Munirah, Halid, Luqman Alhakim, Tan, Kok Tong, Mukri, Mohd Noor Azreet, Arip, Masita, Koh, Hui Moon, Syed Badaruddin, Syarifah Nurul Ain, Raja Sureja, Letchumi, Chun, Geok Ying, TORRE-CISNEROS, JULIAN, MERCHANTE, NICOLAS, LEON, RAFAEL, CARCEL, SHEILA, GARRIDO, JOSE CARLOS, Galun, Eitan, Soriano, Alex, Martínez, José Antonio, Castán, Clara, Paredes, Roger, Dalmau, David, Carbonell, Cristina, Espinosa, Gerard, Castro, Pedro, Muñóz, José, Almuedo, Alex, Prieto, Sergio, Pacheco, Iván, Ratain, Mark, Pisano, Jennifer, Strek, Mary, Adegunsoye, Ayodeji, Karrison, Theodore, Declercq, Jozefien, Van Damme, Karel, De Leeuw, Elisabeth, Bosteels, Cedric, Maes, Bastiaan, Vale, Claire L., Godolphin, Peter J., Fisher, David, Higgins, Julian P. T., Spiga, Francesca, Savovic, Jelena, Tierney, Jayne, Baron, Gabriel, Benbenishty, Julie S., Berry, Lindsay R., Broman, Niklas, Cavalcanti, Alexandre Biasi, Colman, Roos, De Buyser, Stefanie, Derde, Lennie P. G., Omar, Sharifah Faridah, Fernandez-Cruz, Ana, Feuth, Thijs, Garcia, Felipe, Garcia-Vicuna, Rosario, Gonzalez-Alvaro, Isidoro, Gordon, Anthony C., Horby, Peter W., Horick, Nora K., Kumar, Kuldeep, Lambrecht, Bart, Landray, Martin J., Leal, Lorna, Lederer, David J., Merchante, Nicolas, Mohan, Shalini V., Nivens, Michael C., Oksi, Jarmo, Perez-Molina, Jose A., Postma, Simone, Ramanan, Athimalaipet V., Reid, Pankti D., Rutgers, Abraham, Sancho-Lopez, Aranzazu, Seto, Todd B., Sivapalasingam, Sumathi, Soin, Arvinder Singh, Staplin, Natalie, Stone, John H., Strohbehn, Garth W., Sunden-Cullberg, Jonas, Torre-Cisneros, Julian, Tsai, Larry W., van Hoogstraten, Hubert, van Meerten, Tom, Veiga, Viviane Cordeiro, Westerweel, Peter E., Diaz, Janet V., Marshall, John C., Sterne, Jonathan A. C., Translational Immunology Groningen (TRIGR), Stem Cell Aging Leukemia and Lymphoma (SALL), World Health Organization, and Group, WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working

Subjects
Male, medicine.medical_specialty, Randomization, Secondary infection, Placebo, Antibodies, Monoclonal, Humanized, Internal medicine, Cause of Death, Medicine and Health Sciences, Medicine, Humans, Prospective Studies, Prospective cohort study, Glucocorticoids, METAANALYSIS, Cause of death, Aged, Randomized Controlled Trials as Topic, business.industry, Coinfection, Interleukin-6, COVID-19, Odds ratio, General Medicine, Middle Aged, Respiration, Artificial, COVID-19 Drug Treatment, Clinical trial, Hospitalization, Meta-analysis, Disease Progression, Drug Therapy, Combination, Female, business
Abstract

[Importance] Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm., [Objective] To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes., [Data Sources] Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts., [Study Selection] Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria., [Data Extraction and Synthesis] In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance–weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality., [Main Outcomes and Measures] The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days., [Results] A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P, [Conclusions and Relevance] In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality., [Trial Registration] PROSPERO Identifier: CRD42021230155., Funding for administrative and communications support was provided by the World Health Organization.

Published
2021

30. Case Report: Convalescent Plasma, a Targeted Therapy for Patients with CVID and Severe COVID-19

Author

Van Damme, Karel F. A., primary, Tavernier, Simon, additional, Van Roy, Nele, additional, De Leeuw, Elisabeth, additional, Declercq, Jozefien, additional, Bosteels, Cédric, additional, Maes, Bastiaan, additional, De Bruyne, Marieke, additional, Bogaert, Delfien, additional, Bosteels, Victor, additional, Hoste, Levi, additional, Naesens, Leslie, additional, Maes, Piet, additional, Grifoni, Alba, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Depuydt, Pieter, additional, Van Braeckel, Eva, additional, Haerynck, Filomeen, additional, and Lambrecht, Bart N., additional

Published
2020
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31. TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C

Author

Hoste, Levi, Roels, Lisa, Naesens, Leslie, Bosteels, Victor, Vanhee, Stijn, Dupont, Sam, Bosteels, Cedric, Browaeys, Robin, Vandamme, Niels, Verstaen, Kevin, Roels, Jana, Van Damme, Karel F.A., Maes, Bastiaan, De Leeuw, Elisabeth, Declercq, Jozefien, Aegerter, Helena, Seys, Leen, Smole, Ursula, De Prijck, Sofie, Vanheerswynghels, Manon, Claes, Karlien, Debacker, Veronique, Van Isterdael, Gert, Backers, Lynn, Claes, Kathleen B.M., Bastard, Paul, Jouanguy, Emmanuelle, Zhang, Shen-Ying, Mets, Gilles, Dehoorne, Joke, Vandekerckhove, Kristof, Schelstraete, Petra, Willems, Jef, Stordeur, Patrick, Janssens, Sophie, Beyaert, Rudi, Saeys, Yvan, Casanova, Jean-Laurent, Lambrecht, Bart N., Haerynck, Filomeen, and Tavernier, Simon J.

Abstract

In rare instances, pediatric SARS-CoV-2 infection results in a novel immunodysregulation syndrome termed multisystem inflammatory syndrome in children (MIS-C). We compared MIS-C immunopathology with severe COVID-19 in adults. MIS-C does not result in pneumocyte damage but is associated with vascular endotheliitis and gastrointestinal epithelial injury. In MIS-C, the cytokine release syndrome is characterized by IFNγ and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFNγ levels correlate with granzyme B production in CD16+ NK cells and TIM3 expression on CD38+/HLA-DR+ T cells. Single-cell TCR profiling reveals a skewed TCRβ repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3+/CD38+/HLA-DR+ T cells. Using NicheNet, we confirm IFNγ as a central cytokine in the communication between TIM3+/CD38+/HLA-DR+ T cells, CD16+ NK cells, and patrolling monocytes. Normalization of IFNγ, loss of TIM3, quiescence of CD16+ NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis.

Published
2022
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32. Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial

Author

Benoit Misset, Hans Slabbynck, Ursula Smole, Linos Vandekerckhove, Nicolas Dauby, Helena Catharine Aegerter, Nicolas De Schryver, Jozefien Declercq, Catherine Legrand, Levi Hoste, Gil Verschelden, Fre Bauters, Xavier Wittebole, Bastiaan Maes, Eva Van Braeckel, Sébastien Anguille, Catherine Van Der Straeten, Marc Buyse, Sylvie Rottey, Tom Fivez, Dieter Stevens, Stefaan J. Vandecasteele, Maya Hites, Elke Govaerts, I Peene, Karel Van Damme, Simon Tavernier, Frank Hulstaert, Roos Colman, Stefanie De Buyser, Elisabeth De Leeuw, Jeroen Van der Hilst, Filip Moerman, Fabienne Liénart, Leen J M Seys, Leslie Naesens, Filomeen Haerynck, Ingel K. Demedts, Cedric Bosteels, Victor Bosteels, Pieter Depuydt, Johan Van Laethem, Bart N. Lambrecht, Internal Medicine, Supporting clinical sciences, Faculty of Medicine and Pharmacy, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (SLuc) Service de soins intensifs, UCL - SSH/LIDAM/ISBA - Institut de Statistique, Biostatistique et Sciences Actuarielles, Van Laethem, Johan/0000-0002-2490-216X, Hoste, Levi/0000-0001-9733-1049, Naesens, Leslie/0000-0003-1715-0665, Declercq , Jozefien, Van Damme, Karel F. A., De Leeuw, Elisabeth, Maes, Bastiaan, Bosteels, Cedric, Tavernier, Simon J., De Buyser, Stefanie, Colman, Roos, Hites, Maya, Verschelden, Gil, Fivez, Tom, Moerman , Filip, Demedts, Ingel K., Dauby, Nicolas, De Schryver, Nicolas, Govaerts , Elke, Vandecasteele, Stefaan J., Van Laethem, Johan, Anguille, Sebastien, VAN DER HILST, Jeroen, Misset, Benoit, Slabbynck, Hans, Wittebole, Xavier, Lienart, Fabienne, LEGRAND, Catherine, BUYSE, Marc, Stevens, Dieter, Bauters, Fre, Seys, Leen J. M., Aegerter, Helena, Smole, Ursula, Bosteels, Victor, Hoste , Levi, Naesens, Leslie, Haerynck, Filomeen, Vandekerckhove, Linos, Depuydt, Pieter, van Braeckel, Eva, Rottey, Sylvie, Peene, Isabelle, Van Der Straeten, Catherine, Hulstaert, Frank, and Lambrecht, Bart N.

Subjects
Male, Pulmonary and Respiratory Medicine, Population, Antibodies, Monoclonal, Humanized, law.invention, Belgium, Randomized controlled trial, law, Fraction of inspired oxygen, medicine, Humans, Prospective Studies, Hypoxia, education, Aged, education.field_of_study, Interleukin-6, SARS-CoV-2, business.industry, Comment, Hazard ratio, COVID-19, Antibodies, Monoclonal, Middle Aged, medicine.disease, COVID-19 Drug Treatment, Blockade, Oxygen, Cytokine release syndrome, Treatment Outcome, Respiratory failure, Anesthesia, Ferritins, Female, SOFA score, Human medicine, Cytokine Release Syndrome, Respiratory Insufficiency, business, Interleukin-1
Abstract

Background Infections with SARS-CoV-2 continue to cause significant morbidity and mortality. Interleukin (IL)-1 and IL-6 blockade have been proposed as therapeutic strategies in COVID-19, but study outcomes have been conflicting. We sought to study whether blockade of the IL-6 or IL-1 pathway shortened the time to clinical improvement in patients with COVID-19, hypoxic respiratory failure, and signs of systemic cytokine release syndrome. Methods We did a prospective, multicentre, open-label, randomised, controlled trial, in hospitalised patients with COVID-19, hypoxia, and signs of a cytokine release syndrome across 16 hospitals in Belgium. Eligible patients had a proven diagnosis of COVID-19 with symptoms between 6 and 16 days, a ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO2:FiO(2)) of less than 350 mm Hg on room air or less than 280 mm Hg on supplemental oxygen, and signs of a cytokine release syndrome in their serum (either a single ferritin measurement of more than 2000 mu g/L and immediately requiring high flow oxygen or mechanical ventilation, or a ferritin concentration of more than 1000 mu g/L, which had been increasing over the previous 24 h, or lyrnphopenia below 800/mL with two of the following criteria: an increasing ferritin concentration of more than 700 mu g/L, an increasing lactate dehydrogenase concentration of more than 300 international units per L, an increasing C-reactive protein concentration of more than 70 mg/L, or an increasing D-dimers concentration of more than 1000 ng/mL). The COV-AID trial has a 2 x 2 factorial design to evaluate IL-1 blockade versus no IL-1 blockade and IL-6 blockade versus no IL-6 blockade. Patients were randomly assigned by means of permuted block randomisation with varying block size and stratification by centre. In a first randomisation, patients were assigned to receive subcutaneous anakinra once daily (100 mg) for 28 days or until discharge, or to receive no IL-1 blockade (1:2). In a second randomisation step, patients were allocated to receive a single dose of siltuximab (11 mg/kg) intravenously, or a single dose of tocilizumab (8 mg/kg) intravenously, or to receive no IL-6 blockade (1:1:1). The primary outcome was the time to clinical improvement, defined as time from randomisation to an increase of at least two points on a 6-category ordinal scale or to discharge from hospital alive. The primary and supportive efficacy endpoints were assessed in the intention-to-treat population. Safety was assessed in the safety population. This study is registered online with ClinicalTrials.gov (NCT04330638) and EudraCT (2020-001500-41) and is complete. Findings Between April 4, and Dec 6,2020,342 patients were randomly assigned to IL-1 blockade n=112) or no IL-1 blockade (n=230) and simultaneously randomly assigned to IL-6 blockade (n=227; 114 for tocilizumab and 113 for siltuximab) or no IL-6 blockade (n=115). Most patients were male (265 [77%] of 342), median age was 65 years (IQR 54-73), and median Systematic Organ Failure Assessment (SOFA) score at randomisation was 3 (2-4). All 342 patients were included in the primary intention-to-treat analysis. The estimated median time to clinical improvement was 12 days (95% CI 10-16) in the IL-1 blockade group versus 12 days (10-15) in the no IL-1 blockade group (hazard ratio [HR] 0.94 [95% CI 0.73-1.21]). For the IL-6 blockade group, the estimated median time to clinical improvement was 11 days (95% CI 10-16) versus 12 days (11-16) in the no IL-6 blockade group (HR 1.00[0-78-1-29]). 55 patients died during the study, but no evidence for differences in mortality between treatment groups was found. The incidence of serious adverse events and serious infections was similar across study groups. Interpretation Drugs targeting IL-1 or IL-6 did not shorten the time to clinical improvement in this sample of patients with COVID-19, hypoxic respiratory failure, low SOFA score, and low baseline mortality risk. Copyright (C) 2021 Elsevier Ltd. All rights reserved. Belgian Health Care Knowledge Center; VIB Grand Challenges program The authors acknowledge professional support and committed efforts from various organisations and individuals involved in this trial and thank all trial participants and clinicians involved in patient recruitment at the different participating sites. This study was funded by KCE, and KCE was involved in various aspects of the study design, management, and execution (Nelle Stocquart, Jillian Harrison). The VIB Grand Challenges Program (Sofie Bekaert) funded measurements of cytokines and the Ghent University Special Research Fund (BOF) supported the clinical follow-up of patients at Ghent University Hospital (UZ Ghent). The clinical trial team of the Department of Respiratory Medicine at UZ Ghent (Stefanie Vermeersch, Benedicte Demeyere, Anja Delporte) were involved in protocol development, amendment filing, and eCRF construction. The Health Innovation and Research Institute of UZ Ghent was involved in eCRF design, protocol design, ethical committee reporting, drug dispensing, trial monitoring, data cleaning, and sponsor site management (Charlotte Clauwaert, Dries Loncke, Hanife Kokur, Lieselot Van Landuyt, Joke Tommelein, Hélène De Naeyer). The hospital pharmacy of UZ Ghent dispensed drugs to all study sites (Els Kestens). Team members of the Primary Immune Deficiency laboratory (Karlien Claes, Veronique Debacker, Lisa Roels, Zara Declercq) handled samples from all study sites. The authors acknowledge the insights of the data safety monitoring board (Drs Renaat Peleman, Geert Leroux-Roels, Steven Callens, Frank Vermassen, Piet Hoebeke, Karim Vermaelen, A Dupont, Tomasz Burzykowski, and Marnik Vuylsteke under the chairmanship of SR).

Published
2021
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33. Range of motion in femoroacetabular impingement.

Author

Audenaert E, Van Houcke J, Maes B, Vanden Bossche L, Victor J, and Pattyn C

Subjects
Adolescent, Adult, Asymptomatic Diseases, Femoracetabular Impingement diagnostic imaging, Femoracetabular Impingement physiopathology, Humans, Male, Radiography, Young Adult, Femoracetabular Impingement diagnosis, Hip Joint physiopathology, Range of Motion, Articular
Abstract

Recent epidemiological studies have demonstrated that radiographic features specific to femoroacetabular impingement appear far more frequently in healthy and asymptomatic cohorts than previously anticipated. It remains unclear how incidental findings should be interpreted clinically. In addition, several authors have suggested that a decreased range of motion is part of the clinical presentation of femoroacetabular impingement. The purpose of the present study was to describe and analyze differences in range of motion between femoroacetabular impingement patients, asymptomatic individuals with incidental radiographic findings and healthy controls, using a validated electromagnetic tracking system. Furthermore, it was evaluated which motions were clinically relevant and could be used to differentiate between these three groups. We found all evaluated motions to differ significantly between patients and controls. The anterior impingement test showed a significant difference between patients and asymptomatic cases. In conclusion, functional evaluation of the range of motion appeared in this study as a useful tool in the diagnostic work-up of femoracetabular impingement.

Published
2012

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