Brandon Michael Henry1, Stefanie W Benoit2,3, Jens Vikse4, Brandon A Berger5, Christina Pulvino5, Jonathan Hoehn5, James Rose2, Maria Helena Santos de Oliveira6, Giuseppe Lippi7, Justin L Benoit5. 1. Cardiac Intensive Care Unit, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. 2. Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. 3. Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, USA. 4. Clinical Immunology Unit, Stavanger University Hospital, Stavanger, Norway. 5. Department of Emergency Medicine, University of Cincinnati, Cincinnati, OH, USA. 6. Department of Statistics, Federal University of Parana, Curitiba, Brazil. 7. Department of Neuroscience, Biomedicine and Movement, Section of Clinical Biochemistry, University of Verona, Verona, Italy.
Abstract
OBJECTIVES: Severe coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response. The aim of this study was to evaluate the anti-inflammatory cytokine response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with outcomes. METHODS: Adult patients presenting to the emergency department (ED) with laboratory-confirmed COVID-19 were recruited. The primary endpoint was maximum COVID-19 severity within 30 days of index ED visit. RESULTS: A total of 52 COVID-19 patients were enrolled. IL-10 and IL-10/lymphocyte count were significantly higher in patients with severe disease (p<0.05), as well as in those who developed severe acute kidney injury (AKI) and new positive bacterial cultures (all p≤0.01). In multivariable analysis, a one-unit increase in IL-10 and IL-10/lymphocyte count were associated with 42% (p=0.031) and 32% (p=0.013) increased odds, respectively, of severe COVID-19. When standardized to a one-unit standard deviations scale, an increase in the IL-10 was a stronger predictor of maximum 30-day severity and severe AKI than increases in IL-6 or IL-8. CONCLUSIONS: The hyperinflammatory response to COVID-19 is accompanied by a simultaneous anti-inflammatory response, which is associated with poor outcomes and may increase the risk of new positive bacterial cultures. IL-10 and IL-10/lymphocyte count at ED presentation were independent predictors of COVID-19 severity. Moreover, elevated IL-10 was more strongly associated with outcomes than pro-inflammatory IL-6 or IL-8. The anti-inflammatory response in COVID-19 requires further investigation to enable more precise immunomodulatory therapy against SARS-CoV-2.
OBJECTIVES: Severe coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response. The aim of this study was to evaluate the anti-inflammatory cytokine response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with outcomes. METHODS: Adult patients presenting to the emergency department (ED) with laboratory-confirmed COVID-19 were recruited. The primary endpoint was maximum COVID-19 severity within 30 days of index ED visit. RESULTS: A total of 52 COVID-19patients were enrolled. IL-10 and IL-10/lymphocyte count were significantly higher in patients with severe disease (p<0.05), as well as in those who developed severe acute kidney injury (AKI) and new positive bacterial cultures (all p≤0.01). In multivariable analysis, a one-unit increase in IL-10 and IL-10/lymphocyte count were associated with 42% (p=0.031) and 32% (p=0.013) increased odds, respectively, of severe COVID-19. When standardized to a one-unit standard deviations scale, an increase in the IL-10 was a stronger predictor of maximum 30-day severity and severe AKI than increases in IL-6 or IL-8. CONCLUSIONS: The hyperinflammatory response to COVID-19 is accompanied by a simultaneous anti-inflammatory response, which is associated with poor outcomes and may increase the risk of new positive bacterial cultures. IL-10 and IL-10/lymphocyte count at ED presentation were independent predictors of COVID-19 severity. Moreover, elevated IL-10 was more strongly associated with outcomes than pro-inflammatory IL-6 or IL-8. The anti-inflammatory response in COVID-19 requires further investigation to enable more precise immunomodulatory therapy against SARS-CoV-2.
Authors: Brandon M Henry; György Sinkovits; Ivan Szergyuk; Maria Helena Santos de Oliveira; Giuseppe Lippi; Justin L Benoit; Emmanuel J Favaloro; Naomi Pode-Shakked; Stefanie W Benoit; David S Cooper; Veronika Müller; Zsolt Iványi; János Gál; Marienn Réti; László Gopcsa; Péter Reményi; Beáta Szathmáry; Botond Lakatos; János Szlávik; Ilona Bobek; Zita Z Prohászka; Zsolt Förhécz; Dorottya Csuka; Lisa Hurler; Erika Kajdácsi; László Cervenak; Blanka Mező; Petra Kiszel; Tamás Masszi; István Vályi-Nagy; Zoltán Prohászka Journal: Front Med (Lausanne) Date: 2022-04-29
Authors: Rafaela Pires da Silva; João Ismael Budelon Gonçalves; Rafael Fernandes Zanin; Felipe Barreto Schuch; Ana Paula Duarte de Souza Journal: Front Immunol Date: 2021-05-12 Impact factor: 7.561
Authors: Brandon Michael Henry; Ivan Szergyuk; Maria Helena Santos de Oliveira; Giuseppe Lippi; Justin L Benoit; Jens Vikse; Stefanie W Benoit Journal: J Med Virol Date: 2021-05-19 Impact factor: 20.693
Authors: Eunyoung Emily Lee; Kyoung-Ho Song; Woochang Hwang; Sin Young Ham; Hyeonju Jeong; Jeong-Han Kim; Hong Sang Oh; Yu Min Kang; Eun Bong Lee; Nam Joong Kim; Bum Sik Chin; Jin Kyun Park Journal: Sci Rep Date: 2021-04-13 Impact factor: 4.379
Authors: Maria Teresa Sandri; Elena Azzolini; Valter Torri; Sara Carloni; Chiara Pozzi; Michela Salvatici; Michele Tedeschi; Massimo Castoldi; Alberto Mantovani; Maria Rescigno Journal: Sci Rep Date: 2021-06-10 Impact factor: 4.379