Cytokine Kinetics during Progression of COVID-19 in Rwanda Patients: Could IL-9/IFNγ Ratio Predict Disease Severity?

Ella Larissa Ndoricyimpaye; Jacques Van Snick; Rutayisire Robert; Emmanuel Bikorimana; Onesphore Majyambere; Enatha Mukantwari; Thaddée Nshimiyimana; Valens Mbonigaba; Jean Paul Coutelier; Nadine Rujeni

doi:10.3390/ijms241512272

Cytokine Kinetics during Progression of COVID-19 in Rwanda Patients: Could IL-9/IFNγ Ratio Predict Disease Severity?

Int J Mol Sci. 2023 Jul 31;24(15):12272. doi: 10.3390/ijms241512272.

Authors

Affiliations

¹ Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3248, Rwanda.
² de Duve Institute, Université Catholique de Louvain, 1348 Brussels, Belgium.
³ Ludwig Institute for Cancer Research, Universite Catholique de Louvain, 1348 Brussels, Belgium.
⁴ National Reference Laboratory, Rwanda Biomedical Center, Kigali P.O. Box 4285, Rwanda.
⁵ Department of General Nursing, School of Nursing, College of Medicine and Health Science, University of Rwanda, Kigali P.O. Box 3248, Rwanda.

Abstract

For effective treatments and preventive measures against severe COVID-19, it is essential to determine early markers of disease severity in different populations. We analysed the cytokine kinetics of 129 COVID-19 patients with mild symptoms, 68 severe cases, and 20 healthy controls for the first time in Rwanda. Pro-inflammatory (IFNγ, IL-6, TNFα), Treg (IL-10, TGFβ1, TGFβ3), Th9 (IL-9), Th17 (IL-17), and Th2 (IL-4, IL-13) cytokines, total IgM and IgG, as well as gene expressions of FoxP3, STAT5+, IFNγ-R1, and ROR alpha+, were measured at day 1, day 7, day 14, day 21, and day 28 post-infection. Severe cases showed a significantly stronger increase than mild patients in levels of all cytokines (except IL-9) and all gene expression on day 1 of infection. Some cytokine levels dropped to levels comparable to mild cases at later time points. Further analysis identified IFNγ as a marker of severity throughout the disease course, while TGFβ1, IL-6, and IL-17 were markers of severity only at an early phase. Importantly, this study revealed a striking low IL-9 level and high IFNγ/IL-9 ratio in the plasma of patients who later died compared to mild and severe cases who recovered, suggesting that this could be an important biomarker for predicting the severity of COVID-19 and post-COVID-19 syndrome.

Keywords: IFNγ; IL-9; SARS-CoV-2; biomarkers; immune response.

MeSH terms

COVID-19*
Cytokines* / genetics
Humans
Interferon-gamma
Interleukin-17 / genetics
Interleukin-6
Interleukin-9 / genetics
Kinetics
Patient Acuity
Post-Acute COVID-19 Syndrome
Rwanda / epidemiology

Substances

Cytokines
Interleukin-17
Interleukin-9
Interleukin-6
Interferon-gamma

Grants and funding

This research was commissioned by the National Institute for Health Research (NIHR) Global Health Research programme (16/136/33) using UK aid from the UK Government (funding to E.L.N. and N.R.). It was also funded by institutional support to the University of Rwanda and Project Research in Development programmes from ARES-CCD (funding to E.L.N., J.P.C., and N.R.). The views expressed in this publication are those of the authors and not necessarily those of ARES-CCD, the NIHR, or the UK Department of Health and Social Care.