{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T03:44:18Z","timestamp":1785815058060,"version":"3.56.0"},"reference-count":51,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Health Research (NIHR) Global Health Research programme","award":["16\/136\/33"],"award-info":[{"award-number":["16\/136\/33"]}]},{"name":"University of Rwanda and Project Research in Development programmes from ARES-CCD","award":["16\/136\/33"],"award-info":[{"award-number":["16\/136\/33"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 (IFN\u03b3, IL-6, TNF\u03b1), Treg (IL-10, TGF\u03b21, TGF\u03b23), 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+, IFN\u03b3-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 IFN\u03b3 as a marker of severity throughout the disease course, while TGF\u03b21, 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 IFN\u03b3\/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.<\/jats:p>","DOI":"10.3390\/ijms241512272","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T10:08:14Z","timestamp":1690798094000},"page":"12272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cytokine Kinetics during Progression of COVID-19 in Rwanda Patients: Could IL-9\/IFN\u03b3 Ratio Predict Disease Severity?"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5353-5493","authenticated-orcid":false,"given":"Ella Larissa","family":"Ndoricyimpaye","sequence":"first","affiliation":[{"name":"Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3248, Rwanda"},{"name":"de Duve Institute, Universit\u00e9 Catholique de Louvain, 1348 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Van Snick","sequence":"additional","affiliation":[{"name":"Ludwig Institute for Cancer Research, Universite Catholique de Louvain, 1348 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rutayisire","family":"Robert","sequence":"additional","affiliation":[{"name":"Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3248, Rwanda"},{"name":"National Reference Laboratory, Rwanda Biomedical Center, Kigali P.O. Box 4285, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Bikorimana","sequence":"additional","affiliation":[{"name":"Department of General Nursing, School of Nursing, College of Medicine and Health Science, University of Rwanda, Kigali P.O. Box 3248, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onesphore","family":"Majyambere","sequence":"additional","affiliation":[{"name":"Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3248, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4381-2098","authenticated-orcid":false,"given":"Enatha","family":"Mukantwari","sequence":"additional","affiliation":[{"name":"National Reference Laboratory, Rwanda Biomedical Center, Kigali P.O. Box 4285, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thadd\u00e9e","family":"Nshimiyimana","sequence":"additional","affiliation":[{"name":"Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3248, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valens","family":"Mbonigaba","sequence":"additional","affiliation":[{"name":"National Reference Laboratory, Rwanda Biomedical Center, Kigali P.O. Box 4285, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5681-8915","authenticated-orcid":false,"given":"Jean Paul","family":"Coutelier","sequence":"additional","affiliation":[{"name":"Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3248, Rwanda"},{"name":"de Duve Institute, Universit\u00e9 Catholique de Louvain, 1348 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Rujeni","sequence":"additional","affiliation":[{"name":"Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3248, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Adimulam, T., Arumugam, T., Gokul, A., and Ramsuran, V. (2023). Genetic Variants within SARS-CoV-2 Human Receptor Genes May Contribute to Variable Disease Outcomes in Different Ethnicities. Int. J. Mol. 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