AUTHOR=Wolday Dawit , Gebrehiwot Abrha G. , Le Minh An Nguyen , Rameto Muhammed Ahmed , Abdella Saro , Gebreegziabxier Atsbeha , Amogne Wondwossen , Rinke de Wit Tobias F. , Hailu Messay , Tollera Getachew , Tasew Geremew , Tessema Masresha , Miller Matthew , Gillgrass Amy , Bowdish Dawn M. E. , Kaushic Charu , Verschoor Chris P. 

TITLE=Distinct proteomic signatures in Ethiopians predict acute and long-term sequelae of COVID-19

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1575135

DOI=10.3389/fimmu.2025.1575135

ISSN=1664-3224

ABSTRACT=IntroductionLittle is known about the acute and long-term sequelae of COVID-19 and its pathophysiology in African patients, who are known to have a distinct immunological profile compared to Caucasian populations. Here, we established protein signatures to define severe outcomes of acute COVID-19 and determined whether unique protein signatures during the first week of acute illness predict the risk of post-acute sequelae of COVID-19 (Long COVID) in a low-income country (LIC) setting.MethodUsing the Olink inflammatory panel, we measured the abundance of 92 proteins in the plasma of COVID-19 patients (n=55) and non-COVID-19 individuals (n=23). We investigated distinct inflammatory protein signatures in acute severe COVID-19 individuals (n=22) compared to asymptomatic or mild/moderate COVID-19 cases (n=33), and non-COVID-19 controls.ResultsLevels of SLAMF1, CCL25, IL2RB, IL10RA, IL15RA, IL18 and CST5 were significantly upregulated in patients with critical COVID-19 illness compared to individuals negative for COVID-19. The cohort was followed for an average of 20 months, and 23 individuals developed Long COVID, based on the WHO’s case definition, while 32 COVID-19 patients recovered fully. Whereas upregulated levels of SLAMF1, TNF, TSLP, IL15RA, IL18, ADA, CXCL9, CXCL10, IL17C, and NT3 at the acute phase of the illness were associated with increased Long COVID risk, upregulated TRANCE was associated with a reduced risk of developing Long COVID. Protein levels of SLAMF1, IL15RA, and IL18 associated with critical illness during the acute phase of COVID-19 also predicted Long COVID risk.DiscussionPatients with severe COVID-19 and Long COVID outcomes exhibited distinct proteomic signatures. Unravelling the pathophysiology of severe acute COVID-19 and Long COVID before its advent may contribute to designing novel interventions for diagnosing, treating, and monitoring of SARS-CoV-2 infection and its associated acute and long-term consequences.