Little 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 proteomic signatures to define severe outcomes of acute COVID-19 and determined whether proteome 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. Using the Olink inflammatory panel, we measured the expression of 92 proteins in the plasma of COVID-19 patients (n=55) and non-COVID-19 individuals (n=23). We identified distinct inflammatory proteomic 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. Levels 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 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 expression of TRANCE was associated with a reduced risk of developing Long COVID. Proteomic expression levels of SLAMF1, IL15RA, and IL18 associated with critical illness during the acute phase of COVID-19 also predicted Long COVID risk. 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.
