Cecilia Elorm Lekpor ^1,2,3* Felix Botchway ⁴ Adel Driss ^5,6 Alaijah Bashi ⁶ Afua D Abrahams ^2,7 Kwadwo Asamoah Kusi ⁸ Godfred Futagbi ³ Ernest Alema-Mensah ⁹ William Agbozo ¹⁰ Wesley Solomon ¹⁰ Adriana Harbuzariu ¹¹ Andrew A Adjei ² Jonathan K. Stiles ^10*

• ¹ Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, United States
• ² Department of Pathology, Korle-Bu Teaching Hospital, University of Ghana Medical School, Accra, Ghana
• ³ Department of Animal Biology and Conservation Science, University of Ghana, Accra, Ghana
• ⁴ Accra Technical University, Accra, Greater Accra, Ghana
• ⁵ Morehouse School of Medicine, Atlanta, United States
• ⁶ Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia, United States
• ⁷ Korle Bu Teaching Hospital, Accra, Ghana
• ⁸ Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
• ⁹ Department of Community Health and Preventive Medicine, Morehouse School of Medicine, Atlanta, Colorado, United States
• ¹⁰ Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, Colorado, United States
• ¹¹ Emory Stem Cell Core, School of Medicine, Emory University, Atlanta, Georgia, United States

Sickle cell disease (SCD) is a genetic blood disorder caused by a mutation in the HBB gene, which encodes the beta-globin subunit of hemoglobin. This mutation leads to the production of abnormal hemoglobin S (HbS), causing red blood cells to deform into a sickle shape. These deformed cells can block blood flow, leading to complications like chronic hemolysis, anemia, severe pain episodes, and organ damage. SCD includes genotypes such as HbSS, HbSC (where HbC is another abnormal variant of hemoglobin), and HbS/β-thalassemia. Sickle cell trait (SCT), HbAS, represents the carrier state, while other hemoglobin variants include HbCC, HbAC, and the normal HbAA. Over 7.5 million people worldwide live with SCD, with a high mortality rate in sub-Saharan Africa, including Ghana. Despite its prevalence, SCD is underdiagnosed and poorly managed, especially in children. Characterized by intravascular hemolysis, SCD leads to oxidative stress, endothelial activation, and systemic inflammation. Identifying biomarkers indicative of organ damage and systemic processes is vital for understanding SCD and improving patient management. However, research on biomarkers in pediatric SCD in Ghana is limited. This study explores specific biomarkers in pediatric SCD in Ghana, hypothesizing that inflammatory and neuronal injury markers in children with SCD could predict disease outcomes. Clinical data were collected from 377 children aged 3-8 years with various Hb genotypes, including SCD and SCT, at Korle-Bu Teaching Hospital in Accra, Ghana (2021-2022). A total of 80 age- and sex-matched subjects were identified. A cross-sectional study utilized a multiplexed immunoassay to evaluate serum biomarkers, including cytokines, chemokines, vascular injury markers, systemic inflammation markers, cell-free heme scavengers, brain-derived neurotrophic factor (BDNF), and angiogenic factors. Elevated levels of BDNF, Ang-2, CXCL10, CCL11, TNF-α, IL-6, IL-10, IL12p40, ICAM-1, VCAM-1, Tie-2, and VEGFA were observed in HbSS subjects, correlating with hemoglobin, leukocyte, and erythrocyte counts. Heme scavengers like HO-1, hemopexin, and haptoglobin also correlated with these parameters. ROC and AUC analyses showed these markers' potential in predicting SCD outcomes. The findings suggest that a predictive algorithm for these biomarkers could improve SCD management and patient outcomes.