ObjectivesTo analyze variations in blood profile, the extent of hematological disorders, and the impact of comorbidities and COVID-19 vaccination on blood profile parameters and their clinical value for prognostic of SARS-CoV-2 infection. MethodsThis cross-sectional study took place in Douala, Cameroon. A complete blood count and molecular detection of SARS-CoV-2 were performed on patients. Clinical value was appraised using area under the curve (AUC) analysis. ResultsIn total, 420 participants were included. A significant reduction of hematological parameters such as lymphocytes (p < 0.0001), red blood cells (P = 0.0025), mean corpuscular hemoglobin count (P < 0.0001), and platelets (P = 0.02) was seen in SARS-CoV-2 (+) patients. Anisocytosis was the main hematological disorder (95.5%). Normocytic normochromic anemia was predominant in SARS-CoV-2 (+) (35.3%) while microcytic normochromic anemia was more frequently seen in SARS-CoV-2 (-) (16.5%). Neutrophil-to-lymphocyte (NLR) consistently showed statistically significant AUC ∼0.75 upon stratification for age, gender, and comorbidities, with the exception of COVID-19 vaccination uptake. ConclusionIn a context where molecular detection methods are difficultly affordable in health facilities in developing countries such as Cameroon, NLR could be clinically interesting for identifying SARS-CoV-2 infected individuals, especially those with comorbidities.