Background <p>Understanding the factors that influence clinical outcomes of COVID-19 and the safety of various vaccines is important to inform public health strategies, particularly in diverse communities. This study aimed to assess the factors affecting the clinical outcomes of COVID-19 and vaccination safety among the Egyptian population.</p> Methods <p>In a retrospective study, we examined 1597 patients who tested positive for COVID-19. Among them, 1280 patients had received the vaccination, while 317 patients had not. We collected data from medical records, which included clinical characteristics, comorbidities, disease severity, type of vaccination, and adverse hematological effects postvaccination. We calculated the relative risk, odds ratio, and 95% confidence intervals (CIs).</p> Results <p>Among the 1,597 COVID-19 cases, 74.1% were mild, 24.8% were moderate, and 1.1% were severe. Significant factors for moderate/severe cases included male sex (RR 0.78, 95% CI 0.64–0.95), cardiovascular diseases (RR 1.86, 95% CI 1.32–2.64), respiratory diseases (RR 1.40, 95% CI 1.08–1.82), diabetes mellitus (RR 1.41, 95% CI 1.07–1.86), and previous COVID-19 infection (RR 1.22, 95% CI 1.02–1.46). Vaccination reduced the severity risk, with BBIBP-CorV (Sinopharm) showing a significant protective effect (OR 0.78, 95% CI 0.62–0.98). Clinical presentations varied, with 97.6% having an oxygen saturation ≥ 92%. Logistic regression indicated that male sex and BBIBP-CorV (Sinopharm) vaccination were protective factors. Linear regression revealed that the male sex increased hemoglobin and leucocyte counts, whereas BBIBP-CorV (Sinopharm) decreased leucocyte and platelet counts.</p> Conclusion <p>Vaccination, particularly with BBIBP-CorV (Sinopharm), significantly reduces COVID-19 severity among Egyptians, despite various clinical presentations and hematological effects.</p> Clinical trial number <p>Not applicable.</p>