This study evaluated SARS-CoV-2 infection impacts on clinical characteristics, antibody levels, and immune responses in 100 malignant hematological tumor patients. Laboratory assessments included hematological, biochemical, and inflammatory markers. Multivariable analysis identified age (OR = 1.56, p = 0.004), chemotherapy cycles (OR = 1.86, p <
0.001), comorbidities (OR = 3.15, p = 0.015), WBC count (OR = 1.79, p = 0.016), CRP (OR = 2.07, p = 0.007), ferritin (OR = 1.22, p = 0.035), IL-6 (OR = 1.59, p = 0.001), IgG (OR = 2.28, p = 0.037), CD8+ T cells (OR = 2.97, p = 0.005), and NK cells (OR = 0.80, p = 0.019) as COVID-19 risk factors. COVID-19 patients showed significantly higher hospitalization (30.77% vs 10.42%, p = 0.007), ICU admission (23.08% vs 6.25%, p = 0.019), and lower 1-year survival (59.62% vs 87.50%, p = 0.002) versus controls. SARS-CoV-2 infection induces hematological/immune alterations and worsens clinical outcomes in hematological malignancy patients, emphasizing their heightened vulnerability.