Hybrid and Vaccine-Induced Immunity Against SARS-CoV-2 in a Cohort of Hospitalized Patients from the Metropolitan Aburrá Valley, Colombia

Background: Despite hybrid and vaccine-induced immunity, SARS-CoV-2 continues to cause disease. The characterization of humoral and cellular immune responses is essential for guiding prevention strategies and booster dose policies; Methods: A prospective cohort study was conducted with 131 hospitalized patients with confirmed COVID-19 in the Aburrá Metropolitan Valley, Colombia. Clinical and immunological data were evaluated on days 1–3, days 5–7, days 8–12, and 4–5 months after diagnosis. Humoral immunity was assessed by enzyme-linked immunosorbent assay (ELISA), chemiluminescent microparticle immunoassay (CMIA), and neutralization testing, and cellular immunity by CD4+/CD8 T-cell responses. Results: vaccinated patients had higher baseline levels of IgG and neutralizing antibody positivity than unvaccinated patients (ELISA 89.1% vs. 60.0%; CMIA 86.4% vs. 50.0%; neutralizing antibodies 88.2% vs. 65.0%), but cases of severe disease occurred in both groups. Adults aged ≥65 years had higher antibody positivity, but severe disease persisted. Mortality at 28 days was 7.6%, mainly among critically ill patients with comorbidities. Antibodies persisted at 4–5 months but were lower in those with severe acute disease. Those who received the booster dose showed stronger CD4+/CD8+ activation (notably against the Omicron variant) than unvaccinated/partially vaccinated patients. Conclusions: Vaccination improved humoral and cellular responses, but severe breakthrough infections still occurred, particularly in high-risk patients.