Effect of COVID-19 Vaccination on the In-Hospital Prognosis of Patients Admitted during Delta and Omicron Waves in Italy

The study investigates whether COVID-19 vaccination improves in-hospital prognosis among patients infected during periods dominated by the Delta or Omicron variants. As viral evolution led Omicron to overtake Delta due to increased transmissibility, concerns emerged about reduced vaccine effectiveness against infection and severity, waning immunity over time, and differences by vaccine type and dosing regimens. Prior data suggest weaker protection from infection with Omicron than Delta, but booster doses or hybrid immunity can enhance protection, especially in older adults. The objective was to assess the impact of mRNA vaccination on ICU admission and 30-day all-cause mortality among patients presenting to an academic medical center during the Delta and Omicron waves.

Background literature cited indicates: vaccines reduce infection and severity, though effectiveness wanes over time and varies by patient factors, vaccine type, and regimen; booster doses increase antibody levels and protection, with evidence suggesting stronger effectiveness against Delta than Omicron; in older adults, boosters confer additional protection against infection and hospitalization; some studies show Omicron is associated with milder disease by certain severity indices, though ICU/mortality endpoints vary across studies. The authors reference epidemiological and clinical studies from England, Denmark, and elsewhere comparing vaccine performance against Delta and Omicron, as well as data on booster effectiveness and waning immunity.

Design: Retrospective, monocentric observational study at a third-level academic medical center in Rome, Italy (Fondazione Policlinico A. Gemelli IRCCS). Population: Adults ≥18 years without prior known COVID-19 positivity, SARS-CoV-2 RT-PCR positive on nasopharyngeal/oropharyngeal swabs, presenting to the Emergency Room during two periods: Delta wave (1 July–30 September 2021) and Omicron wave (January 2022). Data sources: Electronic health records. Ethics: Approved by local IRB (29 April 2022-N 0014840/22); retrospective consent not required. Variables collected: Vaccination status (COVID-19 and influenza), number/type of COVID-19 vaccine doses, demographics, comorbidities, clinical severity including presence of pneumonia on chest radiograph, pulmonary embolism, oxygen need, laboratory parameters (e.g., BUN, LDH, CRP, procalcitonin, blood counts, D-dimer, fibrinogen, PaO2/FiO2), and in-hospital treatments (anticoagulants, corticosteroids, remdesivir, monoclonal antibodies, tocilizumab, other anti-IL-6). Exposure classification: Unvaccinated (no COVID-19 vaccine) vs vaccinated (≥1 dose), further stratified by one, two, or three doses. Outcomes: Need for ICU admission for at least one day; all-cause 30-day mortality from ED admission. Treatments followed contemporaneous AIFA guidelines (Dec 2020 for Delta period; Oct 2021 update for Omicron). Statistical analysis: Categorical variables compared with chi-square or Fisher’s exact test; continuous variables with Student’s t-test or ANOVA with Bonferroni post hoc where appropriate. Multiple logistic regression models estimated associations of vaccination status with outcomes, adjusting for age, sex, and variables with p<0.01 in univariate analyses; additional models examined variant (Delta vs Omicron) effects adjusting for confounders including vaccine status and treatments. Results reported as odds ratios (OR) with 95% confidence intervals (CI). Analyses performed with IBM SPSS v20.

- Sample: 821 patients; mean age 62 ± 18 years (range 18–100); 59% male. Delta period: 545 (66%); Omicron period: 276 (34%). - Vaccination: 358 (44%) vaccinated overall (7% one dose, 28% two doses, 9% three doses). Vaccinated proportion was higher in Omicron than Delta (57% vs 37%); boosters were more common in Omicron (27% vs 1%). Pfizer 40%, Moderna 29%, AstraZeneca 12%. - Patient profiles: Vaccinated patients were older (68 vs 57 years) and had more comorbidities (≥2 comorbidities: 62% vs 31%). Unvaccinated had worse PaO2/FiO2 at presentation. Tocilizumab use was higher in unvaccinated; monoclonal antibody use higher in vaccinated. - Clinical severity at ED: Interstitial pneumonia in 71%; pulmonary embolism in 3%. Discharge/admission patterns varied by dose; ICU use highest in unvaccinated. - Outcomes (crude): ICU admission overall 20%. ICU by group: unvaccinated 24%, one dose 12%, two doses 17%, three doses 11%. 30-day all-cause mortality overall 14% (unvaccinated 13%, one dose 2%, two doses 17%, three doses 22%). - Adjusted associations (multivariable): Compared with vaccinated, unvaccinated had higher odds of ICU admission (OR 2.0, 95% CI 1.3–3.1). Versus specific dosing groups, unvaccinated had higher ICU odds: vs two doses OR 1.9 (1.1–3.0), vs three doses OR 3.5–3.6 (about 1.5–8.5). For mortality, unvaccinated had higher odds than those with at least one dose (OR 1.7, 95% CI 1.3–2.7), higher than two doses (OR 1.9, 95% CI 1.5–2.9), and higher than one dose (OR 3.9, 95% CI 1.8–19.0). - Variant effect (adjusted): No significant difference in 30-day mortality between waves (OR 0.6, 95% CI 0.3–1.0); ICU admission was more likely during Delta vs Omicron (OR 1.9, 95% CI 1.2–3.1).

The study shows that during the Omicron wave, patients presenting to the ED were older and more comorbid, with a higher vaccination rate than during the Delta wave, likely reflecting vaccine uptake patterns in older populations. Despite greater comorbidity among vaccinated individuals, unvaccinated patients presented with worse respiratory function and had higher adjusted risks of ICU admission and 30-day mortality. Receiving two or three vaccine doses reduced the need for ICU admission compared with being unvaccinated, and even one vaccine dose was associated with reduced 30-day mortality. The lack of observed mortality reduction among booster recipients in crude rates likely reflects confounding by indication and higher non-COVID-related mortality in older, frailer patients prioritized for boosters. Findings are broadly consistent with external studies demonstrating vaccine protection against severe outcomes for both Delta and Omicron, though vaccine effectiveness against Omicron infection is lower than against Delta. Differences with some reports may stem from differing severity endpoints (e.g., oxygen requirements vs ICU/mortality). An observed association of influenza vaccination with lower mortality in a subset aligns with prior literature suggesting broader antiviral immune benefits and health-seeking behaviors among vaccine-adherent individuals.

Among adults hospitalized or evaluated in the ED for COVID-19 during Delta and Omicron predominance, SARS-CoV-2 vaccination was associated with improved in-hospital prognosis. Protection against ICU admission was evident after at least two doses and was independent of the prevailing variant, while 30-day mortality appeared reduced after one or two doses but not clearly after a booster dose, likely due to confounding by patient risk profiles. Ongoing research is needed to confirm protection across emerging variants and to optimize vaccine platforms, schedules, and delivery routes.

- Observational, single-center design with potential selection bias; hospitalization and ICU admission decisions were not standardized. - Variant assignment was inferred from period predominance rather than genomic sequencing; misclassification cannot be excluded. - Antigen test sensitivity differed by variant (lower for Omicron), potentially biasing presentation timing and case mix. - Lacked data on time since vaccination; waning immunity could not be assessed. - Causes of death were not adjudicated; non-COVID deaths may have influenced mortality comparisons, particularly among booster recipients. - Findings pertain to Delta and early Omicron periods and may not generalize to later subvariants (e.g., XBB).