The SARS-CoV-2 pandemic continues to significantly impact hospitals worldwide. The virus's constant spike protein mutations have produced variants that evade vaccine protection. The Omicron variant eventually surpassed Delta due to its higher infectivity. Vaccination has consistently been shown to prevent the virus's spread and reduce disease severity. However, this protection wanes over time and depends on patient characteristics, vaccine type, and immunization regimens. This has led to public concerns about the effectiveness of early vaccines against new variants. While Omicron offered weaker protection against infection compared to Delta, a triple mRNA vaccine dose or prior SARS-CoV-2 infection in patients with two vaccine doses provided protection against Omicron BA.1. A booster dose has been shown to offer greater protection against infection and hospitalization in individuals over 60 compared to two doses, increasing antibody levels and protection. However, a case-control study showed booster doses to be more protective against Delta than Omicron. This study aimed to evaluate the impact of mRNA vaccination on the in-hospital prognosis of SARS-CoV-2 infected patients admitted to an academic medical center during the Delta and Omicron waves in Italy.

Several studies highlight the protective effects of COVID-19 vaccination against severe disease. A large epidemiological study in England demonstrated that mRNA and adenoviral vector vaccines reduced mortality and ICU admissions in patients infected with Delta and Omicron variants, although it couldn't account for antiviral and monoclonal antibody treatments. Another prospective study showed vaccines' effectiveness in preventing severe COVID-19, particularly in elderly patients with comorbidities, though it found the vaccines less potent against Omicron than Delta. This discrepancy might stem from differing outcome measures; the latter study focused on oxygen treatment and positive pressure ventilation rather than ICU admission or mortality, suggesting Omicron causes milder disease based on other severity indexes. Regarding booster doses, a population study in Thailand confirmed their protective effect during both Delta and Omicron waves, although the level of protection was higher in that study, possibly due to differences in patient populations and severity at presentation. Finally, there is evidence that influenza vaccination might also offer reduced COVID-19 mortality, potentially through broad antiviral protection and increased compliance among individuals who receive both vaccines, leading to earlier hospital referrals in less severe conditions.

This retrospective, monocentric observational study was conducted at Fondazione Policlinico Agostino Gemelli-IRCCS in Rome, Italy. The study included patients presenting to the Emergency Room between July 1st and September 30th, 2021 (Delta wave) and January 2022 (Omicron wave). Trained staff collected data on vaccination status (COVID-19 and influenza), clinical characteristics, comorbidities, lung involvement (pneumonia on chest X-ray, pulmonary embolism, oxygen supplementation needs), laboratory parameters, and pharmacological treatment. Only patients over 18 with no prior COVID-19 history were included. Data were extracted from electronic health records; the study was approved by the local ethics committee. All patients had positive SARS-CoV-2 RT-PCR test results. In-hospital treatment followed AIFA guidelines. Outcomes measured were ICU admission (at least one day) and 30-day all-cause mortality. Patients were grouped by vaccination status (unvaccinated, at least one dose, categorized further by number of doses) and prevalent variant. Data were analyzed using descriptive statistics (mean ± SD, percentages). Categorical variables were compared using chi-square or Fisher's exact tests; continuous variables were compared using t-tests or ANOVA with Bonferroni post-hoc tests. Multiple logistic regression analyzed the impact of vaccination status on outcomes, adjusting for age, gender, and other significant univariate variables. Additional models analyzed the impact of the variant, also adjusting for confounders. IBM SPSS version 20.0 was used for statistical analysis.

The study included 821 patients (mean age 62 ± 18 years, 59% male). 66% were infected during the Delta wave, 34% during the Omicron wave. Omicron patients were significantly older and had more comorbidities than Delta patients. Overall, 44% of patients were vaccinated: 7% with one dose, 28% with two, and 9% with a booster dose. Vaccination rates were much higher during the Omicron wave (57%) than the Delta wave (37%). Vaccinated patients were older (68 vs. 57 years) and had a higher rate of comorbidities (62% vs. 31%). Unvaccinated patients had lower PaO2/FiO2 ratios at presentation. Tocilizumab use was higher in unvaccinated patients, while monoclonal antibody use was higher in vaccinated patients. Overall, 20% of patients were admitted to the ICU, and the 30-day mortality rate was 14%. ICU admissions were significantly higher during the Delta wave (OR 1.9, 95% CI 1.2-3.1). Unvaccinated patients had a higher risk of ICU admission (OR 2.0, 95% CI 1.3-3.1) and 30-day mortality (OR 1.7, 95% CI 1.3-2.7). Patients with at least two vaccine doses had a lower risk of ICU admission. Even a single dose was associated with reduced 30-day mortality. After adjusting for confounders, unvaccinated patients had a higher probability of ICU admission (OR 2.0, 95% CI 1.3-3.1) and 30-day mortality (OR 1.7, 95% CI 1.3-2.7) compared to those with at least one dose. The protective effect of vaccination on ICU admission was most evident after two or three doses. There was no significant difference in 30-day mortality between Delta and Omicron waves, but ICU admission was significantly associated with the Delta variant (OR 1.9, 95% CI 1.2-3.1).

This study confirms the significant protection offered by SARS-CoV-2 vaccination against severe COVID-19 in hospitalized patients. The higher vaccination rate during the Omicron wave, likely due to higher vaccination uptake in older individuals, highlights the changing epidemiology and vaccination strategies. The age difference between vaccinated and unvaccinated patients, and consequently the higher prevalence of comorbidities among vaccinated individuals, is a critical observation. The finding that unvaccinated patients presented with worse clinical conditions is consistent with previous literature. The study reveals that two or three vaccine doses significantly reduced the likelihood of ICU admission, regardless of the variant. Interestingly, while one or two doses reduced 30-day mortality, a booster dose did not show a statistically significant further benefit, possibly due to the choice of outcome measures and higher non-COVID-19 mortality in the booster group. The study’s limitations include the potential for selection bias in hospitalization and ICU admission criteria and reliance on prevalent variant data instead of molecular confirmation.

This study demonstrates that SARS-CoV-2 vaccination significantly protects hospitalized COVID-19 patients. Protection against ICU admission is most apparent after two doses and is independent of the viral variant, while mortality reduction is evident with one or two doses, but not a booster dose. As knowledge evolves, further research is needed to confirm protection against other variants and evaluate new vaccines, schedules, and administration methods.

This study has several limitations inherent to observational research. Selection bias is a concern, as hospitalization and ICU admission criteria weren't standardized and relied on clinical judgment, potentially leading to differences between waves. Variant classification was based on the prevalent variant during the study periods rather than molecular testing, and the differing sensitivities of antigenic testing between variants might have introduced selection bias. Lack of information on the time interval between vaccination and COVID-19 infection is another limitation; while waning vaccine efficacy primarily affects protection against infection rather than severity, this absence of data might influence the results. The study focused only on Delta and Omicron variants and may not generalize to other variants.