Association of COVID-19 Vaccinations With Intensive Care Unit Admissions and Outcome of Critically Ill Patients With COVID-19 Pneumonia in Lombardy, Italy

Key Points Question Does COVID-19 vaccination prevent intensive care unit (ICU) admission for COVID-19 pneumonia and improve patient outcomes? Findings In this cohort study of more than 10 million people, vaccines based on mRNA technology or adenoviral vectors significantly decreased the risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality, adjusted for age, heart disease and Pao2/FiO2 at ICU admission, were similar between vaccinated and unvaccinated patients. Meaning COVID-19 vaccines were associated with a lower ICU admission for COVID-19 pneumonia, while no significant association was detected with ICU and hospital mortality.

S4 eTable 1. Anamnestic criteria for selecting the type of vaccine to be administered, according to the indication of the Italian Ministry of Health.
Patients with the following comorbidities preferentially received mRNA vaccines: -Idiopathic pulmonary fibrosis; -All other respiratory conditions requiring oxygen supplementation; -Heart failure (III-IV NYHA); -Cardiogenic shock; -Amyotrophic lateral sclerosis; -Multiple sclerosis; -Muscular dystrophy; -Cerebral palsy; -Immunodeficient patients, or patients on therapies with immunosuppressor drug; -Myasthenia gravis; -Dyssimune neurological disorders; -Type 1 diabetes mellitus ; -Type 2 diabetes mellitus requiring at least two different medications, or with at least two complications; -Addison disease; -Panhypopituitarism; -Chronic dialysis; -All severe pulmonary diseases/pulmonary function impairment or severe immunodeficiency; -Cirrhosis; -Cerebral ischemic-hemorrhagic event with neurological or cognitive impairment; -Stroke in 2020 with a ranking score ≥ 3; -Malignancy in severe stage, not remission; -Immunosuppressive drugs for malignancy in the last six months; -Thalassemia, sickle cell anemia; -Down syndrome; -All patients in the waiting list for solid organ transplantation; -All patients in the waiting list or underwent (after three months and before twelve months) a hematopoietic stem cell donation; -All patients underwent a hematopoietic stem cell donation, even after twelve months, with chronic graft versus host disease and immunosuppressive treatment; -BMI > 35; -AIDS or < 200 CD4.

Time trend analysis of the risk of ICU admission for COVID-19 pneumonia.
The association between vaccination status (vaccinated versus unvaccinated) and the risk of being admitted to the ICU for COVID-19 pneumonia was evaluated by analyzing the time course of daily relative risk (RR). For each day, starting from August 1, 2021, the RR was calculated as follows: where: •°: number of vaccinated individuals admitted to the ICU •°: total number of vaccinated individuals in Lombardy •°: number of unvaccinated individuals admitted to the ICU •°: total number of unvaccinated individuals in Lombardy The moving average method for time series data was used to understand how the risk of ICU admission for COVID-19 pneumonia changed over time in vaccinated and unvaccinated individuals. For each day, we considered the number of vaccinated and unvaccinated individuals admitted to the ICU as the sum of vaccinated and unvaccinated patients admitted to the ICU within the 29-day period from 14 days before and up to 14 days after the selected day. We considered the total number of vaccinated and unvaccinated individuals in Lombardy as the average of the number of all vaccinated and unvaccinated individuals in Lombardy within the 29-day period from 14 days before and up to 14 days after the selected day. In the moving average calculation, we used as denominator the average number of individuals in the 29-days window, because we assumed that it is relatively stable since the daily vaccination capacity was limited. The 29-day period was chosen from several window sizes. We report here tests performed on 1 day (without any windowing function, Figure S2), 15 days ( Figure S3), 29 days ( Figure S4) and 43 days ( Figure S5).
As an example, the RR of being admitted to the ICU for COVID-19 pneumonia on October 1 st , 2021, was computed as:  Abbreviations. V, vaccinated; UnV, unvaccinated; AdV, vaccinated with adenoviral vaccines; mRNA, vaccinated with mRNA vaccines; ≤120, time from the last administered vaccine dose less than or equal to 120 days; >120, time from the last administered vaccine dose more than 120 days; ≤65, individuals and patients with age below or equal to 65-year-old; >65, individuals and patients with age above 65-year-old; ICU, number of patients admitted to the ICU; Pop, number of individuals in Lombardy.

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(10.7%) 0 (0%) eTable 5 indicates the number of available genotypes frequency in the different date ranges considered in the paper. Interestingly, some patients demonstrated more than 1 genotype: *:10 both delta and other; #:2 both delta and omicron, 10 both delta and other, 1 both alpha and delta; @: 2 both delta and omicron, 15 both delta and other, 1 both alpha and delta, 1 both alpha and other; §: 5 both delta and other, 1 both alpha and other; &: 2 both delta and omicron, 1 both alpha and delta.  Abbreviations. CI: confidence interval; OR: odds ratio; RR: relative risk. Note. Predictors were defined using backward stepwise approach. The list od possible predictors was: age, sex, vaccination status, type of comorbidity (hypertension, heart disease, diabetes mellitus, chronic renal disease, liver disease, chronic obstructive pulmonary disease, malignancy), immunosuppressive therapy, number of comorbidities (categorized as 0, 1, 2 and >2), PaO 2 /FiO 2 at ICU admission. eTable 7 reports OR and RR estimates using multivariable logistic and log-binomial model, respectively.
S26 eFigure 14. Relative risk according to the different types of vaccines. eFigure 14 shows trend over time of the relative risk (RR) of being admitted to the ICU with COVID-19 pneumonia using a window size of 29 days. Admissions are stratified by vaccine type. The dashed lines represent less than 5 vaccinated or unvaccinated patients admitted in ICU. Abbreviations. V, vaccinated; UnV, unvaccinated; AdV, vaccinated with adenoviral vaccines; mRNA, vaccinated with mRNA vaccines; ≤120, time from the last administered vaccine dose less than or equal to 120 days; >120, time from the last administered vaccine dose more than 120 days; ≤65, individuals and patients with age below or equal to 65-year-old; >65, individuals and patients with age above 65-year-old; ICU, number of patients admitted to the ICU; Pop, number of individuals in Lombardy.