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

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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.

Abstract

Importance  Data on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2–related pneumonia are scarce.

Objective  To evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU.

Design, Setting, and Participants  This retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021.

Exposures  COVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine).

Main Outcomes and Measures  The incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders.

Results  Among the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] age was 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dose was 0.03 (95% CI, 0.03-0.04; P < .001), whereas IRR of individuals who received an adenoviral vector vaccine after 120 days was 0.21 (95% CI, 0.19-0.24; P < .001). There were 553 patients admitted to an ICU for COVID-19 pneumonia during the study period: 139 patients (25.1%) were vaccinated and 414 (74.9%) were unvaccinated. Compared with unvaccinated patients, vaccinated patients were older (median [IQR]: 72 [66-76] vs 60 [51-69] years; P < .001), primarily male individuals (110 patients [79.1%] vs 252 patients [60.9%]; P < .001), with more comorbidities (median [IQR]: 2 [1-3] vs 0 [0-1] comorbidities; P < .001) and had higher ratio of arterial partial pressure of oxygen (Pao2) and fraction of inspiratory oxygen (FiO2) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P = .007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower Pao2/FiO2 at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients.

Conclusions and Relevance  In this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status. These findings suggest a substantial reduction of the risk of developing COVID-19–related severe acute respiratory failure requiring ICU admission among vaccinated people.

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Article Information

Accepted for Publication: September 8, 2022.

Published: October 27, 2022. doi:10.1001/jamanetworkopen.2022.38871

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Grasselli G et al. JAMA Network Open.

Corresponding Author: Giacomo Grasselli, MD, Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, Milan 20122, Italy (giacomo.grasselli@unimi.it).

Author Contributions: Dr Zanella and Dr Carlesso had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Grasselli and Zanella contributed equally as co–first authors. Drs Pesenti and Fumagalli contributed equally as co–last authors.

Concept and design: Grasselli, Zanella, Carlesso, Florio, Canakoglu, Cabrini, Cecconi, Chiumello, Gemma, Mantovani, Mojoli, Piva, Fumagalli, Pesenti.

Acquisition, analysis, or interpretation of data: Grasselli, Zanella, Florio, Canakoglu, Bellani, Bottino, Cabrini, Castelli, Catena, Cecconi, Cereda, Forastieri Molinari, Foti, Gemma, Giudici, Grazioli, Lombardo, Lorini, Madotto, Mistraletti, Mojoli, Mongodì, Monti, Muttini, Piva, Protti, Rasulo, Scandroglio, Severgnini, Storti.

Drafting of the manuscript: Grasselli, Zanella, Carlesso, Florio, Canakoglu, Cabrini, Cecconi, Chiumello, Forastieri Molinari, Grazioli, Lombardo, Mantovani, Piva, Severgnini.

Critical revision of the manuscript for important intellectual content: Grasselli, Zanella, Florio, Canakoglu, Bellani, Bottino, Cabrini, Castelli, Catena, Cecconi, Cereda, Chiumello, Foti, Gemma, Giudici, Lorini, Madotto, Mantovani, Mistraletti, Mojoli, Mongodì, Monti, Muttini, Piva, Protti, Rasulo, Scandroglio, Storti, Fumagalli, Pesenti.

Statistical analysis: Carlesso, Florio, Canakoglu, Madotto.

Administrative, technical, or material support: Bellani, Catena, Cecconi, Cereda, Foti, Lombardo.

Supervision: Grasselli, Cabrini, Cecconi, Chiumello, Forastieri Molinari, Lorini, Mistraletti, Mojoli, Monti, Piva, Storti, Fumagalli, Pesenti.

Conflict of Interest Disclosures: Dr Grasselli reported receiving grants and personal fees from Fisher & Paykel, grants from Merck Sharp & Dohme, and personal fees from Getinge, Draeger Medical, Pfizer, Biotest, and Cook Medical outside the submitted work. Dr Bellani reported receiving personal fees and grants from Draeger, personal fees from Getinge, personal fees from Dimar SRL, Flowmeter SPA, and GE Healthcare outside the submitted work. Dr Cecconi reported receiving personal fees from Edwards Life Sciences Consultancy and Directed Systems Consultancy outside the submitted work. Dr Mantovani reported receiving personal fees from Novartis (lecturer), Roche (lecturer), Ventana (lecturer), Pierre Fabre (consultancy), Verily (consultancy), Abbvie (consultancy), Bristol Myers Squibb (consultancy), Johnson & Johnson (consultancy), Imcheck (advisory board member), Myeloid Therapeutics (advisory board member), Astra Zeneca (consultancy and lecturer), Biovelocita (advisory board member), BG Fund (advisory board member), Third Rock Venture (consultancy), Biolegend (advisory board member), Verseau Therapeutics (advisory board member), Macrophage Pharma (advisory board member), Ellipses Pharma (advisory board member), and Olatec Therapeutics (advisory board member) outside the submitted work; and receipt of royalties for the sale of reagents related to innate immunity. Dr Mojoli reported receiving personal fees from Seda Spa (lecturer), GE Healthcare (lecturer), and Hamilton Medical (lecturer) outside the submitted work; and consultancy agreement between Hamilton Medical and University of Pavia. Dr Mongodì reported receiving personal fees from GH Healthcare (lecturer) outside the submitted work. Dr Pesenti reported receiving personal fees from Maquet, Xenios, Baxter International, and Boehringer Ingelheim outside the submitted work. No other disclosures were reported.

Funding/Support: This study was (partially) funded by Italian Ministry of Health–Current research IRCCS (Istituto di Ricerca e Cura a Carattere Scientifico).

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

The COVID-19 Lombardy ICU Network: Members of the COVID-19 Lombardy ICU Network appear in Supplement 2.

Additional Contributions: We thank Marina Leonardelli and Patrizia Minunno (Ospedale Maggiore Policlinico) for administrative support. We thank all the health care staff of the COVID-19 Lombardy ICU Network. We thank Osservatorio Epidemiologico Regionale and the Azienda Regionale per l’Innovazione e gli Acquisti (ARIA) S.p.a. for the support of this research. We thank Douglas Slobod, MD, for English revision of the manuscript. These additional contributors were not compensated.

Additional Information: Data are not publicly available. This study is based on databases maintained by Regione Lombardia.

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