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Critical Care Medicine

Association Between Vaccination Status and Mortality Among Intubated Patients With COVID-19–Related Acute Respiratory Distress Syndrome

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JAMA Network Open

Published Online: October 7, 2022

Original Investigation

Article Information and Disclosures

Eirini Grapsa, RN¹;

Georgios Adamos, MD¹;

Ioannis Andrianopoulos, MD²;

Vasiliki Tsolaki, MD³;

Vassilis G. Giannakoulis, MD¹;

Nikitas Karavidas, MD³;

Vassiliki Giannopoulou, MD¹;

Katerina Sarri, MD¹;

Eleftheria Mizi, MD¹;

Evdokia Gavrielatou, MD¹;

Georgios Papathanakos, MD²;

Konstantinos D. Mantzarlis, MD³;

Zafeiria Mastora, MD¹;

Eleni Magira, MD¹;

Vasilios Koulouras, MD²;

Anastasia Kotanidou, MD¹;

Ilias I. Siempos, MD, DSc^1,4

Author Affiliations

¹First Department of Critical Care Medicine and Pulmonary Services, Evangelismos Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece
²Department of Intensive Care Unit, University Hospital of Ioannina, Ioannina, Greece
³Critical Care Department, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, Larissa, Greece
⁴Department of Medicine, Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, New York

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Key Points

Question Is there an association between COVID-19 vaccination status and mortality among critically ill patients who require invasive mechanical ventilation owing to acute respiratory distress syndrome related to COVID-19?

Findings In this multicenter cohort study comprising 265 patients, after adjustment for confounders, full vaccination status compared with controls was associated with lower mortality among critically ill patients who required invasive mechanical ventilation owing to COVID-19–related acute respiratory distress syndrome.

Meaning The findings of this study suggest that full vaccination may be associated with lower mortality among patients who were intubated owing to COVID-19–related acute respiratory distress syndrome; therefore, total benefits of vaccination against COVID-19 may exceed those estimated from the prevention of invasive mechanical ventilation alone.

Abstract

Importance Although vaccination substantially reduces the risk of severe COVID-19, it is yet unknown whether vaccinated patients who develop COVID-19 and require invasive mechanical ventilation have lower mortality than controls.

Objective To examine the association between COVID-19 vaccination status and mortality among critically ill patients who require invasive mechanical ventilation owing to acute respiratory distress syndrome (ARDS) related to COVID-19.

Design, Setting, and Participants This multicenter cohort study was performed between June 7, 2021, and February 1, 2022, among 265 consecutive adult patients with COVID-19 in academic intensive care units who underwent invasive mechanical ventilation owing to ARDS.

Exposures Patients in the full vaccination group had completed the primary COVID-19 vaccination series more than 14 days but less than 5 months prior to intubation. This time threshold was chosen because guidelines from the US Centers for Disease Control and Prevention recommend a booster dose beyond that time. The remaining patients (ie, those who were unvaccinated, partially vaccinated, or fully vaccinated <14 days or >5 months before intubation) comprised the control group.

Main Outcomes and Measures The primary outcome was time from intubation to all-cause intensive care unit mortality. A Cox proportional hazards regression model including vaccination status, age, comorbid conditions, and baseline Sequential Organ Failure Assessment score on the day of intubation was used.

Results A total of 265 intubated patients (170 men [64.2%]; median age, 66.0 years [IQR, 58.0-76.0 years]; 26 [9.8%] in the full vaccination group) were included in the study. A total of 20 patients (76.9%) in the full vaccination group received the BNT162b2 vaccine, and the remaining 6 (23.1%) received the ChAdOx1 nCoV-19 vaccine. Patients in the full vaccination group were older (median age, 72.5 years [IQR, 62.8-80.0 years] vs 66.0 years [IQR, 57.0-75.0 years]) and more likely to have comorbid conditions (24 of 26 [92.3%] vs 160 of 239 [66.9%]), including malignant neoplasm (6 of 26 [23.1%] vs 18 of 239 [7.5%]), than those in the control group. Full vaccination status was significantly associated with lower mortality compared with controls (16 of 26 patients [61.5%] died in the full vaccination group vs 163 of 239 [68.2%] in the control group; hazard ratio, 0.55 [95% CI, 0.32-0.94]; P = .03).

Conclusions and Relevance In this cohort study, full vaccination status was associated with lower mortality compared with controls, which suggests that vaccination might be beneficial even among patients who were intubated owing to COVID-19–related ARDS. These results may inform discussions with families about prognosis.

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Article Information

Accepted for Publication: August 19, 2022.

Published: October 7, 2022. doi:10.1001/jamanetworkopen.2022.35219

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

Corresponding Author: Ilias I. Siempos, MD, DSc, First Department of Critical Care Medicine and Pulmonary Services, Evangelismos Hospital, National and Kapodistrian University of Athens Medical School, 45-47 Ipsilantou St, 10676 Athens, Greece (isiempos@yahoo.com).

Author Contributions: Drs Giannakoulis and Siempos 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. Ms Grapsa and Dr Adamos contributed equally to this work.

Concept and design: Grapsa, Adamos, Giannakoulis, Gavrielatou, Papathanakos, Magira, Koulouras, Kotanidou, Siempos.

Acquisition, analysis, or interpretation of data: Grapsa, Adamos, Andrianopoulos, Tsolaki, Giannakoulis, Karavidas, Giannopoulou, Sarri, Mizi, Gavrielatou, Mantzarlis, Mastora, Magira.

Drafting of the manuscript: Grapsa, Tsolaki, Karavidas, Giannopoulou, Sarri, Mizi, Papathanakos, Koulouras, Siempos.

Critical revision of the manuscript for important intellectual content: Grapsa, Adamos, Andrianopoulos, Tsolaki, Giannakoulis, Gavrielatou, Mantzarlis, Mastora, Magira, Koulouras, Kotanidou.

Statistical analysis: Grapsa, Giannakoulis, Gavrielatou.

Obtained funding: Kotanidou, Siempos.

Administrative, technical, or material support: Grapsa, Tsolaki, Giannopoulou, Sarri, Mizi, Gavrielatou, Mantzarlis, Mastora, Magira.

Supervision: Grapsa, Papathanakos, Koulouras, Kotanidou, Siempos.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by a grant to Dr Siempos from the Hellenic Foundation for Research and Innovation (H.F.R.I.) under the “2nd Call for H.F.R.I Research Projects to support Post-Doctoral Researchers” (Project 80-1/15.10.2020).

Role of the Funder/Sponsor: The funding source 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.

References

Dagan N , Barda N , Kepten E , et al. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med. 2021;384(15):1412-1423. doi:10.1056/NEJMoa2101765 PubMed Google Scholar Crossref

Klompas M . Understanding breakthrough infections following mRNA SARS-CoV-2 vaccination. JAMA. 2021;326(20):2018-2020. doi:10.1001/jama.2021.19063 PubMed Google Scholar Crossref

Cohen MJ , Oster Y , Moses AE , Spitzer A , Benenson S ; Israeli-Hospitals 4th Vaccine Working Group. Association of receiving a fourth dose of the BNT162b vaccine with SARS-CoV-2 infection among health care workers in Israel. JAMA Netw Open. 2022;5(8):e2224657. doi:10.1001/jamanetworkopen.2022.24657 PubMed Google Scholar Crossref

Working WHO ; WHO Working Group on the Clinical Characterisation and Management of COVID-19 Infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis. 2020;20(8):e192-e197. doi:10.1016/S1473-3099(20)30483-7 PubMed Google Scholar Crossref

Tartof SY , Slezak JM , Fischer H , et al. Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study. Lancet. 2021;398(10309):1407-1416. doi:10.1016/S0140-6736(21)02183-8 PubMed Google Scholar Crossref

Tenforde MW , Self WH , Adams K , et al; Influenza and Other Viruses in the Acutely Ill (IVY) Network. Association between mRNA vaccination and COVID-19 hospitalization and disease severity. JAMA. 2021;326(20):2043-2054. doi:10.1001/jama.2021.19499 PubMed Google Scholar Crossref

Ranieri VM , Rubenfeld GD , Thompson BT , et al; ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-2533. doi:10.1001/jama.2012.5669 PubMed Google Scholar Crossref

Centers for Disease Control and Prevention. COVID-19 vaccine boosters. Accessed August 10, 2022. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/booster-shot.html

Gavrielatou E , Xourgia E , Xixi NA , et al. Effect of vitamin C on clinical outcomes of critically ill patients with COVID-19: an observational study and subsequent meta-analysis. Front Med (Lausanne). 2022;9:814587. doi:10.3389/fmed.2022.814587 PubMed Google Scholar Crossref

Siempos II , Xourgia E , Ntaidou TK , et al. Effect of early vs delayed or no intubation on clinical outcomes of patients with COVID-19: an observational study. Front Med (Lausanne). 2020;7:614152. doi:10.3389/fmed.2020.614152 PubMed Google Scholar Crossref

Schenck EJ , Oromendia C , Torres LK , Berlin DA , Choi AMK , Siempos II . Rapidly improving ARDS in therapeutic randomized controlled trials. Chest. 2019;155(3):474-482. doi:10.1016/j.chest.2018.09.031 PubMed Google Scholar Crossref

Harrington JS , Schenck EJ , Oromendia C , Choi AMK , Siempos II . Acute respiratory distress syndrome without identifiable risk factors: a secondary analysis of the ARDS network trials. J Crit Care. 2018;47:49-54. doi:10.1016/j.jcrc.2018.06.002 PubMed Google Scholar Crossref

Centers for Disease Control and Prevention. COVID-19 vaccines for people who are moderately or severely immunocompromised. Accessed August 10, 2022. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html

Chemaitelly H , Tang P , Hasan MR , et al. Waning of BNT162b2 vaccine protection against SARS-CoV-2 infection in Qatar. N Engl J Med. 2021;385(24):e83. doi:10.1056/NEJMoa2114114 PubMed Google Scholar Crossref

Britton A , Fleming-Dutra KE , Shang N , et al. Association of COVID-19 vaccination with symptomatic SARS-CoV-2 infection by time since vaccination and Delta variant predominance. JAMA. 2022;327(11):1032-1041. doi:10.1001/jama.2022.2068 PubMed Google Scholar Crossref

Sanchez E , Price DR , Chung KP , et al. Persistent severe acute respiratory distress syndrome for the prognostic enrichment of trials. PLoS One. 2020;15(1):e0227346. doi:10.1371/journal.pone.0227346 PubMed Google Scholar Crossref

Gavrielatou E , Vaporidi K , Tsolaki V , et al. Rapidly improving acute respiratory distress syndrome in COVID-19: a multi-centre observational study. Respir Res. 2022;23(1):94. doi:10.1186/s12931-022-02015-8 PubMed Google Scholar Crossref

Bergman ZR , Usher M , Olson A , et al. Comparison of outcomes and process of care for patients treated at hospitals dedicated for COVID-19 care vs other hospitals. JAMA Netw Open. 2022;5(3):e220873. doi:10.1001/jamanetworkopen.2022.0873 PubMed Google Scholar Crossref

Mitchell J , Connolly CM , Chiang TP , et al. Comparison of SARS-CoV-2 antibody response after 2-dose mRNA-1273 vs BNT162b2 vaccines in incrementally immunosuppressed patients. JAMA Netw Open. 2022;5(5):e2211897. doi:10.1001/jamanetworkopen.2022.11897 PubMed Google Scholar Crossref

Wang L , Davis PB , Kaelber DC , Volkow ND , Xu R . Comparison of mRNA-1273 and BNT162b2 vaccines on breakthrough SARS-CoV-2 infections, hospitalizations, and death during the Delta-predominant period. JAMA. 2022;327(7):678-680. doi:10.1001/jama.2022.0210 PubMed Google Scholar Crossref

Kranidiotis G , Gerovasili V , Tasoulis A , et al. End-of-life decisions in Greek intensive care units: a multicenter cohort study. Crit Care. 2010;14(6):R228. doi:10.1186/cc9380 PubMed Google Scholar Crossref

Kokkoris S , Gkoufa A , Maneta E , et al. Older adults with severe coronavirus disease 2019 admitted to intensive care unit: prevalence, characteristics and risk factors for mortality. Minerva Anestesiol. Published online April 13, 2022. doi:10.23736/S0375-9393.22.16387-X PubMed Google Scholar Crossref

Lopez Bernal J , Andrews N , Gower C , et al. Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant. N Engl J Med. 2021;385(7):585-594. doi:10.1056/NEJMoa2108891 PubMed Google Scholar Crossref

Bruxvoort KJ , Sy LS , Qian L , et al. Effectiveness of mRNA-1273 against Delta, Mu, and other emerging variants of SARS-CoV-2: test negative case-control study. BMJ. 2021;375:e068848. doi:10.1136/bmj-2021-068848 PubMed Google Scholar Crossref

Pouwels KB , Pritchard E , Matthews PC , et al. Effect of Delta variant on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK. Nat Med. 2021;27(12):2127-2135. doi:10.1038/s41591-021-01548-7 PubMed Google Scholar Crossref

Keehner J , Horton LE , Binkin NJ , et al; SEARCH Alliance. Resurgence of SARS-CoV-2 infection in a highly vaccinated health system workforce. N Engl J Med. 2021;385(14):1330-1332. doi:10.1056/NEJMc2112981 PubMed Google Scholar Crossref

Intensive Care National Audit & Research Centre. COVID-19 report. Accessed August 10, 2022. https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports

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