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

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.

Figure 1.. Survival Curves of Patients Included in the Full Vaccination and Control Groups

For time-to-event analysis from intubation to all-cause intensive care unit mortality, we used a Cox proportional hazards regression model including vaccination status (full vaccination vs control), age, comorbid conditions, and baseline Sequential Organ Failure Assessment score on the day of intubation and plotted the corresponding Cox-generated estimated survival curves. Full vaccination status was significantly associated with lower mortality compared with controls (hazard ratio, 0.55 [95% CI, 0.32-0.94]; P = .03; relative reduction, 45%).

Figure 2.. Survival Curves of Patients Included in the Full Vaccination and Control Groups in the Sensitivity Analysis by Including Only Patients Receiving mRNA Vaccine

For time-to-event analysis from intubation to all-cause intensive care unit mortality, we used a Cox proportional hazards regression model including vaccination status (full vaccination vs control), age, comorbid conditions, and baseline Sequential Organ Failure Assessment score on the day of intubation and plotted the corresponding Cox-generated estimated survival curves. Full vaccination status was significantly associated with lower mortality compared with controls (hazard ratio, 0.47 [95% CI, 0.25-0.87]; P = .02).