Vaccination Tied to Lower Mortality in Ventilated Patients With COVID-19

Heidi Splete

October 12, 2022

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Full vaccination status against COVID-19 was associated with significantly reduced mortality among critically ill patients with COVID-19 who needed mechanical ventilation, according to results of a study that involved 265 adults.

Although COVID-19 vaccination has been demonstrated to be effective at preventing infection, breakthrough infections occur, write Eirini Grapsa, RN, of Kapodistrian University of Athens Medical School, Athens, Greece, and colleagues. The potential protective benefits of vaccination for patients who experience these breakthrough infections, especially cases severe enough to require hospitalization and the need for mechanical ventilation, have not been well studied, the investigators say.

In a study published in JAMA Network Open, the researchers reviewed data from 265 consecutive patients older than 18 years who were admitted to intensive care units at three tertiary care centers with confirmed SARS-CoV-2 infections between June 7, 2021, and February 1, 2022. All patients in the study received invasive mechanical ventilation because of acute respiratory distress syndrome (ARDS). The patients were divided into two groups: 26 patients were in the full vaccination group, and 239 served as control patients. Full vaccination was defined as having completed the primary COVID-19 series more than 14 days but less than 5 months before intubation. The control group included patients who had been fully vaccinated for less than 14 days or more than 5 months, were partially vaccinated, or were not vaccinated. A total of 20 of 26 patients in the full vaccination group received the Pfizer BioNTech BNT162b2 vaccine, as did 25 of the 33 vaccinated patients in the control group.

The median age of the patients overall was 66 years; 36% were women, and 99% were White. Patients in the full vaccination group were more likely to be older and to have comorbidities. The primary outcome was the time from intubation to all-cause mortality.

Overall, mortality was lower among the patients with full vaccination status than among those in the control group (61.5% vs 68.2%; P = .03). Full vaccination also was associated with lower mortality in sensitivity analyses that included (a) only patients who received an mRNA vaccine in the full vaccination group, and (b) only unvaccinated patients in the control group (hazard ratios [HRs], 0.47 and 0.54, respectively).

In a regression model that examined secondary outcomes, the HR was 0.40 for the association between full vaccination and 28-day mortality. No significant differences were seen in length of stay in the intensive care unit (ICU) or length of hospital stay among survivors, nor in the occurrence of bacteremia, use of vasopressors, number of vasopressor-free days, use of continuous kidney replacement therapy (CKRT), number of CKRT-free days, and the number of ventilator-free and ICU-free days.

"Our choice to take time since vaccination into consideration was based on several previous studies indicating that protection against infection from vaccination (specifically with mRNA vaccines, such as BNT162b2, which was administered to 76.9% of patients in the full vaccination group) may decrease over time," the researchers write.

Oxygenation was higher in the full vaccination group than in the control group on the third day after intubation. Previous studies conducted before the COVID-19 pandemic have shown that oxygenation on the third day after intubation may be more strongly associated with mortality than oxygenation on the day of intubation, the researchers note. Bacteremia was higher among the control patients and could have affected mortality, although the difference between vaccinated patients and control patients was not significant, the researchers add.

The study findings were limited by several factors, including small sample size, which prevented direct comparisons of the effectiveness of different numbers of vaccine doses or vaccine types, the researchers note. Other limitations include selection bias and residual confounding variables, they say.

The results demonstrate an association between full vaccination and lower mortality and suggest that vaccination may benefit patients with COVID-19-related ARDS, beyond the need for mechanical ventilation alone, they say. "These results expand our understanding of the outcomes of patients with breakthrough infections," they conclude.

The study was supported by a grant to corresponding author Ilias I. Siempos, MD, from the Hellenic Foundation for Research and Innovation. The researchers have disclosed no relevant financial relationships.

JAMA Netw Open. Published online October 7, 2022. Full text

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