Persistent severe acute respiratory distress syndrome for the prognostic enrichment of trials

Sánchez, Elizabeth; Price, David R.; Chung, Kuei-Pin; Oromendia, Clara; Choi, Augustine M.K.; Schenck, Edward J.; Siempos, Ilias I.

doi:10.1371/journal.pone.0227346

Cited by 11 publications

(10 citation statements)

References 25 publications

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“…This finding is important because evidence both before and during the COVID-19 era showed that, among patients with ARDS, oxygenation on the third day after intubation may be more strongly associated with mortality than oxygenation on the day of intubation. 16,17 Also, the occurrence of bacteremia among survivors was 57.1% (8 of 14) in the full vaccination group vs 73.9% (65 of 88) in the control group, and, although statistically insignificant, this difference in occurrence might be associated with different mortality rates between groups. 18…”

Section: Jama Network Open | Critical Care Medicinementioning

confidence: 88%

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

et al. 2022

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ImportanceAlthough 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresPatients 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 &lt;14 days or &gt;5 months before intubation) comprised the control group.Main Outcomes and MeasuresThe 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.ResultsA 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 RelevanceIn 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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Section: Jama Network Open | Critical Care Medicinementioning

confidence: 88%

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

et al. 2022

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“…In fact, over half of the resolving HRF patients in our study had PaO 2 :FIO 2 < 150 at baseline, indicating that many patients who begin their ICU course with serious respiratory failure improve quickly. The prognostic value of this early trajectory, and the disconnect between initial severity of respiratory failure and subsequent outcomes, has not previously been investigated in acute HRF but has been described in ARDS [10,21,[45][46][47]. Notably, a secondary analysis of randomized trial data showed patients with ARDS that rapidly improved within 1 day had substantially lower mortality than patients with persistent ARDS and that 63% of rapidly improving ARDS patients were moderate or severe at enrollment [10].…”

Section: Discussionmentioning

confidence: 99%

“…The majority of patients with respiratory failure requiring mechanical ventilation are weaned off within three days [19], while others may develop worsening lung injury and/or excessive fibroproliferation contributing to prolonged need for mechanical ventilation and hypoxemia [20]. Using trajectories of clinical and biologic data to classify subphenotypes has helped identify patients at high risk for poor outcomes in such heterogeneous conditions as chronic obstructive pulmonary disease, pneumonia, and acute kidney injury, and can help determine early biologic events that contribute to subsequent clinical course [10,[21][22][23][24][25][26].…”

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confidence: 99%

Identification of persistent and resolving subphenotypes of acute hypoxemic respiratory failure in two independent cohorts

et al. 2021

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Background Acute hypoxemic respiratory failure (HRF) is associated with high morbidity and mortality, but its heterogeneity challenges the identification of effective therapies. Defining subphenotypes with distinct prognoses or biologic features can improve therapeutic trials, but prior work has focused on ARDS, which excludes many acute HRF patients. We aimed to characterize persistent and resolving subphenotypes in the broader HRF population. Methods In this secondary analysis of 2 independent prospective ICU cohorts, we included adults with acute HRF, defined by invasive mechanical ventilation and PaO2-to-FIO2 ratio ≤ 300 on cohort enrollment (n = 768 in the discovery cohort and n = 1715 in the validation cohort). We classified patients as persistent HRF if still requiring mechanical ventilation with PaO2-to-FIO2 ratio ≤ 300 on day 3 following ICU admission, or resolving HRF if otherwise. We estimated relative risk of 28-day hospital mortality associated with persistent HRF, compared to resolving HRF, using generalized linear models. We also estimated fold difference in circulating biomarkers of inflammation and endothelial activation on cohort enrollment among persistent HRF compared to resolving HRF. Finally, we stratified our analyses by ARDS to understand whether this was driving differences between persistent and resolving HRF. Results Over 50% developed persistent HRF in both the discovery (n = 386) and validation (n = 1032) cohorts. Persistent HRF was associated with higher risk of death relative to resolving HRF in both the discovery (1.68-fold, 95% CI 1.11, 2.54) and validation cohorts (1.93-fold, 95% CI 1.50, 2.47), after adjustment for age, sex, chronic respiratory illness, and acute illness severity on enrollment (APACHE-III in discovery, APACHE-II in validation). Patients with persistent HRF displayed higher biomarkers of inflammation (interleukin-6, interleukin-8) and endothelial dysfunction (angiopoietin-2) than resolving HRF after adjustment. Only half of persistent HRF patients had ARDS, yet exhibited higher mortality and biomarkers than resolving HRF regardless of whether they qualified for ARDS. Conclusion Patients with persistent HRF are common and have higher mortality and elevated circulating markers of lung injury compared to resolving HRF, and yet only a subset are captured by ARDS definitions. Persistent HRF may represent a clinically important, inclusive target for future therapeutic trials in HRF.

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“…Patients with persistent severe ARDS have poor clinical outcomes. Identifying this kind of patients at trial enrollment can be an approach to personalized medicine [29].…”

Section: Sars and Mersmentioning

confidence: 99%

COVID-19 Compared with Other Viral Diseases: Novelties, Progress, and Challenges

Wang

Alexander

2020

Electron J Gen Med

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COVID-19 is a newly discovered, highly infectious disease and has rapidly spread into at least 213 countries as a pandemic. This paper is a comprehensive review article of COVID-19 and four other viral diseases, including influenza, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Ebola virus disease (EVD). The cause of COVID-19 is the novel coronavirus-SARS-CoV-2. The transmission of COVID-19 is complex and rapid; therefore, it is difficult to control the spread of the disease. Certified specific antiviral drugs are slowly becoming available for COVID-19, although a few treatments such as Remdesivir, hydroxychloroquine, dexamethasone, and therapeutic plasma exchange (TPE) have been found somewhat effective. Effective vaccines are still in the process of development and several countries, including the USA are conducting Phase 3 trials currently to fast-track the vaccines. All these issues have created significant challenges in reducing the morbidity and mortality of this global infectious disease. COVID-19 has led to vast impacts on public health and the global economy. With economic shutdowns, social distancing, increased handwashing, and sanitizing have been first line therapies for mitigating the spread of COVID-19 and have created a new normal. COVID-19 is different from influenza and previous pandemic diseases, such as SARS, MERS, and EVD, but has some similarities to them. Influenza and these pandemic diseases are introduced in this paper as a comparison with COVID-19. The features of COVID-19, progress achieved in treatment, emerging technologies in testing and diagnosis, and current and future challenges are presented. Specifically, topics regarding COVID-19 in this paper cover basic facts, the questionable origin of COVID-19, testing and diagnosis, pharmaceutical treatment and comfort measures, strategies and management for fighting against COVID-19, and the emotional, psychological, and mental health impacts of shelter-in-place orders and quarantine of COVID-19.

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Persistent severe acute respiratory distress syndrome for the prognostic enrichment of trials

Cited by 11 publications

References 25 publications

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

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

Identification of persistent and resolving subphenotypes of acute hypoxemic respiratory failure in two independent cohorts

COVID-19 Compared with Other Viral Diseases: Novelties, Progress, and Challenges

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