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Association of COVID-19 Acute Respiratory Distress Syndrome With Symptoms of Posttraumatic Stress Disorder in Family Members After ICU Discharge

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To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Is the risk of posttraumatic stress disorder (PTSD) symptoms in family members of intensive care unit (ICU) patients with acute respiratory distress syndrome (ARDS) due to COVID-19 different from that of family members of patients with non–COVID-19 ARDS?

Findings  In a prospective cohort study of 517 family members of ICU patients, PTSD-related symptoms at 90 days after ICU discharge were significantly more common in family members of patients with COVID-19 ARDS compared with non–COVID-19 ARDS (35% vs 19%). In a multivariable analysis adjusting for age, sex, and level of social support, COVID-19 ARDS was independently associated with PTSD-related symptoms in family members (odds ratio, 2.05).

Meaning  ARDS due to COVID-19 was associated with a greater risk-adjusted rate of PTSD symptoms among family members compared with ARDS from other causes.


Importance  Persistent physical and mental disorders are frequent in survivors of COVID-19–related acute respiratory distress syndrome (ARDS). However, data on these disorders among family members are scarce.

Objective  To determine the association between patient hospitalization for COVID-19 ARDS vs ARDS from other causes and the risk of posttraumatic stress disorder (PTSD)–related symptoms in family members.

Design, Setting, and Participants  Prospective cohort study in 23 intensive care units (ICUs) in France (January 2020 to June 2020 with final follow-up ending in October 2020). ARDS survivors and family members (1 family member per patient) were enrolled.

Exposures  Family members of patients hospitalized for ARDS due to COVID-19 vs ARDS due to other causes.

Main Outcomes and Measures  The primary outcome was family member symptoms of PTSD at 90 days after ICU discharge, measured by the Impact of Events Scale-Revised (score range, 0 [best] to 88 [worst]; presence of PTSD symptoms defined by score >22). Secondary outcomes were family member symptoms of anxiety and depression at 90 days assessed by the Hospital Anxiety and Depression Scale (score range, 0 [best] to 42 [worst]; presence of anxiety or depression symptoms defined by subscale scores ≥7). Multivariable logistic regression models were used to determine the association between COVID-19 status and outcomes.

Results  Among 602 family members and 307 patients prospectively enrolled, 517 (86%) family members (median [IQR] age, 51 [40-63] years; 72% women; 48% spouses; 26% bereaved because of the study patient’s death; 303 [50%] family members of COVID-19 patients) and 273 (89%) patients (median [IQR] age, 61 [50-69] years; 34% women; 181 [59%] with COVID-19) completed the day-90 assessment. Compared with non–COVID-19 ARDS, family members of patients with COVID-19 ARDS had a significantly higher prevalence of symptoms of PTSD (35% [103/293] vs 19% [40/211]; difference, 16% [95% CI, 8%-24%]; P < .001), symptoms of anxiety (41% [121/294] vs 34% [70/207]; difference, 8% [95% CI, 0%-16%]; P= .05), and symptoms of depression (31% [91/291] vs 18% [37/209]; difference, 13% [95% CI, 6%-21%]; P< .001). In multivariable models adjusting for age, sex, and level of social support, COVID-19 ARDS was significantly associated with increased risk of PTSD-related symptoms in family members (odds ratio, 2.05 [95% CI, 1.30 to 3.23]).

Conclusions and Relevance  Among family members of patients hospitalized in the ICU with ARDS, COVID-19 disease, as compared with other causes of ARDS, was significantly associated with increased risk of symptoms of PTSD at 90 days after ICU discharge.

Trial Registration  ClinicalTrials.gov Identifier: NCT04341519

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Article Information

Corresponding Author: Elie Azoulay, MD, PhD, Médecine Intensive et Réanimation, APHP, Hôpital Saint-Louis, Paris University, 1 Avenue Claude Vellefaux, 75010 Paris, France (elie.azoulay@aphp.fr).

Accepted for Publication: February 2, 2022.

Published Online: February 18, 2022. doi:10.1001/jama.2022.2017

Author Contributions: Drs Azoulay and Resche-Rigon 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.

Concept and design: Azoulay, Resche-Rigon, Geri, Quenot, Lesieur, Demoule, Guitton, Biard, Pochard, Kentish-Barnes.

Acquisition, analysis, or interpretation of data: Azoulay, Megarbane, Reuter, Labbé, Cariou, Geri, Van der Meersch, Kouatchet, Guisset, Bruneel, Reignier, Souppart, Barbier, Argaud, Quenot, Papazian, Guidet, Thiéry, Klouche, Lesieur, Demoule, Guitton, Capellier, Mourvillier, Biard, Pochard, Kentish-Barnes.

Drafting of the manuscript: Azoulay, Resche-Rigon, Quenot, Lesieur, Biard, Pochard, Kentish-Barnes.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Resche-Rigon, Lesieur, Demoule, Biard.

Obtained funding: Azoulay, Resche-Rigon.

Administrative, technical, or material support: Resche-Rigon, Souppart, Lesieur, Guitton, Mourvillier.

Supervision: Azoulay, Guisset, Bruneel, Quenot, Guidet, Thiéry, Klouche, Lesieur, Guitton, Capellier, Mourvillier, Pochard, Kentish-Barnes.

Conflict of Interest Disclosures: Dr Azoulay reported receipt of personal fees (lectures) from Pfizer, Gilead, Baxter, and Alexion; and institutional research grants from Merck Sharp and Dohme, Pfizer, Baxter, and Alexion outside the submitted work. Dr Labbé reported personal fees from Amomed and grants from LeoPharma outside the submitted work. Dr Cariou reported personal fees from Bard outside the submitted work. Dr Souppart reported grants from French Ministry of Health during the conduct of the study. Dr Barbier reported personal fees from Merck Sharp and Dohme and BioMérieux outside the submitted work. Dr Papazian reported personal fees from Air Liquide Santé and Gettinge and grants from SEDANA outside the submitted work. Dr Thiéry reported personal fees from Amgen outside the submitted work. Dr Demoule reported grants from the French Ministry of Health; grants and personal fees from Philips, Fisher & Paykel, Respinor, and Lungpacer; personal fees from Baxter, Getinge, Gilead, and Lowenstein; and nonfinancial support from Fisher & Paykel outside the submitted work. Dr Capellier reported grants from ASTEN and Baxter; other from Freysenius (conference fees); and personal fees from ARCHEON outside the submitted work. Dr Kentish-Barnes reported grants from French Ministry of Health during the conduct of the study and outside the submitted work. No other disclosures were reported.

Funding/Support: All financial support for the research was provided by the French Ministry of Health.

Role of the Funder/Sponsor: The French Ministry of Health 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.

Additional Contributions: We thank all members of the team from the clinical research unit of the Saint-Louis Hospital: Anne-Juliette Trouiller, MS (senior research assistant), El Mountacer El Abassi, PhD (project manager), Marine Cognat, MS (research coordinator), Zakaria Maakoul, MS (research coordinator), Amine Hanachi, MS (research coordinator), Malika Ghartouchant, MS (research coordinator), and Fatima Ait Seddik, MS (research coordinator); and members from the critical care department of the Saint-Louis Hospital: Philonille Degos, MS, and Clémence Viau, MS, for their help and engagement in the study. None of these individuals received a dedicated compensation for their role in the study.

Additional Information: This study was performed on behalf of the Famirea Study Group.

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