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. 2022 Mar 15;327(11):1042-1050.
doi: 10.1001/jama.2022.2017.

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

Elie Azoulay  1 , Matthieu Resche-Rigon  2 , Bruno Megarbane  3 , Danielle Reuter  4 , Vincent Labbé  5 , Alain Cariou  6 , Guillaume Géri  7 , Guillaume Van der Meersch  8 , Achille Kouatchet  9 , Olivier Guisset  10 , Fabrice Bruneel  11 , Jean Reignier  12 , Virginie Souppart  1 , François Barbier  13 , Laurent Argaud  14 , Jean-Pierre Quenot  15 , Laurent Papazian  16 , Bertrand Guidet  17 , Guillaume Thiéry  18 , Kada Klouche  19 , Olivier Lesieur  20 , Alexandre Demoule  21 , Christophe Guitton  22 , Gilles Capellier  23 , Bruno Mourvillier  24 , Lucie Biard  2 , Frédéric Pochard  25 , Nancy Kentish-Barnes  1
Affiliations

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

Elie Azoulay et al. JAMA. .

Abstract

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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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.. Screening and Selection of Family Member Cohorts for the Study
ARDS indicates acute respiratory distress syndrome; ICU, intensive care unit.
Figure 2.
Figure 2.. Symptoms of Posttraumatic Stress Disorder, Anxiety, and Depression in Family Members of Patients With COVID-19 ARDS vs Non–COVID-19 ARDS
Posttraumatic stress disorder (PTSD) symptoms were measured using the Impact of Event Scale Revised (IES-R; score range, 0 [best] to 88 [worst]; minimal clinically important difference, 0.2; sample sizes, n = 271 for the COVID-19 group and 198 for the non–COVID-19 group). Symptoms of anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS) anxiety and depression subscales (score range for each, 0 [best] to 42 [worst]; minimal clinically important difference, 1.5; anxiety or depression considered present with a score of ≥7 [sample sizes for anxiety, n = 294 for the COVID-19 group and n = 207 for the non–COVID-19 group; sample sizes for depression, n = 291 for the COVID-19 group and n = 209 for the non–COVID-19 group]). Data are reported as median (solid horizontal lines) IQR (vertical height of boxes) scores, and the whiskers extend to the most extreme data point, which is no more than 1.5 times the IQR.
Figure 3.
Figure 3.. Factors Independently Associated With the Presence of PTSD-Related Symptoms in Family Members of Patients With ARDS
Variables considered for the LASSO step included sex, age, marital status, profession, and social support. For the Hosmer and Lemeshow goodness of fit test, P = .26. The sensitivity analyses took into account a center effect and another one that used a set of data after imputation of missing variables provided similar results and are reported in eTables 8 and 9 in the Supplement. aValues are given according to posttraumatic stress disorder (PTSD) status, and values are reported as No./total (%) unless otherwise indicated. bIndicates the odds ratio per 10-years increase. cLevel of social support was evaluated on a scale ranging from 0 (extremely limited) to 10 (extremely effective). dIndicates the odds ratio per additional point of the social support scale.
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