Neurologic Outcomes of Survivors of COVID-19–Associated Acute Respiratory Distress Syndrome Requiring Intubation

Pierre Jaquet, MD; Camille Legouy, MD; Lucie Le Fevre, MD; Alexandra Grinea, MD; Fabrice Sinnah, MD; Guillaume Franchineau, MD; Juliette Patrier, MD; Mehdi Marzouk, MD; Paul-Henri Wicky, MD; Pierre Alexis Geoffroy, MD, PhD; Florence Arnoult, MD; Serafima Vledouts, MD; Etienne de Montmollin, MD, PhD; Lila Bouadma, MD, PhD; Jean-François Timsit, MD, PhD; Tarek Sharshar, MD, PhD; Romain Sonneville, MD, PhD


Crit Care Med. 2022;50(8):e674-e682. 

In This Article

Abstract and Introduction


Objectives: To describe 3–6-month neurologic outcomes of survivors of COVID-19–associated acute respiratory distress syndrome, invasively ventilated in the ICU.

Design: A bicentric prospective study during the two first waves of the pandemic (March to May and September to December, 2020).

Setting: Two academic hospital ICUs, Paris, France.

Patients: Adult COVID-19–associated acute respiratory distress syndrome survivors, invasively ventilated in the ICU, were eligible for a neurologic consultation between 3 and 6 months post ICU discharge.

Interventions: Follow-up by face-to-face neurologic consultation.

Measures and Main Results: The primary endpoint was favorable functional outcome defined by a modified Rankin scale score less than 2, indicating survival with no significant disability. Secondary endpoints included mild cognitive impairment (Montreal Cognitive Assessment score < 26), ICU-acquired weakness (Medical Research Council score < 48), anxiety and depression (Hospital Anxiety and Depression score > 7), and posttraumatic stress disorder (posttraumatic stress disorder checklist for Diagnostic and Statistical Manual of Mental Disorders 5 score > 30). Of 54 eligible survivors, four non-French-speaking patients were excluded, eight patients were lost-to-follow-up, and one died during follow-up. Forty-one patients were included. Time between ICU discharge and neurologic consultation was 3.8 months (3.6–5.9 mo). A favorable functional outcome was observed in 16 patients (39%) and mild cognitive impairment in 17 of 33 patients tested (52%). ICU-acquired weakness, depression or anxiety, and posttraumatic stress disorder were reported in six of 37 cases (16%), eight of 31 cases (26%), and two of 27 cases (7%), respectively. Twenty-nine patients (74%) required rehabilitation (motor, cognitive, or psychologic). ICU and hospital lengths of stay, tracheostomy, and corticosteroids were negatively associated with favorable outcome. By contrast, use of alpha-2 agonists during ICU stay was associated with favorable outcome.

Conclusions: COVID-19–associated acute respiratory distress syndrome requiring intubation led to slight-to-severe functional disability in about 60% of survivors 4 months after ICU discharge. Cognitive impairment, muscle weakness, and psychologic symptoms were frequent. A large multicenter study is warranted to allow identification of modifiable factors for improving long-term outcome.


COVID-19 ranges from an asymptomatic infection to severe respiratory failure and associated nonrespiratory complications and multiple organ failure.[1] Patients with severe COVID-19 may require ICU admission for acute respiratory distress syndrome (ARDS).[2] ARDS survivors may present with severe sequelae that affect nerves, muscles, and the CNS, leading to long-term functional and cognitive impairment.[3]

There is growing recognition that COVID-19 can lead to both acute and long-term neurologic sequelae. Proposed mechanisms of severe acute respiratory syndrome coronavirus 2–associated neurologic complications include direct neuroinvasion and indirect mechanisms of vascular and inflammatory/autoimmune origin.[4] Underrecognition of neurologic manifestations may contribute to an increase in long-term complications and poor outcomes.[5] In addition, there is a high burden of general critical care complications, which can make specific attribution to COVID-19 difficult.

As the pandemic is still ongoing, there is increasing concern about long-term disability in survivors of COVID-19–associated ARDS.[6] The long-term functional consequences of the most severe forms of COVID-19 have been little studied. Of note, most studies conducted to date were monocentric or used telephone interviews.[7–9]

The aim of this study was to describe 3–6-month functional and neuropsychologic outcomes of survivors of COVID-19–associated ARDS requiring invasive mechanical ventilation, during the two first waves of the COVID-19 pandemic.