Assessing the Role of Inflammation in the Development of Delirium and Post-ICU PTSD in Survivors of Acute Respiratory Distress Syndrome due to COVID-19

Abstract: Background/ Significance: Approximately 20-30% of patients with acute respiratory distress syndrome (ARDS) develop symptoms of post-traumatic stress disorder (PTSD) in the months after hospitalization.¹ Delirium is also common in ventilated patients in the Intensive Care Unit (ICU). Though the relationship between delirium and PTSD is not well understood, both have been associated with pro-inflammatory states, highlighting a potential shared neuropathogenesis.^2,3 Coronavirus Disease 2019 (COVID-19) led to a high incidence of both critical illness and delirium, typically with significant systemic inflammation. Accordingly, we will examine the prospective relationships between delirium and markers of inflammation during hospitalization and the incidence of PTSD symptoms following discharge.

Methods: In this retrospective, observational study, participants will consist of 346 adult survivors of critical illness due to COVID-19 in Boston ICUs during Waves 1 (March- June 2020) and 2 (December 2020-January 2021) of the pandemic. We will utilize the Confusion Assessment Method (CAM-ICU) scores and Richmond Agitation Sedation Scale (RASS) scores from the medical record to characterize the presence, duration, and severity of delirium during index hospitalization. Inflammatory status will be characterized with objective markers such as lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), interleukin-6, and C-reactive protein. We will administer surveys validated for the assessment of symptoms of post-traumatic stress, depression, anxiety and cognitive dysfunction, including Impact of Events Scale-Revised, Hospital Anxiety and Depression Scale, and Telephone Montreal Cognitive Assessment.

Results: Data collection and analysis is currently in progress and should be completed by October 2024. Of the initial cohort of surviving patients, 197/346 (57%) were diagnosed with delirium during their hospitalization. We will discuss the relationship between delirium during index hospitalization and the development of symptoms of PTSD on follow-up, as well as the contribution of systemic inflammation during illness to both delirium and PTSD.

Discussion: We hypothesize that both the presence of delirium and higher degrees of systemic inflammation during critical illness due to COVID-19 will predict the development of PTSD symptoms on follow-up assessment. Further research would then be necessary to understand to what extent inflammation mediates the relationship between delirium and PTSD, as well as the effect of treatment-related variables including anti-inflammatory medication.

Conclusions/ Implications: Greater understanding of the relationship between systemic inflammation in critical illness and the development of delirium and PTSD will help elucidate potential shared neuropathogenesis of these highly morbid conditions in patients with ARDS.