Mitigating neurological, cognitive, and psychiatric sequelae of COVID-19-related critical illness

Abstract

Despite advances in the treatment and mitigation of critical illness caused by infection with SARS-CoV-2, millions of survivors have a devastating, post-acute infection syndrome known as long COVID. A large proportion of patients with long COVID have nervous system dysfunction, which is also seen in the distinct but overlapping condition of post-intensive care syndrome (PICS), putting survivors of COVID-19-related critical illness at high risk of long-lasting morbidity affecting multiple organ systems and, as a result, engendering measurable deficits in quality of life and productivity. In this Series paper, we discuss neurological, cognitive, and psychiatric sequelae in patients who have survived critical illness due to COVID-19. We review current knowledge of the epidemiology and pathophysiology of persistent neuropsychological impairments, and outline potential preventive strategies based on safe, evidence-based approaches to the management of pain, agitation, delirium, anticoagulation, and ventilator weaning during critical illness. We highlight priorities for current and future research, including possible therapeutic approaches, and offer considerations for health services to address the escalating health burden of long COVID.

Figure 1:. Potential mechanistic pathways and therapeutic interventions for neuro-LC

An informed approach to mitigating and reversing neuro-LC symptoms will require a detailed understanding of its pathogenesis. The diagram summarises current understanding of potential mechanistic pathways of neuro-LC; many of the pathobiological features overlap with those of the post-intensive care syndrome. Dark green rectangles indicate therapies shown to be effective for acute COVID-19. Lighter green rectangles indicate novel therapeutics that are being studied to prevent or ameliorate neuro-LC. Persistent systemic and neuroinflammatory processes extending beyond the acute infectious stage are a unifying pathway for neuro-LC, although additional, unidentified mechanisms probably exist. Work in other neurological diseases such as stroke, multiple sclerosis, and Guillain-Barré syndrome indicates that this inflammatory cascade, if left unchecked, can lead to neuronal loss, grey and white matter atrophy, hypometabolism, and associated dysfunctional neuronal signalling in the CNS and peripheral nervous system. EBV=Epstein-Barr virus. Neuro-LC=neurological, cognitive, and psychiatric sequelae of COVID-19 (neuro-long COVID). NMDA=N-methyl-D-aspartate.

Figure 2:. Developing a survivorship community for patients with long COVID and PICS

Post-ICU support systems need to be strengthened to provide patients with cognitive and physical rehabilitation, easier connections to the health-care community through referrals from post-ICU clinics and dedicated social workers, and primary care physicians who recognise the manifestations of neuro-LC. Many patients with neurological symptoms meet diagnostic criteria for or have symptoms consistent with ME/CFS. Discerning these symptoms in the management of patients with neuro-LC is imperative because individuals with ME/CFS might need to apply rigorous pacing techniques to avoid cognitive and physical distress exacerbated by therapy. (A) A 32-year-old father, husband, firefighter, and emergency medical technician developed mild acute COVID-19 in October, 2021, despite being fully vaccinated. The patient was healthy, fully functional, and employed before infection, but showed symptoms consistent with cognitive impairment, post-traumatic stress disorder, and precipitous hearing loss after the acute disease, with resultant loss of employment. He had hearing evaluated as part of employment screening in 2014; the picture on the left, taken 8 months after acute COVID-19, shows hearing loss since the previous evaluation. This profound sensorineural hearing impairment as part of long COVID, which necessitated bilateral hearing aids, appears to be permanent. The picture on the right shows the patient in June, 2023, 1 year and 8 months after the acute disease; he has now received the first of two planned cochlear implants and he receives social security disability funds that make up about 50% of his previous income. (B) A support group of individuals with long COVID, facilitated by a neuropsychologist, at the Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN, USA. Patients in these groups have reported that the community saved them from near-certain suicide. We urge the medical community to create a safe place for patients with long COVID to have community in recovery. (C) Patients with long COVID need multidisciplinary clinical care and a support group of like-minded individuals, which should be a priority for long COVID and post-ICU centres worldwide to address the substantial burden of neuro-LC. The panel lists key components of the survivorship clinic and survivorship support group at the authors’ institution. ICU=intensive care unit. ME/CFS=myalgic encephalomyelitis/chronic fatigue syndrome. Neuro-LC=neurological, cognitive, and psychiatric sequelae of COVID-19 (neuro-long COVID). PICS=post-intensive care syndrome.