Delirium in COVID-19: A case series and exploration of potential mechanisms for central nervous system involvement

Abstract

Introduction: Neuropsychiatric manifestations of the coronavirus disease 2019 (COVID-19) have been described, including anosmia, ageusia, headache, paresthesia, encephalitis and encephalopathy. Little is known about the mechanisms by which the virus causes central nervous system (CNS) symptoms, and therefore little guidance is available regarding potential workup or management options.

Cases: We present a series of four consecutive cases, seen by our psychiatry consultation service over a one-week period, each of which manifested delirium as a result of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Discussion: The four cases highlighted here all occurred in older patients with premorbid evidence of cognitive decline. Unique features seen in multiple cases included rigidity, alogia, abulia, and elevated inflammatory markers. In all four cases, a change in mental status was the presenting symptom, and three of the four cases lacked significant respiratory symptoms. In addition to discussing unique features of the cases, we discuss possible pathophysiologic explanations for COVID-19 delirium.

Conclusions: Delirium should be recognized as a potential feature of infection with SARS-CoV-2 and may be the only presenting symptom. Based on the high rates of delirium demonstrated in prior studies, hospitals should consider adding mental status changes to the list of testing criteria. Further research is needed to determine if delirium in COVID-19 represents a primary encephalopathy heralding invasion of the CNS by the virus, or a secondary encephalopathy related to systemic inflammatory response or other factors.

Keywords: Akinetic mutism; COVID-19; Delirium; Encephalopathy; SARS-CoV-2.

Fig. 1

Hypotheses of encephalopathy pathogenesis in COVID-19. Note that the model depicted below is hypothetical in nature and is meant to demonstrate the myriad ways in which SARS-CoV-2 infection may induce encephalopathy. For example, while a hallmark of COVID-19 is ARDS and associated hypoxemia, the mechanism of immune dysfunction in COVID-19 and its role in encephalopathy has yet to be established. Abbreviations: SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2, IRS: immune reconstitution syndrome, BBB: blood-brain barrier, ARDS: acute respiratory distress syndrome, DAD: diffuse alveolar damage, DIC: disseminated intravascular coagulation, PE: pulmonary embolism CVA: cerebrovascular accident, MODS: multiorgan dysfunction syndrome (sepsis), IL1-R: interleukin-1 receptor, LC: locus coeruleus, VTA: ventral tegmental area, SN: substantia nigra, RN: raphe nucleus, ACC: anterior cingulate cortex, FTC: frontotemporal circuits.