Encephalopathy
Encephalopathy, which often presents in infectious disease patients as delirium, is a brain disorder that causes acute or subacute dysfunction in terms of consciousness or altered mental states. The elderly, people with cognitive deficits, and people with hypertension are elevated risk for developing an altered mental state with COVID-19 [52,74]. Cerebral edema, a dangerous condition which can cause elevated intracranial pressure and encephalopathy, has been identified in COVID-19 decedents [75]. Those with a history of neurological damage and acute respiratory distress are at elevated risk for developing encephalopathy as the initial COVID-19 symptom [76]. The risk becomes greater as the COVID-19 becomes more severe; altered consciousness occurs in 2.4% of mild and 15% of severe COVID-19 patients [52]. The risk for delirium, like the risk for worse outcomes with COVID-19, is also associated with older age [77]. The use of sedatives, which is common in critically ill patients, may also be associated with the risk for delirium [78,79]. Social distancing mandated for COVID-19 may actually contribute to the rate of delirium of certain COVID-19 patients, who may feel desperate and panicked as they are isolated, separated from family, alone, and/or denied religious support from a clergyperson [77].
Delirium in hospitalized COVID-19 patients may be the result of direct CNS invasion, induction of CNS inflammatory mediators, a secondary effect of other organ system failures, the effect of sedation, the result of prolonged mechanical ventilation, a psychological manifestation, or caused by environmental factors [77]. In cases of COVID-19, it is thought that delirium caused by direct invasion of the virus into the CNS is relatively rare, but possible, and would likely be accompanied by seizures, altered states of consciousness, or signs of increased intracranial pressure [39,46].
The rates and presentation of encephalopathy and delirium in COVID-19 patients has not been studied. Delirium in COVID-19 patients may be under-reported to date, indeed delirium is thought to be widely under-reported for various conditions unless it is being specifically monitored [79–82]. Case studies of COVID-19-associated delirium appear in the literature [83,84]. Acute necrotizing encephalopathy, although relatively rare, has also been diagnosed in a hospitalized COVID-19 patient [85]. Overall, ICU patients on mechanical ventilation have rates of delirium as high as 70% to 75%, and delirium is associated with mortality and long-term cognitive impairment [86–88].
The causes of COVID-19-associated encephalopathy may involve multiple factors, including metabolic causes, hypoxia, and drug therapy. Symptomatic treatment involves antipyretics, anticonvulsants, and treatment for hypoxia [21]. Early signs of delirium in COVID-19 patients might suggest CNS involvement and, as such, might indicate heightened risk for impending respiratory failure [77].
In a study of 27 pediatric COVID-19 patients with multisystem inflammatory syndrome, 15% (n = 4) exhibited new-onset neurological symptoms, such as encephalopathy, headaches, brainstem, and cerebellar signs, weak muscles, and poor reflexes [89]. Cerebrospinal fluid testing in two patients were acellular; three patients underwent nerve conduction and electromyographical studies, which revealed mild myopathic and neuropathic deficits. All four patients improved, two of whom made a complete recovery over the course of the study [89].