Case Presentation: A 60-year-old male with a history of hypertension, diabetes, and hypercholesterolemia presented to the emergency department for worsening shortness of breath. Subjective and objective data lead to the preliminary diagnosis of bilateral pneumonia, COVID-19 positive, and soon thereafter developed acute hypoxic respiratory failure. This patient had a prolonged ICU course complicated by septic shock, ventricular tachycardia and acute renal failure requiring hemodialysis. Weaning trials off of the ventilator were started, but the patient was unable to be weaned due to critical illness, hypokinetic-rigid state and poor mental status. Despite all weaning attempts, he underwent a tracheostomy with PEG tube placement. He continued to remain in the ICU, with continued poor mental status and functional status. On day 47 due to continued poor neurological status, the patient was started on 25-100 mg of carbidopa-levodopa three times a day and 200 mg of modafinil in the morning. On day 49, he was awake, alert, and able to slowly move the right side of his body. He continued to improve, maintaining alertness and mobility, ultimately being able to be discharged to LTACH while on the carbidopa-levodopa regiment. At the LTACH he was able to be fully weaned off of the ventilator, and began eating more on his own; his tracheostomy was able to be removed, and as he was keeping up with his nutritional needs, his PEG tube was also removed. Patient continued to improve in the LTACH, and was discharged to acute rehab. At the acute rehab, he began walking with a walker, and on day 90 his modafinil and carbidopa/levadopa regiment was stopped. He was able to discharge to home.
Discussion: The COVID-19 disease process is associated with numerous clinical complications including a hyperinflammatory state, severe pneumonia requiring mechanical ventilation, coagulopathy, and most notably, significant neurologic and cognitive impairment. We propose that this cohort of patients has developed depleted dopamine stores in the brain resulting in preserved consciousness, tremors, and intact eye movements. Pharmacodynamic approaches to dopaminergic stimulation in patients with depleted dopamine stores include reversing the disruption in the presynaptic biosynthesis of dopamine via the administration of L-dopa. Neurostimulant medications such as carbidopa-levodopa (sinemet), amantadine, and modafinil have all been shown to improve and accelerate functional recovery and sleep-wake cycles following an acute stroke or total brain injury (TBI) in patients with depleted dopamine stores. We therefore present a case report describing the clinical course of a patient infected with COVID-19 and treated with a combination of 25-100 mg of carbidopa-levodopa three times a day and 200 mg of modafinil daily in the post-ICU, rehabilitation setting. This “Wake-Up Protocol” proved successful in waking up our patients.
Conclusions: In summary, we report that carbidopa-levodopa in combination with modafinil may be an effective treatment regimen for COVID-19 related neurologic dysfunction. This case report highlights the positive influence of neurostimulants following COVID-19 infection complicated by neurological sequelae. Further studies are warranted to examine the effectiveness of carbidopa-levodopa and modafinil or possibly amantadine-modafinil in patients with COVID-19 related encephalopathy or comatose state.