Abulia major and hypoactive delirium in COVID-19 reversed with methylprednisolone pulse therapy

Background: Sars-CoV-2 is a member of the genus Betacoronavirus like the two other coronaviruses viz. SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus). SARS-CoV-2 infection has been associated with neuropsychiatric manifestations in acute and chronic COVID-19 (long COVID-19 syndrome), resulting in social consequences and worsening people's quality of life. Case description: This article is a scenario of two cases of neurological manifestations resulting from infection by SARS-CoV-2 that were reversed with methylprednisolone in a pulse therapy regimen. The first case presents a young patient with symptoms similar to those existing in patients with Alzheimer's and Parkinson's diseases, whose final and presumable diagnosis was Abulia major. The second case exemplifies an elderly person admitted to the hospital due to hypoactive delirium triggered by a urinary tract infection hypothesis. The final diagnosis was hypoactive delirium secondary to COVID-19, with urinary manifestations from SARS-CoV-2 kidney injury. Discussion/Conclusion: The purpose of this article is to warn about phenomena related to COVID-19, whose treatment can be performed with high doses of corticosteroids and with drugs that act positively on dopaminergic and serotonergic pathways. Patient exams and more information are available in the Appendix of this article.


Introduction
COVID-19 is a new disease that causes systemic disease, with the lungs just one of the injured organs. Neuropsychiatric symptoms have been reported in both acute COVID-19 and chronic inflammation triggered by SARS-CoV-2 infection.
This article presents two case reports, whose neuropsychiatric phenomena appear to have a causal relationship with SARS-COV-2 infection, both treated with methylprednisolone with good evolution.
Timeline 2022-07-31 COVID-19 Symptoms (The dates are hypothetical in order to preserve the patient's identity, but respect Case report generated using CARE-writer, care-writer.com the chronology of the interventions) In view of the situation without improvement after 2 months, given the exams and after the introduction of these new hypotheses, we jointly opted to perform methylprednisolone pulse for 3 Case report generated using CARE-writer, care-writer.com days with the possibility of performing immunoglobulin in case of refractoriness, that is, a decision that respected the wife's understanding of the subject.
The protocol and patient's evolution are described bellow: 1. First day (D1): METHYLPREDNISOLONE 1000 mg, intravenous, was performed, via infusion pump in 60 minutes.
3. Promethazine 25 mg, oral tablets, to prevent agitation, in addition to its anti-inflammatory effect on the central nervous system. After 1 year of the manifestations and the resolution of the condition, the patient had a new infection by SARS-CoV-2 (with positive RTPCR for SARS-CoV-2); however, milder than the first. A few days after the onset of symptoms, the patient began to experience tremors, anhedonia, and loss of self-confidence, requiring confirmation from the wife to perform any type of actions or even to answer any questions that were asked. He also showed an attitude of muteness, Case report generated using CARE-writer, care-writer.com increasingly silent and not very reactive to situations. Initially, I called the patient by telephone, where he showed himself with spontaneous speech, reporting the changes he had realized in himself: unwillingness to perform daily activities, sadness, loss of self-confidence, and motor slowing. in a second moment, via videoconference, the patient was silent, and for each question made by me, he needed confirmation from his wife. Unintentionally, this situation sets up "Miller Fisher's telephone effect" (appendix), The possible diagnoses were, in the first COVID-19, Abulia major and, in the second, Abulia minor.
For this new situation, the use of prednisolone 1 mg/kg/day for 3 days, L-dopa and citalopram triggered a global improvement in the patient. A joint discussion was performed with a psychiatrist who was performing the follow-up of the case.

Case 2:
Man, 93 years old, married, independent of performing daily activities, myelodysplasia as a comorbidity [Katz =5 and Lawton = Partially dependent for 5 activities (Appendix)], is admitted to the emergency room due to acute hypoactive delirium. Infection screening was performed. He had a chest X-ray without evidence of pneumonia, a blood count with mild anaemia associated with myelodysplasia, leukocytes ~25,000 (slightly more than the patient usually presents in normal situations due to his comorbidity), and urine routine: leukocyturia 70,000 haematuria: 10,000, hyaline casts). The patient was initially diagnosed with delirium secondary to urinary tract infection. However, when chest tomography was requested, it showed the tomographic pattern of acute COVID-19 (Appendix). The patient began to present sluggishness 4 days ago, so it was assumed that the patient had been symptomatic for approximately 5 days, consistent with the chest tomography image presented (Appendix).
According to epidemiology, signs and symptoms, laboratory changes and tomographic imaging, COVID-19 was the main diagnosis. Urinary alterations are compatible with the lesions caused by SARS-CoV-2 in the renal parenchyma, which have often been confused with urinary tract infections. The patient's daughter signs a consent form, and a pulse therapy regimen was performed with Methylprednisolone 250 mg once a day for three days ¹ . The patient evolved to have an improved condition. He did not develop cytokine storm syndrome and was discharged on the fifth day of hospitalization. Despite more controversies that exist about the use of methylprednisolone and corticosteroids in general, it has been the solution for COVID-19. When used properly and at the right time, the progression of the disease can be blocked.

Patient Perspective
The two cases presented are in acute situations in patients who were previously healthy and independent or partially dependent to perform daily activities. We are facing a new virus with singularities that are still obstacles that prevent the realization of adequate therapy. It is essential to highlight that medical action must always be based on the ethics that govern the medical profession, on not harming, on offering comfort when there is no possibility of cure-always judging each situation properly and considering that the patient has a family that needs support.
The use of corticosteroids, although controversial, has gained increasing evidence in the treatment of COVID-19, with benefits when used on time and in high doses. Corticosteroids are historically used to treat viral or autoimmune meningoencephalitis and the cases presented are examples of good use of the drug, promoting patients' improvement of symptoms with a return to the health status they had before they became ill.
All the families involved signed a consent form for the data to be published; in addition, both families provided me with all the exams to help with the publication of the reported cases.
Methylprednisolone doses were based on the study published by Maryan Edalatfard et al. In addition, the higher doses between 500 and 1000 mg of Methylprednisolone were based on other publications on the subject and on the preliminary results of the COVER-ME-UP study, based on the Tehran protocol. The COVER-ME-UP study was carried out after approval by the National

Conclusion
Corticosteroids have side effects, but they are medicines that have been used for many years, and in the face of an inflammatory disease due to SARS-COV-2 infection, the nonspecific target of steroids has been our best treatment ¹