At a time in everyone’s life, we come to find ourselves in a situation where the music stops, and we must go on.  The unfortunate truth about life is that the unexpected will happen. Some of us learn from it, some of us change because of it and some of us find our life’s calling because of it. The latter was the case for me.  After our dad picked us up from middle school, we spent that afternoon like we had every afternoon that month. We went to the oncology unit at the hospital, where my brother was admitted.



I remember him. I remember the man in the dark blue sarong the same way I remember the lines on back of my own hand. He was hunched over next to a column on a dirty platform at a railway station in Calcutta, India in the middle of the harsh summer sun. His hands were withered, his fingers and toes looked like tiny nubs, and he was completely malnourished and alone. He had opaque blue eyes, as if fog had taken place of his irises and pupils.



I studied insects in college; my favorite insects were the bees (I found them diligent and so helpful to humankind).  One of my favorite classes was about medical diseases caused by insects. My professors noticed my interest in the medical side of things and connected me with a professor who did clinical research. Our work focused on a clinical trial for children with intractable epilepsy and exposed me early on to patient care and patients.


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presentation at hospital which improved as his psychosis improved. Two general mechanisms of central nervous system involvement have been proposed to explain neuropsychiatric symptoms of COVID- 19 infections:

There is a large body of literature that reports the occurrence of obsessions and compulsions in patients who have recently recovered from viral encephalitis. Obsessive-compulsive disorders (OCD) were recognized and linked with von Economo’s encephalitis. To date, OCD has not been reported with COVID-19, but since it has been reported in other viral infections of the brain, it is suspected that COVID-19 may therefore trigger OCD in surviving subjects. (1)

A recent international article by Shah et al. (2020) has reviewed mental health during the Coronavirus pandemic and applied that to information from past outbreaks in pandemics. These authors noted substantial evidence from past studies of the impact of SARS, MERS, influenza, and Ebola epidemics; the at-risk population showed neuropsychiatric linkages. (7)

Neuropsychiatric Complications of COVID-19

It has recently been proposed that not only is the COVID-19 pandemic a significant psychological stressor, but it is also noted to cause significant neuropsychiatric symptoms associated with potential immunologic mechanisms.8 As far as psychological stressors, there are unsettling case reports of suicide deaths related to fears of contracting or spreading COVID-19. The following have also been reported recently in association with infection of the COVID-19 virus: encephalopathies, anosmia, ageusia, chronic neuropsychiatric sequelae such as depression, anxiety, and trauma-related disorders, psychotic disorders, demyelinating and neuromuscular complications, and neurodegenerative disorders. (9)

There is a case report of a 69-year-old Caucasian female with no prior psychiatric history who developed excited catatonia 1 month after acquiring COVID-19. She was seen in the emergency department of a University hospital in San Diego and presented with bizarre behavior, confusion, and paranoid thoughts for four to six weeks. She thought the government was tracking her and thought her husband had drugged her and bugged her phone. Upon presentation, her Glasgow Coma Scale score was 15, and she had a blood pressure of 174/87 with a pulse of 85. Other vital signs were within normal limits. During the first few days of hospitalization, she remained alert and oriented but displayed extreme agitation and aggression that intermittently necessitated restraints. She displayed some rigidity on physical examination, was extremely restless and agitated, demonstrated poor eye contact, and had a flat affect with echolalia and loose associations. She was not thought to be demented nor delirious, because she remained alert and oriented to time, place, and person. She was diagnosed with excited catatonia occurring in association with COVID-19 infection and successfully treated with Lorazepam. What made this patients’ presentation and case history dramatic compared to reports of other studies was that hers was so delayed and appeared more than a month after her original infection.

Frequent delirium has been associated with COVID-19 infection. It is recognized that delirium in patients with COVID-19 has many possible etiologies, and catatonia is a potential outcome. Delirium appears to be common in COVID-19 infection.(10) The authors of this article recommend that the practices of previous delirium studies should be followed, and they suggested using the well-validated Delirium Rating Scale-Revised-98 (DRS-R98) for serial assessments.

A recent neurological and neuropsychiatric surveillance study of 153 patients was presented in Lancet Psychiatry (2020).(11) This study is touted as the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID- 19. Altered mental status was the second most common presentation, also comprising encephalopathy or encephalitis and primarily psychiatric diagnoses, often occurring in younger patients.

Neurologic Complications of COVID-19

The findings of numerous studies show that beyond the acute pulmonary illness, nervous system and neurocognitive disorders, psychiatric disorders, and neurologic disorders, often appear as delayed manifestations of COVID-19.(12) In particular, neurological presentations of COVID-19 may reveal themselves as encephalitis, Guillain-Barré syndrome, and acute disseminated encephalomyelitis,(13) among other neurologic disorders. A preprint from Wuhan, China reports 36% of 214 patients with confirmed COVID-19 manifested neurological disorders.(14)

It is not yet fully clear how SARS-CoV-2 virus infects the brain. Little of the virus is found in CSF, yet oligodendrocytes are susceptible and COVID-19 encephalitis usually is a white matter disease. Patients with neurological complications often require prolonged ICU stays.(14)

Neuroinflammatory crises often are seen but use of IV immunoglobulins increases risk of thromboembolism and is often associated with increased D-dimer levels(15) and may be avoided in some. Delayed neurological side effects of COVID-19 remain to be fully elucidated and diagnostically verified.    


  1. Steardo L Jr, Steardo L, Verkhratsky A. Psychiatric Face of COVID-19. Translational Psychiatry, 10: 1-12 (2020). doi.10.1038/s41398-200- 00949-5
  2. To KK, Tsang OT, Leung WS, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS- CoV-2: an observational cohort study. Lancet Infectious Disease; 20(5) 565- 574
  3. Diger RN, Johnson RW. Aging, microglial cell priming, and a discordant central inflammatory response to signals from the peripheral immune system. Journal of Leukocyte Biology, 84: 932-939 (2008)
  4. Parker C, Slan A, Shalev D, Critchfield A. Abrupt late-onset psychosis as a presentation of Coronavirus 2019 disease (COVID-19): A longitudinal case report. Journal of Psychiatric Practice, 27: 131-136 (2021)
  5. Baig AM. Neurological manifestations in COVID-19 caused by SARS-CoV-2. CNS Neuroscience Therapeutics, 26: 499-501 (2020)
  6. Desforges M, le Coupanec A, Dubeau P, et al. Human coronal viruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system? Viruses, 12: 14 (2019)
  7. Shah K, Kamrai D, Mekala H, et al. Focus on mental health during the Coronavirus (COVID-19) pandemic: applying learnings from past outbreaks. Cureus, 12(3): e7405. doi.10.7759/cureus.7405
  8. Troyer EA, Kohn JN, Hong S. Are we facing a crashing wave of neuropsychiatric sequelae of COVID- 19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain, Behavior, and Immunity, 87:34- 39 (2020)
  9. Zain SM, Muthukanagaraj P, Rahman N. Exited catatonia – a delayed neuropsychiatric complication of COVID-19 infection. Cureus, 13(3): e13891. doi.7759/cureus.13891
  10. Beach SR, Praschan NC, Hogan C, et al. Delirium in Covid-19: A case series and exploration of potential mechanisms for central nervous system development. General Hospital Psychiatry; 65:47-53 (2020)
  11. Varatharaj A, Thomas N, Ellul MA, et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. Lancet Psychiatry, 7:875-882 (2020) Published online June 25, 2020, 0366(20)3087-X
  12. Ziyad AA, Xie Y, Bowe B. High- dimensional characterization of post- acute sequelae of COVID-19. Nature; Published online: 22 April 2021, https// 03553-9
  13. Needham EJ, Chou, SH-Y, Coles AJ et al. Neurological implications of COVID-19 infections. Neurocritical Care; 32: 667-671 (2020), https//doi. org/10.1007/s12028-020-00978-4
  14. Mao L, Wang M, Chen S et al. Neurological manifestations of hospitalized patients with COVID- 19 in Wuhan China: a retrospective case series study, https// 1101/2020.02.22.20026500
  15. Zhou F, Yu T, Du R, et al. Clinical course, and risk factors for mortality of adult inpatients in Wuhan, China: a retrospective cohort study. Lancet; 395: 1054-1062 (2020)

Pandemics have shaken the foundation of society and turned the course of history and the mindset of humanity for centuries. Typhoid fever attacked and devastated Athens in 490 B.C. giving the military society of Sparta upper hand in the Peloponnesian War. The Black Death caused by Yersinia pestis killed a third of the population of Europe and instigated drastic changes in economic relations that ultimately disposed of serfdom and feudalism and laid foundations of Renaissance. The last global epidemic of Spanish Flu responsible for 20 to 50 million deaths coincided with First World War and resulted in conflicts and the birth of Bolshevism. This brought great confusion to mankind.

The COVID-19 pandemic has changed the world and is changing the culture and human interactions in the US, possibly forever. COVID-19, also known as SARS-CoV-2 can linger for a long time at both upper and lower respiratory tracts. (2) SARS-CoV-2 enters the body through various routes and causes systemic and tissue inflammation. This in turn, compromises the blood-brain barrier of the brain and floods it with pro-inflammatory factors. This leads to an increased production and secretion of other pro-inflammatory factors. The combination of systemic inflammation, hypoxia resulting from respiratory failure, and neuro-inflammation may trigger or exacerbate psychiatric, neuropsychiatric, and neurological diseases. (1)

COVID-19 and Psychiatric Illness

Major depressive disorder is one of the most frequent neuropsychiatric disorders linked to inflammatory injury to the brain.


There is ample evidence now in the world literature that COVID- 19 causes inflammation of the brain, and thus there appears to be at least a linkage to COVID-19 and the induction of depression in humans. Systemic infection has been shown to trigger major depression in elderly patients because of age-dependent decreases of immune homeostasis. (3) A review of COVID-19 and bipolar disorder does not give us the same types of literature sources, and the issue is not settled as to what relationship, if any, there is between COVID-19 and bipolar disorder.

COVID-19 is increasingly implicated in mental complications, such as psychosis. There is a potential causal link between COVID-19 infection and psychotic symptoms. However, case reports to this date have been incomplete, as the patients described had known psychiatric histories. One case in the world literature recently reported late-onset psychosis in a middle-aged man with no prior psychiatric history who tested positive for COVID-19 on admission to hospital. He presented with delusions, hallucinations, and disorganized thought and behavior, which subsequently led to inpatient psychiatric hospitalization where he was successfully treated by standard means. (4) This 57-year-old man had an abnormal Montreal Cognitive Assessment Clock- Drawing Test on initial


Robert P. Granacher, Jr., MD, MBA practices clinical and forensic neuropsychiaty in Lexington and Mt. Vernon, KY. He is a noted scientific author and past president of the Kentucky Psychiatric Medical Association. He is currently president-elect of the Lexington Medical Society and Clinical Professor of Psychiatry at the University of Kentucky College of Medicine.