Three teenagers with COVID-19 suddenly developed severe psychological symptoms. Why?

Suicidal ideation, “paranoia-like fear”, delusions, and “foggy brain” have been identified in three adolescents with mild or asymptomatic COVID-19. New studies of their immune response are now identifying potential mechanisms by which these symptoms appear.

Research led by researchers UCSF Weil Neuroscience Laboratory And UCSF Pediatrics first looked for anti-neuronal antibodies (“turncoat” antibodies that could attack brain tissue) in pediatric patients infected with SARS-CoV-2.

During the five months of 2020, a total of 18 children and teens were hospitalized with confirmed COVIDs. UCSF Benioff Children’s Hospital San FranciscoAccording to a study published in JAMA Neurology On October 25, 2021. They included three patients in a study that underwent a neurological assessment.

Researchers examined the cerebrospinal fluid of patients obtained by lumbar puncture and found that SARS-CoV-2 invaded the central nervous system in two patients, both with a history of unspecified depression and anxiety. It turned out that he had an antibody that indicated that he might have. system. The same patient with mild / asymptomatic COVID had anti-neuronal antibodies in the cerebrospinal fluid. This was identified by immunostaining of brain tissue. This suggests that the immune system is out of control by accidentally targeting the brain instead of infectious microbes.

Autoantibody parallel in adults with neurological symptoms

This study follows a study published on May 18, 2021 at the University of California, San Francisco with Yale University. Cell Reports Medicine, It also found high levels of autoantibodies in the cerebrospinal fluid of adult patients with acute COVID who had neurological symptoms such as refractory headaches, seizures, and loss of odor.

“It’s too early to know if COVID is a common trigger for neuropsychiatric disorders, but it seems to be a powerful trigger for the development of autoantibodies,” said the co-author. Samuel Pleasure, MD, PhD, UCSF School of Neurology and UCSF Weil Institute. “Currently, it is completely unclear whether patients who are susceptible to neuropsychiatric disorders are more likely to worsen their symptoms after COVID, or whether COVID infection acts as an independent trigger.”

Efforts to identify autoantibodies shared by patients with similar neuropsychiatric symptoms have so far failed, the co-lead authors said. Christopher Bartley, MD, PhD, UCSF Psychiatry and UCSF Weil Institute. “These autoantibodies may have the most clinical significance as markers of immunomodulatory dysfunction, but we have not found any evidence that they are actually causing the patient’s symptoms. What to do in this area Certainly there are more. “

Unlike most psychiatric symptoms, three patients in the UCSF study show symptoms with sudden onset and rapid progression, representing significant changes from baseline, said the co-lead author of UCSF Pediatrics. Said Claire Johns, MD. “Patients show significant neuropsychiatric symptoms despite mild respiratory symptoms, suggesting potential short-term and long-term effects of COVID.”

After several weeks of hospitalization and continuous psychiatric medication, two UCSF patients whose cerebrospinal fluid was tested positive for SARS-CoV-2 and anti-neuronal antibodies were found to have autoimmune disease. He was treated with intravenous immunoglobulin, an immunomodulatory therapy that suppresses inflammation. Five days later, the first patient showed “more organized thinking, reduced delusions, improved insights”.

The patient was also found to have autoantibodies that target the protein TCF4, which is genetically associated with some cases of schizophrenia. However, “I don’t know that antibodies actually interfere with protein function,” the co-authors said. Michael R. WilsonPlease note that the diagnosis of schizophrenia, MD, UCSF School of Neurology and UCSF Weil Institute, is based on the constellation of symptoms, not specific biomarkers.

The second patient responded moderately to immunotherapy and appeared to have improved cognition and working memory, but continued to have “impaired mood and cognitive symptoms” after 6 months. rice field. A third patient with no history of psychosis and no SARS-CoV-2 or anti-neuronal antibodies in the cerebrospinal fluid recovered completely with psychiatric drugs. His symptoms were ultimately due to the use of recreational drugs.

Immunotherapy promotes a rapid response in adults with mental illness

A more dramatic response was reported in a case study by Yale University and the University of California, San Francisco. Biological psychiatry, April 9, 2021, it recorded a 30-year-old patient with mild symptomatic COVID who appeared in the emergency department of a hospital with delusions, violent explosions, excessive anxiety and delusions. After failing to achieve sustained remission with antipsychotics, he was diagnosed with possible “autoimmunity-mediated psychosis” and treated with intravenous immunoglobulin. His symptoms improved after the first day of treatment and he was eventually discharged without antipsychotics.

“Based on this limited number of patients, we do not know if immunotherapy has played a role in the patient’s clinical course,” Wilson warned. “In the case of two UCSF patients, it cannot be denied that either co-treatment with psychiatric drugs or the passage of time improved independently of immunotherapy.”

Nonetheless, researchers agree that existing autoantibodies are unlikely to exist, and anti-NMDAR encephalitis, which is caused by anti-neuronal antibodies and responds to treatment directed at these rogue antibodies. It points to other disorders with psychiatric symptoms such as syndrome.

Researchers agree that more research is needed, but Pleasure states that one obstacle to expanding this study is the lack of cerebrospinal fluid samples from pediatric patients. I did. “We can’t study cerebrospinal fluid in children very often,” he said. “Children with COVID are rarely ill enough to justify lumbar puncture, and children who are very ill with multiple inflammatory diseases usually have no special reason to do lumbar puncture.”

Meanwhile, growing research suggests that COVID increases the risk of psychiatric and neurological effects. A UK study published earlier this year found that out of approximately 250,000 COVID patients over the age of 10 had an estimated incidence of neurological or psychiatric diagnosis of 34% over the next 6 months. Thirteen percent received the first such diagnosis.

Other authors include Thomas Ngo, Ravi Dandekar, MS, Rita Loudermilk, Bonny Alvarenga, Isobel Hawes, Colin Zameknick, PhD, Kelsey Zorn, MHS, Jessa Alexander, Anne Wapniarski, Joseph Delisi,doctorate, Carla Francisco, MD, Kendal Nash, MD, and Sharon Wheatstock, MD, all UCSF.

This study was supported by the NIH Grant (NIMH R01MH122471; NINDSK08NS096117 and NINDSR01NS118995-14S) and the S10 Shared Instrumentation Grant (1S10OD017993-01A1). And the Brain Research Foundation. Dr. Bartley is supported by Hanna H. Gray Fellowship at Howard Hughes Medical Institute. UC President’s Postdoc Fellowship Program. UCSF John A. Watson Scholarship Program. And Latin Center of Excellence Grant Number D34HP3178.

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