“Paranoia-like fears,” delusions, and a “foggy brain” have been found in three adolescents who had mild or asymptomatic COVID-19, according to a new study. Now, a recent investigation of their immunological responses has identified a possible reason for the emergence of these symptoms.’
UCSF Weill Institute for Neurosciences and UCSF Department of Pediatrics researchers conducted the first study to examine anti-neural antibodies, “turncoat” antibodies that may target brain tissue, in juvenile SARS-CoV-2 patients.
UCSF Benioff Children’s Hospital-San Francisco treated 18 children and teens with proven COVID in 2020, according to research published in JAMA Neurology on Oct. 25, 2021. They included the three patients who had undergone neurological examinations in the research.
Using a lumbar puncture, researchers discovered that two of the patients contained antibodies to SARS-CoV-2 in their cerebrospinal fluid, indicating that the virus had infiltrated the central nervous system. As a result of immunostaining brain tissue, the same patients with mild/asymptomatic COVID also had anti-neural antibodies in their cerebrospinal fluid. Rather than focusing on infectious bacteria, this suggests an overzealous immune system.
UC San Francisco and Yale researchers published their findings in Cell Reports Medicine on May 18, 2021, which indicated that autoantibodies were discovered in the cerebrospinal fluid of adult COVID patients with neurological symptoms, such as intractable headaches, seizures and loss of smell.
Whether COVID is a prevalent cause for neuropsychiatric diseases or not, “it does seem to be a potent trigger for the development of autoantibodies,” co-corresponding author Samuel Pleasure, MD, PhD, of the UCSF Department of Neurology and of the Weill Institute, said in a press release. Patients with a history of neuropsychiatric disorder may be more susceptible to developing worsening symptoms following a COVID infection, or COVID infection may serve as an independent trigger.
Patients with identical neuropsychiatric symptoms have thus far failed to find an autoantibody shared by all of them, says co-first author Christopher Bartley of the UCSF Department of Psychiatry and Behavioral Science. “These autoantibodies may be most clinically meaningful as markers of immune dysregulation, but we haven’t found any evidence that they are actually causing the patients’ symptoms. ” As far as I can tell, there’s a lot more to be done here.”
According to co-first author Claire J. Johns, MD, a pediatrician at the University of California, San Francisco, the three patients in the UCSF study exhibited quick onset and rapid progression of symptoms that represented a considerable change from their baselines. Patients displayed considerable mental manifestations despite modest respiratory symptoms, suggesting possible short and long-term effects of COVID.
Intermittent intravenous immunoglobulin, an immunomodulatory therapy that reduces inflammation, was administered to the two UCSF patients whose cerebrospinal fluid tested positive for SARS-CoV-2 antibodies and anti-neural antibodies after lengthy hospitalizations and psychiatric drugs. There were “less paranoid and improved insight” in the first patient five days later.
Autoantibodies against the protein TCF4, which has been linked to schizophrenia in some families, were also identified in this patient. Co-author Michael R. Wilson, MD, of the UCSF Department of Neurology and of the UCSF Weill Institute said that “we don’t know that antibodies are actually interfering with the protein’s function,” noting that schizophrenia is diagnosed based on the constellation of symptoms rather than the specific biomarker.
However, six months after starting immunotherapy, the second patient was still experiencing “impaired mood and cognitive symptoms,” even if their cognition and working memory had improved. No anti-neural or anti-SARS-CoV-2 antibodies were found in the CSF of the third patient, who had no prior history of psychiatric illness. He recovered completely from his condition thanks to medicine for his condition. The cause of his symptoms was found to be recreational drug use.
However, on April 9th, 2021 the case study by Yale and UCSF, which detailed the delusions and violent outbursts of one 30-year-old patient with modest symptoms of COVID who showed up in the emergency room of the hospital with hyper anxiety and paranoia revealed a more dramatic response. Intravenous immunoglobulin was prescribed when antipsychotic drugs failed to bring about a long-term improvement in his condition. Before long, his symptoms began to improve and he was discharged from the hospital without antipsychotic medication.
We can’t tell for sure that immunotherapy had any effect on the clinical course of these patients,” said Wilson. Two UCSF patients may have recovered without immunotherapy because of concomitant treatment with psychiatric medicines or the passage of time, according to the researchers.
Anti-NMDAR encephalitis syndrome, for example, is caused by anti-neural antibodies, which can be treated by targeting these rogue antibodies.
Even while the researchers agree, more investigation is needed, Pleasure stated that the lack of CSF fluid samples from pediatric patients is an issue. ‘We don’t get to analyze the cerebrospinal fluid in kids very often,’ he stated. Lumbar puncture is not necessary for children with COVID, and children with multisystem inflammation usually don’t have a specific cause to get one.’
As a result, there is increasing evidence that COVID can cause psychological and neurological problems. Among the nearly 250,000 COVID patients older than 10 years old surveyed in the United Kingdom earlier this year, researchers found that 34% of those individuals received a neurological or psychiatric diagnosis in the six months that followed, with 13% receiving their first such diagnosis.