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Doctors Say Mild Covid-19 Likely Triggered Psychiatric Illness in Two Teen Patients

The spinal fluid of two teens experiencing sudden psychiatric symptoms, including delusion, contained antibodies known to attack the nervous system.

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A MRI scan of one of the patients, with the arrow pointing to a suspected lesion.
A MRI scan of one of the patients, with the arrow pointing to a suspected lesion.
Photo: Bartley CM, et al/JAMA Neurology

Researchers in California suspect that covid-19 triggered sudden mental illness in at least two of their teenage patients. Though they caution that a causative link remains uncertain, they say they’ve found evidence of antibodies attacking the brain of their patients post-infection, which could help explain the psychiatric symptoms.

Since the very start of the pandemic, some researchers have warned that covid-19 could contribute to a wave of neurological illness, based on the history of previous pandemics. Since then, studies have shown that covid-19 survivors do seem to be at higher risk for ailments like depression and anxiety. Some researchers and patient advocates have also argued that long covid—the constellation of chronic symptoms reported by some survivors—can include neurological impairments.


The stress of simply having covid-19 could certainly influence a person’s mental health, as could the aftereffects of a severe infection and hospitalization. But it’s possible that the virus itself could directly impact the nervous system and brain, even in mild cases, and these interactions could then lead to a higher risk of neurological and psychiatric disorders. Because mental illness is unfortunately common and often linked to a variety of influences, it can be difficult to show cause and effect from any one thing, including a viral infection.

But doctors at the University of California, San Francisco (UCSF) Benioff Children’s Hospital say they’ve come across a few cases in the past year where covid-19 does seem to have been a primary trigger for a patient’s sudden mental illness. In a new paper published Monday in JAMA Neurology, they describe teen patients who developed newly documented psychiatric symptoms, including extreme mood swings, paranoid delusions, and suicidal ideation, after a confirmed but mild or asymptomatic case of covid-19. It’s the timing of these events that suggests the symptoms were connected to the infection, study author Sam Pleasure, a UCSF neurologist, told Gizmodo.


In the spinal fluid of two patients, the team also found antibodies to the coronavirus, known as SARS-COV-2, as well as autoantibodies to the nervous system. In one patient, these traitor antibodies seemed to target a gene responsible for making a protein called transcription factor 4 (TCF4), which is notable because variations of the gene have been linked to psychiatric disorders including schizophrenia. The patients had a history of some mental health problems, such as anxiety and tics, but not to the extent documented by the doctors.

A third teenage patient had neither kind of antibody in their nervous system, and it was determined that the most likely cause of their symptoms was an unknown drug they had taken days earlier.

But with the other two, those antibodies indicate that the coronavirus can reach the nervous system and stir up trouble there. It may be that the virus isn’t directly causing these symptoms, but rather that it helps generate a self-destructive immune response.

“We know that covid-19 is a potent stimulus for increased inflammatory responses, and one possible cause of these symptoms is that they are associated with this ‘generic’ increase in inflammation,” Pleasure explained in an email.


In the two patients where covid-19 was seen as a likely trigger, the doctors chose to treat them with immunotherapy, including steroids to tamp down inflammation. One patient seemed to respond well and by a month later had stopped reporting delusions and twitching. The second patient seemed to respond modestly to the immunotherapy, and by the six-month mark they were still improved but continued to have memory problems and trouble concentrating.

The authors found other reports of similarly timed cases among hospitalized adult covid-19 patients. Pleasure noted that immune-related problems after an infection have been documented well before covid-19, often linked to viral infections. These post-infection cases in general seem to be rare, but there are still many unknowns.


“We don’t at this point know how common this is with covid-19 infection and may be seeing patients primarily because of the very large numbers of infected people at about the same time,” Pleasure said.

To better understand these cases and definitively establish a link between sudden psychiatric illness and covid-19 would require more research, which the authors say they’re conducting now.


“We are working on studying larger numbers of prospectively followed patients with post-covid neurologic and psychiatric symptoms,” Pleasure said. “We are also able to compare such patients to ‘controls,’ i.e. patients after covid without neuropsychiatric symptoms.”