ROCHESTER, Minn. — Psychiatric conditions and cancer predicted a threefold greater risk of severe outcomes from COVID-19 among younger people who tested positive for the illness, according to a recent study by the Rochester Epidemiology Project of Mayo Clinic.

It's an unexpected finding from a project that affirmed the familiar list of risk factors for severe infection for all persons, but also identified previously unidentified risk factors unique to a subgroup of persons under 44 hospitalized with COVID-19 during 2020.

The study, published last month in the journal Mayo Clinic Proceedings, looked at common characteristics of almost 10,000 persons who tested positive for COVID-19 between March and September 2020, then developed severe outcomes as defined by hospitalization or death.

"Developmental disorders, personality disorders, and affective disorders, schizophrenia, and other psychoses," the paper stated, "were most strongly associated with risk of severe infection." For younger persons, heart disease, and chronic neurologic, endocrine and blood disorders all raised risk as well.

The elevated hazard ratio for those with psychiatric diagnoses was rivaled only by the risk unique to younger persons with cancer, who saw a threefold jump in risk of severe COVID-19. Cancer did not predict worse outcomes from COVID-19 in older persons.

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The psychiatric conditions which predicted worse outcomes included a two-fold increase in risk for those diagnosed with depression, anxiety and bipolar disorder, a seven fold risk for those diagnosed with schizophrenia and psychosis, and a threefold risk for personality disorders.

Psychiatric disorders share no identifiable biomarkers, making the findings all the more puzzling.

"That was really surprising to us, and we did talk about it quite a lot with our group," says Dr. Jennifer St. Sauver, lead author and professor of epidemiology at Mayo Clinic. St. Sauver says her team ruled out the effects on COVID-19 of some behavioral variables associated with mental illness, but held open the possibility of others.

"If you have very, very severe developmental disorders or psychiatric disorders," she says, "you might be more likely to live in a group setting, and we thought that might put you at an increased risk for acquiring the disease. But it wasn't obvious as to why you would have a more severe outcome, particularly if you're a younger person."

The researchers also speculated that delayed care could have been a factor in making younger persons with psychiatric diagnoses do poorly with COVID-19. But apart from access to care, the higher rates of hospitalization remained confusing.

"Why, biologically, would a group of people with personality disorders be at higher risk?" she says. "Particularly if they are young and they don't have other comorbidities. But we're seeing such a high hazard ratio it's a flag that this is a group that should be looked at in more detail."

The study did not explore the possible role of common psychiatric treatments in increasing the risk of poor outcomes from COVID-19, or in raising the risk of underlying conditions which themselves raise risk of poor outcomes from the illness.

St. Sauver believes treatments for cancer likely play a role in its relationship to severe COVID-19 in younger persons.

"When you're young and undergoing any cancer," St. Sauver said, "chances are it's a little more aggressive form of cancer, with more aggressive treatment. We didn't specifically collect data on cancer treatment, so we can't say that's what the cause is. But that's our speculation."

Severe outcomes from COVID-19 were highest among the oldest group studied, independent of chronic conditions. That group was followed by those aged 45-64. In keeping with previous findings, male sex, Hispanic ethnicity, Asian race, obesity and seven or more chronic conditions were associated with increase risk of severe infection overall.