Antipsychotic-induced immune dysfunction: A consideration for COVID-19 risk

Patients with severe mental illness are more susceptible to infections for a variety of reasons, some associated with the underlying disease and some due to environmental factors including housing insecurity, smoking, poor access to healthcare, and medications used to treat these disorders. This increased susceptibility to respiratory infections may contribute to risk of COVID-19 infection in patients with severe mental illness or those in inpatient settings. Atypical antipsychotic (AA) medications are FDA approved to treat symptoms associated with schizophrenia, bipolar disorder, depression and irritability associated with autism. Our team and others have shown that AA may have anti-inflammatory properties that may contribute to their efficacy in the treatment of mental health disorders. Additionally, AA are widely prescribed off-label for diverse indications to non-psychotic patients including older adults, who are also at increased risk for COVID-19 complications and mortality. The aim of this study was to determine if AA medications such as risperidone (RIS) alter the ability to mount an appropriate response to an acute inflammatory or adaptive immune challenge using a preclinical model. Short-term treatment of healthy mice with a dose of RIS that achieves plasma concentrations within the low clinical range resulted in disrupted response to an inflammatory (LPS) challenge compared to vehicle controls. Furthermore, RIS also prevented treated animals from mounting an antibody response following vaccination with Pneumovax23®. These data indicate that short-to intermediate-term exposure to clinically relevant levels of RIS dysregulate innate and adaptive immune responses, which may affect susceptibility to respiratory infections, including COVID-19.