Favorable responses to upadacitinib, a JAK1 inhibitor, in long COVID patients with predominant neuropsychiatric symptoms: case reports in 2 autistic patients and one typically developing patient.

Three people (including two with autism) had ongoing brain-related symptoms after COVID-19 infection. They were given a medication called upadacitinib that helps control inflammation in the body. All three patients showed improvement in their behavioral symptoms and blood tests showed less inflammation. This suggests the medication might help with long-term COVID symptoms affecting the brain, though more research is needed.

This case report describes three patients (two with autism spectrum disorder, one neurotypical) who experienced long COVID with neuropsychiatric symptoms resembling encephalopathy. All patients were treated with upadacitinib, a JAK1 inhibitor that blocks type 1 interferon signaling pathways thought to contribute to long COVID neuropsychiatric symptoms. Treatment resulted in improved behavioral symptoms and less activated immune profiles in peripheral blood monocytes. The authors suggest that long COVID may be particularly difficult to diagnose in autistic individuals due to overlapping symptoms with existing behavioral challenges.

This preliminary evidence suggests potential therapeutic benefits of JAK inhibitors for long COVID-associated neuropsychiatric symptoms in both autistic and neurotypical populations.

These preliminary findings suggest JAK1 inhibitors may benefit long COVID neuropsychiatric symptoms in both autistic and neurotypical individuals. However, larger controlled studies are needed before clinical recommendations. Clinicians should consider long COVID as potential contributor to worsening symptoms in autistic patients post-COVID infection.

Case report with only three patients provides very preliminary evidence. No control group, randomization, or blinding. Unclear follow-up duration and outcome measurement methods. Cannot establish causation or generalizability to broader populations.

The long-term impact of coronavirus disease 2019 (COVID-19) has become evident over the past 3-4 years, with the recognition of post-COVID long-term sequelae, often referred to as long COVID. Neuropsychiatric symptoms are one of the hallmarks of long COVID. In severe cases, it can even present features of encephalopathy. Since some of the neuropsychiatric symptoms associated with long COVID overlap symptoms found in neuropsychiatric disorders, it has been difficult to sort out the effects of long COVID in such subjects.

This is especially true in patients diagnosed with autism spectrum disorders (ASD), given their difficult behavioral symptoms and other co-morbid conditions. COVID-19 is thought to affect the onset or progress of encephalopathy symptoms by activation of the immune system through the type 1 interferon (IFN) signaling pathway. In that case, treatment would require an immunomodulating agent that targets such pathways. However, such measures may not be applied to ASD subjects, in whom long COVID may not even be considered as the cause of their symptoms.

In this study, we present the beneficial effects of upadacitinib, a JAK (janus kinase) 1 inhibitor, that blocks downstream signaling of type 1 IFNs, on 3 patients, 2 with ASD and one without ASD. In these patients, long COVID was thought to have triggered or aggravated encephalopathy-like symptoms. The beneficial effects of upadacitinib were not only noted by an improvement of their behavioral symptoms but also shown by an improvement of monocyte cytokine profiles (less activated state); peripheral blood monocytes were used as surrogates of microglial cells. These three cases presented highlight a possible use of JAK inhibitors for treating long COVID-associated neuropsychiatric symptoms in both ASD and non-ASD subjects.

The presented cases highlight the inherent difficulty of diagnosing long COVID in ASD cases.