Neurological symptoms are recognized in patients with COVID-19, and include anosmia, ageusia, cognitive impairments as well as more severe complications including encephalitis and ischemic strokes. Furthermore, persistent cognitive impairment including 'brain fog' is recognised as part of the long COVID syndrome. While SARS-CoV-2 has been shown to infect cells of the central nervous system (CNS) in vitro and in vivo, it is unclear whether direct infection of the CNS or indirect mechanisms including activation of the coagulation cascade or immune activation are the key drivers of COVID-19 neuropathology. We investigated whether inactivated SARS-CoV-2, or spike protein, can disrupt the integrity of the blood-brain barrier (BBB) and characterised neuroinflammation in the absence of infection. Using an in vitro model of the BBB composed of primary human microvascular endothelial cells, astrocytes, pericytes and microglia, we observed BBB disruption following exposure of the model to SARS-CoV-2 or spike protein. Importantly, loss of BBB integrity was observed in response to luminal (mimicking 'blood side') or abluminal ('brain side') exposure to inactivated virus or spike protein. Transcriptional upregulation of a range of chemokines, inflammatory cytokines and adhesion factors, and release of inflammatory cytokines from BBB models was also observed in response to luminal or abluminal SARS-CoV-2 or spike protein exposure. These data indicate that BBB disruption and immune activation in vitro occurs in response to SARS-CoV-2 in the absence of infection, highlighting the importance of the host immune system in BBB disruption during SARS-CoV-2 infection.

The COVID-19 pandemic has caused substantial worldwide disruptions in health, economy, and society, manifesting symptoms such as loss of smell (anosmia) and loss of taste (ageusia), that can result in prolonged sensory impairment. Establishing the host genetic etiology of anosmia and ageusia in COVID-19 will aid in the overall understanding of the sensorineural aspect of the disease and contribute to possible treatments or cures. By using human genome sequencing data from the University of Iowa (UI) COVID-19 cohort (N = 187) and the National Institute of Health All of Us (AoU) Research Program COVID-19 cohort (N = 947), we investigated the genetics of anosmia and/or ageusia by employing feature selection techniques to construct a novel variant and gene prioritization pipeline, utilizing machine learning methods for the classification of patients. Models were assessed using a permutation-based variable importance (PVI) strategy for final prioritization of candidate variants and genes. The highest held-out test set area under the receiver operating characteristic (AUROC) curve for models and datasets from the UI cohort was 0.735 and 0.798 for the variant and gene analysis respectively and for the AoU cohort was 0.687 for the variant analysis. Our analysis prioritized several novel and known candidate host genetic factors involved in immune response, neuronal signaling, and calcium signaling supporting previously proposed hypotheses for anosmia/ageusia in COVID-19.

We report two case studies that examine the therapeutic potential of structured psilocybin-containing mushroom biomass regimens administered within a clinical framework, evaluating their impact on mental health outcomes as well as associated somatic symptoms. Two patients underwent the De La Haye Psilocybin Treatment Protocol (DPTP), which integrates micro- and high-doses (combined psilocybin and psilocin content of 1-2 mg versus 40-60 mg) with psychohistoriographic psychotherapy. Follow-up included an integration session and subsequent office visits, including the completion of the Revised Mystical Experience Questionnaire (MEQ-30) two months post-treatment. Case 1 described a 29-year-old female with social anxiety, self-criticism, chronic musculoskeletal pain, and a recent diagnosis of diabetes. Post-treatment, she reported reduced shame, increased self-confidence, and substantial reductions in pain severity. Case 2 involved a 44-year-old female presenting with depression, hopelessness, and long-COVID-related anosmia and ageusia. She reported enhanced psychological resilience, improved mood, and resolution of diffuse body aches. Following the therapeutic dose, she also reported a 80-90% recovery of smell and taste after three years of dysfunction, post COVID-19 infection. The MEQ-30 scores were both high, indicating profound mystical-type experiences. These cases demonstrate improvements in psychological and somatic symptoms following participation in the DPTP. While the pain reduction and observed recovery of olfactory and gustatory function is noteworthy, spontaneous improvements cannot be excluded and further controlled investigation is warranted.

Taste disturbance is relatively common after acute stroke but is often overlooked because it is subjective and frequently overshadowed by more prominent neurological deficits. Gustatory dysfunction specifically associated with putaminal hemorrhage has rarely been reported. We describe a 43-year-old right-handed woman who developed acute bilateral loss of taste in close temporal association with a left putaminal hemorrhage, despite clinically preserved olfaction and only mild sensory symptoms. Brain magnetic resonance imaging demonstrated a small left putaminal hemorrhage with surrounding edema extending toward the thalamic region. Electrogustometry performed on hospital day 11, after partial subjective improvement, revealed bilateral but asymmetric gustatory impairment. Alternative causes, including peripheral cranial nerve dysfunction, medication-induced dysgeusia, postinfectious etiologies, and metabolic abnormalities, were considered less likely based on the clinical course and diagnostic evaluation. Her taste disturbance gradually improved and was completely resolved within two months. In this patient, the temporal association and imaging findings suggest, but do not prove, transient dysfunction of adjacent subcortical gustatory pathways, including thalamocortical projections or fibers near the internal capsule. Gustatory disturbance after putaminal hemorrhage is rarely reported and may be underrecognized in routine stroke assessment. Targeted inquiry regarding taste perception and, when available, objective gustatory testing may improve detection and characterization of this subtle manifestation in patients with deep hemispheric stroke.

Coronavirus disease 2019 (COVID-19)-associated encephalitis is a rare but severe neurological complication. Conventional diagnostic tools, such as magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) studies, may yield normal results despite significant functional brain impairment. Brain positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) has emerged as a valuable adjunctive imaging modality in such cases. We report the case of a 54-year-old woman with COVID-19 who presented with anosmia, ageusia, and altered behavior. Neurological examination revealed cognitive deficits, including bradyphrenia and mixed aphasia. Routine MRI and CSF analyses were unremarkable. However, brain 18F-FDG PET/CT revealed cortical hypometabolism in frontal and temporal lobes and cerebellar changes, consistent with immune-mediated encephalitis. The patient received immunosuppressive therapy with corticosteroids and intravenous immunoglobulin, leading to gradual clinical improvement and complete recovery at 3 months. This case highlights the diagnostic challenge of COVID-19-associated encephalitis when routine studies are inconclusive. PET/CT functional imaging can detect metabolic brain changes not apparent on structural imaging, supporting immune-mediated pathogenesis. Early recognition and immunotherapy may improve neurological outcomes. To conclude, brain 18F-FDG PET/CT is a useful diagnostic adjunct in COVID-19-related encephalitis with normal MRI and negative CSF, aiding timely diagnosis and treatment monitoring.

Long COVID affects a substantial proportion of individuals recovering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, yet its underlying pathophysiology remains poorly understood. Although autoimmunity is increasingly implicated in disease pathogenesis, routine diagnostics frequently fail to detect relevant immune dysregulation. To address this gap, we analyzed sera from Long COVID patients (n = 114) and pre-pandemic controls (n = 36) using tissue-based Western blotting targeting cardiac, pulmonary, and vascular antigens, alongside standard ANA HEp-2 testing. Longitudinal samples were additionally evaluated to assess autoantibody dynamics. Autoantibodies were detected in the majority of patients (83% vs. 53% in controls; p < 0.05), showing a dominant cardiovascular pattern. While cardiac (54% vs. 33% in controls; p = 0.16) and pulmonary (34% vs. 30% in controls; p = 0.50) prevalences did not reach significance, vascular autoreactivity was markedly elevated in Long COVID (34% vs. 8% in controls; p < 0.05). Responses exhibited broad polyreactivity and IgM dominance, with longitudinal follow-up showing persistent IgM and the emergence of additional isotypes. Clinically, cardiac autoreactivity was associated with hypertension and headache, while the overall autoreactivity correlated with anosmia and ageusia. In contrast, ANA HEp-2 testing showed no discriminatory value or clinical associations. Distinct autoreactivity patterns further aligned with female sex and clinical parameters (C-reactive protein, creatinine, troponin, body mass index). Together, these findings reveal a high burden of tissue-specific autoantibodies invisible to standard ANA screening. This persistent, IgM-skewed profile suggests ongoing immune dysregulation and may reflect a previously underrecognized component of the immunological response in long COVID, highlighting the need for targeted immunodiagnostic approaches beyond routine serology.