John Murphy, M.D., MPH, DPH President Covid-19 long-haul Foundation<\/p>\n\n\n\n
Coronavirus disease 2019 (COVID\u201119), caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2011CoV\u20112), emerged in late 2019 as a global respiratory pathogen. Yet it rapidly became clear that its reach extended far beyond the airways. Among the most intriguing and distressing of its neuropsychiatric sequelae are hallucinations<\/strong>\u2014sensory experiences that arise in the absence of external stimuli\u2014and the broader disturbances of cognition and perception in which they are embedded. Understanding these phenomena requires weaving together virology, neurobiology, and clinical observation.<\/p>\n\n\n\n Hallucinations during or after COVID\u201119 rarely arise from a single cause; instead, they emerge from the confluence of direct and indirect mechanisms<\/strong> by which the virus and ensuing host response impact the nervous system.<\/p>\n\n\n\n SARS\u2011CoV\u20112 may exert effects on the central nervous system (CNS) via its known affinity for the ACE2 receptor, expressed across neural cells and vascular endothelium. Through this gateway, the virus may enter neural tissue, potentially traveling along peripheral nerves (e.g., olfactory pathways) into deeper brain structures. Such mechanisms offer a plausible route for direct CNS involvement, though detection of viral RNA in cerebrospinal fluid is rare.<\/p>\n\n\n\n Perhaps the most robustly supported path to hallucinations is neuroinflammation<\/strong>. Acute infection triggers a systemic cytokine surge\u2014with interleukins and tumor necrosis factors crossing a disrupted blood\u2011brain barrier (BBB) to activate microglia (the resident immune cells of the CNS). Activated microglia release further inflammatory mediators, perturbing neuronal networks involved in perception and attention. These inflammatory cascades underpin not just hallucinations but also broader delirium and cognitive dysfunction. <\/p>\n\n\n\n Severe respiratory involvement, especially in hospitalized patients, can result in hypoxia\u2014reduced oxygen to the brain\u2014compromising cerebral metabolism and triggering cortical dysfunction. Such hypoxic insults are strongly implicated in acute delirium, of which hallucinations are a hallmark feature.<\/p>\n\n\n\n SARS\u2011CoV\u20112 induces endothelial injury and a procoagulant state, leading to microthrombi in cerebral vessels. Microvascular compromise may impair regional perfusion in perceptual and executive networks of the brain, contributing to aberrant sensory experiences.<\/p>\n\n\n\n Critically ill patients often receive sedatives, opioids, or corticosteroids, each of which independently predisposes to delirium and psychosis. These factors compound viral effects to produce complex sensory disturbances.<\/p>\n\n\n\n Under physiological conditions, perception emerges from coordinated activity<\/strong> of cortical and subcortical networks integrating external stimuli with internal models of the world. SARS\u2011CoV\u20112\u2013associated inflammation and hypoxia disrupt these networks, particularly in the prefrontal cortex<\/strong>, temporal lobes<\/strong>, and thalamo\u2011cortical circuits<\/strong>, leading to false percepts<\/strong> that manifest as hallucinations.<\/p>\n\n\n\n The BBB, a selective shield between the bloodstream and neural tissue, often becomes compromised in COVID\u201119. Its breakdown allows peripheral cytokines and immune cells to infiltrate the brain, propagating inflammation and neuronal dysregulation, particularly in regions governing sensory integration.<\/p>\n\n\n\n Microglia, once activated, can prune synapses excessively and secrete neurotoxic factors, destabilizing network activity essential for distinguishing internal signals from external reality. This dysregulation may underlie both auditory<\/strong> and visual hallucinations<\/strong> documented in mild and severe COVID\u201119 patients. Case reports have described such phenomena even in individuals without prior psychiatric history.<\/p>\n\n\n\n During acute COVID\u201119, especially in hospitalized patients, hallucinations commonly appear within the context of delirium<\/strong>: a state of fluctuating awareness, disorientation, and cognitive disruption. Delirium itself can manifest in up to one\u2011third of hospitalized patients<\/strong>, increasing with age and severity of illness.<\/p>\n\n\n\n Clinically, hallucinations in this phase may be visual<\/strong> (e.g., shadows, figures), auditory<\/strong> (voices), or mixed. They often co\u2011occur with sleep cycle disturbance and agitation, and may wax and wane with fever or metabolic instability.<\/p>\n\n\n\n Beyond the acute infection, a subset of individuals develops a post\u2011acute COVID\u201119 syndrome<\/strong> (commonly termed Long COVID<\/em>) in which neuropsychiatric symptoms endure for weeks to months. These may include cognitive fog, intrusive sensory experiences, and mood dysregulation. While quantitative data on hallucination prevalence are limited, persistent sensory misperceptions have been reported in both clinical series and case reports.<\/p>\n\n\n\n The prognosis for hallucinations varies widely. In many cases associated with acute delirium\u2014particularly those driven by reversible metabolic factors\u2014the hallucinatory experiences abate as systemic illness resolves. For others, particularly those with prolonged inflammation<\/strong> or microvascular injury<\/strong>, symptoms may persist into convalescence.<\/p>\n\n\n\n Persistent cognitive symptoms including altered perception may linger beyond 12 weeks, often entwined with fatigue and sleep disturbance. The severity of initial disease, age, comorbidities, and degree of neuroinflammation appear to influence long\u2011term outcomes.<\/p>\n\n\n\n Recovery often unfolds over months. Cognitive rehabilitation, management of sleep disorders, inflammatory modulation when appropriate, and psychological support play roles in improving outcomes. Importantly, early recognition and management of delirium in acute settings reduce the risk of long\u2011term cognitive decline.<\/p>\n\n\n\n Hallucinations in COVID\u201119 are not mere curiosities but clinically significant expressions<\/strong> of how SARS\u2011CoV\u20112 can perturb the brain\u2019s delicate balance of perception, attention, and integration. They emerge from intertwined mechanisms<\/strong>\u2014viral, immunologic, vascular, metabolic, and iatrogenic\u2014and span a clinical continuum from acute delirium to chronic sensory disturbance. Understanding their etiology and trajectory remains a frontier of pandemic neuroscience, but the growing corpus of research underscores one truth: the effects of COVID\u201119 extend deeply into the human psyche and nervous system.<\/p>\n\n\n\n John Murphy, M.D., MPH, DPH President Covid-19 long-haul Foundation Coronavirus disease 2019 (COVID\u201119), caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2011CoV\u20112), emerged in late 2019 as a global respiratory […]<\/p>\n","protected":false},"author":2,"featured_media":14233,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[661,91,144,1378,369],"tags":[],"class_list":["post-14231","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-ace2-receptors","category-cns","category-endothelium","category-hallucination","category-neurotropism"],"_links":{"self":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/14231","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=14231"}],"version-history":[{"count":3,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/14231\/revisions"}],"predecessor-version":[{"id":14235,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/14231\/revisions\/14235"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/media\/14233"}],"wp:attachment":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=14231"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=14231"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=14231"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
\n\n\n\nEtiology: How SARS\u2011CoV\u20112 Intersects the Brain<\/strong><\/h2>\n\n\n\n
Neurotropism and Neuroinvasion<\/strong><\/h3>\n\n\n\n
Neuroinflammation<\/strong><\/h3>\n\n\n\n
Hypoxia and Metabolic Derangements<\/strong><\/h3>\n\n\n\n
Microvascular Injury<\/strong><\/h3>\n\n\n\n
Medication and ICU Factors<\/strong><\/h3>\n\n\n\n
\n\n\n\nPhysiology and Pathology: The Neural Substrate of Hallucinations<\/strong><\/h2>\n\n\n\n
Disruption of Neural Networks<\/strong><\/h3>\n\n\n\n
Blood\u2013Brain Barrier Integrity<\/strong><\/h3>\n\n\n\n
Microglial Activation and Synaptic Dysregulation<\/strong><\/h3>\n\n\n\n
\n\n\n\nClinical Course: From Acute Illness to Long COVID<\/strong><\/h2>\n\n\n\n
Acute Phase Hallucinations<\/strong><\/h3>\n\n\n\n
Subacute and Post\u2011Acute Neuropsychiatric Symptoms<\/strong><\/h3>\n\n\n\n
\n\n\n\nPrognosis: Resolution, Persistence, and Recovery<\/strong><\/h2>\n\n\n\n
Factors Predicting Course<\/strong><\/h3>\n\n\n\n
Long COVID and Chronic Neuropsychiatric Sequelae<\/strong><\/h3>\n\n\n\n
Recovery Pathways<\/strong><\/h3>\n\n\n\n
\n\n\n\nConclusion<\/strong><\/h2>\n\n\n\n
\n\n\n\nFootnotes<\/strong><\/h3>\n\n\n\n
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