Neuropsychiatry of COVID Flashcards
Why was concern for possible neuropsychiatric complications high at the start of the pandemic?
Because of what has been seen with other coronaviruses and SARS (e.g. fatigue)
What is Guillain-Barre syndrome?
A condition where the immune system attacks the nerves of the PNS, easing to rapid muscke weakness and possible paralysis
Why did we see an increase in GBS cases during the pandemic?
Because an increased number of patients were being seen so we were more likely to detect more cases
What is the major problem with interpreting research on the neuropsychiatric manifestations of COVID?
Larger numbers tested = increased liklihood of seeing rare complications
Important we determine what is DIRECTLY related
What are the most common acute neuropsychiatric manifestations of COVID?
▪️Fatigue
▪️Myalgia
▪️Depression
▪️Anxiety
▪️Headaches
What is the most common severe neuropsychiatric symptom of covid?
Delirium (up to 40%)
How long do common neuropsychiatric manifestations of COVID usually last?
Not long - tend to resolve promptly regardless of illness severity
What are some of the rarer neuropsychiatric symptoms of covid?
▪️Encephalitis
▪️Psychosis
▪️Catatonia
BUT causality is unclear
What is the main risk factor for stroke or microvascular alterations following covid infection?
Cerebral vasculopathy
What is the relationship between covid and psychiatric diagnosis?
Bidirectional!
▪️Increased rates of diagnosis in those with covid
▪️Increased risk of covid and mortality in those with prior diagnosis
What risk factors are common to both covid infection and psychiatric disorder?
▪️Ethnic minorities
▪️Low SES
▪️Lifestyle factors (e.g smoking, poor physical health)
▪️South/west London
What percentage of people admitted to hospital for covid had had a stroke and how did they differ from non-covid stroke admissions?
2%
More young people than would be expected
How many patients experience delirium in the acute phase of covid?
1/3
What are the main risk factors for delirium in covid?
▪️More severe infection
▪️Older age
▪️Dementia
What outcomes are associated with delirium in covid?
▪️Worse outcomes
▪️Greater risk of subsequent dementia
▪️Risk of cognitive deterioration regardless of illness severity
How do rates of dementia diagnosis following covid compare to other respiratory tract infections?
2x greater
Why might covid infection increase the risk for cognitive decline and dementia?
▪️Delirium
▪️Time spent in ITU (although also seen in milder cases)
▪️Medications
▪️Raised inflammatory response
▪️Lack of prior immunity
What are the four principle mechanisms through which covid may effect the brain?
▪️Direct viral infection
▪️Inflammation and parainfectious cytokine storm
▪️Vasculopathy/Vasculitis
▪️Post-infectious antibody-mediated
What is the theory of direct viral infection?
▪️Covid can infect the brain directly through nose via the BBB or neuronal transport
▪️This can then cause structural damage
What is the proposed evidence behind the mechanism of direct viral infection?
▪️Entry via ACE2 receptors in olfactory bulb explains anosmia
▪️SARS-CoV-2 have replicated in neurons in vitro
▪️Evidence of cerebral inflammation and leukoencephalopayhy in postmortem and imaging
What are the main limitations of the direct infection theory?
▪️Little evidence
▪️Viral RNA largely a sense from CSF and post mortem samples
What is the theory behind inflammation as a mechanism for neuropsychiatrc symptoms in covid?
▪️Covid induces inflammatory state mediated by cytokine release
▪️This has multi-systemic effects, including on CNS
What is the evidence for the inflammatory mechanism of symptoms?
▪️Proinflammatory cytokines shown in covid patients with delirium (e.g. IL-6, IFN-γ)
▪️Inflammatory response greater in those with delirium
▪️Common with most viral infections
What is the main argument against the inflammation mechanism?
Response may be greater in covid than other viruses due to lack of prior immunity
What is the proposed vasculopathy/vasculitis mechanism for neuropsychiatrc symptoms in covid?
▪️Blood vessels leak and dilate, increasing the propensity to form clots
▪️Covid interferes with the ability to efficiently fix these problems
BUT rare!
What is the main evidence for the vasculopathy/vasculitis mechanism?
▪️Higher than expected stroke rate
▪️Thromboembolic complications likely mediated by increased blood coagulability and inflammatory endothelial impairment
What is the evidence for a post-infectious antibody mediated mechanism?
▪️Some reports of covid associated autoimmune encephalitis
▪️Anti SARS-CoV-2 antibodies found in CSF of encephalopathy covid patients
▪️Autoantibodies found in CSF of ICU covid patients
BUT very rare!
Why were differences in neurodevelopmental age seen in babies born during the pandemic?
▪️Possibly lockdown/stress factors
▪️NOT in utero effects of maternal infection
Based on other postviral syndromes, such as SARS and MERS, what did we expect from long covid?
▪️Chronic myalgia
▪️Fatigue
▪️PTSD
▪️Depression and anxiety
What are the NICE guidelines for post-covid syndrome?
▪️Any symptoms that developed during or after infection and persisted for more than 12 weeks
▪️Usually a cluster of symptoms that fluctuate and change over time
▪️Can affect any system in the body
What are the main symptoms seen with long covid?
▪️Fatigue/post-exertional malaise
▪️Cognitive dysfunction (brain fog)
▪️Cardiorespiratory symptoms (e.g. breathlessness)
What symptoms are typically not included in post-covid syndrome?
Anosmia and loss of taste
What other factors may contribute to post-covid syndrome?
▪️Post-ICU syndrome
▪️Focal neurology (e.g. stroke)
Both indicating to severity of infection
How many people were reported to have long covid in the UK in June 2022?
2 million
What structural brain changes have been observed in association with SARS-CoV-2 infection and long covid?
▪️Significant reductions in thickness of certain brain areas
▪️Particularly orbitofrontal cortex and left parahippocampal gyrus
▪️Due to chronic anosmia?
What is the main issue with interpreting structural brain changes following COVID?
So many possible factors involved, cannot say whether it’s directly caused by the virus
How long does covid stay in the body?
Usually roughly a month but potentially for several in GI tract
NOT necessarily active!
BUT need larger studies
Is long covid caused by persistence of virus in the body?
Unlikely
Is long covid an ongoing response to lingering virus?
Unlikely - no difference in inflammatory markers between cases and controls
How might long covid be views as a functional disorder?
▪️Symptoms arise from relationship between sensory input and appraisal
▪️Severity and disability is perceived, moderated and maintained by cognitive processes
▪️Expectancy mediates this
What was found in the French study looking at serology in long covid?
▪️Positive serology did not increase risk of long symptoms
▪️Strong belief was associated with persistent fatigue and concentration difficulties
What factors are associated with increased risk of negative post-covid outcomes prior to infection?
▪️Depression
▪️Anxiety
▪️Worry and perceived stress
▪️Loneliness
NOT classic risk factors e.g. smoking
What are the main conclusions for the mechanisms of long covid?
▪️Limited evidence for structural damage, immune response, or chronic infection
▪️Psychological factors likely important
How can we manage long covid?
▪️Better sleep for fatigue
▪️Treat mood and anxiety issues as you would in primary cases
▪️Onward referrals (e.g. nerve clinic)
▪️Address medical comorbidities
▪️Make sure people feel listened to and acknowledged
▪️Education (dualistic interpretation)
▪️PT/OT/CBT
▪️Slow/phased return to work
Do vaccines improve long covid?
Yes - functional response based on expectations?
Most neuro/psych complications of the vaccines are likely ___________ rather than ____________
▪️Correlations
▪️Causative
Why were rare adverse effects of vaccines, such as cerebral venous sinus thrombosis, only detected in post-vaccine trials?
Pre-vaccine clinical trials are not typically high powered enough to detect very small risks (small samples)
What percentage of vaccine reactions are likely NOT caused by the vaccine?
~66%
Why might covid vaccines have an increased risk of functional responses?
▪️Worry over vaccines and increased negative expectation
▪️Videos circulating media
Psychogenic illness!
