Possible mechanisms of pathogenesis for the neuropsychiatric manifestations of COVID-19.

Mechanism of Details Neuropsychiatric effects

pathogenesis

 • Exaggerated immune response  • Encephalopathy

Direct injury (Blood  • Cytokines increasing blood-  • Delirium and acute
circulation) brain-barrier (BBB) confusional state
Koyuncu et al., 2013 Desforges et al.,
( ;  permeability
2020
)

Direct injury (Neuronal  • Predilection for olfactory  • Anosmia

route) epithelium, bulb and vagal  • Dysguesia
(Mori, 2015; Bohmwald et al., 2018) centers  • Psychiatric disorders
 • Anterograde and retrograde
neural proliferation via dynein
and kinesin
 • Structural preference for the
forebrain, basal ganglia and
hypothalamus

Hypoxic injury  • Impaired pulmonary exchange  • Encephalopathy

(Abdennour et al., 2012; Guo et al., and pulmonary oedema can  • Somnolence
2020
) cause cerebral hypoxia  • Coma
 • Cerebral oedema, vasodilation,  • Headache
ischaemia and vascular  • Confusion
congestion
 • Increased intracranial pressure

Dysregulated  • Cytokine storm (surge of  • Encephalitis

immunomodulation peripheral IL-6,8,10,18, TNF-  • MODS
Mechanism of Details Neuropsychiatric effects
pathogenesis

(Fu et al., 2020; Mehta et al., alpha, etc.)  • Acute psychosis

2020 Wan et al., 2020
;  )  • Systemic Inflammatory  • Seizures
Response Syndrome (SIRS)
 • Upregulation of
oligodendrocytes and astrocytes
(increased release of IL-15,
TNF-alpha)
 • Leaky BBB
 • Disturbed neurotransmission

Immune cell  • Increased neuro-inflammation  • Both acute and chronic

transmigration to CNS  • Microglial activation neuropsychiatric effects
(Wohleb et al., 2015; Desforges et al.,  • Neural and glial cells as latent
2020
) ‘viral-carriers’

ACE-2 and CoV spike  • Vascular and endothelial  • Cerebro-vascular

protein interaction damage accidents
(Miller and Arnold, 2019; Wrapp et al.,  • Hyper-coagulability  • Pulmonary and cerebral
2020
)  • Increased blood-pressure venous
 • Microangiopathy thromboembolism
 • Risk of chronic
neurodegeneration

Autoimmunity  • Molecular mimicry (cross-  • Demyelination

(Kim et al., 2017; Rose, 2017) reaction of myelin, glia and  • GBS
beta-2 glycoprotein with viral  • Neuropathy
epitopes
Mechanism of Details Neuropsychiatric effects
pathogenesis

Miscellaneous  • High ‘viral-latency’ in CNS  • Persistent or relapsing-

(Reinhold and Rittner, 2017)
 • Lack of MHC in brain remitting neurological
 • Homeostasis of neural issue sequelae
 • Reactivation of seizures
 • Chronic psychiatric
conditions