Impact of COVID-19 on neurological, psychological and other mental health outcomes

There is increasing evidence suggesting that COVID-19 causes both acute and chronic neurological or psychological symptoms. Caregivers of COVID-19 patients also show a higher than average prevalence of mental health concerns. These symptoms result from multiple different factors. SARS-Coronavirus-2 (SARS-CoV-2) directly infects olfactory neurons (smell) and nerve cells expressing taste receptors. Although these cells communicate directly with the brain, the virus does not exhibit strong infection of other nerve cells in the central nervous system. Many of the neurological sequelae appear to result from damage to the vascular cells of the brain or from damage resulting from hypoxia (i.e., limitations in the oxygen supply for the brain). Chronic effects of COVID-19 can lead to a prolonged inflammatory state, which can increase symptoms resembling an autoimmune disorder. Many patients with COVID-19 experience psychological symptoms that can arise either from the direct actions of the virus, the chronic increase in inflammation or secondary effects, such as post-traumatic stress disorder. Large community-based testing has also found small but measurable average post-infection cognitive deficits, with larger effects among people who report ongoing symptoms and after more severe or earlier-variant infections. SARS-CoV-2 can be detected in the brain and cerebrospinal fluid acutely by polymerase chain reaction, and is thought to enter via the olfactory system. Cranial nerve (including facial nerve and vagus nerve, which mediate taste) provides an additional route of entry. SARS-CoV-2 has been detected in endothelial cells by electron microscopy, although such a method provides evidence that demonstrates the presence of the virus, but does not convey the amount of virus that is present (qualitative rather than quantitative).

Acute neurologic symptoms The fraction of subjects who experience symptoms following an infection with SARS-CoV-2 varies by age. Between 10 and 20% of patients who are infected generally exhibit the clinical syndrome, known as COVID-19. The number of COVID-19 infections are highest in subjects between ages 18–65, while the risk of severe disease or death jumps after age 50 and increases with age. About 35% of patients with symptoms of COVID-19 experience neurological complications. Neurological symptoms are not unique to COVID-19; infection with SARS-CoV-1 and MERS-CoV also give rise to acute and delayed neurological symptoms including peripheral neuropathy, myopathy, Guillain–Barré syndrome and Bickerstaff brainstem encephalitis. Loss of the sense of taste or smell are among the earliest and most common symptoms of COVID-19. Roughly 81% of patients with clinical COVID-19 experience disorders of smell (46% anosmia, 29% hyposmia, and 6% dysosmia). Disorders of taste occur in 94% of patients (ageusia 45%, hypogeusia 23%, and dysgeusia 26%). Most patients recover their sense of taste or smell within 8 days. Delirium is also a common manifestation of the infection, particularly in the elderly. Recent evidence from a longitudinal study supports an inflammatory basis for delirium. Many patients with COVID-19 also experience more severe neurological symptoms. These symptoms include, headache, nausea, vomiting, impaired consciousness, encephalitis, myalgia and acute cerebrovascular disease including stroke, venous sinus, thrombosis and intracerebral hemorrhage. Increasing attention has focused on cerebrovascular accidents (e.g., stroke), which are reported in up to 5% of hospitalized patients, and occur in both old and young patients. Guillain–Barré syndrome, acute myelitis and encephalomyelitis have also been reported. Guillain–Barré syndrome arises as an autoimmune disorder, that leads to progressive muscle weakness, difficulty walking and other symptoms reflecting reduced signaling to muscles. The cases of myelitis could arise from direct infection of muscle via local angiotensin-converting enzyme 2, the receptor for SARS CoV-2. COVID-19 can also cause severe disease in children. Some children with COVID-19 who develop Kawasaki disease, which is a multi-system inflammatory syndrome that also cerebrovascular disease and neurologic involvement.

Disorders of smell (olfaction) and taste (gustation) As mentioned above, many COVID-19 patients suffer from disorders of taste or smell. 41% to 62% of patients (depending on the particular study) have disorders of the sense of smell (olfaction), which can present as anosmia (loss of olfaction), hyposmia (reduced olfaction) or parosmia (distortion of olfaction). However, loss of olfaction is not unique to COVID-19; approximately 13% of patients with influenza also lose olfaction, as do patients with MERS-CoV and Ebola virus. Among the patients with COVID-19, 50% of patients recover olfaction within 14 days, and 89% of patients have complete resolution of their loss of olfaction within 4 weeks. Only 5% of COVID-19 patients experience a loss of olfaction lasting more than 40 days.

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