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

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 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). 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. 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. Little if any virus directly infects these neurons themselves. Olfactory training helps to "teach" the new olfactory neurons how to link with the brain so that odors can be noticed and then recognized. Patients experiencing loss of smell for more than 2 weeks are also recommended to obtain a referral to an ear nose and throat (ENT) physician. Oral corticosteroid therapy can help, but is optional. alpha-lipoic acid is another remedy that has been proposed, but the accumulated literature on this suggests that it does not improve symptoms or recovery. ==Chronic neurologic symptoms==

as a result of viral infection (e.g., influenza, herpes simplex, and hepatitis C) has been linked to the onset of psychiatric illness across numerous publications. Coronavirus infections are defined as neurotropic viral infections (i.e., they tend to target the nervous system) which increases the risk of neuroinflammation and the induction of immune system dysfunction. people had increased risk of several neurologic sequelae including headache, memory problems, smell problems and stroke; the risk was evident even among people whose acute disease was not severe enough to necessitate hospitalization; the risk was higher among hospitalized, and highest among those who needed ICU care during the acute phase of the infection. One paper suggests that seizures tend to occur in COVID-19 patients with a prior history of seizure disorder or cerebrovascular infarcts, however no reviews are yet available to provide data on the incidence relative to the general population. Acute epileptic seizures and status epilepticus tend to be the seizures reported. Many pathways involved in Alzheimer's disease progression are also implicated in the antiviral response to COVID-19, including the NLRP3 inflammasome, interleukin-6, and ACE-2. ==Acute psychiatric symptoms==

Reported prevalence of mental health disorders vary depending on the study. In one review, 35% of patients had mild forms of anxiety, insomnia, and depression and 13% of patients had moderate to severe forms. Another review reports frequencies of depression and anxiety of 47% and 37%. According to a large meta-analysis, depression occurs in 23.0% (16.1 to 26.1) and anxiety in 15.9% (5.6 to 37.7). These psychological symptoms correlate with blood based biomarkers, such as C-reactive protein, which is an inflammatory protein. A case report of acute psychiatric disturbance noted an attempted suicide by a patient who had no prior noted psychiatric problems. ==Chronic psychiatric symptoms==

A 2021 article published in Nature reports increased risk of depression, anxiety, sleep problems, and substance use disorders among post-acute COVID-19 patients. Other symptoms are also prevalent, but are reported in fewer articles; these symptoms include sleep disorder (100% of patients) and disorder of attention and concentration (20%). such as higher rates of anxiety in southern China than northern China. There is also increasing evidence to suggest that ongoing psychiatric symptoms, including post-traumatic stress and depression, may contribute to fatigue in post-COVID syndrome. ==Pediatric symptoms==

Children also exhibit neurological or mental health symptoms associated with COVID-19, although the rate of severe disease is much lower among children than adults. Children with COVID-19 appear to exhibit similar rates as adults for loss of taste and smell. Kawasaki syndrome, a multi-system inflammatory syndrome, has received extensive attention. About 16% of children experience some type of neurological manifestation of COVID-19, such as headache or fatigue. About 1% of children have severe neurological symptoms. About 15% of children with Kawasaki syndrome exhibit severe neurological symptoms, such as encephalopathy. COVID-19 does not appear to elicit epilepsy de novo in children, but it can bring out seizures in children with prior histories of epilepsy. COVID-19 has not been associated with strokes in children. Guilliain Barre Syndrome also appears to be rare in children. == Cognitive symptoms ==

In September 2024, a human challenge study was published; the study lasted from 6 March 2021 to 11 July 2022, with 36 people assigned to acquire a controlled dose of SARS-CoV-2. The authors of the paper noted that the cognitive test results corroborated previous studies quantifying the impact of COVID-19 on various cognitive functions, but that a study with a larger sample size would be needed to properly account for confounding factors. A large community study in England (112,964 completers) reported objectively measurable—but generally small—deficits in global cognition after SARS-CoV-2 infection, with larger deficits among people whose symptoms had not resolved ≥12 weeks ("unresolved" persistent symptoms). Estimated standardized differences versus a no-COVID group were about −0.23 to −0.24 SD among those who had recovered (short-duration or resolved persistent symptoms) and −0.42 SD among those with unresolved persistent symptoms. The largest deficits were on memory, reasoning, and executive-function tasks; deficits were greater after infections during earlier variant periods (original/Alpha) than during later periods (e.g., Omicron), and were more pronounced among individuals who had been hospitalized (especially ICU). The longer-term persistence and clinical significance remain uncertain. == Research into COVID-19 induced brain damage ==

Neurological complications in COVID-19 are a result of SARS-CoV-2 infection or a complication of post infection which can be due to (1) direct SARS-CoV-2 invasion on the CNS via systemic circulation or olfactory epithelium directed trans-synaptic mechanism; (2) Inflammatory mediated CNS damage due to cytokine storm and endothelitis; (3) Thrombosis mediated CNS damage due to SARS-CoV-2 interaction with host ACE2 receptor resulting in ACE2 downregulation, coagulation cascade activation, and multiple organ dysfunction; (4) Hypoxemic respiratory failures and cardiorespiratory effects due to SARS-CoV-2 invasion on brain stem.. SARS-CoV-2 could also enter the brain through retrograde transmission. There is ongoing research about the short- and long-term damage COVID-19 may possibly cause to the brain. Another study identified neuroinflammation and an activation of adaptive and innate immune cells in the brain stem of COVID-19 patients. Brain-scans and cognitive tests of 785 UK Biobank participants (401 positive cases) suggests COVID-19 is associated with, at least temporary, changes to the brain that include: • (greater) "reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus;" • "changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex;" • "reduction in global brain size" • as well as (greater) cognitive decline between the two time points of selected cognitive tests It has been identified that anosmia present during the acute phase of illness can be a risk factor for developing brain damage. A study revealed that patients recovering from COVID-19 who experienced anosmia during the acute episode exhibited impulsive decision-making, functional brain alterations, cortical thinning, and changes in white matter integrity. A study indicates that SARS-CoV-2 builds tunneling nanotubes from nose cells to gain access to the brain. == Ethnoracial Disparities in Cognitive Effects of Long COVID ==

An April 2023 study published in Journal of the National Medical Association performed a quantitative secondary analysis on data collected from the Household Pulse Survey (HHPS) between June and October 2022. 108,000 responses were sampled weekly and were representative with respect to geographic location, race, and gender. A logistic regression analysis was conducted on responses to Phase 3.6 which includes questions on long COVID symptoms, vaccinations, and demographic characteristics. The study found that racial disparities in long COVID prevalence mirror those seen in acute COVID-19. In particular, Blacks and Hispanics were significantly more likely to report long COVID than Whites. Additionally, females also showed a higher likelihood of long COVID compared to males. The study indicated that disparities existed beyond racial and ethnic lines. Individuals with private health insurance and those vaccinated were less likely to report long COVID. Factors such as socioeconomic status, healthcare access, and occupational exposure are critical in understanding these disparities, as they can influence both the likelihood of contracting COVID-19 and the severity of its long-term effects. Overall, an understanding of the social determinants of health is needed to comprehensively address cognitive effects of Long COVID. ==References==