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

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While acute symptoms of COVID-19 act on the lungs, there is increasing evidence suggesting that COVID-19 causes both acute and chronic neurological [1] or psychological symptoms. [2] Caregivers of COVID-19 patients also show a higher than average prevalence of mental health concerns. [2] These symptoms result from multiple different factors.

Contents

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. [1] 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. [2]

SARS-CoV-2 can be detected in the brain and cerebrospinal fluid(CSF) acutely by PCR, and is thought to enter via the olfactory system. [3] Cranial nerve (including facial nerve and vagus nerve, which mediate taste) provides an additional route of entry. [3] 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). [3]

Acute COVID-19 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 with SARS-CoV-2 generally exhibit the clinical syndrome, known as COVID-19. The number of COVID-19 infections [4] are highest in subjects between ages 18 – 65, while the risk of severe disease or death [4] jumps after age 50 and increases with age. About 35% of patients with symptoms of COVID-19 experience neurological complications. [1] [5] However, 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–Barre Syndrome and Bickerstaff brainstem encephalitis. [6] The influenza pandemic of 1918 was well known for producing post-viral Parkinsonism, which was memorialized in the writings of Oliver Sacks and the movie Awakenings .

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). [1] 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. [1] Delirium is also a common manifestation of COVID-19 infection, particularly in the elderly. Recent evidence from a longitudinal study supports an inflammatory basis for delirium [7] . 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 haemorrhage. [1] [3] [8] [9]

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. [1] Guillain–Barre Syndrome, acute myelitis and encephalomyelitis have also been reported. [9] Guillain–Barre Syndrome arises as an autoimmune disorder, that leads to progressive muscle weakness, difficulty walking and other symptoms reflecting reduced signaling to muscles. [9] The cases of myelitis could arise from direct infection of muscle via local Angiotensin-converting enzyme 2, the receptor for SARS CoV-2. [3] 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. [1] [9]

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). [10] However, loss of olfaction is not unique to COVID-19; approximately 12.5% of patients with influenza also lose olfaction, as do patients with MERS-CoV and Ebola virus. [10] 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. [11] [10] Only 5% of COVID-19 patients experience a loss of olfaction lasting more than 40 days. [10]

Structure of the olfactory epithelium. SARS-CoV-2 infects the support cells (sustentacular cells), which injures the olfactory neurons in the olfactory epithelium leading to loss of smell. New olfactory neurons regenerate from the basal cells. Location of olfactory ensheathing cells (OECs) within the olfactory system.png
Structure of the olfactory epithelium. SARS-CoV-2 infects the support cells (sustentacular cells), which injures the olfactory neurons in the olfactory epithelium leading to loss of smell. New olfactory neurons regenerate from the basal cells.

The SARS-CoV-2 virus appears to attack the sustentacullar cells (also referred to as "support cells"), which are the cells that surround and support olfactory receptor neurons. [11] [12] Little if any virus directly infects the olfactory receptor neurons themselves. [11] However, SARS-CoV-2 infection of the sustentacullar cells can lead to desquamation (shedding) of the olfactory epithelium, with collateral loss of olfactory receptor neurons and anosmia. [11] However, the olfactory epithelium is continually regenerated, and neurons that are damaged are typically replaced in about 14 days. [11] The nerve cells controlling taste, termed the gustatory nerve cells, turn over even faster, being renewed in about 10 days. [11]

Clinical help exists for patients experiencing disorders of olfaction. Patients who experience of loss of smell for longer than two weeks are recommended to obtain olfactory training. [13] Olfactory training helps to "teach" the new olfactory neurons how to link with the brain so that odors can be noticed and then recognized. [13] Personal accounts of the process of olfactory training post COVID-19 infection have been covered in media outlets such as the New York Times. [14] 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. [13] Oral corticosteroid therapy can help, but is optional. [13] 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. [13]

Chronic COVID-19 neurologic symptoms

Impact of COVID-19 on neurological and psychiatric outcomes in the subsequent 6 months compared with other respiratory tract infections Impact of COVID-19 on neurological and psychiatric outcomes in the subsequent 6 months compared with other respiratory tract infections.jpg
Impact of COVID-19 on neurological and psychiatric outcomes in the subsequent 6 months compared with other respiratory tract infections

A study of 236,379 COVID-19 survivors showed that the "estimated incidence of a neurological or psychiatric diagnosis in the following 6 months" after diagnosed infection was 33.62% with 12.84% "receiving their first such diagnosis" and higher risks being associated with COVID-19 severity. [16] [15]

A large study showed that post COVID-19, [17] 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. [17] About 20% of COVID-19 cases that pass through the intensive care unit (ICU) have chronic neurologic symptoms (beyond loss of smell and taste). [1] Of the patients that had an MRI, 44% had findings upon MRI, such as a FLAIR signal (fluid-attenuated inversion recovery signal), leptomeningeal spaces and stroke. [1] [13] Neuropathological studies of COVID-19 victims show microthrombi and cerebral infarctions. [1] The most common observations are hypoxic damage, which is attributable to use of ventilators. [5] However, many patients who died exhibited perivascular T cells (55%) and microglial cell activation (50%). Guillain–Barre Syndrome occurs in COVID-19 survivors at a rate of 5 per 1000 cases, which is about 500 times the normal incidence of 1 per 100,000 cases. [1] A related type of autoimmune syndrome, termed Miller-Fisher Syndrome, also occurs. [1]

COVID-19 patients who were hospitalized may also experience seizures. [18] A recent paper suggests that seizures tend to occur in COVID-19 patients with a prior history of seizure disorder or cerebrovascular infarcts, [19] 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. [18] 57% of the cases occur among patients who had experienced respiratory or gastrointestinal symptoms. [18] Although treatment with benzodiazepines would seem to be contraindicated because of the risk of respiratory depression, COVID-19 patients with acute epileptic seizures who are treated have a 96% favorable outcome, while patients with acute epileptic seizures who are not treated appear to have higher rates of mortality (5-39%). [18]

Acute COVID-19 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. [20] Another review reports frequencies of depression and anxiety of 47% and 37%. [21] 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). [22] These psychological symptoms correlate with blood based biomarkers, such as C-reactive protein, which is an inflammatory protein. [21] There have been case reports of acute psychiatric disturbance and attempted suicide in the context of acute COVID-19 infection. [23]

Chronic COVID-19 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. [17] In 2020, a Lancet Psychiatry review reported occurrence of the following post-COVID-19 psychiatric symptoms: traumatic memories (30%), decreased memory (19%), fatigue (19%), irritability (13%), insomnia (12%) and depressed mood (11%). [24] 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%). [13] These accumulated problems lead to a general (and quantified) reduction in the quality of life and social functioning (measured with the SF-36 scale). [13]

Mental health symptoms in the general population and among health care providers

According to mental health experts, the COVID-19 pandemic has caused negative effects on people's mental health around the globe. These effects can manifest as increased anxiety and insecurity, greater fears, and discrimination. [25]

Experts[ who? ] claim that changes to ones environment can cause large amounts of distress and insecurity. COVID-19 spreads rapidly which is why people feel more panic and anxiety. Additionally, anxiety and fear associated with infection can lead to discriminatory behaviors, which then lead to increasingly negative social behaviors, worsening mental health. [25]

A study in South Africa reported high proportions of people who met the criteria for anxiety (46%) and depressive disorder (47%). Of these people, less than 20% consulted a formal health practitioner (i.e. 12% if they didn't have a pre-existing mental health condition). [26]

A study used a broader participant scope by including all healthcare workers in the participant sample. The study showed that doctors had slightly higher rates of anxiety and depression. Kamberi's study concludes that 34.1% of doctors specifically and 26.9% of nurses reported mild levels of anxiety. [27]   While the larger representation showed health care workers expressed that 26.9% showed mild levels of anxiety and 35.2% expressed mild to moderate depression levels in all of the health care participants. [27] Kamberi's study shows that regardless of your medical field, all healthcare fields are susceptible to experience mental health concerns.   [27]

COVID-19 impacts mental health of health care providers, but it's effect varies based on their specific medical profession. Doctors and nurses appear to experience similar rates of mental health challenges with high rates of anxiety (40-45%), depression (12-30%), moderate and severe insomnia (62% and 27%, respectively). [28]

In a cross-sectional research study conducted in Portugal, an online survey was produced to collect data surrounding the direct comparison of mental health in health care professionals and the general population. [29] It was found that on average there was a significantly higher percentage of health care workers experiencing signs of mental health disorders compared to the general population of Portugal.

Health care workers also frequently exhibit symptoms of more severe disorders developing like post-traumatic stress disorder (14%). [28] In general, about 50% of health care workers exhibit some form of negative emotions. [28] A cross-sectional study determined the stress levels and presence of Post-Traumatic Stress Disorder (PTSD) symptoms in nurses. The results of Leng's study showed 5.6% of nurses exhibited significant PTSD symptoms and 22% scored positively on stress levels. [30] The researchers admit significant changes were not seen in stress or PTSD levels as expected indicating disagreement. This study disclosed a significant link between nursing and mental health specifically PTSD was not shown. This contradicts the study in the beginning of the paragraph. Despite this, the journal mentioned other similar studies that discovered far stronger correlations and believed a correlation to still be true. [31]

When specifically examining Post-Traumatic Stress Disorder in nurses during the pandemic, there are many factors contributing to the decline. [32] Nurses are experiencing the toll of Covid-19 first-hand in hospitals, including increased mortality statistics and virus exposure. These experiences may trigger abhorrent thoughts of past disease outbreaks or may even contribute to lasting emotional stress in the future.

Post Traumatic Stress Disorder is not the only serious complication coming arising in the nursing field. A journal investigated a relationship with suicide rates in nursing finding “elevated suicide rates for nurses compared with other, non-healthcare providers.”

It is crucial to understand how mental health disorders can be combatted and managed. There are numerous options, some include solutions done directly or others require medical intercession. [33]

Pediatric symptoms of COVID-19

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. [34] Children with COVID-19 appear to exhibit similar rates as adults for loss of taste and smell. [34] Kawasaki syndrome, a multi-system inflammatory syndrome, has received extensive attention. [1] About 16% of children experience some type of neurological manifestation of COVID-19, such as headache or fatigue. [34] About 1% of children have severe neurological symptoms. [34] About 15% of children with Kawasaki syndrome exhibit severe neurological symptoms, such as encephalopathy. [34] 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. [34] COVID-19 has not been associated with strokes in children. [34] Guilliain Barre Syndrome also appears to be rare in children. [34]

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Anorexia (symptom) Medical symptom

Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others indicate a serious clinical condition or pose a significant risk.

Anosmia Inability to smell

Anosmia, also known as smell blindness, is the loss of the ability to detect one or more smells. Anosmia may be temporary or permanent. It differs from hyposmia, which is a decreased sensitivity to some or all smells.

Severe acute respiratory syndrome Disease caused by severe acute respiratory syndrome coronavirus

Severe acute respiratory syndrome (SARS) is a viral respiratory disease of zoonotic origin caused by severe acute respiratory syndrome coronavirus, the first identified strain of the SARS coronavirus species severe acute respiratory syndrome–related coronavirus (SARSr-CoV). The syndrome caused the 2002–2004 SARS outbreak. Around late 2017, Chinese scientists traced the virus through the intermediary of Asian palm civets to cave-dwelling horseshoe bats in Xiyang Yi Ethnic Township, Yunnan.

Olfactory system Sensory system used for smelling

The olfactory system, or sense of smell, is the sensory system used for smelling (olfaction). Olfaction is one of the special senses, that have directly associated specific organs. Most mammals and reptiles have a main olfactory system and an accessory olfactory system. The main olfactory system detects airborne substances, while the accessory system senses fluid-phase stimuli.

Ageusia is the loss of taste functions of the tongue, particularly the inability to detect sweetness, sourness, bitterness, saltiness, and umami. It is sometimes confused with anosmia – a loss of the sense of smell. Because the tongue can only indicate texture and differentiate between sweet, sour, bitter, salty, and umami, most of what is perceived as the sense of taste is actually derived from smell. True ageusia is relatively rare compared to hypogeusia – a partial loss of taste – and dysgeusia – a distortion or alteration of taste.

PANDAS hypothesis in pediatric medicine

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Phantosmia, also called an olfactory hallucination or a phantom odor, is smelling an odor that is not actually there. It can occur in one nostril or both. Unpleasant phantosmia, cacosmia, is more common and is often described as smelling something that is burned, foul, spoiled, or rotten. Experiencing occasional phantom smells is normal and usually goes away on its own in time. When hallucinations of this type do not seem to go away or when they keep coming back, it can be very upsetting and can disrupt an individual's quality of life.

Hyposmia, or microsmia, is a reduced ability to smell and to detect odors. A related condition is anosmia, in which no odors can be detected. Some of the causes of olfaction problems are allergies, nasal polyps, viral infections and head trauma. In 2012 an estimated 9.8 million people aged 40 and older in the United States had hyposmia and an additional 3.4 million had anosmia/severe hyposmia.

Dysosmia is a disorder described as any qualitative alteration or distortion of the perception of smell. Qualitative alterations differ from quantitative alterations, which include anosmia and hyposmia. Dysosmia can be classified as either parosmia or phantosmia. Parosmia is a distortion in the perception of an odorant. Odorants smell different from what one remembers. Phantosmia is the perception of an odor when no odorant is present. The cause of dysosmia still remains a theory. It is typically considered a neurological disorder and clinical associations with the disorder have been made. Most cases are described as idiopathic and the main antecedents related to parosmia are URTIs, head trauma, and nasal and paranasal sinus disease. Dysosmia tends to go away on its own but there are options for treatment for patients that want immediate relief.

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COVID-19 Contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease has since spread worldwide, leading to an ongoing pandemic.

Mental health during the COVID-19 pandemic Psychological aspect of viral outbreak

The COVID-19 pandemic has impacted the mental health of people around the world. Similar to the past respiratory viral epidemics, such as the SARS-CoV, MERS-CoV, and the influenza epidemics, the COVID-19 pandemic has caused anxiety, depression, and post-traumatic stress disorder symptoms in different population groups, including the healthcare workers, general public, and the patients and quarantined individuals. The Guidelines on Mental Health and Psychosocial Support of the Inter-Agency Standing Committee of the United Nations recommends that the core principles of mental health support during an emergency are "do no harm, promote human rights and equality, use participatory approaches, build on existing resources and capacities, adopt multi-layered interventions and work with integrated support systems." COVID-19 is affecting people's social connectedness, their trust in people and institutions, their jobs and incomes, as well as imposing a huge toll in terms of anxiety and worry.

Sherry Hsiang-Yi Chou is a Canadian neurologist and an Associate Professor of Critical Care Medicine, Neurology, and Neurosurgery at the University of Pittsburgh. She is a Fellow of the Neurocritical Care Society and the Society of Critical Care Medicine. During the COVID-19 pandemic Chou assembled a worldwide team of physicians and scientists to better understand the neurological impacts of SARS-CoV-2, forming the Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID). The first report of this large, multicenter, multicontinent consortium found that neurological manifestations are present in 8 out of 10 adult patients hospitalized with COVID-19 and are associated with increased mortality.

Symptoms of COVID-19 Overview of the symptoms of COVID-19

Symptoms of COVID-19 are variable, ranging from mild symptoms to severe illness. Common symptoms include headache, loss of smell and taste, nasal congestion and runny nose, cough, muscle pain, sore throat, fever, diarrhea, and breathing difficulties. People with the same infection may have different symptoms, and their symptoms may change over time. Three common clusters of symptoms have been identified: one respiratory symptom cluster with cough, sputum, shortness of breath, and fever; a musculoskeletal symptom cluster with muscle and joint pain, headache, and fatigue; a cluster of digestive symptoms with abdominal pain, vomiting, and diarrhea. In people without prior ear, nose, and throat disorders, loss of taste combined with loss of smell is associated with COVID-19.

Multisystem inflammatory syndrome in children Disease of children; pediatric comorbidity from COVID-19

Multisystem inflammatory syndrome in children (MIS-C), or paediatric inflammatory multisystem syndrome, or systemic inflammatory syndrome in COVID19 (SISCoV), is a rare systemic illness involving persistent fever and extreme inflammation following exposure to SARS-CoV-2, the virus responsible for COVID-19. It can rapidly lead to medical emergencies such as insufficient blood flow around the body. Failure of one or more organs can occur. A warning sign is unexplained persistent fever with severe symptoms following exposure to COVID-19. Prompt referral to paediatric specialists is essential, and families need to seek urgent medical assistance. Most affected children will need intensive care.

Impact of the COVID-19 pandemic on healthcare workers

The COVID-19 pandemic has impacted healthcare workers physically and psychologically. Healthcare workers are more vulnerable to COVID-19 infection than the general population due to frequent contact with infected individuals. Healthcare workers have been required to work under stressful conditions without proper protective equipment, and make difficult decisions involving ethical implications. Health and social systems across the globe are struggling to cope. The situation is especially challenging in humanitarian, fragile and low-income country contexts, where health and social systems are already weak. Services to provide sexual and reproductive health care risk being sidelined, which will lead to higher maternal mortality and morbidity.

Impact of the COVID-19 pandemic on other health issues Health consequences of outbreak beyond the COVID-19 disease itself

The COVID-19 pandemic has had many impacts on global health beyond those caused by the COVID-19 disease itself. It has led to a reduction in hospital visits for other reasons. There have been 38 per cent fewer hospital visits for heart attack symptoms in the United States and 40 per cent fewer in Spain. The head of cardiology at the University of Arizona said, "My worry is some of these people are dying at home because they're too scared to go to the hospital." There is also concern that people with strokes and appendicitis are not seeking timely treatment. Shortages of medical supplies have impacted people with various conditions.

There is no specific, effective treatment or cure for coronavirus disease 2019 (COVID-19), the disease caused by the SARS-CoV-2 virus. One year into the pandemic, highly effective vaccines have now been introduced and are beginning to slow the spread of SARS-CoV-2; however, for those awaiting vaccination, as well as for the estimated millions of immunocompromised persons who are unlikely to respond robustly to vaccination, treatment remain important. Thus, the lack of progress developing effective treatments means that the cornerstone of management of COVID-19 has been supportive care, which includes treatment to relieve symptoms, fluid therapy, oxygen support and prone positioning as needed, and medications or devices to support other affected vital organs.

Long COVID Long-term symptoms of COVID-19

Long COVID, also known as post-COVID-19 syndrome, post-acute sequelae of COVID-19 (PASC), or chronic COVID syndrome (CCS), is a condition characterized by long-term sequelae appearing or persisting after the typical convalescence period of COVID-19. Long COVID can affect nearly every organ system with sequelae including respiratory system disorders, nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, malaise, fatigue, musculoskeletal pain, and anemia. A wide range of symptoms are commonly discussed, including fatigue, headaches, shortness of breath, anosmia, parosmia, muscle weakness, low fever and cognitive dysfunction.

Smell training or olfactory training is the act of regularly sniffing or exposing oneself to robust aromas with the intention of regaining a sense of smell. The stimulating smells used are often selected from major smell categories, such as aromatic, flowery, fruity, and resinous. It is used as a rehabilitative therapy to help people who have anosmia or post-viral olfactory dysfunction, a symptom of COVID-19. It was considered a promising experimental treatment in a 2017 meta-analysis.

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