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

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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 acutely by polymerase chain reaction, 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 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 [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] 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. [6]

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 the infection, particularly in the elderly. [7] Recent evidence from a longitudinal study supports an inflammatory basis for delirium. [8] 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. [1] [3] [9] [10]

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–Barré syndrome, acute myelitis and encephalomyelitis have also been reported. [10] Guillain–Barré syndrome arises as an autoimmune disorder, that leads to progressive muscle weakness, difficulty walking and other symptoms reflecting reduced signaling to muscles. [10] 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] [10]

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). [11] 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. [11] 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. [12] [11] Only 5% of COVID-19 patients experience a loss of olfaction lasting more than 40 days. [11]

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 olfactory epithelium (sustentacullar or "support" cells), which are the cells that surround and support olfactory receptor neurons. [12] [13] Little if any virus directly infects these neurons themselves. [12] 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. [12] However, the olfactory epithelium is continually regenerated, and neurons that are damaged are typically replaced in about 14 days. [12] The nerve cells controlling taste, termed the gustatory nerve cells, turn over even faster, being renewed in about 10 days. [12]

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. [14] Olfactory training helps to "teach" the new olfactory neurons how to link with the brain so that odors can be noticed and then recognized. [14] Personal accounts of the process of olfactory training post COVID-19 infection have been covered in media outlets such as the New York Times. [15] 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. [14] Oral corticosteroid therapy can help, but is optional. [14] 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. [14]

Chronic 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
Long COVID's prevalence varies by age and gender in the United States Statista long covid.jpg
Long COVID's prevalence varies by age and gender in the United States
This section is an excerpt from Long COVID § Epidemiology.[ edit ]

Estimates of the prevalence of long COVID vary widely. The estimates depend on the definition of long COVID, the population studied, [17] as well as a number of other methodological differences, such as whether a comparable cohort of individuals without COVID-19 were included, [18] what kinds of symptoms are considered representative of long COVID, [18] and whether long COVID is assessed through a review of symptoms, through self-report of long COVID status, or some other method. [19]

In general, estimates of long COVID incidence based on statistically random sampling of the population are much lower than those based on certified infection, which has a tendency to skew towards more serious cases (including over-representation of hospitalized patients). Further, since incidence appears to be correlated with severity of infection, it is lower in vaccinated groups, on reinfection and during the omicron era, meaning that the time when data was recorded is important. For example, the UK's Office for National Statistics reported [20] in February 2023 (based on random sampling) that "2.4% of adults and 0.6% of children and young people reported long COVID following a second COVID-19 infection".

By the end of 2023, roughly 400 million people had or have had long COVID. This may be a conservative estimate, as it is based on studies counting those with specific long COVID symptoms only, and not counting those who developed long COVID after an asymptomatic infection. While hospitalised people have higher risks of getting long COVID, most long-haulers had a mild infection and were able to recover from the acute infection at home. [21]

An April 2022 meta-analysis estimated that the pooled incidence of post-COVID conditions after infection was 43%, with estimates ranging between 9% and 81%. People who had been hospitalised with COVID saw a higher prevalence of 54%, while 34% of nonhospitalised people developed long COVID after acute infection. [17] However, a more recent (April 2024) meta-analysis [22] estimated a pooled incidence of 9%.

In the United States in June 2023, 6% of the population indicated having long COVID, as defined as symptoms that last for 3 months or more. [23] This percentage had stayed stable since January that year, but was a decrease compared to June 2022. [23] Of people who had had a prior COVID infection, 11% indicated having long COVID. A quarter of those reported significant limitation in activity. [23] A study by the Medical Expenditure Panel Survey estimated that nearly 18 million people — had suffered from long COVID as of 2023, building on a study sponsored by the Agency for Healthcare Research and Quality. [24]

In a large population cohort study in Scotland, 42% of respondents said they had not fully recovered after 6 to 18 months after catching COVID, and 6% indicated they had not recovered at all. The risk of long COVID was associated with disease severity; people with asymptomatic infection did not have increased risk of long COVID symptoms compared to people who had never been infected. Those that had been hospitalised had 4.6 times higher odds of no recovery compared to nonhospitalised people. [25]

Long COVID is less common in children and adolescents than in adults. [26] Around 16% of children and adolescents develop long COVID following infection. [27]

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. [28] [16]

Neuroinflammation 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. [29] 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. [29] Psychotic disorders are characterized by neuroinflammation, more specifically maternal inflammation, and abnormally high mesolimbic dopamine (DA) signaling. [29] Excess inflammation following a COVID-19 infection can alter neurotransmitter signaling which contributes to development of psychotic and mood related disorders. [29]

A large study showed that post COVID-19, [30] 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. [30] 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] [14] 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. [31] One paper suggests that seizures tend to occur in COVID-19 patients with a prior history of seizure disorder or cerebrovascular infarcts, [32] 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. [31] 57% of the cases occur among patients who had experienced respiratory or gastrointestinal symptoms. [31] 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%). [31]

A large scale study of 6,245,282 patients have revealed an increased risk of Alzheimer's disease diagnosis following COVID-19 infection. [33] 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. [34] [35]

Acute psychiatric symptoms

Reported prevalence of mental health disorders vary depending on the study. [36] In one review, 35% of patients had mild forms of anxiety, insomnia, and depression and 13% of patients had moderate to severe forms. [37] Another review reports frequencies of depression and anxiety of 47% and 37%. [38] 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). [39] These psychological symptoms correlate with blood based biomarkers, such as C-reactive protein, which is an inflammatory protein. [38]

A case report of acute psychiatric disturbance noted an attempted suicide by a patient who had no prior noted psychiatric problems. [40]

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. [30] 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%). [41] 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%). [14] These accumulated problems lead to a general (and quantified) reduction in the quality of life and social functioning (measured with the SF-36 scale). [14] There is also increasing evidence to suggest that ongoing psychiatric symptoms, including post-traumatic stress [42] and depression, [43] 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. [44] Children with COVID-19 appear to exhibit similar rates as adults for loss of taste and smell. [44] 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. [44] About 1% of children have severe neurological symptoms. [44] About 15% of children with Kawasaki syndrome exhibit severe neurological symptoms, such as encephalopathy. [44] 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. [44] COVID-19 has not been associated with strokes in children. [44] Guilliain Barre Syndrome also appears to be rare in children. [44]

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. [45] The purpose of the study was to more definitively account for confounding factors, potentially exhibited by previous observational studies, as well as self-reporting on cognition performance. None of the volunteers were vaccinated. Among the study participants, 2 were eliminated due to prior infection, 18 showed "sustained viral load", and were designated as "infected", with the remainder designated "uninfected". Of the 11 cognitive tasks administered across multiple sessions, Object Memory, both Immediate and Delayed, yielded the largest differences between the "infected" and "uninfected" groups, with the "infected" group performing worse, particularly in Object Memory Immediate. [46]

Cognitive changes were still observed after around one year, and the authors noted that this would likely be the sole human challenge study involving SARS-CoV-2. [46]

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. [47]

There is ongoing research about the short- and long-term damage COVID-19 may possibly cause to the brain. [36] including in cases of 'long COVID'. For instance, a study showed how COVID-19 may cause microvascular brain pathology and endothelial cell-death, disrupting the blood–brain barrier. [48] [49] Another study identified neuroinflammation and an activation of adaptive and innate immune cells in the brain stem of COVID-19 patients. [50] 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: [51]

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. [52]

A study indicates that SARS-CoV-2 builds tunneling nanotubes from nose cells to gain access to the brain. [53] [54]

Related Research Articles

<span class="mw-page-title-main">Acute disseminated encephalomyelitis</span> Autoimmune disease

Acute disseminated encephalomyelitis (ADEM), or acute demyelinating encephalomyelitis, is a rare autoimmune disease marked by a sudden, widespread attack of inflammation in the brain and spinal cord. As well as causing the brain and spinal cord to become inflamed, ADEM also attacks the nerves of the central nervous system and damages their myelin insulation, which, as a result, destroys the white matter. The cause is often a trigger such as from viral infection or vaccinations.

<span class="mw-page-title-main">Anosmia</span> 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.

<span class="mw-page-title-main">Olfactory system</span> Sensory system used for smelling

The olfactory system, or sense of smell, is the sensory system used for olfaction. Olfaction is one of the special senses directly associated with 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. True ageusia is relatively rare compared to hypogeusia – a partial loss of taste – and dysgeusia – a distortion or alteration of taste.

A sequela is a pathological condition resulting from a disease, injury, therapy, or other trauma. Derived from the Latin word meaning "sequel", it is used in the medical field to mean a complication or condition following a prior illness or disease.

<span class="mw-page-title-main">PANDAS</span> Hypothesis in pediatric medicine

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a controversial hypothetical diagnosis for a subset of children with rapid onset of obsessive-compulsive disorder (OCD) or tic disorders. Symptoms are proposed to be caused by group A streptococcal (GAS), and more specifically, group A beta-hemolytic streptococcal (GABHS) infections. OCD and tic disorders are hypothesized to arise in a subset of children as a result of a post-streptococcal autoimmune process. The proposed link between infection and these disorders is that an autoimmune reaction to infection produces antibodies that interfere with basal ganglia function, causing symptom exacerbations, and this autoimmune response results in a broad range of neuropsychiatric symptoms.

<span class="mw-page-title-main">Intestinal pseudo-obstruction</span> Medical condition

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Phantosmia, also called an olfactory hallucination or a phantom odor, is smelling an odor that is not actually there. This is intrinsically suspicious as the formal evaluation and detection of relatively low levels of odour particles is itself a very tricky task in air epistemology. 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.

Hypogeusia can be defined as the reduced ability to taste things. Due to a lack of stratification, the prevalence of hypogeusia, as well as hyposmia, may not be accurately known. Additionally, reviews do not always make distinctions between ageusia and hypogeusia, often classifying them as the same in certain circumstances and studies. The severity of the loss of taste from hypogeusia is not clearly outlined in current research due to these reasons.

Guillain–Barré syndrome (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. Typically, both sides of the body are involved, and the initial symptoms are changes in sensation or pain often in the back along with muscle weakness, beginning in the feet and hands, often spreading to the arms and upper body. The symptoms may develop over hours to a few weeks. During the acute phase, the disorder can be life-threatening, with about 15% of people developing weakness of the breathing muscles requiring mechanical ventilation. Some are affected by changes in the function of the autonomic nervous system, which can lead to dangerous abnormalities in heart rate and blood pressure.

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.

<span class="mw-page-title-main">Sense of smell</span> Sense that detects smells

The sense of smell, or olfaction, is the special sense through which smells are perceived. The sense of smell has many functions, including detecting desirable foods, hazards, and pheromones, and plays a role in taste.

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The University of Pennsylvania Smell Identification Test (UPSIT) is a test that is commercially available for smell identification to test the function of an individual's olfactory system.

<span class="mw-page-title-main">COVID-19</span> Contagious disease caused by SARS-CoV-2

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. The first known case was identified in Wuhan, China, in December 2019. Most scientists believe the SARS-CoV-2 virus entered into human populations through natural zoonosis, similar to the SARS-CoV-1 and MERS-CoV outbreaks, and consistent with other pandemics in human history. Social and environmental factors including climate change, natural ecosystem destruction and wildlife trade increased the likelihood of such zoonotic spillover. The disease quickly spread worldwide, resulting in the COVID-19 pandemic.

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<span class="mw-page-title-main">Symptoms of COVID-19</span>

The symptoms of COVID-19 are variable depending on the type of variant contracted, ranging from mild symptoms to a potentially fatal illness. Common symptoms include coughing, fever, loss of smell (anosmia) and taste (ageusia), with less common ones including headaches, nasal congestion and runny nose, muscle pain, sore throat, diarrhea, eye irritation, and toes swelling or turning purple, and in moderate to severe cases, breathing difficulties. People with the COVID-19 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; and a cluster of digestive symptoms with abdominal pain, vomiting, and diarrhea. In people without prior ear, nose, or throat disorders, loss of taste combined with loss of smell is associated with COVID-19 and is reported in as many as 88% of symptomatic cases.

<span class="mw-page-title-main">Multisystem inflammatory syndrome in children</span> 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 COVID-19 (SISCoV), is a rare systemic illness involving persistent fever and extreme inflammation following exposure to SARS-CoV-2, the virus responsible for COVID-19. Studies suggest that MIS-C occurred in 31.6 out of 100,000 people under 21 who were infected with COVID-19. MIS-C has also been monitored as a potential, rare pediatric adverse event following COVID-19 vaccination. Research suggests that COVID-19 vaccination lowers the risk of MIS-C, and in cases where symptoms develop after vaccine, is likely extremely rare or related to factors like recent exposure to 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.

Long COVID or long-haul COVID is a group of health problems persisting or developing after an initial period of COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. The World Health Organization defines long COVID as starting three months after the initial COVID-19 infection, but other agencies define it as starting at four weeks after the initial infection.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Koralnik IJ, Tyler KL (July 2020). "COVID-19: A Global Threat to the Nervous System". Annals of Neurology. 88 (1): 1–11. doi:10.1002/ana.25807. PMC   7300753 . PMID   32506549.
  2. 1 2 3 Hossain MM, Tasnim S, Sultana A, Faizah F, Mazumder H, Zou L, et al. (2020). "Epidemiology of mental health problems in COVID-19: a review". F1000Research. 9: 636. doi: 10.12688/f1000research.24457.1 . PMC   7549174 . PMID   33093946.
  3. 1 2 3 4 5 Al-Sarraj S, Troakes C, Hanley B, Osborn M, Richardson MP, Hotopf M, et al. (February 2021). "Invited Review: The spectrum of neuropathology in COVID-19". Neuropathology and Applied Neurobiology. 47 (1): 3–16. doi: 10.1111/nan.12667 . hdl: 11343/252622 . PMID   32935873.
  4. 1 2 CDC (2020-03-28). "COVID Data Tracker". Centers for Disease Control and Prevention. Retrieved 2021-03-05.
  5. 1 2 Mukerji SS, Solomon IH (January 2021). "What can we learn from brain autopsies in COVID-19?". Neuroscience Letters. 742: 135528. doi:10.1016/j.neulet.2020.135528. PMC   7687409 . PMID   33248159.
  6. ↑ Troyer EA, Kohn JN, Hong S (July 2020). "Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms". Brain, Behavior, and Immunity. 87: 34–39. doi:10.1016/j.bbi.2020.04.027. PMC   7152874 . PMID   32298803.
  7. ↑ Barthorpe A, Rogers JP (2021-12-08). "Coronavirus infections from 2002-2021: Neuropsychiatric Manifestations". Sleep Medicine. 91: 282–288. doi:10.1016/j.sleep.2021.11.013. ISSN   1389-9457. PMC   8651478 . PMID   35221210.
  8. ↑ Saini A, Oh TH, Ghanem DA, Castro M, Butler M, Sin Fai Lam CC, Posporelis S, Lewis G, David AS, Rogers JP (2021-10-15). "Inflammatory and blood gas markers of COVID-19 delirium compared to non-COVID-19 delirium: a cross-sectional study". Aging & Mental Health. 26 (10): 2054–2061. doi: 10.1080/13607863.2021.1989375 . ISSN   1360-7863. PMID   34651536. S2CID   238990849.
  9. ↑ Bobker SM, Robbins MS (September 2020). "COVID-19 and Headache: A Primer for Trainees". Headache. 60 (8): 1806–1811. doi:10.1111/head.13884. PMC   7300928 . PMID   32521039.
  10. 1 2 3 4 Harapan BN, Yoo HJ (January 2021). "Neurological symptoms, manifestations, and complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19)". Journal of Neurology. 268 (9): 3059–3071. doi:10.1007/s00415-021-10406-y. PMC   7826147 . PMID   33486564.
  11. 1 2 3 4 Mastrangelo A, Bonato M, Cinque P (March 2021). "Smell and taste disorders in COVID-19: From pathogenesis to clinical features and outcomes". Neuroscience Letters. 748: 135694. doi:10.1016/j.neulet.2021.135694. PMC   7883672 . PMID   33600902.
  12. 1 2 3 4 5 6 Meunier N, Briand L, Jacquin-Piques A, Brondel L, Pénicaud L (2021-01-26). "COVID 19-Induced Smell and Taste Impairments: Putative Impact on Physiology". Frontiers in Physiology. 11: 625110. doi: 10.3389/fphys.2020.625110 . ISSN   1664-042X. PMC   7870487 . PMID   33574768.
  13. ↑ Veronese S, Sbarbati A (2021-03-03). "Chemosensory Systems in COVID-19: Evolution of Scientific Research". ACS Chemical Neuroscience. 12 (5): 813–824. doi:10.1021/acschemneuro.0c00788. ISSN   1948-7193. PMC   7885804 . PMID   33559466.
  14. 1 2 3 4 5 6 7 8 Hopkins C, Alanin M, Philpott C, Harries P, Whitcroft K, Qureishi A, Anari S, Ramakrishnan Y, Sama A, Davies E, Stew B (2021). "Management of new onset loss of sense of smell during the COVID-19 pandemic – BRS Consensus Guidelines". Clinical Otolaryngology. 46 (1): 16–22. doi:10.1111/coa.13636. ISSN   1749-4478. PMC   7461026 . PMID   32854169.
  15. ↑ Rao T (2021-03-02). "Will Fish Sauce and Charred Oranges Return the World Covid Took From Me?". The New York Times. ISSN   0362-4331 . Retrieved 2021-03-24.
  16. 1 2 Taquet M, Geddes JR, Husain M, Luciano S, Harrison PJ (1 May 2021). "6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records". The Lancet Psychiatry. 8 (5): 416–427. doi: 10.1016/S2215-0366(21)00084-5 . ISSN   2215-0366. PMC   8023694 . PMID   33836148.
  17. 1 2 Chen C, Haupert SR, Zimmermann L, Shi X, Fritsche LG, Mukherjee B (November 2022). "Global Prevalence of Post-Coronavirus Disease 2019 (COVID-19) Condition or Long COVID: A Meta-Analysis and Systematic Review". The Journal of Infectious Diseases. 226 (9): 1593–1607. doi:10.1093/infdis/jiac136. PMC   9047189 . PMID   35429399.
  18. 1 2 Nasserie T, Hittle M, Goodman SN (May 2021). "Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19: A Systematic Review". JAMA Network Open. 4 (5): e2111417. doi:10.1001/jamanetworkopen.2021.11417. PMC   8155823 . PMID   34037731. Archived from the original on 28 April 2024. Retrieved 8 April 2024.
  19. ↑ "Technical article: Updated estimates of the prevalence of post-acute symptoms among people with coronavirus (COVID-19) in the UK - Office for National Statistics". www.ons.gov.uk. 16 September 2021. Archived from the original on 8 April 2024. Retrieved 8 April 2024.
  20. ↑ "New-onset, self-reported long COVID after coronavirus (COVID-19) reinfection in the UK: 23 February 2023". 23 February 2023.
  21. ↑ Al-Aly Z, Davis H, McCorkell L, Soares L, Wulf-Hanson S, Iwasaki A, Topol EJ (August 2024). "Long COVID science, research and policy". Nature Medicine. 30 (8): 2148–2164. doi: 10.1038/s41591-024-03173-6 . PMID   39122965.
  22. ↑ "New research examines the risk of developing Long Covid". 25 April 2024.
  23. 1 2 3 Ford ND, Slaughter D, Edwards D, Dalton A, Perrine C, Vahratian A, Saydah S (August 2023). "Long COVID and Significant Activity Limitation Among Adults, by Age – United States, June 1–13, 2022, to June 7–19, 2023". MMWR. Morbidity and Mortality Weekly Report. 72 (32): 866–870. doi:10.15585/mmwr.mm7232a3. PMC   10415000 . PMID   37561665.
  24. ↑ McMahan I (15 July 2024). "About 7 percent of U.S. adults have had long covid, report says". The Washington Post.
  25. ↑ Hastie CE, Lowe DJ, McAuley A, Winter AJ, Mills NL, Black C, Scott JT, O'Donnell CA, Blane DN, Browne S, Ibbotson TR, Pell JP (October 2022). "Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study". Nature Communications. 13 (1): 5663. Bibcode:2022NatCo..13.5663H. doi:10.1038/s41467-022-33415-5. PMC   9556711 . PMID   36224173.
  26. ↑ Zheng YB, Zeng N, Yuan K, Tian SS, Yang YB, Gao N, Chen X, Zhang AY, Kondratiuk AL, Shi PP, Zhang F, Sun J, Yue JL, Lin X, Shi L, Lalvani A, Shi J, Bao YP, Lu L (May 2023). "Prevalence and risk factor for long COVID in children and adolescents: A meta-analysis and systematic review". Journal of Infection and Public Health. 16 (5): 660–672. doi:10.1016/j.jiph.2023.03.005. PMC   9990879 . PMID   36931142.
  27. ↑ Jiang L, Li X, Nie J, Tang K, Bhutta ZA (August 2023). "A Systematic Review of Persistent Clinical Features After SARS-CoV-2 in the Pediatric Population". Pediatrics. 152 (2). doi:10.1542/peds.2022-060351. PMC   10389775 . PMID   37476923.
  28. ↑ "The early results are in: Two-thirds of Australia's severe COVID sufferers are in for the long haul". www.abc.net.au. 9 May 2021. Retrieved 10 May 2021.
  29. 1 2 3 4 Jansen van Vuren EE, Steyn SF, Brink CB, Möller MM, Viljoen FP, Harvey BH (March 2021). "The neuropsychiatric manifestations of COVID-19: Interactions with psychiatric illness and pharmacological treatment". Biomedicine & Pharmacotherapy. 135: 111200. doi:10.1016/j.biopha.2020.111200. PMC   7834135 . PMID   33421734.
  30. 1 2 3 Al-Aly Z, Xie Y, Bowe B (2021-04-22). "High-dimensional characterization of post-acute sequalae of COVID-19". Nature. 594 (7862): 259–264. Bibcode:2021Natur.594..259A. doi: 10.1038/s41586-021-03553-9 . ISSN   1476-4687. PMID   33887749.
  31. 1 2 3 4 Dono F, Nucera B, Lanzone J, Evangelista G, Rinaldi F, Speranza R, Troisi S, Tinti L, Russo M, Di Pietro M, Onofrj M (2021). "Status epilepticus and COVID-19: A systematic review". Epilepsy & Behavior. 118: 107887. doi:10.1016/j.yebeh.2021.107887. PMC   7968345 . PMID   33743344.
  32. ↑ Waters BL, Michalak AJ, Brigham D, Thakur KT, Boehme A, Claassen J, Bell M (2021-02-04). "Incidence of Electrographic Seizures in Patients With COVID-19". Frontiers in Neurology. 12: 614719. doi: 10.3389/fneur.2021.614719 . ISSN   1664-2295. PMC   7890122 . PMID   33613431.
  33. ↑ Gonzalez-Fernandez E, Huang J (2023-09-01). "Cognitive Aspects of COVID-19". Current Neurology and Neuroscience Reports. 23 (9): 531–538. doi:10.1007/s11910-023-01286-y. ISSN   1534-6293. PMID   37490194. S2CID   260132167.
  34. ↑ Rahman MA, Islam K, Rahman S, Alamin M (March 2021). "Neurobiochemical Cross-talk Between COVID-19 and Alzheimer's Disease". Molecular Neurobiology. 58 (3): 1017–1023. doi:10.1007/s12035-020-02177-w. ISSN   0893-7648. PMC   7571527 . PMID   33078369.
  35. ↑ Wang H, Lu J, Zhao X, Qin R, Song K, Xu Y, Zhang J, Chen Y (December 2021). "Alzheimer's disease in elderly COVID-19 patients: potential mechanisms and preventive measures". Neurological Sciences. 42 (12): 4913–4920. doi:10.1007/s10072-021-05616-1. ISSN   1590-1874. PMC   8455804 . PMID   34550494.
  36. ↑ Mukerji SS, Solomon IH (2021-01-18). "What can we learn from brain autopsies in COVID-19?". Neuroscience Letters. 742: 135528. doi:10.1016/j.neulet.2020.135528. ISSN   1872-7972. PMC   7687409 . PMID   33248159.
  37. 1 2 Hossain MM, Tasnim S, Sultana A, Faizah F, Mazumder H, Zou L, McKyer EL, Ahmed HU, Ma P (2020). "Epidemiology of mental health problems in COVID-19: a review". F1000Research. 9: 636. doi: 10.12688/f1000research.24457.1 . ISSN   2046-1402. PMC   7549174 . PMID   33093946.
  38. ↑ Rogers JP, Watson CJ, Badenoch J, Cross B, Butler M, Song J, Hafeez D, Morrin H, Rengasamy ER, Thomas L, Ralovska S (2021-06-03). "Neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives". Journal of Neurology, Neurosurgery & Psychiatry. 92 (9): 932–941. doi: 10.1136/jnnp-2021-326405 . hdl: 20.500.11820/448ac1f4-795d-4cb5-af76-62a8ec36c95c . ISSN   0022-3050. PMID   34083395. S2CID   235334764.
  39. ↑ Gillett G, Jordan I (2020). "Severe psychiatric disturbance and attempted suicide in a patient with COVID-19 and no psychiatric history". BMJ Case Reports. 13 (10): e239191. doi: 10.1136/bcr-2020-239191 . PMC   7783370 . PMID   33130587.
  40. ↑ Rogers JP, Chesney E, Oliver D, Pollak TA, McGuire P, Fusar-Poli P, Zandi MS, Lewis G, David AS (July 2020). "Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic". The Lancet. Psychiatry. 7 (7): 611–627. doi:10.1016/S2215-0366(20)30203-0. ISSN   2215-0374. PMC   7234781 . PMID   32437679.
  41. ↑ Harenwall S, Heywood-Everett S, Henderson R, Smith J, McEnery R, Bland AR (2022). "The Interactive Effects of Post-Traumatic Stress Symptoms and Breathlessness on Fatigue Severity in Post-COVID-19 Syndrome". Journal of Clinical Medicine. 11 (20): 6214. doi: 10.3390/jcm11206214 . ISSN   2077-0383. PMC   9604889 . PMID   36294534.
  42. ↑ Al-Jassas HK, Al-Hakeim HK, Maes M (2022-01-15). "Intersections between pneumonia, lowered oxygen saturation percentage and immune activation mediate depression, anxiety, and chronic fatigue syndrome-like symptoms due to COVID-19: A nomothetic network approach". Journal of Affective Disorders. 297: 233–245. doi:10.1016/j.jad.2021.10.039. ISSN   0165-0327. PMC   8541833 . PMID   34699853.
  43. 1 2 3 4 5 6 7 8 Boronat S (2021-02-18). "Neurologic Care of COVID-19 in Children". Frontiers in Neurology. 11: 613832. doi: 10.3389/fneur.2020.613832 . ISSN   1664-2295. PMC   7935545 . PMID   33679571.
  44. ↑ "SARS-CoV-2 Human Challenge Characterisation Study". 2022-07-28.
  45. 1 2 Trender W, Hellyer PJ, Killingley B, Kalinova M, Mann AJ, Catchpole AP, Menon D, Needham E, Thwaites R, Chiu C, Scott G, Hampshire A (2024). "Changes in memory and cognition during the SARS-CoV-2 human challenge study". eClinicalMedicine. 76. doi:10.1016/j.eclinm.2024.102842.
  46. ↑ Mathew B, Kumar R, Harilal S, M S, Pappachan LK, PR R (April 2022). "Current Perspective of COVID-19 on Neurology: A Mechanistic Insight". Combinatorial Chemistry & High Throughput Screening. 25 (5): 763–767. doi:10.2174/1386207324666210805121828. ISSN   1386-2073. PMID   34353250. S2CID   236933857.
  47. ↑ "Study reveals how COVID-19 can directly damage brain cells". New Atlas. 25 October 2021. Retrieved 16 November 2021.
  48. ↑ Jan Wenzel, et al. (November 2021). "The SARS-CoV-2 main protease Mpro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells". Nature Neuroscience. 24 (11): 1522–1533. doi:10.1038/s41593-021-00926-1. ISSN   1546-1726. PMC   8553622 . PMID   34675436.
  49. ↑ Schwabenland M, Salié H, Tanevski J, Killmer S, Lago MS, Schlaak AE, Mayer L, Matschke J, Püschel K, Fitzek A, Ondruschka B (2021-06-09). "Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions". Immunity. 54 (7) (published June 2021): 1594–1610.e11. doi:10.1016/j.immuni.2021.06.002. PMC   8188302 . PMID   34174183.
  50. ↑ Douaud G, Lee S, Alfaro-Almagro F, Arthofer C, Wang C, McCarthy P, Lange F, Andersson JL, Griffanti L, Duff E, Jbabdi S, Taschler B, Keating P, Winkler AM, Collins R, Matthews PM, Allen N, Miller KL, Nichols TE, Smith SM (7 March 2022). "SARS-CoV-2 is associated with changes in brain structure in UK Biobank". Nature. 604 (7907): 697–707. Bibcode:2022Natur.604..697D. doi:10.1038/s41586-022-04569-5. ISSN   1476-4687. PMC   9046077 . PMID   35255491.
  51. ↑ Kausel L, Figueroa-Vargas A (2024). "Patients recovering from COVID-19 who presented with anosmia during their acute episode have behavioral, functional, and structural brain alterations". Scientific Reports. 14 (1): 19049. doi:10.1038/s41598-024-69772-y. PMC   11329703 . PMID   39152190.
  52. ↑ "Coronavirus may enter the brain by building tiny tunnels from the nose". New Scientist. Retrieved 23 August 2022.
  53. ↑ Pepe A, Pietropaoli S, Vos M, Barba-Spaeth G, Zurzolo C (22 July 2022). "Tunneling nanotubes provide a route for SARS-CoV-2 spreading". Science Advances. 8 (29): eabo0171. Bibcode:2022SciA....8O.171P. doi: 10.1126/sciadv.abo0171 . ISSN   2375-2548. PMC   9299553 . PMID   35857849.
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