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 suggests 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.

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 COVID19 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]

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] 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[edit]

The fraction of subjects who experience symptoms following an infection with Coronavirus 2 (SARS-CoV-2) varies by age. Between 10-20% of patients who are infected with SARS-Coronavirus-2 (SARS-CoV-2) generally exhibit the clinical syndrome, known as COVID-19. The number of COVID19 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 disorders of smell (46% anosmia, 29% hyposmia, and 6% dysosmia).[1] Similarly for taste, disorders of taste occur in 94% of patients (ageusia 45%, hypogeusia 23%, and dysgeusia 26%). Importantly, most patients recover their sense of taste or smell within 8 days.[1] 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][7][8]

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.[8] Guillain–Barre Syndrome arises as an autoimmune disorder, that leads to progressive muscle weakness, difficulty walking and other symptoms reflecting reduced signaling to muscles.[8] 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][8]

Disorders of Smell (Olfaction) and Taste (Gustation)[edit]

As mentioned above, many COVID-19 patients suffer from disorders of taste or smell. 41- -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).[9] 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.[9] 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.[10][9] Only 5% of COVID-19 patients experience a loss of olfaction lasting more than 40 days.[9]

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.[10][11] Little if any virus directly infects the olfactory receptor neurons themselves.[10] 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.[10] Luckily, the olfactory epithelium is continually regenerated, and neurons that are damaged are typically replaced in about 14 days.[10] The nerve cells controlling taste, termed the gustatory nerve cells, turn over even faster, being renewed in about 10 days.[10]

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.[12] Olfactory training helps to "teach" the new olfactory neurons how to link with the brain so that we can actually notice and then recognize odors.[12] Readers might consult a media article for a personal account of the process of olfactory training.[13] 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.[12] Oral corticosteroid therapy can help, but is optional.[12] 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.[12]

Post-COVID-19 neurologic symptoms[edit]

A large study showed that post-COVID-19,[14] 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.[15] About 20% of COVID19 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 a MRI, 44% had findings upon MRI, such as a FLAIR signal (fluid-attenuated inversion recovery signal), leptomeningeal spaces and stroke.[1][12] 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]

Seizures also occur among COVID-19 patients who were hospitalized and are discussed in a recent review.[16] A recent paper suggests that seizures tend to occur in COVID-19 patients with a prior history of seizure disorder or cerebrovascular infarcts,[17] 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.[16] 57% of the cases occur among patients who had experienced respiratory or gastrointestinal symptoms.[16] It is important to note that 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%).[16]

Acute COVID-19 psychiatric symptoms[edit]

Reported prevalence of mental health disorders vary depending on the study. In one review, anxiety, depression, insomnia and distress are reported in up to 35% patients had mild, and 13% of patients had moderate to severe psychological symptoms.[18] Another review reports frequencies of depression and anxiety of 47% and 37%.[19] These psychological symptoms correlate with blood based biomarkers, such as C-reactive protein, which is an inflammatory protein.[19]There have been case reports of acute psychiatric disturbance and attempted suicide in the context of acute COVID-19 infection.[20]

Chronic COVID-19 psychiatric symptoms[edit]

These include (but may not be limited to) increased risk of depression, anxiety, sleep problems, and substance use disorders.[21] Chronic symptoms abound among patients recovering from COVID-19. Common symptoms occurring in patients with chronic post-COVID-19 the types and frequency of symptoms for which there is abundant information include: traumatic memories (30%), decreased memory (19%), fatigue (19%), irritability (13%), insomnia (12%) and depressed mood (11%).[22] 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%).[12] These accumulated problems lead to a general (and quantified) reduction in the quality of life and social functioning (measured with the SF-36 scale).[12]

Mental Health Symptoms among People and Caregivers of COVID-19 Patients[edit]

COVID-19 is a highly contagious global pandemic. This affects people's mental health. According to mental health experts, the COVID-19 pandemic has caused negative effects on people's mental health around the globe. These effects manifest from increased anxiety and insecurity, greater fears, and discrimination.[23]

Experts say people tend to feel a lot of anxiety and insecurity when the environment is changed. COVID-19, which spreads rapidly and rapidly, is why people feel more panic and anxiety. Another reason mentioned by the experts in the growing rumor. This causes fear in everyone. Additionally, anxiety and fear associated with infection can lead to discriminatory behaviors. These things lead to increasingly negative social behaviors, making mental health not improving and worse.[23]

COVID-19 also impacts on health care providers. 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).[24] Health care workers also frequently exhibit symptoms of post-traumatic stress disorder (14%).[24] In general, about 50% of health care workers exhibit some form of negative emotions.[24]

Pediatric Symptoms of COVID-19[edit]

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.[25] Children with COVID-19 appear to exhibit similar rates as adults for loss of taste and smell.[25] exhibit 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.[25] About 1% of children have severe neurological symptoms.[25] About 15% of children with Kawasaki syndrome exhibit severe neurological symptoms, such as encephalopathy.[25] 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.[25] COVID-19 also has not been associated with strokes in children.[25] Guilliain Barre Syndrome also appears to be rare in children[25]

References[edit]

  1. ^ a b c d e f g h i j k l m 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. ^ a b c 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. ^ a b c d e 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. PMID 32935873.
  4. ^ a b CDC (2020-03-28). "COVID Data Tracker". Centers for Disease Control and Prevention. Retrieved 2021-03-05.
  5. ^ a b 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, Emily A.; Kohn, Jordan N.; Hong, Suzi (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. ^ 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.
  8. ^ a b c d 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. doi:10.1007/s00415-021-10406-y. PMC 7826147. PMID 33486564.
  9. ^ a b c d Mastrangelo, Andrea; Bonato, Matteo; Cinque, Paola (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.
  10. ^ a b c d e f Meunier, Nicolas; Briand, Loïc; Jacquin-Piques, Agnès; Brondel, Laurent; Pénicaud, Luc (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.
  11. ^ Veronese, Sheila; Sbarbati, Andrea (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.
  12. ^ a b c d e f g h Hopkins, Claire; Alanin, Mikkel; Philpott, Carl; Harries, Phil; Whitcroft, Katherine; Qureishi, Ali; Anari, Shahram; Ramakrishnan, Yujay; Sama, Anshul; Davies, Elgan; Stew, Ben (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.
  13. ^ Rao, Tejal (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.
  14. ^ Al-Aly, Ziyad; Xie, Yan; Bowe, Benjamin (2021-04-22). "High-dimensional characterization of post-acute sequalae of COVID-19". Nature: 1–8. doi:10.1038/s41586-021-03553-9. ISSN 1476-4687.
  15. ^ Al-Aly, Ziyad; Xie, Yan; Bowe, Benjamin (2021-04-22). "High-dimensional characterization of post-acute sequalae of COVID-19". Nature: 1–8. doi:10.1038/s41586-021-03553-9. ISSN 1476-4687.
  16. ^ a b c d Dono, Fedele; Nucera, Bruna; Lanzone, Jacopo; Evangelista, Giacomo; Rinaldi, Fabrizio; Speranza, Rino; Troisi, Serena; Tinti, Lorenzo; Russo, Mirella; Di Pietro, Martina; Onofrj, Marco (2021). "Status epilepticus and COVID-19: A systematic review". Epilepsy & Behavior. 118: 107887. doi:10.1016/j.yebeh.2021.107887. PMC 7968345. PMID 33743344.
  17. ^ Waters, Brandon L.; Michalak, Andrew J.; Brigham, Danielle; Thakur, Kiran T.; Boehme, Amelia; Claassen, Jan; Bell, Michelle (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.
  18. ^ Mukerji, Shibani S.; Solomon, Isaac H. (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.
  19. ^ a b Hossain, Md Mahbub; Tasnim, Samia; Sultana, Abida; Faizah, Farah; Mazumder, Hoimonty; Zou, Liye; McKyer, E. Lisako J.; Ahmed, Helal Uddin; Ma, Ping (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.
  20. ^ Gillett, George; Jordan, Iain (2020). "Severe psychiatric disturbance and attempted suicide in a patient with COVID-19 and no psychiatric history". BMJ Case Reports (13): e239191. doi:10.1136/bcr-2020-239191.
  21. ^ Al-Aly, Ziyad; Xie, Yan; Bowe, Benjamin (2021-04-22). "High-dimensional characterization of post-acute sequalae of COVID-19". Nature: 1–8. doi:10.1038/s41586-021-03553-9. ISSN 1476-4687.
  22. ^ Rogers, Jonathan P.; Chesney, Edward; Oliver, Dominic; Pollak, Thomas A.; McGuire, Philip; Fusar-Poli, Paolo; Zandi, Michael S.; Lewis, Glyn; David, Anthony S. (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.
  23. ^ a b Usher, Kim; Durkin, Joanne; Bhullar, Navjot (10 April 2020). "The COVID‐19 Pandemic and Mental Health Impacts". Wiley Online Library. Retrieved 6 April 2021.
  24. ^ a b c Hossain, Md Mahbub; Tasnim, Samia; Sultana, Abida; Faizah, Farah; Mazumder, Hoimonty; Zou, Liye; McKyer, E. Lisako J.; Ahmed, Helal Uddin; Ma, Ping (2020-06-23). "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.
  25. ^ a b c d e f g h Boronat, Susana (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.
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