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

Source: Wikipedia, the free encyclopedia.

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.

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] 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] 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.[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]

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.[12][13] Little if any virus directly infects the olfactory receptor 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 COVID-19 neurologic symptoms

Impact of COVID-19 on neurological and psychiatric outcomes in the subsequent 6 months compared with other respiratory tract infections[16]

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.[17][16]

A large study showed that post COVID-19,[18] 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.[18] 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.[19] One paper suggests that seizures tend to occur in COVID-19 patients with a prior history of seizure disorder or cerebrovascular infarcts,[20] 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.[19] 57% of the cases occur among patients who had experienced respiratory or gastrointestinal symptoms.[19] 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%).[19]

Acute COVID-19 psychiatric symptoms

Reported prevalence of mental health disorders vary depending on the study.[21] In one review, 35% of patients had mild forms of anxiety, insomnia, and depression and 13% of patients had moderate to severe forms.[22] Another review reports frequencies of depression and anxiety of 47% and 37%.[23] 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).[24] These psychological symptoms correlate with blood based biomarkers, such as C-reactive protein, which is an inflammatory protein.[23] There have been case reports of acute psychiatric disturbance and attempted suicide in the context of acute COVID-19 infection.[25]

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.[18] 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%).[26] 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]

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.[27]

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.[27]

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).[28]

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.[29]  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.[29] Kamberi's study shows that regardless of your medical field, all healthcare fields are susceptible to experience mental health concerns.  [29]

COVID-19 impacts mental health of health care providers, but its 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).[30]

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.[31] 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.[citation needed]

Health care workers also frequently exhibit symptoms of more severe disorders developing like post-traumatic stress disorder (14%).[30] In general, about 50% of health care workers exhibit some form of negative emotions.[30] 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.[32] 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.[33]

When specifically examining Post-Traumatic Stress Disorder in nurses during the pandemic, there are many factors contributing to the decline.[34] 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.[34]

  • Contact a medical provider
  • Contact a local or national Mental Health Hotline
  • Take time to perform self-care
  • Increase nutritional food intake
  • Talk to a trusted friend or family member

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.[35] Children with COVID-19 appear to exhibit similar rates as adults for loss of taste and smell.[35] 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.[35] About 1% of children have severe neurological symptoms.[35] About 15% of children with Kawasaki syndrome exhibit severe neurological symptoms, such as encephalopathy.[35] 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.[35] COVID-19 has not been associated with strokes in children.[35] Guilliain Barre Syndrome also appears to be rare in children.[35]

Research into COVID-19 induced brain damage

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.[37][38] Another study identified neuroinflammation and an activation of adaptive and innate immune cells in the brain stem of COVID-19 patients.[39] Long COVID may contribute to inflammaging in aged individuals and lead to long term brain changes, rendering patients vulnerable to the development of neurodegenerative diseases.[40] 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:[41]

References

  1. ^ a b c d e f g h i j k l m n 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. ^ Barthorpe, Amber; Rogers, Jonathan P. (2021-12-08). "Coronavirus infections from 2002-2021: Neuropsychiatric Manifestations". Sleep Medicine. doi:10.1016/j.sleep.2021.11.013. ISSN 1389-9457. PMC 8651478. PMID 35221210.
  8. ^ Saini, Aman; Oh, Tae Hyun; Ghanem, Dory Anthony; Castro, Megan; Butler, Matthew; Sin Fai Lam, Chun Chiang; Posporelis, Sotiris; Lewis, Glyn; David, Anthony S.; Rogers, Jonathan P. (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: 1–8. 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. ^ 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. 268 (9): 3059–3071. doi:10.1007/s00415-021-10406-y. PMC 7826147. PMID 33486564.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ 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.
  16. ^ a b Taquet, Maxime; Geddes, John R.; Husain, Masud; Luciano, Sierra; Harrison, Paul J. (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. ^ "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.
  18. ^ a b c Al-Aly, Ziyad; Xie, Yan; Bowe, Benjamin (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.
  19. ^ 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.
  20. ^ 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.
  21. ^ Zhang R, Sun C, Chen X, Han Y, Zang W, Jiang C, Wang J, Wang J (April 2022). "COVID-19-Related Brain Injury: The Potential Role of Ferroptosis". J Inflamm Res. 15: 2181–2198. doi:10.2147/JIR.S353467. PMC 8994634. PMID 35411172.
  22. ^ 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.
  23. ^ 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.
  24. ^ Rogers, Jonathan P.; Watson, Cameron J.; Badenoch, James; Cross, Benjamin; Butler, Matthew; Song, Jia; Hafeez, Danish; Morrin, Hamilton; Rengasamy, Emma Rachel; Thomas, Lucretia; Ralovska, Silviya (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. ISSN 0022-3050. PMID 34083395. S2CID 235334764.
  25. ^ 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 (10): e239191. doi:10.1136/bcr-2020-239191. PMC 7783370. PMID 33130587.
  26. ^ 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.
  27. ^ a b Usher, Kim; Durkin, Joanne; Bhullar, Navjot (10 April 2020). "The COVID‐19 Pandemic and Mental Health Impacts". International Journal of Mental Health Nursing. 29 (3): 315–318. doi:10.1111/inm.12726. PMC 7262128. PMID 32277578.
  28. ^ Man, Jeroen De; Smith, Mario R.; Schneider, Marguerite; Tabana, Hanani (2021-07-28). "An exploration of the impact of COVID-19 on mental health in South Africa". Psychology, Health & Medicine. 27 (1): 120–130. doi:10.1080/13548506.2021.1954671. ISSN 1354-8506. PMID 34319182. S2CID 236471921.
  29. ^ a b c Kamberi, Fatjona; Sinaj, Enkeleda; Jaho, Jerina; Subashi, Brunilda; Sinanaj, Glodiana; Jaupaj, Kristela; Stramarko, Yllka; Arapi, Paola; Dine, Ledia; Gurguri, Arberesha; Xhindoli, Juljana (October 2021). "Impact of COVID-19 pandemic on mental health, risk perception and coping strategies among health care workers in Albania - evidence that needs attention". Clinical Epidemiology and Global Health. 12: 100824. doi:10.1016/j.cegh.2021.100824. PMC 8567021. PMID 34751254.
  30. ^ 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.
  31. ^ Sampaio, Francisco; Sequeira, Carlos; Teixeira, Laetitia (October 2020). "Nurses' Mental Health During the Covid-19 Outbreak: A Cross-Sectional Study". Journal of Occupational & Environmental Medicine. 62 (10): 783–787. doi:10.1097/JOM.0000000000001987. hdl:10284/8914. ISSN 1076-2752. PMID 32769803. S2CID 221084766.
  32. ^ Leng, Min; Wei, Lili; Shi, Xiaohui; Cao, Guorong; Wei, Yuling; Xu, Hong; Zhang, Xiaoying; Zhang, Wenwen; Xing, Shuyun; Wei, Holly (March 2021). "Mental distress and influencing factors in nurses caring for patients with COVID ‐19". Nursing in Critical Care. 26 (2): 94–101. doi:10.1111/nicc.12528. ISSN 1362-1017. PMID 33448567.
  33. ^ Davidson, Judy E.; Stuck, Amy R.; Zisook, Sidney; Proudfoot, James (May 2018). "Testing a Strategy to Identify Incidence of Nurse Suicide in the United States". The Journal of Nursing Administration. 48 (5): 259–265. doi:10.1097/NNA.0000000000000610. ISSN 1539-0721. PMID 29672372. S2CID 5001693.
  34. ^ a b COVID-19 and Mental Health: Self-Care for Nursing Staff. (2021). Arizona Nurse, 74(2), 14–15.
  35. ^ 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.
  36. ^ Zhang R, Sun C, Chen X, Han Y, Zang W, Jiang C, Wang J, Wang J (April 2022). "COVID-19-Related Brain Injury: The Potential Role of Ferroptosis". J Inflamm Res. 15: 2181–2198. doi:10.2147/JIR.S353467. PMC 8994634. PMID 35411172.
  37. ^ "Study reveals how COVID-19 can directly damage brain cells". New Atlas. 25 October 2021. Retrieved 16 November 2021.
  38. ^ 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.{{cite journal}}: CS1 maint: uses authors parameter (link)
  39. ^ Schwabenland, Marius; Salié, Henrike; Tanevski, Jovan; Killmer, Saskia; Lago, Marilyn Salvat; Schlaak, Alexandra Emilia; Mayer, Lena; Matschke, Jakob; Püschel, Klaus; Fitzek, Antonia; Ondruschka, Benjamin (2021-06-09). "Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions". Immunity (published June 2021). 54 (7): 1594–1610.e11. doi:10.1016/j.immuni.2021.06.002. PMC 8188302. PMID 34174183.{{cite journal}}: CS1 maint: date and year (link)
  40. ^ Domingues, Renato; Lippi, Alice; Setz, Cristian; Outeiro, Tiago F.; Krisko, Anita (2020-09-29). "SARS-CoV-2, immunosenescence and inflammaging: partners in the COVID-19 crime". Aging (Albany NY). 12 (18): 18778–18789. doi:10.18632/aging.103989. ISSN 1945-4589. PMC 7585069. PMID 32991323.
  41. ^ Douaud, Gwenaëlle; Lee, Soojin; Alfaro-Almagro, Fidel; Arthofer, Christoph; Wang, Chaoyue; McCarthy, Paul; Lange, Frederik; Andersson, Jesper L. R.; Griffanti, Ludovica; Duff, Eugene; Jbabdi, Saad; Taschler, Bernd; Keating, Peter; Winkler, Anderson M.; Collins, Rory; Matthews, Paul M.; Allen, Naomi; Miller, Karla L.; Nichols, Thomas E.; Smith, Stephen M. (7 March 2022). "SARS-CoV-2 is associated with changes in brain structure in UK Biobank". Nature: 1–17. doi:10.1038/s41586-022-04569-5. ISSN 1476-4687.