Psychological and Cognitive Effects of Long COVID: History
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Contributor:
Rosaria De Luca
,
Mirjam Bonanno
,
Rocco Salvatore Calabrò

Long COVID is a clinical syndrome characterized by profound fatigue, neurocognitive difficulties, muscle pain, weakness, and depression, lasting beyond the 3–12 weeks following infection with SARS-CoV-2.

  • Long COVID syndrome
  • psychometric assessment
  • behavioral alterations

1. Introduction

Because of the COVID-19 pandemic, caused by SARS-CoV-2, many individuals experience post-infection long-lasting symptoms, namely post-COVID syndrome or Long COVID [1][2]. Long COVID is characterized by the persistence of exhausting fatigue, neurocognitive difficulties such as mental fog, muscle pain, and weakness, as well as depression, lasting beyond the 3–12 weeks following SARS-CoV-2 infection [3]. According to Naik et al., the most common symptoms are myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), insomnia (1.4%), mood disturbances (0.48%), and anxiety (0.6%) [4][5]. The persistence of the symptoms seems to be linked to immune dysregulation due to harmful inflammation, although the exact causes are still unknown [6][7]. Recently, a huge number of studies have reported immune abnormalities, such as an increase in the innate immune system activity, chronic fatigue/myalgic syndrome, encephalomyelitis [8], fibromyalgia [9], cognitive dysfunction [10], depression, and other mental health disorders [11][12][13]. Concerning the latter disorders, neuroinflammation may play a key role in the onset of symptoms, through either an activation of microglia or auto-immune reactions [14][15]. Indeed, Long COVID often presents with “brain fog”, which is characterized by low energy, concentration problems, disorientation, and difficulty finding the right words [16][17]. However, long-term psychological, cognitive, or adverse mental health consequences of COVID-19 have recently begun to be recognized. Hampshire et al. [18] showed that COVID-19 could have a multi-domain impact on human cognition, as assessed using psychometric subtests. In particular, people who had recovered from the infectious disease, including those no longer reporting symptoms, may exhibit significant cognitive deficits as compared to controls, when controlled for age, gender, education level, income, racial–ethnic group, pre-existing medical disorders, tiredness, depression, and anxiety. Moreover, Ocsovszky et al. [19] found a positive correlation between the level of depressive symptoms and anxiety in a Long COVID non-hospitalized cohort. Depression and anxiety have been shown to have a negative impact on symptom perception and also contribute to a higher number of symptoms in a non-hospitalized sample, suggesting a bi-directional interconnection between the clinical and psychological factors [20][21][22][23]. Therefore, multidisciplinary rehabilitation interventions are necessary to better manage individuals with Long COVID. In fact, cognitive rehabilitation, including compensatory and metacognitive strategies, which are usually administered to patients with brain injury, can be also applied to the Long COVID population [24][25].

2. Neurological Manifestations of Long COVID

The neurological manifestations (NMs) of Long COVID remain an outstanding issue since the pathogenic mechanisms are poorly understood despite the high prevalence of the symptoms. The most commonly reported NMs are fatigue (72%), muscle aches/myalgia (57%), and headache (53%) [26]. Orrù G. et al. [27] also included loss of smell and loss of concentration, as well as insomnia and reduced quality of life. However, it has been pointed out that anosmia and dysgeusia are more commonly related to the acute COVID-19 infection as these specific symptoms generally resolve [28]. Conversely, symptoms such as headaches, anxiety, depression, brain fog, fatigue, and insomnia are more likely to belong to the post-infection syndrome. NM onset may be due to an association between biological and psychological factors. In fact, SARS-CoV-2 could remain in brain tissue long-term, affecting neuronal loss over time, in association with systemic inflammation and cerebrovascular changes, as recently demonstrated by Desai et al. [29]. Notably, inflammation may induce neuron injury/damage through the release of the cytotoxic and chemotactic mediators, activating the surrounding microglial cells and intensifying the microglia-mediated neuroinflammation [30]. This cytotoxins release causes neuronal loss and neurodegeneration, accounting for the cross-talk between the neurons and glial cells in the neuroinflammation status [31]. To overcome these negative implications, steroids have been successfully used, especially in the acute phase and in the most severely affected patients [32]. Moreover, to counteract prostaglandin-mediated inflammation, non- steroidal anti-inflammatory drugs may be used in different stages of the disease [33]. Some researchers considered the use of Palmitoylethanolamide (PEA) in the treatment of Long COVID, showing that the compound could resolve these inflammatory processes, reducing the progression of chronic inflammation and promoting positive effects on the neurological system [34]. It has been highlighted that the peripheral activation of the trigemino-vascular system, through the inflammatory cytokine storm, is strictly involved in the development of headaches [35]. Headache, from continuous mild pain to severe migraine, seems to be one of the most common and persistent COVID-19 sequelae, and it is often accompanied with trigeminal neuralgia. Neuropathic pain due to Long COVID is underestimated compared to the other symptoms, although the main clinical features of neuropathic pain in COVID-19 patients, i.e., a prickling sensation (defined as a sensation of electric shock, burns, paresthesia, and hyperalgesia), have been well described [36][37].
Many patients complained of subtle cognitive impairment and behavioral changes that may be difficult for them to describe. These symptoms are often collectively referred to as “brain fog” or “mental clouding” [38]. However, the correlation between these self-reported symptoms and objective dysfunctions remains an unclear question. Di Stadio et al. [39] investigated the possible correlation between mental clouding and olfactory dysfunction: they found that the former might interfere with the capacity of the individual to identify odors, indirectly affecting olfactory function. In addition, subjects who suffered from mental clouding, headache, or both presented a more severe olfactory dysfunction compared to those patients without neurological complaints.

3. Cognitive Dysfunctions, Psychiatric Symptoms, and Behavioral Alterations

Cognitive dysfunctions are becoming the most popular symptoms in the research of Long COVID. In fact, cognitive symptoms have been reported in around 70% of the subjects [40][41]. Davis et al. [42] showed a high impact of post-COVID-19 cognitive dysfunction and/or memory impairment in daily working abilities, accounting for 86% of the sample affected. Guo et al. found a similar prevalence of cognitive symptoms: 77.8% of the patients presented difficulty in concentrating, 69% brain fog, 67.5% forgetfulness, 59.5% tip-of-the-tongue word-finding problems, and 43.7% semantic disfluency (saying or typing the wrong word) [43]. In addition, it has been shown that cognitive symptoms are more likely to develop in subjects affected by fatigue, cardiopulmonary, neurological, and autoimmune symptoms. However, in current clinical practice, it is very difficult to understand and define the “type and severity of the self-reported cognitive deficits”, such as brain fog and difficulty concentrating, and consequently to more objectively measure cognitive performance. Indeed, most studies focused on the prevalence of cognitive alterations due to Long COVID, but not on the psychometric tools to measure the cognitive domains affected by the post-SARS-CoV-2 infection [44]. To overcome this issue, Alemanno et al. measured the cognitive abilities of patients in the COVID-19 post-acute phase that had experienced severe disease, using the Montreal Cognitive Assessment (MoCA). They have observed that 80% of patients reported cognitive alterations, especially in memory abilities, executive functioning, and language skills [45]. It has been observed that 33% of individuals in an intensive care unit showed a dysexecutive syndrome associated with inattention, disorientation, and reduced planning movements in response to the verbal indications [46]. Hosp et al. found a possible correlation between the cognitive dysfunctions and neurological abnormalities revealed with positron emission tomography, showing a predominant frontoparietal hypometabolism that correlated with poor MoCA scores [47], with lower scores in verbal memory and executive functions. However, these studies are limited to severely ill and old-age patients, and it is very challenging for clinicians to determine the nature of these dysfunctions and whether they are specific to COVID-19 or are more a-specific, such as a general consequence of acute respiratory distress. Indeed, some survivors of critical disease are recognized as experiencing long-term cognitive loss [48], particularly if they experience delirium [49][50].
In this context, it is important to know whether these deficits may also involve younger populations, as demonstrated by Almeria et al. in patients aged 24–60. This research reported that patients with neurological sequelae had lower performance in attention, memory, and executive function, suggesting an association between symptomatology and cognitive deficits [51].
Recent literature regarding the long-term neuropsychiatric sequelae of COVID-19 focused on self-reported symptoms through questionnaires administered either in-person or by telephone interviews [52][53][54]. Notably, Long COVID has been found to cause anxiety and depression symptoms as well as other neuropsychiatric and cognitive sequelae [55][56][57][58][59]. Indeed, the incidence of anxiety, depression, and post-traumatic stress was 42%, 31%, and 28%, respectively, in an Italian sample [60]. Considering the alarming impact of COVID-19 on mental health, Clemente et al. investigated the correlation between the psychological status of patients who had recovered from the SARS-CoV-2 infection and their inflammatory status, showing that survivors are at risk of developing psychiatric sequelae, such as anxiety, depression, and somatization symptoms, as well as sleep disorders [61][62][63]. An interesting association has also been demonstrated between high ferritin blood levels and sleep disturbances, stress, depression, and suicidal ideation [64][65].
To summarize, the SARS-CoV-2 epidemic was associated with psychiatric and cognitive complications, as confirmed by several researchers [66][67][68][69], and patients with preexisting psychiatric disorders reported the worsening of previous symptoms [70][71][72][73]. These findings could support the idea that those who have experienced the COVID-19 infection may be at a higher risk for neurodegeneration and dementia. In fact, COVID-19-related cardiovascular and cerebrovascular disease may also contribute to a higher long-term risk of cognitive decline and dementia in recovered individuals [74].
Moreover, a vast number of studies showed that obesity and diabetes have been associated with worse outcomes during the COVID-19 infection. In fact, people with obesity have an increased prevalence of diseases such as renal insufficiency, cardiovascular diseases, Type 2 diabetes mellitus, certain types of cancers, and a significant degree of endothelial dysfunction. These conditions are major risk factors for the disease severity and mortality associated with COVID-19 [75][76]. In particular, Vimercate et al. (2021) have shown that obesity is associated also with worse Long COVID symptoms such as respiratory diseases and hypertension, suggesting that being affected by overweight or obesity is associated with prolonged symptoms after resolution [77]. Today, limited evidence has shown that the clinical and socio-demographical features of the patients (such as the number of symptoms in the first week, age, and sex) before the COVID-19 infection play a key role in the prediction of Long COVID’s duration [78]. Notably, Bellou et al. have investigated the association of 91 unique prognostic factors, divided into seven different categories, including demographic and anthropometric individual characteristics, biomarkers, symptoms, clinical signs, medical history and comorbid diseases, and medications, thus facilitating the selection of candidate predictors for a prognostic model [79]. In this context, Wang et al. found that psychological distress before the COVID-19 infection, including depression, anxiety, worry, perceived stress, and loneliness, was associated with a 32–46% increased risk of Long COVID [80]. For all these reasons, urgent in-person neuropsychological and neuropsychiatric assessments on Long COVID individuals are needed.

This entry is adapted from the peer-reviewed paper 10.3390/jcm11216554

References

  1. Sarker, A.; Ge, Y. Mining long-COVID symptoms from Reddit: Characterizing post-COVID syndrome from patient reports. JAMIA Open 2021, 4, ooab075.
  2. Haran, J.P.; Bradley, E.; Zeamer, A.L.; Cincotta, L.; Salive, M.C.; Dutta, P.; Mutaawe, S.; Anya, O.; Meza-Segura, M.; Moormann, A. Inflammation-type dysbiosis of the oral microbiome associates with the duration of COVID-19 symptoms and long COVID. JCI Insight. 2021, 6, e152346.
  3. Mondelli, V.; Pariante, C.M. What can neuroimmunology teach us about the symptoms of long-COVID? Oxford Open Immunol. 2021, 2, iqab004.
  4. Naik, S.; Haldar, S.N.; Soneja, M.; Mundadan, N.G.; Garg, P.; Mittal, A.; Desai, D.; Trilangi, P.K.; Chakraborty, S.; Begam, N.N.; et al. Post COVID-19 sequelae: A prospective observational study from Northern India. Drug Discov. Ther. 2021, 15, 254–260.
  5. Dantzer, R.; O’Connor, J.C.; Freund, G.G.; Johnson, R.W.; Kelley, K.W. From inflammation to sickness and depression: When the immune system subjugates the brain. Nat. Rev. Neurosci. 2008, 9, 46–56.
  6. Raison, C.L.; Lin, J.M.; Reeves, W.C. Association of peripheral inflammatory markers with chronic fatigue in a population-based sample. Brain Behav. Immun. 2009, 23, 327–337.
  7. Mondelli, V.; Vernon, A.C.; Turkheimer, F.; Dazzan, P.; Pariante, C.M. Brain microglia in psychiatric disorders. Lancet Psychiatry 2017, 4, 563–572.
  8. Russell, A.; Hepgul, N.; Nikkheslat, N.; Borsini, A.; Zajkowska, Z.; Moll, N.; Forton, D.; Agarwal, K.; Chalder, T.; Mondelli, V.; et al. Persistent fatigue induced by interferon-alpha: A novel, inflammation-based, proxy model of chronic fatigue syndrome. Psychoneuroendocrinology 2019, 100, 276–285.
  9. Albrecht, D.S.; Forsberg, A.; Sandstrom, A.; Bergan, C.; Kadetoff, D.; Protsenko, E.; Lampa, J.; Lee, Y.C.; Höglund, C.O.; Catana, C.; et al. Brain glial activation in fibromyalgia—A multi-site positron emission tomography investigation. Brain Behav. Immun. 2019, 75, 72–83.
  10. Marsland, A.L.; Gianaros, P.J.; Kuan, D.C.; Sheu, L.K.; Krajina, K.; Manuck, S.B. Brain morphology links systemic inflammation to cognitive function in midlife adults. Brain Behav. Immun. 2015, 48, 195–204.
  11. Stefanou, M.I.; Palaiodimou, L.; Bakola, E.; Smyrnis, N.; Papadopoulou, M.; Paraskevas, G.P.; Rizos, E.; Boutati, E.; Grigoriadis, N.; Krogias, C.; et al. Neurological manifestations of long-COVID syndrome: A narrative review. Ther. Adv. Chronic. Dis. 2022, 13, 20406223221076890.
  12. Seeßle, J.; Waterboer, T.; Hippchen, T.; Simon, J.; Kirchner, M.; Lim, A.; Müller, B.; Merle, U. Persistent Symptoms in Adult Patients 1 Year After Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study. Clin. Infect. Dis. 2022, 74, 1191–1198.
  13. Hossain, M.A.; Hossain, K.M.A.; Saunders, K.; Uddin, Z.; Walton, L.M.; Raigangar, V.; Sakel, M.; Shafin, R.; Hossain, M.S.; Kabir, M.F.; et al. Prevalence of Long COVID symptoms in Bangladesh: A prospective Inception Cohort Study of COVID-19 survivors. BMJ Glob. Health 2021, 6, e006838.
  14. Martelletti, P.; Bentivegna, E.; Spuntarelli, V.; Luciani, M. Long-COVID Headache. SN Compr. Clin. Med. 2021, 3, 1704–1706.
  15. Castanares-Zapatero, D.; Chalon, P.; Kohn, L.; Dauvrin, M.; Detollenaere, J.; Maertens de Noordhout, C.; Primus-de Jong, C.; Cleemput, I.; Van den Heede, K. Pathophysiology and mechanism of long COVID: A comprehensive review. Ann. Med. 2022, 54, 1473–1487.
  16. Torjesen, I. COVID-19: Long COVID symptoms among hospital inpatients show little improvement after a year, data suggest. BMJ 2021, 375, n3092.
  17. Jennings, G.; Monaghan, A.; Xue, F.; Duggan, E.; Romero-Ortuño, R. Comprehensive Clinical Characterisation of Brain Fog in Adults Reporting Long COVID Symptoms. J. Clin. Med. 2022, 11, 3440.
  18. Hampshire, A.; Trender, W.; Chamberlain, S.R.; Jolly, A.E.; Grant, J.E.; Patrick, F.; Mazibuko, N.; Williams, S.C.; Barnby, J.M.; Hellyer, P.; et al. Cognitive deficits in people who have recovered from COVID-19. EClinicalMedicine 2021, 39, 101044.
  19. Ocsovszky, Z.; Otohal, J.; Berényi, B.; Juhász, V.; Skoda, R.; Bokor, L.; Dohy, Z.; Szabó, L.; Nagy, G.; Becker, D.; et al. The associations of long-COVID symptoms, clinical characteristics and affective psychological constructs in a non-hospitalized cohort. Physiol. Int. 2022, 109, 230–245.
  20. Yelin, D.; Margalit, I.; Nehme, M.; Bordas-Martínez, J.; Pistelli, F.; Yahav, D.; Guessous, I.; Durà-Miralles, X.; Carrozzi, L.; Shapira-Lichter, I.; et al. Patterns of Long COVID Symptoms: A Multicenter Cross Sectional Study. J. Clin. Med. 2022, 11, 898.
  21. Mariani, C.; Borgonovo, F.; Capetti, A.F.; Oreni, L.; Cossu, M.V.; Pellicciotta, M.; Armiento, L.; Bocchio, S.; Dedivitiis, G.; Lupo, A.; et al. Persistence of Long-COVID symptoms in a heterogenous prospective cohort. J. Infect. 2022, 84, 722–746.
  22. Burton, A.; Aughterson, H.; Fancourt, D.; Philip, K.E.J. Factors shaping the mental health and well-being of people experiencing persistent COVID-19 symptoms or ‘long COVID’: Qualitative study. BJPsych Open 2022, 8, e72.
  23. Yaksi, N.; Teker, A.G.; Imre, A. Long COVID in Hospitalized COVID-19 Patients: A Retrospective Cohort Study. Iran J. Public Health 2022, 51, 88–95.
  24. Cha, C.; Baek, G. Symptoms and management of long COVID: A scoping review. J. Clin. Nurs. 2021. online ahead of print.
  25. Tang, S.W.; Leonard, B.E.; Helmeste, D.M. Long COVID, neuropsychiatric disorders, psychotropics, present and future. Acta Neuropsychiatr. 2022, 34, 109–126.
  26. Neurology, T.L. The Lancet Neurology. Long COVID: Understanding the Neurological Effects. Lancet Neurol. 2021, 20, 247.
  27. Orrù, G.; Bertelloni, D.; Diolaiuti, F.; Mucci, F.; Di Giuseppe, M.; Biella, M.; Gemignani, A.; Ciacchini, R.; Conversano, C. Long-COVID Syndrome? A Study on the Persistence of Neurological, Psychological and Physiological Symptoms. Healthcare 2021, 9, 575.
  28. Premraj, L.; Kannapadi, N.V.; Briggs, J.; Seal, S.M.; Battaglini, D.; Fanning, J.; Suen, J.; Robba, C.; Fraser, J.; Cho, S.M. Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis. J. Neurol. Sci. 2022, 434, 120162.
  29. Desai, A.D.; Lavelle, M.; Boursiquot, B.C.; Wan, E.Y. Long-term complications of COVID-19. Am. J. Physiol. Cell Physiol. 2022, 322, C1–C11.
  30. Zhang, Z.J.; Jiang, B.C.; Gao, Y.J. Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain. Cell Mol. Life Sci. 2017, 74, 3275–3291.
  31. Leitner, G.R.; Wenzel, T.J.; Marshall, N.; Gates, E.J.; Klegeris, A. Targeting toll-like receptor 4 to modulate neuroinflammation in central nervous system disorders. Expert. Opin. Ther. Targets 2019, 23, 865–882.
  32. Sen, S.; Singh, B.; Biswas, G. Corticosteroids: A boon or bane for COVID-19 patients? Steroids 2022, 188, 109102.
  33. Robb, C.T.; Goepp, M.; Rossi, A.G.; Yao, C. Non-steroidal anti-inflammatory drugs, prostaglandins, and COVID-19. Br. J. Pharmacol. 2020, 177, 4899–4920.
  34. Fonnesu, R.; Thunuguntla, V.B.S.C.; Veeramachaneni, G.K.; Bondili, J.S.; La Rocca, V.; Filipponi, C.; Spezia, P.G.; Sidoti, M.; Plicanti, E.; Quaranta, P.; et al. Palmitoylethanolamide (PEA) Inhibits SARS-CoV-2 Entry by Interacting with S Protein and ACE-2 Receptor. Viruses 2022, 14, 1080.
  35. Caronna, E.; Ballvé, A.; Llauradó, A.; Gallardo, V.J.; Ariton, D.M.; Lallana, S.; López Maza, S.; Olivé Gadea, M.; Quibus, L.; Restrepo, J.L.; et al. Headache: A striking prodromal and persistent symptom, predictive of COVID-19 clinical evolution. Cephalalgia 2020, 40, 1410–1421.
  36. Widyadharma, I.P.E.; Sari, N.N.S.P.; Pradnyaswari, K.E.; Yuwana, K.T.; Adikarya, I.P.G.D.; Tertia, C.; Wijayanti, I.; Indrayani, I.; Utami, D. Pain as clinical manifestations of COVID-19 infection and its management in the pandemic era: A literature review. Egypt J. Neurol. Psychiatr. Neurosurg. 2020, 56, 121.
  37. Research Accessibility Team (RAT). The microvascular hypothesis underlying neurologic manifestations of long COVID-19 and possible therapeutic strategies. Cardiovasc. Endocrinol. Metab. 2021, 10, 193–203.
  38. Grisanti, S.G.; Garbarino, S.; Barisione, E.; Aloè, T.; Grosso, M.; Schenone, C.; Pardini, M.; Biassoni, E.; Zaottini, F.; Picasso, R.; et al. Neurological long-COVID in the outpatient clinic: Two subtypes, two courses. J. Neurol. Sci. 2022, 439, 120315.
  39. Di Stadio, A.; Brenner, M.J.; De Luca, P.; Albanese, M.; D’Ascanio, L.; Ralli, M.; Roccamatisi, D.; Cingolani, C.; Vitelli, F.; Camaioni, A.; et al. Olfactory Dysfunction, Headache, and Mental Clouding in Adults with Long-COVID-19: What Is the Link between Cognition and Olfaction? A Cross-Sectional Study. Brain Sci. 2022, 12, 154.
  40. Cirulli, E.; Barrett, K.M.S.; Riffle, S.; Bolze, A.; Neveux, I.; Dabe, S.; Joseph, J.; James, T. Long-term COVID-19 symptoms in a large unselected population. medRxiv 2020.
  41. Ziauddeen, N.; Gurdasani, D.; O’Hara, M.E.; Hastie, C.; Roderick, P.; Yao, G.; Alwan, N.A. Characteristics and impact of Long COVID: Findings from an online survey. PLoS ONE 2020, 17, e0264331.
  42. Davis, H.E.; Assaf, G.S.; McCorkell, L.; Wei, H.; Low, R.J.; Re’em, Y.; Redfield, S.; Austin, J.P.; Akrami, A. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClin. Med. 2021, 38, 3820561.
  43. Guo, P.; Ballesteros, A.B.; Yeung, S.P.; Liu, R.; Saha, A.; Curtis, L.; Kaser, M.; Haggard, M.P.; Cheke, L.G. COVCOG 1: Factors predicting cognitive symptoms in Long COVID. A first publication from the COVID and Cognition Study. medRxiv 2022.
  44. Ferrucci, R.; Dini, M.; Rosci, C.; Capozza, A.; Groppo, E.; Reitano, M.R.; Allocco, E.; Poletti, B.; Brugnera, A.; Bai, F.; et al. One-year cognitive follow-up of COVID-19 hospitalized patients. Eur. J. Neurol. 2022, 29, 2006–2014.
  45. Alemanno, F.; Houdayer, E.; Parma, A.; Spina, A.; Del Forno, A.; Scatolini, A.; Angelone, S.; Brugliera, L.; Tettamanti, A.; Beretta, L.; et al. COVID-19 cognitive deficits after respiratory assistance in the subacute phase: A COVID-rehabilitation unit experience. PLoS ONE 2021, 16, e0246590.
  46. Ferrucci, R.; Dini, M.; Groppo, E.; Rosci, C.; Reitano, M.R.; Bai, F.; Poletti, B.; Brugnera, A.; Silani, V.; D’Arminio Monforte, A.; et al. Long-Lasting Cognitive Abnormalities after COVID-19. Brain Sci. 2021, 11, 235.
  47. Hosp, J.A.; Dressing, A.; Blazhenets, G.; Bormann, T.; Rau, A.; Schwabenland, M.; Thurow, J.; Wagner, D.; Waller, C.; Niesen, W.; et al. Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19. Brain 2021, 144, 1263–1276.
  48. Helms, J.; Kremer, S.; Merdji, H.; Clere-Jehl, R.; Schenck, M.; Kummerlen, C.; Collange, O.; Boulay, C.; Fafi-Kremer, S.; Ohana, M.; et al. Neurologic features in severe SARS-CoV-2 infection. N. Engl. J. Med. 2020, 382, 2268–2270.
  49. Iwashyna, T.J.; Ely, E.W.; Smith, D.M.; Langa, K.M. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 2010, 304, 1787–1794.
  50. Pandharipande, P.P.; Girard, T.D.; Jackson, J.C.; Morandi, A.; Thompson, J.L.; Pun, B.T.; Brummel, N.E.; Hughes, C.G.; Vasilevskis, E.E.; Shintani, A.K.; et al. Long-term cognitive impairment after critical illness. N. Engl. J. Med. 2013, 369, 1306–1316.
  51. Almeria, M.; Cejudo, J.C.; Sotoca, J.; Deus, J.; Krupinski, J. Cognitive profile following COVID-19 infection: Clinical predictors leading to neuropsychological impairment. Brain Behav. Immunity Health 2020, 9, 100163.
  52. Chen, A.K.; Wang, X.; McCluskey, L.P.; Morgan, J.C.; Switzer, J.A.; Mehta, R.; Tingen, M.; Su, S.; Harris, R.A.; Hess, D.C.; et al. Neuropsychiatric sequelae of long COVID-19: Pilot results from the COVID-19 neurological and molecular prospective cohort study in Georgia, USA. Brain Behav. Immun. Health 2022, 24, 100491.
  53. Graham, E.L.; Clark, J.R.; Orban, Z.S.; Lim, P.H.; Szymanski, A.L.; Taylor, C.; DiBiase, R.M.; Jia, D.T.; Balabanov, R.; Ho, S.U.; et al. Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized COVID-19 long haulers. Ann. Clin. Transl. Neurol. 2021, 8, 1073–1085.
  54. Taquet, M.; Geddes, J.R.; Husain, M.; Luciano, S.; Harrison, P.J. 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: A retrospective cohort study using electronic health records. Lancet Psychiatry 2021, 8, 416–427.
  55. Braga, L.W.; Oliveira, S.B.; Moreira, A.S.; Pereira, M.E.; Carneiro, V.S.; Serio, A.S.; Freitas, L.F.; Isidro, H.B.L.; Souza, L.M.N. Neuropsychological manifestations of long COVID in hospitalized and non-hospitalized Brazilian Patients. NeuroRehabilitation 2022, 50, 391–400.
  56. Nakamura, Z.M.; Nash, R.P.; Laughon, S.L.; Rosenstein, D.L. Neuropsychiatric complications of COVID-19. Curr. Psychiatry Rep. 2021, 23, 25.
  57. Taquet, M.; Luciano, S.; Geddes, J.R.; Harrison, P.J. Bidirectional associations between COVID-19 and psychiatric disorder: Retrospective cohort studies of 62 354 COVID-19 cases in the USA. Lancet Psychiatry 2021, 8, 130–140.
  58. Pistarini, C.; Fiabane, E.; Houdayer, E.; Vassallo, C.; Manera, M.R.; Alemanno, F. Cognitive and emotional disturbances due to COVID-19: An exploratory study in the rehabilitation setting. Front. Neurol. 2021, 12, 643646.
  59. Holdsworth, D.A.; Chamley, R.; Barker-Davies, R.; O’Sullivan, O.; Ladlow, P.; Mitchell, J.L.; Dewson, D.; Mills, D.; May, S.; Cranley, M.; et al. Comprehensive clinical assessment identifies specific neurocognitive deficits in working-age patients with long-COVID. PLoS ONE 2022, 17, e0267392.
  60. Mazza, M.G.; Palladini, M.; De Lorenzo, R.; Magnaghi, C.; Poletti, S.; Furlan, R.; Ciceri, F.; Rovere-Querini, P.; Benedetti, F.; COVID-19 BioB Outpatient Clinic Study Group. Persistent psychopathology and neurocognitive impairment in COVID-19 survivors: Effect of inflammatory biomarkers at three-month follow-up. Brain Behav. Immun. 2021, 94, 138–147.
  61. Clemente, I.; Sinatti, G.; Cirella, A.; Santini, S.J.; Balsano, C. Alteration of Inflammatory Parameters and Psychological Post-Traumatic Syndrome in Long-COVID Patients. Int. J. Environ. Res. Public Health 2020, 19, 7103.
  62. Gasnier, M.; Choucha, W.; Radiguer, F.; Faulet, T.; Chappell, K.; Bougarel, A.; Kondarjian, C.; Thorey, P.; Baldacci, A.; Ballerini, M.; et al. Comorbidity of long COVID and psychiatric disorders after a hospitalisation for COVID-19: A cross-sectional study. J. Neurol. Neurosurg. Psychiatry 2022, 93, 1091–1098.
  63. Vindegaard, N.; Benros, M.E. COVID-19 pandemic and mental health consequences: Systematic review of the current evidence. Brain Behav. Immun. 2020, 89, 531–542.
  64. Kim, K.M.; Hwang, H.R.; Kim, Y.J.; Lee, J.G.; Yi, Y.H.; Tak, Y.J.; Lee, S.H.; Chung, S.I. Association between Serum-Ferritin Levels and Sleep Duration, Stress, Depression, and Suicidal Ideation in Older Koreans: Fifth Korea National Health and Nutrition Examination Survey 2010. Korean J. Fam. Med. 2019, 40, 380–387.
  65. Sykes, D.L.; Holdsworth, L.; Jawad, N.; Gunasekera, P.; Morice, A.H.; Crooks, M.G. Post-COVID-19 Symptom Burden: What is Long-COVID and How Should We Manage It? Lung 2021, 199, 113–119.
  66. Rogers, J.P.; Chesney, E.; Oliver, D.; Pollak, T.A.; McGuire, P.; Fusar-Poli, P.; Zandi, M.S.; Lewis, G.; David, A.S. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: A systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry 2020, 7, 611–627.
  67. Mak, I.W.; Chu, C.M.; Pan, P.C.; Yiu, M.G.; Chan, V.L. Long-term psychiatric morbidities among SARS survivors. Gen. Hosp. Psychiatry 2009, 31, 318–326.
  68. Park, H.Y.; Park, W.B.; Lee, S.H.; Kim, J.L.; Lee, J.J.; Lee, H.; Shin, H.-S. Posttraumatic stress disorder and depression of survivors 12 months after the outbreak of Middle East respiratory syndrome in South Korea. BMC Public Health 2020, 20, 605.
  69. Naidu, S.B.; Shah, A.J.; Saigal, A.; Smith, C.; Brill, S.E.; Goldring, J.; Hurst, J.R.; Jarvis, H.; Lipman, M.; Mandal, S. The high mental health burden of “Long COVID” and its association with on-going physical and respiratory symptoms in all adults discharged from hospital. Eur. Respir. J. 2021, 57, 2004364.
  70. Li, D.; Wang, Q.; Jia, C.; Lv, Z.; Yang, J. An Overview of Neurological and Psychiatric Complications During Post-COVID Period: A Narrative Review. J. Inflamm. Res. 2022, 15, 4199–4215.
  71. Zeng, N.; Zhao, Y.M.; Yan, W.; Li, C.; Lu, Q.D.; Liu, L.; Ni, S.Y.; Mei, H.; Yuan, K.; Shi, L.; et al. A systematic review and meta-analysis of long term physical and mental sequelae of COVID-19 pandemic: Call for research priority and action. Mol. Psychiatry 2022, 1–11.
  72. Douaud, G.; Lee, S.; Alfaro-Almagro, F.; Arthofer, C.; Wang, C.; McCarthy, P.; Lange, F.; Andersson, J.L.R.; Griffanti, L.; Duff, E.; et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature 2022, 604, 697–707.
  73. de Erausquin, G.A.; Snyder, H.; Carrillo, M.; Hosseini, A.A.; Brugha, T.S.; Seshadri, S. CNS SARS-CoV-2 Consortium. The chronic neuropsychiatric sequelae of COVID-19: The need for a prospective study of viral impact on brain functioning. Alzheimers Dement. 2021, 17, 1056–1065.
  74. Azeem, F.; Durrani, R.; Zerna, C.; Smith, E.E. Silent brain infarcts and cognitive decline: Systematic review and meta-analysis. J. Neurol. 2020, 267, 502–512.
  75. Hajifathalian, K.; Kumar, S.; Newberry, C.; Shah, S.; Fortune, B.; Krisko, T.; Ortiz-Pujols, S.; Zhou, X.K.; Dannenberg, A.J.; Kumar, R.; et al. Obesity is Associated with Worse Outcomes in COVID-19: Analysis of Early Data from New York City. Obesity 2000, 28, 1606–1612.
  76. Raveendran, A.V.; Misra, A. Post COVID-19 Syndrome (“Long COVID”) and Diabetes: Challenges in Diagnosis and Management. Diabetes Metab. Syndr. 2021, 15, 102235.
  77. Vimercati, L.; De Maria, L.; Quarato, M.; Caputi, A.; Gesualdo, L.; Migliore, G.; Cavone, D.; Sponselli, S.; Pipoli, A.; Inchingolo, F.; et al. Association between Long COVID and Overweight/Obesity. J. Clin. Med. 2021, 10, 4143.
  78. Sudre, C.H.; Murray, B.; Varsavsky, T.; Graham, M.S.; Penfold, R.S.; Bowyer, R.C.; Pujol, J.C.; Klaser, K.; Antonelli, M.; Canas, L.S.; et al. Attributes and predictors of long COVID. Nat. Med. 2021, 27, 626–631.
  79. Bellou, V.; Tzoulaki, I.; van Smeden, M.; Moons, K.; Evangelou, E.; Belbasis, L. Prognostic factors for adverse outcomes in patients with COVID-19: A field-wide systematic review and meta-analysis. Eur. Respir. J. 2022, 59, 2002964.
  80. Wang, S.; Quan, L.; Chavarro, J.E.; Slopen, N.; Kubzansky, L.D.; Koenen, K.C.; Kang, J.H.; Weisskopf, M.G.; Branch-Elliman, W.; Roberts, A.L. Associations of Depression, Anxiety, Worry, Perceived Stress, and Loneliness Prior to Infection With Risk of Post–COVID-19 Conditions. JAMA Psychiatry 2022, 79, 1081–1091.
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