Neuropsychiatric Disorders and COVID-19: What We Know So Far
Abstract
:1. Introduction
2. Manifestations
2.1. Neurological Disorder
2.1.1. Meningoencephalitis
2.1.2. Anosmia and Ageusia
2.1.3. Acute Cerebral Vascular Disease
2.1.4. Intracerebral Hemorrhage (ICH) and Cerebral Venous Sinus Thrombosis
2.1.5. Stroke
2.1.6. Seizure
2.1.7. Ataxia
2.1.8. Myelitis
2.1.9. Rhabdomyolysis
2.2. Neuropsychiatric Disorder
2.2.1. Depression and Anxiety
2.2.2. Sleep and Stress Disorders
2.2.3. Addiction and Substance Abuse
2.3. Post-COVID Neurological Manifestations
2.3.1. Parkinson’s and Alzheimer’s Disorders, Guillain–Barré Syndrome
2.3.2. COVID-19 Infection and Loss of Memory
3. Mechanism
Inflammatory Markers on Neuro-COVID Pathogenesis
4. Pharmacological Approaches
5. Modelling the Disease
6. Concluding Remarks
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Kwong, K.C.N.K.; Mehta, P.R.; Shukla, G.; Mehta, A.R. COVID-19, SARS and MERS: A neurological perspective. J. Clin. Neurosci. 2020, 77, 13–16. [Google Scholar] [CrossRef]
- Werner, C.; Scullen, T.; Mathkour, M.; Zeoli, T.; Beighley, A.; Kilgore, M.D.; Carr, C.; Zweifler, R.M.; Aysenne, A.; Maulucci, C.M.; et al. Neurological Impact of Coronavirus Disease of 2019: Practical Considerations for the Neuroscience Community. World Neurosurg. 2020, 139, 344–354. [Google Scholar] [CrossRef] [PubMed]
- Zhou, P.; Yang, X.-L.; Wang, X.-G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.-R.; Zhu, Y.; Li, B.; Huang, C.-L.; et al. Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020, 588, E6. [Google Scholar] [CrossRef]
- Ahmad, I.; Rathore, F.A. Neurological manifestations and complications of COVID-19: A literature review. J. Clin. Neurosci. 2020, 77, 8–12. [Google Scholar] [CrossRef]
- Herman, C.; Mayer, K.; Sarwal, A. Scoping review of prevalence of neurologic comorbidities in patients hospitalized for COVID-19. Neurology 2020, 95, 77–84. [Google Scholar] [CrossRef]
- Vonck, K.; Garrez, I.; De Herdt, V.; Hemelsoet, D.; Laureys, G.; Raedt, R.; Boon, P. Neurological manifestations and neuro-invasive mechanisms of the severe acute respiratory syndrome coronavirus type 2. Eur. J. Neurol. 2020, 27, 1578–1587. [Google Scholar] [CrossRef] [PubMed]
- Mao, L.; Jin, H.; Wang, M.; Hu, Y.; Chen, S.; He, Q.; Chang, J.; Hong, C.; Zhou, Y.; Wang, D.; et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020, 77, 683–690. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 395, 497–506. [Google Scholar] [CrossRef] [Green Version]
- Zhou, Y.; Li, W.; Wang, D.; Mao, L.; Jin, H.; Li, Y.; Hong, C.; Chen, S.; Chang, J.; He, Q.; et al. Clinical time course of COVID-19, its neurological manifestation and some thoughts on its management. Stroke Vasc. Neurol. 2020, 5, 177–179. [Google Scholar] [CrossRef]
- Kumar, S.; Veldhuis, A.; Malhotra, T. Neuropsychiatric and Cognitive Sequelae of COVID-19. Front. Psychol. 2021, 12. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef] [PubMed]
- Pilotto, A.; Odolini, S.; Masciocchi, S.; Comelli, A.; Volonghi, I.; Gazzina, S.; Nocivelli, S.; Pezzini, A.; Focà, E.; Caruso, A.; et al. Steroid-Responsive Encephalitis in Coronavirus Disease 2019. Ann. Neurol. 2020, 88, 423–427. [Google Scholar] [CrossRef] [PubMed]
- Paterson, R.W.; Brown, R.L.; Benjamin, L.; Nortley, R.; Wiethoff, S.; Bharucha, T.; Jayaseelan, D.L.; Kumar, G.; Raftopoulos, R.E.; Zambreanu, L.; et al. The emerging spectrum of COVID-19 neurology: Clinical, radiological and laboratory findings. Brain 2020, 143, 3104–3120. [Google Scholar] [CrossRef] [PubMed]
- Varatharaj, A.; Thomas, N.; Ellul, M.A.; Davies, N.W.S.; Pollak, T.A.; Tenorio, E.L.; Sultan, M.; Easton, A.; Breen, G.; Zandi, M.; et al. CoroNerve Study Group. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: A UK-wide surveillance study. Lancet Psychiatry 2020, 7, 875–882. [Google Scholar] [CrossRef]
- von Weyhern, C.H.; Kaufmann, I.; Neff, F.; Kremer, M. Early evidence of pronounced brain involvement in fatal COVID-19 outcomes. Lancet 2020, 395, e109. [Google Scholar] [CrossRef]
- Klopfenstein, T.; Kadiane-Oussou, N.J.; Toko, L.; Royer, P.Y.; Lepiller, Q.; Gendrin, V.; Zayet, S. Features of anosmia in COVID-19. Med. Mal. Infect. 2020, 50, 436–439. [Google Scholar] [CrossRef]
- Meinhardt, J.; Radke, J.; Dittmayer, C.; Franz, J.; Thomas, C.; Mothes, R.; Laue, M.; Schneider, J.; Brünink, S.; Greuel, S.; et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nature Neurosci. 2021, 24, 168–175. [Google Scholar] [CrossRef]
- Meng, L.; Hua, F.; Bian, Z. Coronavirus Disease 2019 (COVID-19): Emerging and Future Challenges for Dental and Oral Medicine. J. Dent. Res. 2020, 99, 481–487. [Google Scholar] [CrossRef] [Green Version]
- Plasschaert, L.W.; Žilionis, R.; Choo-Wing, R.; Savova, V.; Knehr, J.; Roma, G.; Klein, A.M.; Jaffe, A.B. A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte. Nature 2018, 560, 377–381. [Google Scholar] [CrossRef]
- Moriguchi, T.; Harii, N.; Goto, J.; Harada, D.; Sugawara, H.; Takamino, J.; Ueno, M.; Sakata, H.; Kondo, K.; Myose, N.; et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int. J. Infect. Dis. 2020, 94, 55–58. [Google Scholar] [CrossRef] [PubMed]
- Vollono, C.; Rollo, E.; Romozzi, M.; Frisullo, G.; Servidei, S.; Borghetti, A.; Calabresi, P. Focal status epilepticus as unique clinical feature of COVID-19: A case report. Seizure 2020, 78, 109–112. [Google Scholar] [CrossRef]
- Asadi-Pooya, A.A. Seizures associated with coronavirus infections. Seizure 2020, 79, 49–52. [Google Scholar] [CrossRef] [PubMed]
- Uygun, Ö.; Ertaş, M.; Ekizoğlu, E.; Bolay, H.; Özge, A.; Kocasoy Orhan, E.; Çağatay, A.A.; Baykan, B. Headache characteristics in COVID-19 pandemic-a survey study. J. Headache Pain 2020, 21, 121. [Google Scholar] [CrossRef] [PubMed]
- Lippi, G.; Plebani, M.; Henry, B.M. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin. Chim. Acta 2020, 506, 145–148. [Google Scholar] [CrossRef] [PubMed]
- Thepmankorn, P.; Bach, J.; Lasfar, A.; Zhao, X.; Souayah, S.; Chong, Z.Z.; Souayah, N. Cytokine storm induced by SARS-CoV-2 infection: The spectrum of its neurological manifestations. Cytokine 2021, 138, 155404. [Google Scholar] [CrossRef]
- Merkler, A.E.; Parikh, N.S.; Mir, S.; Gupta, A.; Kamel, H.; Lin, E.; Lantos, J.; Schenck, E.J.; Goyal, P.; Bruce, S.S.; et al. Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza. JAMA Neurol. 2020, 77, 1366–1372. [Google Scholar] [CrossRef]
- Dijkstra, F.; Van den Bossche, T.; Willekens, B.; Cras, P.; Crosiers, D. Myoclonus and cerebellar ataxia following Coronavirus Disease 2019 (COVID-19). Mov. Disord. Clin. Pract. 2020, 7, 974–976. [Google Scholar] [CrossRef]
- Chow, C.C.N.; Magnussen, J.; Ip, J.; Su, Y. Acute transverse myelitis in COVID-19 infection. BMJ Case Rep. 2020, 13. [Google Scholar] [CrossRef] [PubMed]
- Zanin, L.; Saraceno, G.; Panciani, P.P.; Renisi, G.; Signorini, L.; Migliorati, K.; Fontanella, M.M. SARS-CoV-2 can induce brain and spine demyelinating lesions. Acta Neurochir. 2020, 162, 1491–1494. [Google Scholar] [CrossRef]
- Suwanwongse, K.; Shabarek, N. Clinical features and outcome of HIV/SARS-CoV-2 coinfected patients in The Bronx, New York city. J. Med. Virol. 2020, 92, 2387–2389. [Google Scholar] [CrossRef]
- Bodnar, B.; Patel, K.; Ho, W.; Luo, J.J.; Hu, W. Cellular mechanisms underlying neurological/neuropsychiatric manifestations of COVID-19. J. Med. Virol. 2021, 93, 1983–1998. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- Lv, H.; Wu, N.C.; Tsang, O.T.-Y.; Yuan, M.; Perera, R.A.P.M.; Leung, W.S.; So, R.T.Y.; Chan, J.M.C.; Yip, G.K.; Chik, T.S.H.; et al. Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections. bioRxiv 2020. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Lam, J.Y.; Wong, W.M.; Yuen, C.K.; Cai, J.P.; Au, S.W.; Chan, J.F.; To, K.K.W.; Kok, K.H.; Yuen, K.Y. Accurate Diagnosis of COVID-19 by a Novel Immunogenic Secreted SARS-CoV-2 orf8 Protein. mBio 2020, 11. [Google Scholar] [CrossRef]
- Liotta, E.M.; Batra, A.; Clark, J.R.; Shlobin, N.A.; Hoffman, S.C.; Orban, Z.S.; Koralnik, I.J. Frequent neurologic manifestations and encephalopathy-associated morbidity in Covid-19 patients. Ann. Clin. Transl. Neurol. 2020, 7, 2221–2230. [Google Scholar] [CrossRef] [PubMed]
- Iqbal, A.; Iqbal, K.; Arshad Ali, S.; Azim, D.; Farid, E.; Baig, M.D.; Bin Arif, T.; Raza, M. The COVID-19 Sequelae: A Cross-Sectional Evaluation of Post-recovery Symptoms and the Need for Rehabilitation of COVID-19 Survivors. Cureus 2021, 13, e13080. [Google Scholar] [CrossRef] [PubMed]
- Mazza, M.G.; Palladini, M.; De Lorenzo, R.; Magnaghi, C.; Poletti, S.; Furlan, R.; Ciceri, F.; Rovere-Querini, P.; Benedetti, F. 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. [Google Scholar] [CrossRef]
- Shang, Y.F.; Liu, T.; Yu, J.N.; Xu, X.R.; Zahid, K.R.; Wei, Y.C.; Wang, X.H.; Zhou, F.L. Half-year follow-up of patients recovering from severe COVID-19: Analysis of symptoms and their risk factors. J. Intern. Med. 2021, 290, 444–450. [Google Scholar] [CrossRef]
- De Lorenzo, R.; Cinel, E.; Cilla, M.; Compagnone, N.; Ferrante, M.; Falbo, E.; Patrizi, A.; Castellani, J.; Magnaghi, C.; Calvisi, S.L.; et al. Physical and psychological sequelae at three months after acute illness in COVID-19 survivors. Panminerva Med. 2021. [Google Scholar] [CrossRef]
- Sami, R.; Soltaninejad, F.; Amra, B.; Naderi, Z.; Javanmard, S.H.; Iraj, B.; Ahmadi, S.H.; Shayganfar, A.; Dehghan, M.; Khademi, N.; et al. A one-year hospital-based prospective COVID-19 open-cohort in the Eastern Mediterranean region: The Khorshid COVID Cohort (KCC) study. PLoS ONE 2020, 15, e0241537. [Google Scholar] [CrossRef] [PubMed]
- Augustin, M.; Schommers, P.; Stecher, M.; Dewald, F.; Gieselmann, L.; Gruell, H.; Horn, C.; Vanshylla, K.; Di Cristanziano, V.; Osebold, L.; et al. Post-COVID syndrome in non-hospitalised patients with COVID-19: A longitudinal prospective cohort study. Lancet Reg. Health Eur. 2021, 6, 100122. [Google Scholar] [CrossRef] [PubMed]
- 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. Author Correction: Attributes and predictors of long COVID. Nat. Med. 2021, 27, 1116. [Google Scholar] [CrossRef]
- Tan, W.; Hao, F.; McIntyre, R.S.; Jiang, L.; Jiang, X.; Zhang, L.; Zhao, X.; Zou, Y.; Hu, Y.; Luo, X.; et al. Is returning to work during the COVID-19 pandemic stressful? A study on immediate mental health status and psychoneuroimmunity prevention measures of Chinese workforce. Brain, Behav. Immun. 2020, 87, 84–92. [Google Scholar] [CrossRef]
- Wang, C.; Pan, R.; Wan, X.; Tan, Y.; Xu, L.; McIntyre, R.S.; Choo, F.N.; Tran, B.; Ho, R.; Sharma, V.K.; et al. A longitudinal study on the mental health of general population during the COVID-19 epidemic in China. Brain Behav. Immun. 2020, 87, 40–48. [Google Scholar] [CrossRef] [PubMed]
- Lindqvist, D.; Wolkowitz, O.M.; Mellon, S.; Yehuda, R.; Flory, J.D.; Henn-Haase, C.; Bierer, L.M.; Abu-Amara, D.; Coy, M.; Neylan, T.C.; et al. Proinflammatory milieu in combat-related PTSD is independent of depression and early life stress. Brain Behav. Immun. 2014, 42, 81–88. [Google Scholar] [CrossRef]
- Passos, I.C.; Vasconcelos-Moreno, M.P.; Costa, L.G.; Kunz, M.; Brietzke, E.; Quevedo, J.; Salum, G.; Magalhães, P.V.; Kapczinski, F.; Kauer-Sant’Anna, M. Inflammatory markers in post-traumatic stress disorder: A systematic review, meta-analysis, and meta-regression. Lancet Psychiatry 2015, 2, 1002–1012. [Google Scholar] [CrossRef]
- Sparks, S.W. Posttraumatic Stress Syndrome: What Is It? J. Trauma Nurs. 2018, 25, 60–65. [Google Scholar] [CrossRef]
- Liu, N.; Zhang, F.; Wei, C.; Jia, Y.; Shang, Z.; Sun, L.; Wu, L.; Sun, Z.; Zhou, Y.; Wang, Y.; et al. Prevalence and predictors of PTSS during COVID-19 outbreak in China hardest-hit areas: Gender differences matter. Psychiatry Res. 2020, 287, 112921. [Google Scholar] [CrossRef]
- Halpin, S.J.; McIvor, C.; Whyatt, G.; Adams, A.; Harvey, O.; McLean, L.; Walshaw, C.; Kemp, S.; Corrado, J.; Singh, R.; et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J. Med. Virol. 2020, 93, 1013–1022. [Google Scholar] [CrossRef]
- Horn, M.; Wathelet, M.; Fovet, T.; Amad, A.; Vuotto, F.; Faure, K.; Astier, T.; Noël, H.; Henry, M.; Duhem, M.H.S.; et al. Is COVID-19 Associated with Posttraumatic Stress Disorder? J. Clin. Psychiatry 2020, 82. [Google Scholar] [CrossRef]
- Schou, T.M.; Joca, S.; Wegener, G.; Bay-Richter, C. Psychiatric and neuropsychiatric sequelae of COVID-19—A systematic review. Brain Behav. Immun. 2021. [Google Scholar] [CrossRef] [PubMed]
- Gualano, M.R.; Lo Moro, G.; Voglino, G.; Bert, F.; Siliquini, R. Effects of Covid-19 Lockdown on Mental Health and Sleep Disturbances in Italy. Int. J. Environ. Res. Public Health 2020, 17, 4779. [Google Scholar] [CrossRef] [PubMed]
- Kawohl, W.; Nordt, C. COVID-19, unemployment, and suicide. Lancet Psychiatry 2020, 7, 389–390. [Google Scholar] [CrossRef]
- Dubey, M.J.; Ghosh, R.; Chatterjee, S.; Biswas, P.; Chatterjee, S.; Dubey, S. COVID-19 and addiction. Diabetes Metab. Syndr. Clin. Res. Rev. 2020, 14, 817–823. [Google Scholar] [CrossRef] [PubMed]
- Ornell, F.; Moura, H.F.; Scherer, J.N.; Pechansky, F.; Kessler, F.H.P.; von Diemen, L. The COVID-19 pandemic and its impact on substance use: Implications for prevention and treatment. Psychiatry Res. 2020, 289, 113096. [Google Scholar] [CrossRef] [PubMed]
- Arya, S.; Gupta, R. COVID-19 outbreak: Challenges for Addiction services in India. Asian J. Psychiatry 2020, 51, 102086. [Google Scholar] [CrossRef] [PubMed]
- Volkow, N.D. Collision of the COVID-19 and Addiction Epidemics. Ann. Intern. Med. 2020, 173, 61–62. [Google Scholar] [CrossRef] [Green Version]
- Columb, D.; Hussain, R.; O’Gara, C. Addiction psychiatry and COVID-19: Impact on patients and service provision. Ir. J. Psychol. Med. 2020, 37, 164–168. [Google Scholar] [CrossRef] [PubMed]
- Oronsky, B.; Larson, C.; Hammond, T.C.; Oronsky, A.; Kesari, S.; Lybeck, M.; Reid, T.R. A Review of Persistent Post-COVID Syndrome (PPCS). Clin. Rev. Allergy Immunol. 2021, 1–9. [Google Scholar] [CrossRef]
- Nath, J.; Chowdhury, A.F.; Nath, A.K. Analyzing COVID-19 Challenges in Bangladesh. Preprints 2020. [Google Scholar] [CrossRef]
- Guedj, E.; Verger, A.; Cammilleri, S. PET imaging of COVID-19: The target and the number. Eur. J. Nucl. Med. Mol. Imaging 2020, 47, 1636–1637. [Google Scholar] [CrossRef] [PubMed]
- Delano, M.J.; Ward, P.A. The immune system’s role in sepsis progression, resolution, and long-term outcome. Immunol. Rev. 2016, 274, 330–353. [Google Scholar] [CrossRef]
- Yong, S.E.F.; Anderson, D.E.; Wei, W.; Pang, J.; Ni Chia, W.; Tan, C.W.; Teoh, Y.L.; Rajendram, P.; Toh, M.P.H.S.; Poh, C.; et al. Connecting clusters of COVID-19: An epidemiological and serological investigation. Lancet Infect. Dis. 2020, 20, 809–815. [Google Scholar] [CrossRef]
- de Pablo, G.S.; Vaquerizo-Serrano, J.; Catalan, A.; Arango, C.; Moreno, C.; Ferre, F.; Shin, J.I.; Sullivan, S.; Brondino, N.; Solmi, M.; et al. Impact of coronavirus syndromes on physical and mental health of health care workers: Systematic review and meta-analysis. J. Affect. Disord. 2020, 275, 48–57. [Google Scholar] [CrossRef] [PubMed]
- Bureau, B.L.; Obeidat, A.; Dhariwal, M.S.; Jha, P. Peripheral Neuropathy as a Complication of SARS-Cov-2. Cureus 2020, 12, 11452. [Google Scholar] [CrossRef]
- Finsterer, J.; Stollberger, C. Update on the neurology of COVID-19. J. Med. Virol. 2020, 92, 2316–2318. [Google Scholar] [CrossRef]
- Reichard, R.R.; Kashani, K.B.; Boire, N.A.; Constantopoulos, E.; Guo, Y.; Lucchinetti, C.F. Neuropathology of COVID-19: A spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology. Acta Neuropathol. 2020, 140, 1–6. [Google Scholar] [CrossRef]
- Gu, J.; Gong, E.; Zhang, B.; Zheng, J.; Gao, Z.; Zhong, Y.; Zou, W.; Zhan, J.; Wang, S.; Xie, Z.; et al. Multiple organ infection and the pathogenesis of SARS. J. Exp. Med. 2005, 202, 415–424. [Google Scholar] [CrossRef]
- Yi, Y.; Lagniton, P.N.; Ye, S.; Li, E.; Xu, R.-H. COVID-19: What has been learned and to be learned about the novel coronavirus disease. Int. J. Biol. Sci. 2020, 16, 1753–1766. [Google Scholar] [CrossRef]
- Wiegelmann, H.; Speller, S.; Verhaert, L.-M.; Schirra-Weirich, L.; Wolf-Ostermann, K. Psychosocial interventions to support the mental health of informal caregivers of persons living with dementia—A systematic literature review. BMC Geriatr. 2021, 21, 1–17. [Google Scholar] [CrossRef] [PubMed]
- Zlotnik, G.; Vansintjan, A. Memory: An Extended Definition. Front. Psychol. 2019, 10, 2523. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Budson, A.E.; Price, B.H. Memory Dysfunction. N. Engl. J. Med. 2005, 352, 692–699. [Google Scholar] [CrossRef]
- Carfì, A.; Bernabei, R.; Landi, F. Persistent Symptoms in Patients After Acute COVID-19. JAMA 2020, 324, 603–605. [Google Scholar] [CrossRef] [PubMed]
- Tenforde, M.W.; Kim, S.S.; Lindsell, C.J.; Rose, E.B.; Shapiro, N.I.; Files, D.C.; Gibbs, K.W.; Erickson, H.L.; Steingrub, J.S.; Smithline, H.A.; et al. Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network—United States, March–June 2020. MMWR. Morb. Mortal. Wkly. Rep. 2020, 69, 993–998. [Google Scholar] [CrossRef]
- Guedj, E.; Campion, J.Y.; Dudouet, P.; Kaphan, E.; Bregeon, F.; Tissot-Dupont, H.; Guis, S.; Barthelemy, F.; Habert, P.; Ceccaldi, M.; et al. 18F-FDG brain PET hypometabolism in patients with long COVID. Eur. J. Nucl. Med. Mol. Imaging 2021, 48, 2823–2833. [Google Scholar] [CrossRef]
- Guedj, E.; Million, M.; Dudouet, P.; Tissot-Dupont, H.; Bregeon, F.; Cammilleri, S.; Raoult, D. 18F-FDG brain PET hypometabolism in post-SARS-CoV-2 infection: Substrate for persistent/delayed disorders? Eur. J. Nucl. Med. Mol. Imaging 2021, 48, 592–595. [Google Scholar] [CrossRef]
- Bodranghien, F.; Bastian, A.A.; Casali, C.C.; Hallett, M.M.; Louis, E.E.; Manto, M.; Mariën, P.; Nowak, D.A.D.; Schmahmann, J.D.; Serrao, M.M.; et al. Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome. Cerebellum 2016, 15, 369–391. [Google Scholar] [CrossRef] [Green Version]
- Marvel, C.L.; Morgan, O.; Kronemer, S.I. How the motor system integrates with working memory. Neurosci. Biobehav. Rev. 2019, 102, 184–194. [Google Scholar] [CrossRef]
- Serrano-Castro, P.J.; Estivill-Torrús, G.; Cabezudo-García, P.; Reyes-Bueno, J.A.; Petersen, N.C.; Aguilar-Castillo, M.A.; Suárez-Pérez, J.; Jiménez-Hernández, M.D.; Moya-Molina, M.Á.; Oliver-Martos, B.; et al. Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: A delayed pandemic? Neurologia (Engl. Ed.) 2020, 35, 245–251. [Google Scholar] [CrossRef]
- Baig, A.M.; Khaleeq, A.; Ali, U.; Syeda, H. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chem. Neurosci. 2020, 11, 995–998. [Google Scholar] [CrossRef] [Green Version]
- Lu, Y.; Li, X.; Geng, D.; Mei, N.; Wu, P.-Y.; Huang, C.-C.; Jia, T.; Zhao, Y.; Wang, D.; Xiao, A.; et al. Cerebral Micro-Structural Changes in COVID-19 Patients—An MRI-based 3-month Follow-up Study. EClinicalMedicine 2020, 25, 100484. [Google Scholar] [CrossRef] [PubMed]
- Zou, X.; Chen, K.; Zou, J.; Han, P.; Hao, J.; Han, Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front. Med. 2020, 14, 185–192. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cirulli, E.; Barrett, K.M.S.; Riffle, S.; Bolze, A.; Neveux, I.; Dabe, S.; Grzymski, J.J.; Lu, J.T.; Washington, N.L. Long-term COVID-19 symptoms in a large unselected population. medRxiv 2020. [Google Scholar] [CrossRef]
- Garrigues, E.; Janvier, P.; Kherabi, Y.; Le Bot, A.; Hamon, A.; Gouze, H.; Doucet, L.; Berkani, S.; Oliosi, E.; Mallart, E.; et al. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J. Infect. 2020, 81, e4–e6. [Google Scholar] [CrossRef] [PubMed]
- Søraas, A.; Bø, R.; Kalleberg, K.T.; Støer, N.C.; Ellingjord-Dale, M.; Landrø, N.I. Self-reported Memory Problems 8 Months After COVID-19 Infection. JAMA Netw. Open 2021, 4, e2118717. [Google Scholar] [CrossRef] [PubMed]
- 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. EClinicalMedicine 2021, 101019. [Google Scholar] [CrossRef]
- Kim, L.J.; Martinez, D.; Fiori, C.Z.; Baronio, D.; Kretzmann, N.A.; Barros, H.M.T. Hypomyelination, memory impairment, and blood–brain barrier permeability in a model of sleep apnea. Brain Res. 2015, 1597, 28–36. [Google Scholar] [CrossRef] [PubMed]
- Kotfis, K.; Roberson, S.W.; Wilson, J.E.; Dabrowski, W.; Pun, B.T.; Ely, E.W. COVID-19: ICU delirium management during SARS-CoV-2 pandemic. Crit. Care 2020, 24, 176. [Google Scholar] [CrossRef]
- Templeton, S.P.; Kim, T.S.; O’Malley, K.; Perlman, S. Maturation and Localization of Macrophages and Microglia During Infection with a Neurotropic Murine Coronavirus. Brain Pathol. 2008, 18, 40–51. [Google Scholar] [CrossRef]
- Prüss, H. Autoantibodies in neurological disease. Nat. Rev. Immunol. 2021, 1–16. [Google Scholar] [CrossRef]
- Diano, S.; Farr, S.A.; Benoit, S.C.; McNay, E.C.; Silva, I.; Horvath, B.; Gaskin, F.S.; Nonaka, N.; Jaeger, L.B.; Banks, W.A.; et al. Ghrelin controls hippocampal spine synapse density and memory performance. Nat. Neurosci. 2006, 9, 381–388. [Google Scholar] [CrossRef] [PubMed]
- Jafari, A.; Sadeghpour, S.; Ghasemnejad-Berenji, H.; Pashapour, S.; Ghasemnejad-Berenji, M. Potential Antioxidative, Anti-inflammatory and Immunomodulatory Effects of Ghrelin, an Endogenous Peptide from the Stomach in SARS-CoV2 Infection. Int. J. Pept. Res. Ther. 2021, 27, 1875–1883. [Google Scholar] [CrossRef] [PubMed]
- Yorulmaz, H.; Özkök, E.; Ates, G.; Tamer, S. Investigation of the effectiveness of ghrelin treatment in lung tissue of rats with sepsis. Bratisl. Med J. 2018, 118, 585–590. [Google Scholar] [CrossRef] [Green Version]
- Wu, Y.; Xu, X.; Chen, Z.; Duan, J.; Hashimoto, K.; Yang, L.; Liu, C.; Yang, C. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav. Immun. 2020, 87, 18–22. [Google Scholar] [CrossRef]
- Li, Y.C.; Bai, W.Z.; Hashikawa, T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J. Med. Virol. 2020, 92, 552–555. [Google Scholar] [CrossRef]
- Qi, F.; Qian, S.; Zhang, S.; Zhang, Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem. Biophys. Res. Commun. 2020, 526, 135–140. [Google Scholar] [CrossRef]
- Yachou, Y.; El Idrissi, A.; Belapasov, V.; Ait Benali, S. Neuroinvasion, neurotropic, and neuroinflammatory events of SARS-CoV-2: Understanding the neurological manifestations in COVID-19 patients. Neurol. Sci. Off. J. Ital. Neurol. Soc. Ital. Soc. Clin. Neurophysiol. 2020, 41, 2657–2669. [Google Scholar]
- Lou, B.; Li, T.D.; Zheng, S.F.; Su, Y.Y.; Li, Z.Y.; Liu, W.; Yu, F.; Ge, S.X.; Zou, Q.D.; Yuan, Q.; et al. Serology characteristics of SARS-CoV-2 infection after exposure and post-symptom onset. Eur. Respir. J. 2020, 56. [Google Scholar] [CrossRef]
- Nouri-Vaskeh, M.; Alizadeh, L. Fecal transmission in COVID-19: A potential shedding route. J. Med. Virol. 2020, 92, 1731–1732. [Google Scholar] [CrossRef] [Green Version]
- Shepley-McTaggart, A.; Sagum, C.A.; Oliva, I.; Rybakovsky, E.; DiGuilio, K.; Liang, J.; Bedford, M.T.; Cassel, J.; Sudol, M.; Mullin, J.M.; et al. SARS-CoV-2 Envelope (E) protein interacts with PDZ-domain-2 of host tight junction protein ZO1. PLoS ONE 2021, 16, e0251955. [Google Scholar] [CrossRef]
- Tay, M.Z.; Poh, C.M.; Rénia, L.; MacAry, P.A.; Ng, L.F.P. The trinity of COVID-19: Immunity, inflammation and intervention. Nat. Rev. Immunol. 2020, 20, 363–374. [Google Scholar] [CrossRef] [PubMed]
- Kandemirli, S.G.; Dogan, L.; Sarikaya, Z.T.; Kara, S.; Akinci, C.; Kaya, D.; Kaya, Y.; Yildirim, D.; Tuzuner, F.; Yildirim, M.S.; et al. Brain MRI Findings in Patients in the Intensive Care Unit with COVID-19 Infection. Radiology 2020, 297, E232–E235. [Google Scholar] [CrossRef] [PubMed]
- Chousterman, B.G.; Swirski, F.; Weber, G.F. Cytokine storm and sepsis disease pathogenesis. Semin. Immunopathol. 2017, 39, 517–528. [Google Scholar] [CrossRef] [PubMed]
- Ribeiro, D.E.; Oliveira-Giacomelli, Á.; Glaser, T.; Arnaud-Sampaio, V.F.; Andrejew, R.; Dieckmann, L.; Baranova, J.; Lameu, C.; Ratajczak, M.Z.; Ulrich, H. Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology. Mol. Psychiatry 2021, 26, 1044–1059. [Google Scholar] [CrossRef] [PubMed]
- Cloutier, M.; Nandi, M.; Ihsan, A.U.; Chamard, H.A.; Ilangumaran, S.; Ramanathan, S. ADE and hyperinflammation in SARS-CoV2 infection- comparison with dengue hemorrhagic fever and feline infectious peritonitis. Cytokine 2020, 136, 155256. [Google Scholar] [CrossRef]
- Mahmud-Al-Rafat, A.; Asim, M.H.; Taylor-Robinson, A.W.; Majumder, A.; Muktadir, A.; Muktadir, H.; Karim, M.; Khan, I.; Ahasan, M.M.; Billah, M. A combinational approach to restore cytokine balance and to inhibit virus growth may promote patient recovery in severe COVID-19 cases. Cytokine 2020, 136, 155228. [Google Scholar] [CrossRef]
- Mahmudpour, M.; Roozbeh, J.; Keshavarz, M.; Farrokhi, S.; Nabipour, I. COVID-19 cytokine storm: The anger of inflammation. Cytokine 2020, 133, 155151. [Google Scholar] [CrossRef] [PubMed]
- Noroozi, R.; Branicki, W.; Pyrc, K.; Łabaj, P.P.; Pospiech, E.; Taheri, M.; Ghafouri-Fard, S. Altered cytokine levels and immune responses in patients with SARS-CoV-2 infection and related conditions. Cytokine 2020, 133, 155143. [Google Scholar] [CrossRef]
- Isacson, O. The Consequences of Coronavirus-Induced Cytokine Storm Are Associated with Neurological Diseases, Which May Be Preventable. Front. Neurol. 2020, 11, 745. [Google Scholar] [CrossRef]
- Koçer, A.; Koçer, E.; Memişoğullari, R.; Domaç, F.M.; Yüksel, H. Interleukin-6 Levels in Tension Headache Patients. Clin. J. Pain 2010, 26, 690–693. [Google Scholar] [CrossRef] [PubMed]
- Yip, M.S.; Leung, H.L.; Li, P.H.; Cheung, C.Y.; Dutry, I.; Li, D.; Daëron, M.; Bruzzone, R.; Peiris, J.S.M.; Jaume, M. Antibody-dependent enhancement of SARS coronavirus infection and its role in the pathogenesis of SARS. Hong Kong Med. J. 2016, 22, 25–31. [Google Scholar] [CrossRef] [Green Version]
- Zhang, C.; Wu, Z.; Li, J.-W.; Zhao, H.; Wang, G.-Q. Cytokine release syndrome in severe COVID-19: Interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int. J. Antimicrob. Agents 2020, 55, 105954. [Google Scholar] [CrossRef]
- Richardson, P.J.; Ottaviani, S.; Prelle, A.; Stebbing, J.; Casalini, G.; Corbellino, M. CNS penetration of potential anti-COVID-19 drugs. J. Neurol. 2020, 267, 1880–1882. [Google Scholar] [CrossRef] [PubMed]
- Koprich, J.B.; Reske-Nielsen, C.; Mithal, P.; Isacson, O. Neuroinflammation mediated by IL-1beta increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson’s disease. J. Neuroinflamm. 2008, 5, 8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Deleidi, M.; Hallett, P.J.; Koprich, J.B.; Chung, C.-Y.; Isacson, O. The Toll-Like Receptor-3 Agonist Polyinosinic:Polycytidylic Acid Triggers Nigrostriatal Dopaminergic Degeneration. J. Neurosci. 2010, 30, 16091–16101. [Google Scholar] [CrossRef] [Green Version]
- Chen, G.; Wu, D.; Guo, W.; Cao, Y.; Huang, D.; Wang, H.; Wang, T.; Zhang, X.; Chen, H.; Yu, H.; et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J. Clin. Investig. 2020, 130, 2620–2629. [Google Scholar] [CrossRef] [Green Version]
- Ferrarese, C.; Mascarucci, P.; Zoia, C.; Cavarretta, R.; Frigo, M.; Begni, B.; Sarinella, F.; Frattola, L.; De Simoni, M.G. Increased Cytokine Release from Peripheral Blood Cells after Acute Stroke. Br. J. Pharmacol. 1999, 19, 1004–1009. [Google Scholar] [CrossRef] [Green Version]
- Intiso, D.; Zarrelli, M.M.; Lagioia, G.; Di Rienzo, F.; De Ambrosio, C.C.; Simone, P.; Tonali, P.; Cioffi†, R.P. Tumor necrosis factor alpha serum levels and inflammatory response in acute ischemic stroke patients. Neurol. Sci. 2004, 24, 390–396. [Google Scholar] [CrossRef]
- Ellul, M.A.; Benjamin, L.; Singh, B.; Lant, S.; Michael, B.D.; Easton, A.; Kneen, R.; Defres, S.; Sejvar, J.; Solomon, T. Neurological associations of COVID-19. Lancet Neurol. 2020, 19, 767–783. [Google Scholar] [CrossRef]
- Espíndola, O.M.; Gomes, Y.C.P.; Brandão, C.O.; Torres, R.C.; Siqueira, M.; Soares, C.N.; Lima, M.A.S.D.; Leite, A.C.C.B.; Venturotti, C.O.; Carvalho, A.J.C.; et al. Inflammatory Cytokine Patterns Associated with Neurological Diseases in Coronavirus Disease 2019. Ann. Neurol. 2021, 89, 1041–1045. [Google Scholar] [CrossRef] [PubMed]
- Sy, M.; Kitazawa, M.; Medeiros, R.; Whitman, L.; Cheng, D.; Lane, T.E.; LaFerla, F.M. Inflammation Induced by Infection Potentiates Tau Pathological Features in Transgenic Mice. Am. J. Pathol. 2011, 178, 2811–2822. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bastos, M.S.; Coelho-Dos-Reis, J.G.; Zauli, D.A.G.; Naveca, F.G.; Monte, R.L.; Pimentel, J.P.; Macário, V.M.K.; Da Silva, N.L.; Peruhype-Magalhães, V.; Pascoal-Xavier, M.A.; et al. Divergent cerebrospinal fluid cytokine network induced by non-viral and different viral infections on the central nervous system. BMC Infect. Dis. 2015, 15, 1–9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nagafuchi, M.; Nagafuchi, Y.; Sato, R.; Imaizumi, T.; Ayabe, M.; Shoji, H.; Ichiyama, T. Adult Meningism and Viral Meningitis, 1997–2004: Clinical Data and Cerebrospinal Fluid Cytokines. Intern. Med. 2006, 45, 1209–1212. [Google Scholar] [CrossRef] [Green Version]
- Kirschenbaum, D.; Imbach, L.L.; Ulrich, S.; Rushing, E.J.; Keller, E.; Reimann, R.R.; Frauenknecht, K.; Lichtblau, M.; Witt, M.; Hummel, T.; et al. Inflammatory olfactory neuropathy in two patients with COVID-19. Lancet 2020, 396, 166. [Google Scholar] [CrossRef]
- Henkin, R.I.; Schmidt, L.; Velicu, I. Interleukin 6 in Hyposmia. JAMA Otolaryngol. Neck Surg. 2013, 139, 728–734. [Google Scholar] [CrossRef] [Green Version]
- Abdulsalam, M.A.; Abdulsalam, A.J.; Shehab, D. Generalized status epilepticus as a possible manifestation of COVID-19. Acta Neurol. Scand. 2020, 142, 297–298. [Google Scholar] [CrossRef]
- Kuroda, N. Epilepsy and COVID-19: Associations and important considerations. Epilepsy Behav. 2020, 108, 107122. [Google Scholar] [CrossRef]
- Yasri, S.; Wiwanikit, V. COVID-19 and epilepsy. Ann. Indian Acad. Neurol. 2020, 23, S43. [Google Scholar] [CrossRef]
- Lehtimäki, K.; Keränen, T.; Huhtala, H.; Hurme, M.; Ollikainen, J.; Honkaniemi, J.; Palmio, J.; Peltola, J. Regulation of IL-6 system in cerebrospinal fluid and serum compartments by seizures: The effect of seizure type and duration. J. Neuroimmunol. 2004, 152, 121–125. [Google Scholar] [CrossRef] [PubMed]
- Kaushik, A.; Gupta, S.; Sood, M.; Sharma, S.; Verma, S. A Systematic Review of Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 Infection. Pediatr. Infect. Dis. J. 2020, 39, e340–e346. [Google Scholar] [CrossRef] [PubMed]
- Kaushik, D.; Bhandari, R.; Kuhad, A. TLR4 as a therapeutic target for respiratory and neurological complications of SARS-CoV-2. Expert Opin. Ther. Targets 2021, 25, 491–508. [Google Scholar] [CrossRef] [PubMed]
- Natoli, S.; Oliveira, V.; Calabresi, P.; Maia, L.; Pisani, A. Does SARS-Cov-2 invade the brain? Translational lessons from animal models. Eur. J. Neurol. 2020, 27, 1764–1773. [Google Scholar] [CrossRef] [PubMed]
- Hobbs, E.C.; Reid, T.J. Animals and SARS-CoV-2: Species susceptibility and viral transmission in experimental and natural conditions, and the potential implications for community transmission. Transbound. Emerg. Dis. 2021, 68, 1850–1867. [Google Scholar] [CrossRef]
- Bao, L.; Deng, W.; Huang, B.; Gao, H.; Liu, J.; Ren, L.; Wei, Q.; Yu, P.; Xu, Y.; Qi, F.; et al. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature 2020, 583, 830–833. [Google Scholar] [CrossRef]
- Zhang, B.Z.; Chu, H.; Han, S.; Shuai, H.; Deng, J.; Hu, Y.F.; Gong, H.R.; Lee, A.C.Y.; Zou, Z.; Yau, T.; et al. SARS-CoV-2 infects human neural progenitor cells and brain organoids. Cell Res. 2020, 30, 928–931. [Google Scholar] [CrossRef]
- Song, E.; Zhang, C.; Israelow, B.; Lu-Culligan, A.; Prado, A.V.; Skriabine, S.; Lu, P.; Weizman, O.E.; Liu, F.; Dai, Y.; et al. Neuroinvasion of SARS-CoV-2 in human and mouse brain. J. Exp. Med. 2021, 218, e20202135. [Google Scholar] [CrossRef] [PubMed]
- Ju, X.; Zhu, Y.; Wang, Y.; Li, J.; Zhang, J.; Gong, M.; Ren, W.; Li, S.; Zhong, J.; Zhang, L.; et al. A novel cell culture system modeling the SARS-CoV-2 life cycle. PLoS Pathog. 2021, 17, e1009439. [Google Scholar] [CrossRef] [PubMed]
- Mansoor, S.; Kelly, S.; Murphy, K.; Waters, A.; Siddiqui, N.S. COVID-19 pandemic and the risk of infection in multiple sclerosis patients on disease modifying therapies: “what the bleep do we know?”. Egypt. J. Neurol. Psychiatry Neurosurg. 2020, 56, 1–3. [Google Scholar] [CrossRef]
- Matías-Guiu, J.; Alvarez-Sabin, J.; Ara, J.R.; Arenillas, J.; Casado-Naranjo, I.; Castellanos, M.; Jimenez-Hernandez, M.; Lainez-Andres, J.; Moral, E.; Morales, A.; et al. Will neurological care change over the next 5 years due to the COVID-19 pandemic? Key informant consensus survey. Neurología (Engl. Ed.) 2020, 35, 252–257. [Google Scholar] [CrossRef]
- Asadi-Pooya, A.A.; Simani, L. Central nervous system manifestations of COVID-19: A systematic review. J. Neurol. Sci. 2020, 413, 116832. [Google Scholar] [CrossRef] [PubMed]
Disorders | Disorders Presentation | |||
---|---|---|---|---|
Acute Phase during Infection | After Infection (3, 6, or 12 Months after) | Are Already Present before the Infection | Come after Infection | |
Neurological Disorders | ||||
Headache and Dizziness | X | X | X | |
Anosmia and Ageusia | X | X | X | |
Acute ischemic stroke | X | X | X | |
Intracerebral hemorrhage (ICH) | X | X | ||
Cerebral venous sinus thrombosis | X | X | X | |
Encephalopathy with symptoms that may range from mere headache, fever and neck rigidity | X | X | X | |
Seizure | X | X | X | |
Ataxia | X | X | ||
Myelitis | X | X | ||
Rhabdomyolysis | X | X | ||
Guillain–Barré syndrome | X | X | ||
Stroke | X | X | ||
Alzheimer’s disease | X | X | ||
Parkinson’s disease | X | X | ||
Loss of memory | X | X | ||
Neuropsychiatric Disorders | ||||
Depression | X | X | ||
Anxiety | X | X | X | |
Sleep disorders | X | X | X | |
Stress disorders | X | X | ||
Addiction and substance abuse | X | X |
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Majolo, F.; Silva, G.L.d.; Vieira, L.; Anli, C.; Timmers, L.F.S.M.; Laufer, S.; Goettert, M.I. Neuropsychiatric Disorders and COVID-19: What We Know So Far. Pharmaceuticals 2021, 14, 933. https://doi.org/10.3390/ph14090933
Majolo F, Silva GLd, Vieira L, Anli C, Timmers LFSM, Laufer S, Goettert MI. Neuropsychiatric Disorders and COVID-19: What We Know So Far. Pharmaceuticals. 2021; 14(9):933. https://doi.org/10.3390/ph14090933
Chicago/Turabian StyleMajolo, Fernanda, Guilherme Liberato da Silva, Lucas Vieira, Cetin Anli, Luís Fernando Saraiva Macedo Timmers, Stefan Laufer, and Márcia Inês Goettert. 2021. "Neuropsychiatric Disorders and COVID-19: What We Know So Far" Pharmaceuticals 14, no. 9: 933. https://doi.org/10.3390/ph14090933
APA StyleMajolo, F., Silva, G. L. d., Vieira, L., Anli, C., Timmers, L. F. S. M., Laufer, S., & Goettert, M. I. (2021). Neuropsychiatric Disorders and COVID-19: What We Know So Far. Pharmaceuticals, 14(9), 933. https://doi.org/10.3390/ph14090933