Role of Neuroinflammation Mediated Potential Alterations in Adult Neurogenesis As a Factor for Neuropsychiatric Symptoms in Post-Acute COVID-19 Syndrome-A Narrative Review

Overview

Journal PeerJ

Specialties Biology
Environmental Health
General Medicine

Date 2022 Nov 10

PMID 36353605

Authors

Jayakumar Saikarthik

Ilango Saraswathi

Abdulaziz Alarifi

Abdulrahman A Al-Atram

Suresh Mickeymaray

Anand Paramasivam

Saleem Shaikh

Mathew Jeraud

Abdulaziz S Alothaim

Affiliations

Soon will be listed here.

Abstract

Persistence of symptoms beyond the initial 3 to 4 weeks after infection is defined as post-acute COVID-19 syndrome (PACS). A wide range of neuropsychiatric symptoms like anxiety, depression, post-traumatic stress disorder, sleep disorders and cognitive disturbances have been observed in PACS. The review was conducted based on PRISMA-S guidelines for literature search strategy for systematic reviews. A cytokine storm in COVID-19 may cause a breach in the blood brain barrier leading to cytokine and SARS-CoV-2 entry into the brain. This triggers an immune response in the brain by activating microglia, astrocytes, and other immune cells leading to neuroinflammation. Various inflammatory biomarkers like inflammatory cytokines, chemokines, acute phase proteins and adhesion molecules have been implicated in psychiatric disorders and play a major role in the precipitation of neuropsychiatric symptoms. Impaired adult neurogenesis has been linked with a variety of disorders like depression, anxiety, cognitive decline, and dementia. Persistence of neuroinflammation was observed in COVID-19 survivors 3 months after recovery. Chronic neuroinflammation alters adult neurogenesis with pro-inflammatory cytokines supressing anti-inflammatory cytokines and chemokines favouring adult neurogenesis. Based on the prevalence of neuropsychiatric symptoms/disorders in PACS, there is more possibility for a potential impairment in adult neurogenesis in COVID-19 survivors. This narrative review aims to discuss the various neuroinflammatory processes during PACS and its effect on adult neurogenesis.

Citing Articles

Pathophysiological, Neuropsychological, and Psychosocial Influences on Neurological and Neuropsychiatric Symptoms of Post-Acute COVID-19 Syndrome: Impacts on Recovery and Symptom Persistence.

Malioukis A, Snead R, Marczika J, Ambalavanan R Biomedicines. 2025; 12(12.

PMID: 39767737 PMC: 11673694. DOI: 10.3390/biomedicines12122831.

Methylphenidate for the Treatment of Post-COVID Cognitive Dysfunction (Brain Fog).

Clark P, Rosenberg P, Oh E, Parker A, Vannorsdall T, Azola A J Med Cases. 2024; 15(8):195-200.

PMID: 39091579 PMC: 11287906. DOI: 10.14740/jmc4254.

Microbes and Mental Illness: Past, Present, and Future.

Bransfield R, Mao C, Greenberg R Healthcare (Basel). 2024; 12(1).

PMID: 38200989 PMC: 10779437. DOI: 10.3390/healthcare12010083.

The Search for Diagnostic Criteria to Divide the Wistar Rat Population into Phenotypes during Modeling of Post-Traumatic Stress Disorder.

Kondashevskaya M, Aleksankina V, Artemeva K Bull Exp Biol Med. 2024; 176(2):235-240.

PMID: 38194068 DOI: 10.1007/s10517-024-06002-5.

In Between the Psychological and Physiological Self - The Impact of Covid-19 Pandemic on the Neuro-Socio-Ecological and Inflammatory Mind-Body-Brain System.

Scalabrini A, Palladini M, Mazza M, Mucci C, Northoff G, Benedetti F Clin Neuropsychiatry. 2023; 20(4):342-350.

PMID: 37791086 PMC: 10544257. DOI: 10.36131/cnfioritieditore20230414.

References

Sulzer D, Antonini A, Leta V, Nordvig A, Smeyne R, Goldman J . COVID-19 and possible links with Parkinson's disease and parkinsonism: from bench to bedside. NPJ Parkinsons Dis. 2020; 6:18. PMC: 7441399. DOI: 10.1038/s41531-020-00123-0. View

Orihuela R, McPherson C, Harry G . Microglial M1/M2 polarization and metabolic states. Br J Pharmacol. 2015; 173(4):649-65. PMC: 4742299. DOI: 10.1111/bph.13139. View

Barry D, McDermott K . Differentiation of radial glia from radial precursor cells and transformation into astrocytes in the developing rat spinal cord. Glia. 2005; 50(3):187-97. DOI: 10.1002/glia.20166. View

John G, Lee S, Brosnan C . Cytokines: powerful regulators of glial cell activation. Neuroscientist. 2003; 9(1):10-22. DOI: 10.1177/1073858402239587. View

Marxreiter F, Regensburger M, Winkler J . Adult neurogenesis in Parkinson's disease. Cell Mol Life Sci. 2012; 70(3):459-73. PMC: 11113680. DOI: 10.1007/s00018-012-1062-x. View

Manjili R, Zarei M, Habibi M, Manjili M . COVID-19 as an Acute Inflammatory Disease. J Immunol. 2020; 205(1):12-19. PMC: 7333792. DOI: 10.4049/jimmunol.2000413. View

Li Y, Bai W, 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(6):552-555. PMC: 7228394. DOI: 10.1002/jmv.25728. View

Mathieu P, Piantanida A, Pitossi F . Chronic expression of transforming growth factor-beta enhances adult neurogenesis. Neuroimmunomodulation. 2010; 17(3):200-1. DOI: 10.1159/000258723. View

Wiersinga W, Rhodes A, Cheng A, Peacock S, Prescott H . Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020; 324(8):782-793. DOI: 10.1001/jama.2020.12839. View

10.

Nuzzo D, Vasto S, Scalisi L, Cottone S, Cambula G, Rizzo M . Post-Acute COVID-19 Neurological Syndrome: A New Medical Challenge. J Clin Med. 2021; 10(9). PMC: 8124354. DOI: 10.3390/jcm10091947. View

11.

Villar-Cheda B, Valenzuela R, Rodriguez-Perez A, Guerra M, Labandeira-Garcia J . Aging-related changes in the nigral angiotensin system enhances proinflammatory and pro-oxidative markers and 6-OHDA-induced dopaminergic degeneration. Neurobiol Aging. 2010; 33(1):204.e1-11. DOI: 10.1016/j.neurobiolaging.2010.08.006. View

12.

Nestler E, Barrot M, DiLeone R, Eisch A, Gold S, Monteggia L . Neurobiology of depression. Neuron. 2002; 34(1):13-25. DOI: 10.1016/s0896-6273(02)00653-0. View

13.

Rabiee A, Nikayin S, Hashem M, Huang M, Dinglas V, Bienvenu O . Depressive Symptoms After Critical Illness: A Systematic Review and Meta-Analysis. Crit Care Med. 2016; 44(9):1744-53. PMC: 7418220. DOI: 10.1097/CCM.0000000000001811. View

14.

Imai Y, Kuba K, Neely G, Yaghubian-Malhami R, Perkmann T, van Loo G . Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell. 2008; 133(2):235-49. PMC: 7112336. DOI: 10.1016/j.cell.2008.02.043. View

15.

Lotrich F, Albusaysi S, Ferrell R . Brain-derived neurotrophic factor serum levels and genotype: association with depression during interferon-α treatment. Neuropsychopharmacology. 2013; 38(6):985-95. PMC: 3629388. DOI: 10.1038/npp.2012.263. View

16.

Kirby E, Muroy S, Sun W, Covarrubias D, Leong M, Barchas L . Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2. Elife. 2013; 2:e00362. PMC: 3628086. DOI: 10.7554/eLife.00362. View

17.

Ryan S, OKeeffe G, OConnor C, Keeshan K, Nolan Y . Negative regulation of TLX by IL-1β correlates with an inhibition of adult hippocampal neural precursor cell proliferation. Brain Behav Immun. 2013; 33:7-13. DOI: 10.1016/j.bbi.2013.03.005. View

18.

Ni H, Hu S, Sheng W, Olson J, Cheeran M, Chan A . High-level expression of functional chemokine receptor CXCR4 on human neural precursor cells. Brain Res Dev Brain Res. 2004; 152(2):159-69. DOI: 10.1016/j.devbrainres.2004.06.015. View

19.

Rhea E, Banks W . Role of the Blood-Brain Barrier in Central Nervous System Insulin Resistance. Front Neurosci. 2019; 13:521. PMC: 6558081. DOI: 10.3389/fnins.2019.00521. View

20.

Suh H, Zhao M, Derico L, Choi N, Lee S . Insulin-like growth factor 1 and 2 (IGF1, IGF2) expression in human microglia: differential regulation by inflammatory mediators. J Neuroinflammation. 2013; 10:37. PMC: 3607995. DOI: 10.1186/1742-2094-10-37. View