Role of Neuroimmune Interactions in COVID-19-related Cardiovascular Damage

Abstract

Coronavirus disease 2019 (COVID-19) has caused a global pandemic impacting over 200 countries/regions and more than 200 million patients worldwide. Among the infected patients, there is a high prevalence of COVID-19-related cardiovascular injuries. However, the specific mechanisms linking cardiovascular damage and COVID-19 remain unclear. The COVID-19 pandemic also has exacerbated the mental health burden of humans. Considering the close association between neuroimmune interactions and cardiovascular disease, this review assessed the complex pathophysiological mechanisms connecting neuroimmune interactions and cardiovascular disease. It was revealed that the mental health burden might be a pivotal accomplice causing COVID-19-associated cardiovascular damage. Specifically, the proinflammatory status of patients with a terrible mood state is closely related to overdrive of the hypothalamus-pituitary-adrenal (HPA) axis, sympathovagal imbalance, and endothelial dysfunction, which lead to an increased risk of developing cardiovascular injury during COVID-19. Therefore, during the prevention and treatment of cardiovascular complications in COVID-19 patients, particular attention should be given to relieve the mental health burden of these patients.

Keywords

neuroimmune interactions / COVID-19 / mental health burden / autonomic nervous system / endothelial dysfunction

References

[1] LiYC, BaiWZ, HashikawaT. 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

[2] LiuY, YangY, ZhangC, et al.. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci, 2020, 63(3): 364-674

[3] WangL, HeW, YuX, et al.. Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up. J Infect, 2020, 80(6): 639-645

[4] CaoY, LiL, FengZ, et al.. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Disc, 2020, 6(1): 11

[5] KumarS, MauryaVK, PrasadAK, et al.. Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV). Virusdisease, 2020, 31(1): 13-21

[6] XuH, ZhongL, DengJ, et al.. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci, 2020, 12(1): 8

[7] SouthAM, DizDI, ChappellMC. COVID-19, ACE2, and the cardiovascular consequences. Am J Physiol Heart Circ Physiol, 2020, 318(5): H1084-H1090

[8] HuangC, WangY, LiX, et al.. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, 395(10223): 497-506

[9] LiuB, LiM, ZhouZ, et al.. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?. J Autoimmun, 2020, 111: 102452

[10] RizzoP, Vieceli Dalla SegaF, FortiniF, et al.. COVID-19 in the heart and the lungs: could we “Notch” the inflammatory storm?. Basic Res Cardiol, 2020, 115(3): 31

[11] TanW, AboulhosnJ. The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease. Int J Cardiol, 2020, 309: 70-77

[12] SantosCF. Reflections about the impact of the SARS-COV-2/COVID-19 pandemic on mental health. Braz J Psychiatry, 2020, 42(3): 329

[13] LiangL, RenH, CaoR, et al.. The Effect of COVID-19 on Youth Mental Health. Psychiatr Quarterly, 2020, 91(3): 841-852

[14] HalarisADantzerR, CapuronL. Inflammation-Associated Co-morbidity Between Depression and Cardiovascular Disease. Inflammation-Associated Depression: Evidence, Mechanisms and Implications, 2017, Cham, Springer International Publishing: 45-70

[15] KadoyaM, KoyamaH. Sleep, Autonomic Nervous Function and Atherosclerosis. Int J Mol Sci, 2019, 20(4): 794

[16] CarterP, ReynoldsJ, CarterA, et al.. The impact of psychiatric comorbidities on the length of hospital stay in patients with heart failure. Int J Cardiol, 2016, 207: 292-296

[17] WangD, HuB, HuC, et al.. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus—Infected Pneumonia in Wuhan, China. JAMA, 2020, 323(11): 1061-1069

[18] ShiS, QinM, ShenB, et al.. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol, 2020, 5(7): 802-810

[19] BhatrajuPK, GhassemiehBJ, NicholsM, et al.. Covid-19 in Critically Ill Patients in the Seattle Region—Case Series. New Engl J Med, 2020, 382(21): 2012-2022

[20] GuoT, FanY, ChenM, et al.. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol, 2020, 5(7): 811-818

[21] ZhengYY, MaYT, ZhangJY, et al.. COVID-19 and the cardiovascular system. Nat Rev Cardiol, 2020, 17(5): 259-260

[22] ClerkinKJ, FriedJA, RaikhelkarJ, et al.. COVID-19 and Cardiovascular Disease. Circulation, 2020, 141(20): 1648-1655

[23] ZhaiY, DuX. Addressing collegiate mental health amid COVID-19 pandemic. Psychiatry Res, 2020, 288: 113003

[24] HuangY, ZhaoN. Generalized anxiety disorder, depressive symptoms and sleep quality during COVID-19 outbreak in China: a web-based cross-sectional survey. Psychiatry Res, 2020, 288: 112954

[25] MocciaL, JaniriD, PepeM, et al.. Affective temperament, attachment style, and the psychological impact of the COVID-19 outbreak: an early report on the Italian general population. Brain Behav Immun, 2020, 87: 75-79

[26] KangL, LiY, HuS, et al.. The mental health of medical workers in Wuhan, China dealing with the 2019 novel coronavirus. Lancet Psychiatry, 2020, 7(3): e14

[27] MoY, DengL, ZhangL, et al.. Work stress among Chinese nurses to support Wuhan in fighting against COVID-19 epidemic. J Nurs Manag, 2020, 28(5): 1002-1009

[28] MabenJ, BridgesJ. Covid-19: Supporting nurses’ psychological and mental health. J Clin Nurs, 2020, 29(15–16): 2742-2750

[29] ChavanSS, PavlovVA, TraceyKJ. Mechanisms and therapeutic relevance of neuro-immune communication. Immunity, 2017, 46(6): 927-942

[30] YooBB, MazmanianSK. The Enteric Network: Interactions between the Immune and Nervous Systems of the Gut. Immunity, 2017, 46(6): 910-926

[31] LaiNY, MillsK, ChiuIM. Sensory neuron regulation of gastrointestinal inflammation and bacterial host defence. J Intern Med, 2017, 282(1): 5-23

[32] BorovikovaLV, IvanovaS, ZhangM, et al.. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature, 2000, 405(6785): 458-462

[33] HuH, MaF, WeiX, et al.. Coronavirus fulminant myocarditis treated with glucocorticoid and human immunoglobulin. Eur Heart J, 2020, 42(2): 206

[34] ZengJH, LiuYX, YuanJ, et al.. First case of COVID-19 complicated with fulminant myocarditis: a case report and insights. Infection, 2020, 48(5): 773-777

[35] ZhuH, RheeJW, ChengP, et al.. Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response. Curr Cardiol Rep, 2020, 22(5): 32

[36] MehtaP, McAuleyDF, BrownM, et al.. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet, 2020, 395(10229): 1033-1034

[37] FemeníaT, Giménez-CassinaA, CodeluppiS, et al.. Disrupted Neuroglial Metabolic Coupling after Peripheral Surgery. J Neurosci, 2018, 38(2): 452-464

[38] WalkerKA, GrossAL, MoghekarAR, et al.. Association of peripheral inflammatory markers with connectivity in large-scale functional brain networks of non-demented older adults. Brain Behav Immun, 2020, 87: 388-396

[39] LopezRB, BrownRL, WuELL, et al.. Emotion Regulation and Immune Functioning During Grief: Testing the Role of Expressive Suppression and Cognitive Reappraisal in Inflammation Among Recently Bereaved Spouses. Psychosom Med, 2020, 82(1): 2-9

[40] MaesM, YirmyiaR, NorabergJ, et al.. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis, 2009, 24(1): 27-53

[41] LiD, WangY, JinX, et al.. NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in mice. J Neuroinflammation, 2020, 17(1): 126

[42] PetraliaMC, MazzonE, FagoneP, et al.. The cytokine network in the pathogenesis of major depressive disorder. Close to translation?. Autoimmun Rev, 2020, 19(5): 102504

[43] ZhangJ, LinW, TangM, et al.. Inhibition of JNK ameliorates depressive-like behaviors and reduces the activation of pro-inflammatory cytokines and the phosphorylation of glucocorticoid receptors at serine 246 induced by neuroinflammation. Psychoneuroendocrinology, 2020, 113: 104580

[44] RomanM, IrwinMR. Novel neuroimmunologic therapeutics in depression: A clinical perspective on what we know so far. Brain Behav Immun, 2020, 83: 7-21

[45] SlavichGM, IrwinMR. From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychol Bull, 2014, 140(3): 774-815

[46] McAlpineCS, KissMG, RattikS, et al.. Sleep modulates haematopoiesis and protects against atherosclerosis. Nature, 2019, 566(7744): 383-387

[47] JohnsonJD, BarnardDF, KulpAC, et al.. Neuroendocrine Regulation of Brain Cytokines After Psychological Stress. J Endocr Soc, 2019, 3(7): 1302-1320

[48] HaoG, YoussefNA, DavisCL, et al.. The role of DNA methylation in the association between childhood adversity and cardiometabolic disease. Int J Cardiol, 2018, 255: 168-174

[49] PetersEM, LiezmannC, KlappBF, et al.. The neuroimmune connection interferes with tissue regeneration and chronic inflammatory disease in the skin. Ann N Y Acad Sci, 2012, 1262: 118-126

[50] TonhajzerovaI, SekaninovaN, Bona OlexovaL, et al.. Novel Insight into Neuroimmune Regulatory Mechanisms and Biomarkers Linking Major Depression and Vascular Diseases: The Dilemma Continues. Int J Mol Sci, 2020, 21(7): 2317

[51] OrtegaE, GálvezI, Martín-CorderoL. Adrenergic Regulation of Macrophage-Mediated Innate/Inflammatory Responses in Obesity and Exercise in this Condition: Role of β2 Adrenergic Receptors. Endoc Metab Immune Disord Drug Targets, 2019, 19(8): 1089-1099

[52] AgacD, EstradaLD, MaplesR, et al.. The beta2-adrenergic receptor controls inflammation by driving rapid IL-10 secretion. Brain Behav Immun, 2018, 74: 176-185

[53] TraceyKJ. The inflammatory reflex. Nature, 2002, 420(6917): 853-859

[54] ShiS, LiangJ, LiuT, et al.. Depression increases sympathetic activity and exacerbates myocardial remodeling after myocardial infarction: evidence from an animal experiment. PloS One, 2014, 9(7): e101734

[55] DoreyTW, MoghtadaeiM, RoseRA. Altered heart rate variability in angiotensin II—mediated hypertension is associated with impaired autonomic nervous system signaling and intrinsic sinoatrial node dysfunction. Heart Rhythm, 2020, 17(8): 1360-1370

[56] OkadaH, YoshidaS, HaraA, et al.. Vascular endothelial injury exacerbates coronavirus disease 2019: The role of endothelial glycocalyx protection. Microcirculation, 2021, 28(3): e12654

[57] BalintB, JaremekV, ThorburnV, et al.. Left atrial microvascular endothelial dysfunction, myocardial inflammation and fibrosis after selective insular cortex ischemic stroke. Int J Cardiol, 2019, 292: 148-155

[58] ToyaT, SaraJD, AhmadA, et al.. Incremental Prognostic Impact of Peripheral Microvascular Endothelial Dysfunction on the Development of Ischemic Stroke. J Am Heart Assoc, 2020, 9(9): e015703

[59] AntoninoT, MarioD, AntonioP. Endothelial Dysfunction and Inflammation in Ischemic Stroke Pathogenesis. Curr Pharm Des, 2020, 26(34): 4209-4219

[60] KuangY, LiX, LiuX, et al.. Vascular endothelial S1pr1 ameliorates adverse cardiac remodelling via stimulating reparative macrophage proliferation after myocardial infarction. Cardiovasc Res, 2021, 117(2): 585-299

[61] SchmitzSL, AbosiOJ, PersonsJE, et al.. Impact of Mood on Endothelial Function and Arterial Stiffness in Bipolar Disorder. Heart Mind (Mumbai), 2018, 2(3): 78-84

[62] SauvetF, ArnalPJ, Tardo-DinoPE, et al.. Protective effects of exercise training on endothelial dysfunction induced by total sleep deprivation in healthy subjects. Int J Cardiol, 2017, 232: 76-85

[63] JinX, JinC, NakamuraK, et al.. Increased dipeptidyl peptidase-4 accelerates chronic stress-related thrombosis in a mouse carotid artery model. J Hypertens, 2020, 38(8): 1504-1513

[64] SawickiCM, McKimDB, WohlebES, et al.. Social defeat promotes a reactive endothelium in a brain region-dependent manner with increased expression of key adhesion molecules, selectins and chemokines associated with the recruitment of myeloid cells to the brain. Neuroscience, 2015, 302: 151-164

[65] FiedorowiczJG, CoryellWH, RiceJP, et al.. Vasculopathy Related to Manic/Hypomanic Symptom Burden and First-Generation Antipsychotics in a Sub-Sample from the Collaborative Depression Study. Psychother Psychosom, 2012, 81(4): 235-243

[66] GuptaAK, JneidH, AddisonD, et al.. Current Perspectives on Coronavirus Disease 2019 and Cardiovascular Disease: A White Paper by the JAHA Editors. J Am Heart Assoc, 2020, 9(12): e017013

[67] GuanWJ, LiangWH, HeJX, et al.. Cardiovascular comorbidity and its impact on patients with COVID-19. Eur Respir J, 2020, 55(6): 2001227