Long COVID, Non-COVID19 Excess Deaths, and Post-Pandemic Cardiovascular Disease Risks: Mechanistic Links and Intervention Opportunities Mechanistic Links and Intervention Opportunities
Main Article Content
Abstract
Persistent non-COVID19 excess mortality is a major post-pandemic health crisis without clear explanation. In current review, the hypothesis of Long COVID’s causal link to the non-COVID19 excess mortality was studied by applying time-lag correlation analysis between the excess death with COVID19 and the excess death without COVID19 in Australia between Jan 2020 and Mar 2023, which revealed a remarkable correlation that coincided with the disease severity of the corresponding variants including Delta, Omicron BA.1-BA.3, and Omicron BA.4-BA.5 waves. Based on the correlating epidemiological findings, known immunity-mediated pathologies of Long COVID such as endothelial damage, thrombosis, and bleeding were explored in contemplating acute coronary syndrome as a precipitating mechanism of the non-COVID19 excess death. The identified mechanistic linkage of non-COVID19 excess mortality to Long COVID paves ways for its countermeasures. Additional measures of using nasal hygiene products to curb the airborne infection risks, reserved physical exercise in the months after the recovery of COVID19, closer management of cardiovascular diseases (CVD) and diabetic risk factors, and root-level Long COVID treatments tailored to treating the dysfunctional immunity around macrophages and neutrophils are proposed to reduce the non-COVID19 excess deaths.
Keywords:
COVID19, excess mortality, excess death, CVD, cardiovascular diseases, hypertension, blood pressure, hypercholesterolemia, dyslipidemia, cholesterol, microvascular rarefaction, SARS-CoV-2, blood clots, thrombosis, neutrophils, macrophage, immunity, immune dysfunction, Long COVID, acute coronary syndrome, ACS
Article Details
How to Cite
CHUNG, Jinhyuk Fred.
Long COVID, Non-COVID19 Excess Deaths, and Post-Pandemic Cardiovascular Disease Risks: Mechanistic Links and Intervention Opportunities.
Medical Research Archives, [S.l.], v. 11, n. 9, sep. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4454>. Date accessed: 21 nov. 2024.
doi: https://doi.org/10.18103/mra.v11i9.4454.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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12. Ward IL, Bermingham C, Ayoubkhani D, et al. Risk of covid-19 related deaths for SARS-CoV-2 omicron (B.1.1.529) compared with delta (B.1.617.2): retrospective cohort study. Bmj. 2022;378:e070695. doi:10.1136/bmj-2022-070695
13. Robertson C, Kerr S, Sheikh A. Severity of Omicron BA.5 variant and protective effect of vaccination: national cohort and matched analyses in Scotland. The Lancet Regional Health – Europe. 2023;28doi:10.1016/j.lanepe.2023.100638
14. Loyer C, Lapostolle A, Urbina T, et al. Impairment of neutrophil functions and homeostasis in COVID-19 patients: association with disease severity. Critical Care. 2022/05/30 2022;26(1):155. doi:10.1186/s13054-022-04002-3
15. George PM, Reed A, Desai SR, et al. A persistent neutrophil-associated immune signature characterizes post–COVID-19 pulmonary sequelae. Science translational medicine. 2022;14(671):eabo5795. doi:10.1126/scitranslmed.abo5795
16. Wu Y, Wei S, Wu X, Li Y, Han X. Neutrophil extracellular traps in acute coronary syndrome. Journal of Inflammation. 2023/05/10 2023;20(1):17.
doi:10.1186/s12950-023-00344-z
17. Giannis D, Ziogas IA, Gianni P. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol. Jun 2020;127:104362. doi:10.1016/j.jcv.2020.104362
18. Singh R, Bajpai M, Yadav P, et al. Sustained expression of inflammatory monocytes and activated T cells in COVID-19 patients and recovered convalescent plasma donors. medRxiv. 2020:2020.11.17.20233668. doi:10.1101/2020.11.17.20233668
19. Zhang D, Guo R, Lei L, et al. COVID-19 infection induces readily detectable morphologic and inflammation-related phenotypic changes in peripheral blood monocytes. Journal of leukocyte biology. Oct 11 2020; doi:10.1002/JLB.4HI0720-470R
20. MacDonald L, Alivernini S, Tolusso B, et al. COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes. JCI Insight. 07/08/ 2021;6(13)doi:10.1172/jci.insight.147413
21. Basso C, Leone O, Rizzo S, et al. Pathological features of COVID-19-associated myocardial injury: a multicentre cardiovascular pathology study. European heart journal. 2020;41(39):3827-3835. doi:10.1093/eurheartj/ehaa664
22. Hennon TR, Penque MD, Abdul-Aziz R, et al. COVID-19 associated Multisystem Inflammatory Syndrome in Children (MIS-C) guidelines; a Western New York approach. Prog Pediatr Cardiol. 2020:101232-101232. doi:10.1016/j.ppedcard.2020.101232
23. Worku D. Multisystem Inflammatory Syndrome in Adults (MIS-A) and SARS-CoV2: An Evolving Relationship. BioMed. 2023;3(1):195-201.
24. Theobald SJ, Simonis A, Georgomanolis T, et al. Long-lived macrophage reprogramming drives spike protein-mediated inflammasome activation in COVID-19. EMBO Molecular Medicine. 2021;n/a(n/a):e14150. doi:https://doi.org/10.15252/emmm.202114150
25. Osiaevi I, Schulze A, Evers G, et al. Persistent capillary rarefication in long COVID syndrome. Angiogenesis. 2023/02/01 2023;26(1):53-61. doi:10.1007/s10456-022-09850-9
26. Mulligan CB, Arnott RD. The Young were not Spared: What Death Certificates Reveal about Non-Covid Excess Deaths. INQUIRY: The Journal of Health Care Organization, Provision, and Financing. 2022;59:00469580221139016. doi:10.1177/00469580221139016
27. Han L, Zhao S, Li S, et al. Excess cardiovascular mortality across multiple COVID-19 waves in the United States from March 2020 to March 2022. Nature Cardiovascular Research. 2023/03/01 2023;2(3):322-333. doi:10.1038/s44161-023-00220-2
28. Chen B, Julg B, Mohandas S, Bradfute SB, Force RMPT. Viral persistence, reactivation, and mechanisms of long COVID. eLife. 2023/05/04 2023;12:e86015. doi:10.7554/eLife.86015
29. Yonker LM, Swank Z, Bartsch YC, et al. Circulating Spike Protein Detected in Post–COVID-19 mRNA Vaccine Myocarditis. Circulation. 2023;147(11):867-876. doi:doi:10.1161/CIRCULATIONAHA.122.061025
30. Shimizu J, Sasaki T, Koketsu R, et al. Reevaluation of antibody-dependent enhancement of infection in anti-SARS-CoV-2 therapeutic antibodies and mRNA-vaccine antisera using FcR- and ACE2-positive cells. Scientific reports. 2022/09/16 2022;12(1):15612. doi:10.1038/s41598-022-19993-w
31. Cao Y, Yisimayi A, Jian F, et al. BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. Nature. 2022/08/01 2022;608(7923):593-602. doi:10.1038/s41586-022-04980-y
32. Döring Y, Soehnlein O, Weber C. Neutrophil Extracellular Traps in Atherosclerosis and Atherothrombosis. Circulation research. 2017;120(4):736-743. doi:doi:10.1161/CIRCRESAHA.116.309692
33. Bobryshev YV, Ivanova EA, Chistiakov DA, Nikiforov NG, Orekhov AN. Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis. Biomed Res Int. 2016;2016:9582430. doi:10.1155/2016/9582430
34. Mosorin M, Surcel HM, Laurila A, et al. Detection of Chlamydia pneumoniae-reactive T lymphocytes in human atherosclerotic plaques of carotid artery. Arteriosclerosis, thrombosis, and vascular biology. Apr 2000;20(4):1061-7. doi:10.1161/01.atv.20.4.1061
35. Baptista de Barros Ribeiro Dourado LP, Santos M, Moreira-Gonçalves D. Nets, pulmonary arterial hypertension, and thrombo-inflammation. Journal of molecular medicine. May 2022;100(5):713-722. doi:10.1007/s00109-022-02197-0
36. Justin Rucker A, Crowley SD. The role of macrophages in hypertension and its complications. Pflugers Archiv : European journal of physiology. Apr 2017;469(3-4):419-430. doi:10.1007/s00424-017-1950-x
37. Zhang J, Crowley SD. Role of T lymphocytes in hypertension. Curr Opin Pharmacol. Apr 2015;21:14-9. doi:10.1016/j.coph.2014.12.003
38. Martinod K, Wagner DD. Thrombosis: tangled up in NETs. Blood. May 1 2014;123(18):2768-76. doi:10.1182/blood-2013-10-463646
39. Mallat Z. Macrophages. Arteriosclerosis, thrombosis, and vascular biology. 2017;37(8):e92-e98. doi:doi:10.1161/ATVBAHA.117.309730
40. Shahneh F, Grill A, Klein M, et al. Specialized regulatory T cells control venous blood clot resolution through SPARC. Blood. Mar 18 2021;137(11):1517-1526. doi:10.1182/blood.2020005407
41. Shi Z, Jiang Y, Weir-McCall J, Wang X, Teng Z. COVID-19 and atherosclerosis: looking beyond the acute crisis. Emergency and Critical Care Medicine. 2022;2(1):1-4. doi:10.1097/ec9.0000000000000031
42. Delalić Đ, Jug J, Prkačin I. ARTERIAL HYPERTENSION FOLLOWING COVID-19: A RETROSPECTIVE STUDY OF PATIENTS IN A CENTRAL EUROPEAN TERTIARY CARE CENTER. Acta Clin Croat. Jun 2022;61(Suppl 1):23-27. doi:10.20471/acc.2022.61.s1.03
43. Katsoularis I, Fonseca-Rodríguez O, Farrington P, et al. Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study. Bmj. 2022;377:e069590. doi:10.1136/bmj-2021-069590
44. Xu E, Xie Y, Al-Aly Z. Risks and burdens of incident dyslipidaemia in long COVID: a cohort study. Lancet Diabetes Endocrinol. Feb 2023;11(2):120-128. doi:10.1016/s2213-8587(22)00355-2
45. Rizvi AA, Kathuria A, Al Mahmeed W, et al. Post-COVID syndrome, inflammation, and diabetes. J Diabetes Complications. Nov 2022;36(11):108336. doi:10.1016/j.jdiacomp.2022.108336
46. Bowe B, Xie Y, Al-Aly Z. Acute and postacute sequelae associated with SARS-CoV-2 reinfection. Nature medicine. 2022/11/01 2022;28(11):2398-2405. doi:10.1038/s41591-022-02051-3
47. Utrero-Rico A, Ruiz-Ruigómez M, Laguna-Goya R, et al. A Short Corticosteroid Course Reduces Symptoms and Immunological Alterations Underlying Long-COVID. Biomedicines. Oct 26 2021;9(11) doi:10.3390/biomedicines9111540
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