Myocardial injury and related mortality in hospitalized patients with COVID-19 during the Omicron pandemic: new perspectives and insights

Wu He; Ke Xu; Li Ni; Junfang Wu; Yuxuan Zhang; Kun Miao; Luyun Wang; Dao Wen Wang

doi:10.1016/j.virs.2023.10.005

December 2023

. doi: 10.1016/j.virs.2023.10.005

Citation: Wu He, Ke Xu, Li Ni, Junfang Wu, Yuxuan Zhang, Kun Miao, Luyun Wang, Dao Wen Wang. Myocardial injury and related mortality in hospitalized patients with COVID-19 during the Omicron pandemic: new perspectives and insights .VIROLOGICA SINICA, 2023, 38(6) : 940-950. http://dx.doi.org/10.1016/j.virs.2023.10.005

Omicron大流行期间COVID-19住院患者的心肌损伤和死亡率：新的角度和见解

何武 ^a,b ,
徐克 ^a,b ,
倪黎 ^a,b ,
吴俊芳 ^a,b ,
章禹轩 ^a,b ,
苗琨 ^a,b ,
汪璐芸 ^a,b ,
汪道文 ^a,b,,

a. 华中科技大学同济医学院附属同济医院心血管内科, 湖北武汉, 430030;
b. 心血管病遗传与分子机制湖北省重点实验室, 湖北武汉, 430030

通讯作者： 汪道文, dwwang@tjh.tjmu.edu.cn
收稿日期： 2023-07-04
录用日期： 2023-10-09

摘要

心肌损伤是新型冠状病毒肺炎（COVID-19）患者最常见且与预后不良相关的临床问题之一。然而，在Omicron毒株流行期间，COVID-19患者的心肌损伤尚未得到充分调查与研究。我们对武汉同济医院确诊的2690例Omicron感染的COVID-19患者进行了回顾性研究。结果表明，心肌损伤组占COVID-19患者的30.8%。在倾向评分匹配（PSM）前后与非心肌损伤组相比，心肌损伤组患者的住院死亡率更高（PSM前调整后的危险比[HR]为10.61，95%置信区间[CI]为7.76–14.51，P<0.001；PSM后调整后的HR为2.70，95%置信区间为1.86–3.93，P<0.001）。此外，心肌损伤组患者的细胞因子（IL-1β、IL-6、IL-10和TNF-α）水平高于非心肌损伤组，并且心肌损伤组较高的细胞因子水平与死亡率增加相关。对COVID-19患者的分析表明，在心肌损伤组使用ACEI/ARB可显著降低新冠肺炎患者的死亡率（调整后的HR为0.52，95% CI为0.38–0.71，P<0.001）。此外，Omicron感染患者血管紧张素II水平升高，且在心肌损伤组更高。总而言之，本研究表明在Omicron大流行期间合并心肌损伤的COVID-19患者所占比例和死亡率均较高高，而心肌损伤与心肌炎症具有一定的相关性。
- COVID-19
- , Omicron
- , 心肌损伤
- , 住院死亡率
- , 细胞因子风暴

Myocardial injury and related mortality in hospitalized patients with COVID-19 during the Omicron pandemic: new perspectives and insights

Wu He ^a,b ,
Ke Xu ^a,b ,
Li Ni ^a,b ,
Junfang Wu ^a,b ,
Yuxuan Zhang ^a,b ,
Kun Miao ^a,b ,
Luyun Wang ^a,b ,
Dao Wen Wang ^a,b,,

a. Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China;
b. Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, 430030, China

Corresponding author: Dao Wen Wang, dwwang@tjh.tjmu.edu.cn
Received Date: 04 July 2023
Accepted Date: 09 October 2023

Abstract

Myocardial injury is one of the most common comorbidity in SARS-CoV-2 infected patients, and has poor prognosis. However, the incidence of myocardial injury in patients with SARS-CoV-2 infection has not been sufficiently investigated during the Omicron wave. We conducted a retrospective study of 2690 patients with confirmed SARS-CoV-2 Omicron infection from Tongji Hospital. The results indicated that the myocardial injury accounted for 30.8% of the total patients with SARS-CoV-2 infection and was associated with higher in-hospital mortality than those without injury before and after propensity score matching (PSM) [adjusted hazard ratio (HR), 10.61; 95% confidence interval (CI), 7.76–14.51; P < 0.001; adjusted HR, 2.70; 95% CI, 1.86–3.93; P < 0.001; respectively]. Further, the levels of cytokines (IL-1β, IL-6, IL-10, and TNF-α) in patients with myocardial injury were higher than those without injury, and the higher levels of cytokines in the myocardial injury group were associated with increased mortality. Administration of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) could significantly reduce the mortality in patients with myocardial injury (adjusted HR, 0.52; 95% CI, 0.38–0.71; P < 0.001). Additionally, the level of angiotensin II increased in patients with SARS-CoV-2 infection was even higher in myocardial injury group compared to those without injury. Collectively, the study summarized the clinical characteristic and outcome of SARS-CoV-2 infected patients with myocardial injury during the Omicron wave in China, and validated the protective role of ACEI/ARB in improving the survival of those with myocardial injury.
- COVID-19
- , Omicron
- , Myocardial injury
- , In-hospital mortality
- , Cytokine storm

References
1. Ababneh MJ, Al-Kasasbeh A, Jarrah M, Malkawi L, Sanduka O, Smadi AM, Smadi MM. 2022. Myocardial injury and its correlation to mortality in hospitalized covid-19 patients: A retrospective cohort study. Front Cardiovasc Med, 9: 1039655.
2. Ammirati E, Wang DW. 2020. Sars-cov-2 inflames the heart. The importance of awareness of myocardial injury in covid-19 patients. Int J Cardiol, 311: 122-123.
3. Artico J, Shiwani H, Moon JC, Gorecka M, McCann GP, Roditi G, Morrow A, Mangion K, Lukaschuk E, Shanmuganathan M, Miller CA, Chiribiri A, Prasad SK, Adam RD, Singh T, Bucciarelli-Ducci C, Dawson D, Knight D, Fontana M, Manisty C, Treibel TA, Levelt E, Arnold R, Macfarlane PW, Young R, McConnachie A, Neubauer S, Piechnik SK, Davies RH, Ferreira VM, Dweck MR, Berry C, Greenwood JP. 2023. Myocardial involvement after hospitalization for covid-19 complicated by troponin elevation: A prospective, multicenter, observational study. Circulation, 147: 364-374.
4. Bonow RO, Fonarow GC, O'Gara PT, Yancy CW. 2020. Association of coronavirus disease 2019 (covid-19) with myocardial injury and mortality. JAMA Cardiol, 5: 751-753.
5. Cao Z, Gao W, Bao H, Feng H, Mei S, Chen P, Gao Y, Cui Z, Zhang Q, Meng X, Gui H, Wang W, Jiang Y, Song Z, Shi Y, Sun J, Zhang Y, Xie Q, Xu Y, Ning G, Gao Y, Zhao R. 2023. Vv116 versus nirmatrelvir-ritonavir for oral treatment of covid-19. N Engl J Med, 388: 406-417.
6. Case BC, Shea C, Rappaport H, Cellamare M, Zhang C, Zhu M, Medranda GA, Satler LF, Ben-Dor I, Hashim H, Rogers T, Waksman R. 2023. The evolving impact of myocardial injury in patients with covid-19 amid the omicron wave of the pandemic. Am J Cardiol, 190: 54-60.
7. Castiello T, Georgiopoulos G, Finocchiaro G, Claudia M, Gianatti A, Delialis D, Aimo A, Prasad S. 2022. Covid-19 and myocarditis: A systematic review and overview of current challenges. Heart Fail Rev, 27: 251-261.
8. Chen C, Li H, Hang W, Wang DW. 2020. Cardiac injuries in coronavirus disease 2019 (covid-19). J Mol Cell Cardiol, 145: 25-29.
9. Chen F, Cheng Z, Peng Y, Wang Z, Huang C, Liu D, Wang B, Pan B, Guo W. 2021. A liquid chromatography-tandem mass spectrometry (lc-ms/ms)-based assay for simultaneous quantification of aldosterone, renin activity, and angiotensin ii in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci, 1179: 122740.
10. Chung MK, Zidar DA, Bristow MR, Cameron SJ, Chan T, Harding CV, 3rd, Kwon DH, Singh T, Tilton JC, Tsai EJ, Tucker NR, Barnard J, Loscalzo J. 2021. Covid-19 and cardiovascular disease: From bench to bedside. Circ Res, 128: 1214-1236.
11. Del Rio C, Omer SB, Malani PN. 2022. Winter of omicron-the evolving covid-19 pandemic. Jama, 327: 319-320.
12. Faust JS, Du C, Liang C, Mayes KD, Renton B, Panthagani K, Krumholz HM. 2022. Excess mortality in massachusetts during the delta and omicron waves of covid-19. Jama, 328: 74-76.
13. Ferreira VM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechtem U, Kindermann I, Gutberlet M, Cooper LT, Liu P, Friedrich MG. 2018. Cardiovascular magnetic resonance in nonischemic myocardial inflammation: Expert recommendations. J Am Coll Cardiol, 72: 3158-3176.
14. Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, Wang H, Wan J, Wang X, Lu Z. 2020. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (covid-19). JAMA Cardiol, 5: 811-818.
15. Hanson PJ, Liu-Fei F, Ng C, Minato TA, Lai C, Hossain AR, Chan R, Grewal B, Singhera G, Rai H, Hirota J, Anderson DR, Radio SJ, McManus BM. 2022. Characterization of covid-19-associated cardiac injury: Evidence for a multifactorial disease in an autopsy cohort. Lab Invest, 102: 814-825.
16. Hartmann C, Miggiolaro A, Motta JDS, Baena Carstens L, Busatta Vaz De Paula C, Fagundes Grobe S, Hermann de Souza Nunes L, Lenci Marques G, Libby P, Zytynski Moura L, de Noronha L, Pellegrino Baena C. 2021. The pathogenesis of covid-19 myocardial injury: An immunohistochemical study of postmortem biopsies. Front Immunol, 12: 748417.
17. Henning RJ. 2022. Cardiovascular complications of covid-19 severe acute respiratory syndrome. Am J Cardiovasc Dis, 12: 170-191.
18. Iuliano AD, Brunkard JM, Boehmer TK, Peterson E, Adjei S, Binder AM, Cobb S, Graff P, Hidalgo P, Panaggio MJ, Rainey JJ, Rao P, Soetebier K, Wacaster S, Ai C, Gupta V, Molinari NM, Ritchey MD. 2022. Trends in disease severity and health care utilization during the early omicron variant period compared with previous sars-cov-2 high transmission periods - united states, december 2020-january 2022. MMWR Morb Mortal Wkly Rep, 71: 146-152.
19. Jansson S, Blixt PJ, Didriksson H, Jonsson C, Andersson H, Hedström C, Engvall J, Aneq M, Chew MS. 2022. Incidence of acute myocardial injury and its association with left and right ventricular systolic dysfunction in critically ill covid-19 patients. Ann Intensive Care, 12: 56.
20. Koc HC, Xiao J, Liu W, Li Y, Chen G. 2022. Long covid and its management. Int J Biol Sci, 18: 4768-4780.
21. Kotecha T, Knight DS, Razvi Y, Kumar K, Vimalesvaran K, Thornton G, Patel R, Chacko L, Brown JT, Coyle C, Leith D, Shetye A, Ariff B, Bell R, Captur G, Coleman M, Goldring J, Gopalan D, Heightman M, Hillman T, Howard L, Jacobs M, Jeetley PS, Kanagaratnam P, Kon OM, Lamb LE, Manisty CH, Mathurdas P, Mayet J, Negus R, Patel N, Pierce I, Russell G, Wolff A, Xue H, Kellman P, Moon JC, Treibel TA, Cole GD, Fontana M. 2021. Patterns of myocardial injury in recovered troponin-positive covid-19 patients assessed by cardiovascular magnetic resonance. Eur Heart J, 42: 1866-1878.
22. Kundura L, Gimenez S, Cezar R, André S, Younas M, Lin YL, Portalès P, Lozano C, Boulle C, Reynes J, Vincent T, Mettling C, Pasero P, Muller L, Lefrant JY, Roger C, Claret PG, Duvnjak S, Loubet P, Sotto A, Tran TA, Estaquier J, Corbeau P. 2022. Angiotensin ii induces reactive oxygen species, DNA damage, and t-cell apoptosis in severe covid-19. J Allergy Clin Immunol, 150: 594-603.e592.
23. Leng L, Ma J, Zhang PP, Xu SC, Li X, Jin Y, Cai J, Tang R, Zhao L, He ZC, Li MS, Zhang H, Zhou LR, Wu ZH, Li TR, Zhu YP, Wang YJ, Wu HB, Ping YF, Yao XH, Zhu CH, Guo HT, Tan LY, Liang ZY, Bian XW, Zhang SY. 2022. Spatial region-resolved proteome map reveals mechanism of covid-19-associated heart injury. Cell Rep, 39: 110955.
24. Li C, Wang DW, Zhao C. 2021. Cardiovascular involvement in patients with 2019 novel coronavirus disease. J Transl Int Med, 9: 152-160.
25. Li C, Jiang J, Wang F, Zhou N, Veronese G, Moslehi JJ, Ammirati E, Wang DW. 2020. Longitudinal correlation of biomarkers of cardiac injury, inflammation, and coagulation to outcome in hospitalized covid-19 patients. J Mol Cell Cardiol, 147: 74-87.
26. Li K, Shi J, Liu X, Ward MP, Wang Z, Liu R, Zhao Z, Yin Y, Liu Y, Hong J, Huang J, Chen X, Zhang Z. 2023. Early warning signals for omicron outbreaks in china: A retrospective study. J Med Virol, 95: e28341.
27. Li M, Wang H, Tian L, Pang Z, Yang Q, Huang T, Fan J, Song L, Tong Y, Fan H. 2022a. Covid-19 vaccine development: Milestones, lessons and prospects. Signal Transduct Target Ther, 7: 146.
28. Li Y, Pei H, Zhou C, Lou Y. 2022b. Myocardial injury predicts risk of short-term all-cause mortality in patients with covid-19: A dose-response meta-analysis. Front Cardiovasc Med, 9: 850447.
29. Lim GB. 2020. Myocardial injury in patients with covid-19. Nat Rev Cardiol, 17: 454.
30. Lin YF, Wu X, Li Y, Bian J, Li K, Jiang Y, Lu Z, Zhang B, Yang C, Sun C, Sun L, Zou H. 2023. Impact of combination preventative interventions on hospitalization and death under the pandemic of sars-cov-2 omicron variant in china. J Med Virol, 95: e28335.
31. Melillo F, Napolano A, Loffi M, Regazzoni V, Boccellino A, Danzi GB, Cappelletti AM, Rovere-Querini P, Landoni G, Ingallina G, Stella S, Ancona F, Dagna L, Scarpellini P, Ripa M, Castagna A, Tresoldi M, Zangrillo A, Ciceri F, Agricola E. 2022. Myocardial injury in patients with sars-cov-2 pneumonia: Pivotal role of inflammation in covid-19. Eur J Clin Invest, 52: e13703.
32. Metkus TS, Sokoll LJ, Barth AS, Czarny MJ, Hays AG, Lowenstein CJ, Michos ED, Nolley EP, Post WS, Resar JR, Thiemann DR, Trost JC, Hasan RK. 2021. Myocardial injury in severe covid-19 compared with non-covid-19 acute respiratory distress syndrome. Circulation, 143: 553-565.
33. Nishiga M, Wang DW, Han Y, Lewis DB, Wu JC. 2020. Covid-19 and cardiovascular disease: From basic mechanisms to clinical perspectives. Nat Rev Cardiol, 17: 543-558.
34. Siripanthong B, Asatryan B, Hanff TC, Chatha SR, Khanji MY, Ricci F, Muser D, Ferrari VA, Nazarian S, Santangeli P, Deo R, Cooper LT, Jr., Mohiddin SA, Chahal CAA. 2022. The pathogenesis and long-term consequences of covid-19 cardiac injury. JACC Basic Transl Sci, 7: 294-308.
35. Stuber M, Baggish AL. 2023. Acute myocardial injury in the covid-heart study: Emphasizing scars while reassuring scares. Circulation, 147: 375-377.
36. Tajbakhsh A, Gheibi Hayat SM, Taghizadeh H, Akbari A, Inabadi M, Savardashtaki A, Johnston TP, Sahebkar A. 2021. Covid-19 and cardiac injury: Clinical manifestations, biomarkers, mechanisms, diagnosis, treatment, and follow up. Expert Rev Anti Infect Ther, 19: 345-357.
37. Telenti A, Arvin A, Corey L, Corti D, Diamond MS, García-Sastre A, Garry RF, Holmes EC, Pang PS, Virgin HW. 2021. After the pandemic: Perspectives on the future trajectory of covid-19. Nature, 596: 495-504.
38. Wadhera RK, Figueroa JF, Rodriguez F, Liu M, Tian W, Kazi DS, Song Y, Yeh RW, Joynt Maddox KE. 2021. Racial and ethnic disparities in heart and cerebrovascular disease deaths during the covid-19 pandemic in the united states. Circulation, 143: 2346-2354.
39. Wang JJ, Edin ML, Zeldin DC, Li C, Wang DW, Chen C. 2020a. Good or bad: Application of raas inhibitors in covid-19 patients with cardiovascular comorbidities. Pharmacol Ther, 215: 107628.
40. Wang K, Gheblawi M, Nikhanj A, Munan M, MacIntyre E, O'Neil C, Poglitsch M, Colombo D, Del Nonno F, Kassiri Z, Sligl W, Oudit GY. 2022. Dysregulation of ace (angiotensin-converting enzyme)-2 and renin-angiotensin peptides in sars-cov-2 mediated mortality and end-organ injuries. Hypertension, 79: 365-378.
41. Wang M, Liu Z, Wang Z, Li K, Tian Y, Lu W, Hong J, Peng X, Shi J, Zhang Z, Mei G. 2023. Clinical characteristics of 1139 mild cases of the sars-cov-2 omicron variant infected patients in shanghai. J Med Virol, 95: e28224.
42. Wang T, Du Z, Zhu F, Cao Z, An Y, Gao Y, Jiang B. 2020b. Comorbidities and multi-organ injuries in the treatment of covid-19. Lancet, 395: e52.
43. Wolfler A, Mannarino S, Giacomet V, Camporesi A, Zuccotti G. 2020. Acute myocardial injury: A novel clinical pattern in children with covid-19. Lancet Child Adolesc Health, 4: e26-e27.
44. Yeo YH, Wang M, He X, Lv F, Zhang Y, Zu J, Li M, Jiao Y, Ebinger JE, Patel JK, Cheng S, Ji F. 2023. Excess risk for acute myocardial infarction mortality during the covid-19 pandemic. J Med Virol, 95: e28187.
45. Zhang P, Zhu L, Cai J, Lei F, Qin JJ, Xie J, Liu YM, Zhao YC, Huang X, Lin L, Xia M, Chen MM, Cheng X, Zhang X, Guo D, Peng Y, Ji YX, Chen J, She ZG, Wang Y, Xu Q, Tan R, Wang H, Lin J, Luo P, Fu S, Cai H, Ye P, Xiao B, Mao W, Liu L, Yan Y, Liu M, Chen M, Zhang XJ, Wang X, Touyz RM, Xia J, Zhang BH, Huang X, Yuan Y, Loomba R, Liu PP, Li H. 2020. Association of inpatient use of angiotensin-converting enzyme inhibitors and angiotensin ii receptor blockers with mortality among patients with hypertension hospitalized with covid-19. Circ Res, 126: 1671-1681.
Proportional views
Electronic Supplementary Material

10.1016j.virs.2023.10.005-ESM.docx