The Impact of Long COVID on Cardiovascular System: Clinical Manifestations, Mechanisms, and Principles of Diagnosis and Treatment

doi:10.12114/j.issn.1007-9572.2024.0058

Abstract

Abstract:

The outbreak of COVID-19 has had a huge impact globally. After the infection, a considerable number of patients have been affected by a series of lingering symptoms or sequelae with strong heterogeneity, which we temporarily refer to as long COVID. Compared to the well-studied cardiovascular complications caused by COVID-19 during the acute phase, the cardiovascular sequelae in long COVID require greater attention. This review includes the clinical manifestations, mechanisms, and principles of diagnosis and management of cardiovascular sequelae in long COVID, aiming to improve the disease's understanding and reduce its harm scientifically.

Key words: COVID-19, Long COVID, Cardiovascular diseases, Review

摘要：

新型冠状病毒感染传播在全球造成了巨大的影响。在急性期感染结束后，有相当一部分感染者受到了后遗症的影响，目前暂将这一组涉及症状广泛、异质性强的临床症候群称为长新冠综合征。新型冠状病毒感染急性期相关的心血管并发症因其严重性已受到学界广泛的关注，但急性期感染结束后的心血管受累情况亟需被重视。本文就长新冠综合征心血管系统的常见临床表现、发生机制和诊治原则进行综述，意在提高人们对于长新冠综合征心血管系统并发症的认识，从而更加科学合理地应对和降低疾病带来的危害。

关键词: 新型冠状病毒感染, 长新冠综合征, 心血管疾病, 综述

CLC Number:

R 563.12

ZHONG Minshan,SUN Wei,KONG Xiangqing. The Impact of Long COVID on Cardiovascular System: Clinical Manifestations, Mechanisms, and Principles of Diagnosis and Treatment[J]. Chinese General Practice, 2024, 27(27): 3325-3330. DOI: 10.12114/j.issn.1007-9572.2024.0058.
钟旻珊,孙伟,孔祥清. 长新冠综合征对心血管系统的影响：临床表现、机制与诊治原则[J]. 中国全科医学, 2024, 27(27): 3325-3330. DOI: 10.12114/j.issn.1007-9572.2024.0058.

References 54

[1]	World Health Organization. WHO COVID-19 dashboard[EB/OL]. （2024-02-04）[2024-02-18].
[2]	World Health Organization Europe. Post COVID-19 condition （Long COVID）[EB/OL]. （2022-12-07）[2024-02-18].
[3]	CDC. Post-COVID Conditions[EB/OL]//U.S. Centers for Disease Control and Prevention. （2023-07-20）[2024-02-18].
[4]	The U.S. Department of Health and Human Services. LONG COVID TERMS&DEFINITIONS[EB/OL]//LONG COVID TERMS&DEFINITIONS. （2024-03-26）[2024-04-11].
[5]	National Institute for Health and Care Excellence，Royal College of General Practitioners，Scottish Intercollegiate Guidelines Network. COVID-19 rapid guideline：managing the long-term effects of COVID-19[Z/OL]. （2024-01-25）[2024-02-18].
[6]	U.S. Department of Health and Human Services，Office of the Assistant Secretary for Health. National Research Action Plan on Long COVID[A/OL]. [2024-02-18].
[7]	栾涛，杨罡，王帅颖，等. "长新冠"综合征研究最新进展[J]. 实用医学杂志，2023，39（10）：1195-1200. DOI：10.3969/j.issn.1006-5725.2023.10.001.
[8]	GUO T，FAN Y Z，CHEN M，et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 （COVID-19）[J]. JAMA Cardiol，2020，5（7）：811-818. DOI：10.1001/jamacardio.2020.1017.
[9]	COMMITTEE W，GLUCKMAN T J，BHAVE N M，et al. 2022 ACC expert consensus decision pathway on cardiovascular sequelae of COVID-19 in adults：myocarditis and other myocardial involvement，post-acute sequelae of SARS-CoV-2 infection，and return to play：a report of the American college of cardiology solution set oversight committee[J]. J Am Coll Cardiol，2022，79（17）：1717-1756. DOI：10.1016/j.jacc.2022.02.003.
[10]	DAVIS H，ASSAF G，MCCORKELL L，et al. Characterizing Long COVID in an International Cohort：7 Months of Symptoms and Their Impact （preprint）[J/OL]. [2024-02-18].
[11]	HUANG L X，YAO Q，GU X Y，et al. 1-year outcomes in hospital survivors with COVID-19：a longitudinal cohort study[J]. Lancet，2021，398（10302）：747-758. DOI：10.1016/S0140-6736(21)01755-4.
[12]	HUANG L，ZHAO P J，TANG D Z，et al. Cardiac involvement in patients recovered from COVID-2019 identified using magnetic resonance imaging[J]. JACC Cardiovasc Imaging，2020，13（11）：2330-2339. DOI：10.1016/j.jcmg.2020.05.004.
[13]	PUNTMANN V O，CARERJ M L，WIETERS I，et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 （COVID-19）[J]. JAMA Cardiol，2020，5（11）：1265-1273. DOI：10.1001/jamacardio.2020.3557.
[14]	LAI Y J，LIU S H，MANACHEVAKUL S，et al. Biomarkers in long COVID-19：a systematic review[J]. Front Med，2023，10：1085988. DOI：10.3389/fmed.2023.1085988.
[15]	GRÜN S，SCHUMM J，GREULICH S，et al. Long-term follow-up of biopsy-proven viral myocarditis[J]. JACC，2012，59（18）：1604-1615. DOI：10.1016/j.jacc.2012.01.007.
[16]	GULATI A，JABBOUR A，ISMAIL T F，et al. Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy[J]. JAMA，2013，309（9）：896-908. DOI：10.1001/jama.2013.1363.
[17]	PUNTMANN V O，CARR-WHITE G，JABBOUR A，et al. T1-mapping and outcome in nonischemic cardiomyopathy：all-cause mortality and heart failure[J]. JACC Cardiovasc Imaging，2016，9（1）：40-50. DOI：10.1016/j.jcmg.2015.12.001.
[18]	PUNTMANN V O，CARR-WHITE G，JABBOUR A，et al. Native T1 and ECV of noninfarcted myocardium and outcome in patients with coronary artery disease[J]. J Am Coll Cardiol，2018，71（7）：766-778. DOI：10.1016/j.jacc.2017.12.020.
[19]	VISCO V，VITALE C，RISPOLI A，et al. Post-COVID-19 syndrome：involvement and interactions between respiratory，cardiovascular and nervous systems[J]. J Clin Med，2022，11（3）：524. DOI：10.3390/jcm11030524.
[20]	DAVIS H E，MCCORKELL L，VOGEL J M，et al. Long COVID：major findings，mechanisms and recommendations[J]. Nat Rev Microbiol，2023，21（3）：133-146. DOI：10.1038/s41579-022-00846-2.
[21]	SANTORO F，NÚÑEZ-GIL I J，VIANA-LLAMAS M C，et al. Risk prediction of major cardiac adverse events and all-cause death following covid-19 hospitalization at one year follow-up：the HOPE-2 score[J]. Eur J Intern Med，2024：S0953-S6205（24）00096-7. DOI：10.1016/j.ejim.2024.03.002.
[22]	LAM I C H，ZHANG R，MAN K K C，et al. Persistence in risk and effect of COVID-19 vaccination on long-term health consequences after SARS-CoV-2 infection[J]. Nat Commun，2024，15（1）：1716. DOI：10.1038/s41467-024-45953-1.
[23]	TSAMPASIAN V，BÄCK M，BERNARDI M，et al. Cardiovascular disease as part of Long COVID：a systematic review[J]. Eur J Prev Cardiol，2024：zwae070. DOI：10.1093/eurjpc/zwae070.
[24]	BLOMBERG B，MOHN K G I，BROKSTAD K A，et al. Long COVID in a prospective cohort of home-isolated patients[J]. Nat Med，2021，27（9）：1607-1613. DOI：10.1038/s41591-021-01433-3.
[25]	MUNBLIT D，BOBKOVA P，SPIRIDONOVA E，et al. Incidence and risk factors for persistent symptoms in adults previously hospitalized for COVID-19[J]. Clin Exp Allergy，2021，51（9）：1107-1120. DOI：10.1111/cea.13997.
[26]	OGUNGBE O，GILOTRA N A，DAVIDSON P M，et al. Cardiac postacute sequelae symptoms of SARS-CoV-2 in community-dwelling adults：cross-sectional study[J]. Open Heart，2022，9（2）：e002084. DOI：10.1136/openhrt-2022-002084.
[27]	GARG M，MARALAKUNTE M，GARG S，et al. The conundrum of long-COVID-19：a narrative review[J]. Int J Gen Med，2021，14：2491-2506. DOI：10.2147/IJGM.S316708.
[28]	LINDNER D，FITZEK A，BRÄUNINGER H，et al. Association of cardiac infection with SARS-CoV-2 in confirmed COVID-19 autopsy cases[J]. JAMA Cardiol，2020，5（11）：1281-1285. DOI：10.1001/jamacardio.2020.3551.
[29]	SWANK Z，SENUSSI Y，MANICKAS-HILL Z，et al. Persistent circulating severe acute respiratory syndrome coronavirus 2 spike is associated with post-acute coronavirus disease 2019 sequelae[J]. Clin Infect Dis，2023，76（3）：e487-490. DOI：10.1093/cid/ciac722.
[30]	LONG Q X，TANG X J，SHI Q L，et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections[J]. Nat Med，2020，26（8）：1200-1204. DOI：10.1038/s41591-020-0965-6.
[31]	LARSEN N W，STILES L E，SHAIK R，et al. Characterization of autonomic symptom burden in long COVID：a global survey of 2 314 adults[J]. Front Neurol，2022，13：1012668. DOI：10.3389/fneur.2022.1012668.
[32]	GARLAND E M，GAMBOA A，NWAZUE V C，et al. Effect of high dietary sodium intake in patients with postural tachycardia syndrome[J]. J Am Coll Cardiol，2021，77（17）：2174-2184. DOI：10.1016/j.jacc.2021.03.005.
[33]	RAJ S R，BOURNE K M，STILES L E，et al. Postural orthostatic tachycardia syndrome（POTS）：priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting - Part 2[J]. Auton Neurosci，2021，235：102836. DOI：10.1016/j.autneu.2021.102836.
[34]	EL-MEDANY A，ADAMS Z H，BLYTHE H C，et al. Carotid body dysregulation contributes to Long COVID symptoms[J]. Commun Med，2024，4（1）：20. DOI：10.1038/s43856-024-00447-5.
[35]	LATARO R M，MORAES D J A，GAVA F N，et al. P2X3 receptor antagonism attenuates the progression of heart failure[J]. Nat Commun，2023，14（1）：1725. DOI：10.1038/s41467-023-37077-9.
[36]	LIBBY P，LÜSCHER T. COVID-19 is，in the end，an endothelial disease[J]. Eur Heart J，2020，41（32）：3038-3044. DOI：10.1093/eurheartj/ehaa623.
[37]	宋时旭，郑雅莉，高占成. 长新冠综合征概述[J]. 中国实用内科杂志，2023，43（9）：705-708. DOI：10.19538/j.nk2023090101.
[38]	SCHULTHEIß C，WILLSCHER E，PASCHOLD L，et al. From online data collection to identification of disease mechanisms：the IL-1ß，IL-6 and TNF-α cytokine triad is associated with post-acute sequelae of COVID-19 in a digital research cohort[J]. SSRN Journal，2021. DOI：10.2139/ssrn.3963839.
[39]	SOLLINI M，CICCARELLI M，CECCONI M，et al. Vasculitis changes in COVID-19 survivors with persistent symptoms：an[18F]FDG-PET/CT study[J]. Eur J Nucl Med Mol Imaging，2021，48（5）：1460-1466. DOI：10.1007/s00259-020-05084-3.
[40]	WALLUKAT G，HOHBERGER B，WENZEL K，et al. Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms[J]. J Transl Autoimmun，2021，4：100100. DOI：10.1016/j.jtauto.2021.100100.
[41]	KLEIN J，WOOD J，JAYCOX J R，et al. Distinguishing features of long COVID identified through immune profiling[J]. Nature，2023，623（7985）：139-148. DOI：10.1038/s41586-023-06651-y.
[42]	RAVEENDRAN A V. Long COVID-19：challenges in the diagnosis and proposed diagnostic criteria[J]. Diabetes Metab Syndr，2021，15（1）：145-146. DOI：10.1016/j.dsx.2020.12.025.
[43]	FAGHY M A，TATLER A，CHIDLEY C，et al. The physiologic benefits of optimizing cardiorespiratory fitness and physical activity - From the cell to systems level in a post-pandemic world[J]. Prog Cardiovasc Dis，2024：S0033-0620(24)00028-8. DOI：10.1016/j.pcad.2024.02.006.
[44]	NICE cautions against using graded exercise therapy for patients recovering from covid-19[J]. BMJ，2020，370：m2933. DOI：10.1136/bmj.m2933.
[45]	FAGHY M A，DUNCAN R，HUME E，et al. Developing effective strategies to optimize physical activity and cardiorespiratory fitness in the long Covid population- The need for caution and objective assessment[J]. Prog Cardiovasc Dis，2024：S0033-0620(24)00039-2. DOI：10.1016/j.pcad.2024.03.003.
[46]	BATEMAN L，BESTED A C，BONILLA H F，et al. Myalgic encephalomyelitis/chronic fatigue syndrome：essentials of diagnosis and management[J]. Mayo Clin Proc，2021，96（11）：2861-2878. DOI：10.1016/j.mayocp.2021.07.004.
[47]	FU Q，VANGUNDY T B，SHIBATA S，et al. Exercise training versus propranolol in the treatment of the postural orthostatic tachycardia syndrome[J]. Hypertension，2011，58（2）：167-175. DOI：10.1161/HYPERTENSIONAHA.111.172262.
[48]	RENTSCH C T，BECKMAN J A，TOMLINSON L，et al. Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States：cohort study[J]. BMJ，2021，372：n311. DOI：10.1136/bmj.n311.
[49]	WANG C，YU C，JING H，et al. Long COVID：The Nature of Thrombotic Sequelae Determines the Necessity of Early Anticoagulation[J/OL]. [2024-02-22].
[50]	MEIZLISH M L，GOSHUA G，LIU Y W，et al. Intermediate-dose anticoagulation，aspirin，and in-hospital mortality in COVID-19：a propensity score-matched analysis[J]. Am J Hematol，2021，96（4）：471-479. DOI：10.1002/ajh.26102.
[51]	SANTORO F，NUÑEZ-GIL I J，VITALE E，et al. Antiplatelet therapy and outcome in COVID-19：the Health Outcome Predictive Evaluation Registry[J]. Heart，2022，108（2）：130-136. DOI：10.1136/heartjnl-2021-319552.
[52]	LERMAN A，BURNETT J C Jr，HIGANO S T，et al. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans[J]. Circulation，1998，97（21）：2123-2128. DOI：10.1161/01.cir.97.21.2123.
[53]	The U.S. Department of Health Human Services Office for Civil Rights. Guidance on＂Long COVID＂as a Disability Under the ADA，Section 504，and Section 1557[EB/OL]. （2021-01-26）[2024-02-18].
[54]	World Health Organization Emergency Preparedness （WPE），WHO Headquarters （HQ）. From emergency response to long-term COVID-19 disease management：sustaining gains made during the COVID-19 pandemic（Strategic Preparedness and Response plan for 2023-2025）[Z/OL]. （2023-05-03）[2024-02-22].