Myocarditis and Myocardial Injury in Long COVID Syndrome: A Comprehensive Review of the Literature

Abstract:

The repercussions of coronavirus disease 2019 (COVID-19) have been devastating on a global scale. Long COVID, which affects patients for weeks or even months after their initial infection, is not limited to individuals with severe symptoms and can affect people of all ages. The condition can impact various physiological systems, leading to chronic health conditions and long-term disabilities that present  significant challenges for healthcare systems worldwide.

This review explores the link between long COVID and cardiovascular complications such as myocardial injury and myocarditis. It also highlights the prevalence of these complications and identifies risk factors for their development in long COVID patients.

Myocardial injury occurs due to direct cellular damage and T-cell-mediated cytotoxicity resulting in elevated cardiac biomarkers. Diagnostic techniques like electrocardiogram, troponin level testing, and magnetic resonance imaging can help identify myocarditis, but endomyocardial biopsy is considered the goldstandard diagnostic technique.

Guideline-directed medical therapy is recommended for COVID-19 myocarditis patients for better prognosis while being monitored under comprehensive care management approaches. Therefore, it’s critical to develop effective screening techniques specifically for vulnerable populations while conducting further research that addresses the effects of long COVID on society’s physical health.

Source: Paruchuri S, Farwa U, Jabeen S, et al. (July 25, 2023) Myocarditis and Myocardial Injury in Long COVID Syndrome: A Comprehensive Review of the Literature. Cureus 15(7): e42444. DOI 10.7759/cureus.42444 https://assets.cureus.com/uploads/review_article/pdf/162949/20230725-18887-1iha61y.pdf (Full text as PDF file)

Long COVID and its cardiovascular consequences: What is known?

Abstract:

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high morbidity and mortality and has been a source of substantial challenges for healthcare systems globally. Despite a full recovery, a significant proportion of patients demonstrate a broad spectrum of cardiovascular, pulmonary and neurological symptoms that are believed to be caused by long-term tissue damage and pathological inflammation, which play a vital role in disease development. Microvascular dysfunction also causes significant health problems.

This review aimed to critically appraise the current data on the long-term cardiovascular sequelae of coronavirus disease 2019 (COVID-19), with a primary focus on cardiovascular symptoms such as chest pain, fatigue, palpitations, and breathlessness, and more significant disease entities including myocarditis, pericarditis and postural tachycardia syndrome. Potential risk factors identified in recent studies that contribute towards the development of long COVID are also included alongside a summary of recent advances in diagnostics and putative treatment options.

Source: Składanek JA, Leśkiewicz M, Gumiężna K, Baruś P, Piasecki A, Klimczak-Tomaniak D, Sygitowicz G, Kochman J, Grabowski M, Tomaniak M. Long COVID and its cardiovascular consequences: What is known? Adv Clin Exp Med. 2023 Jun 30. doi: 10.17219/acem/167482. Epub ahead of print. PMID: 37386857. https://advances.umw.edu.pl/en/ahead-of-print/167482/ (Full text)

Cardiac MRI Findings in Patients Clinically Referred for Evaluation of Post-Acute Sequelae of SARS-CoV-2 Infection

Abstract:

Persistent or recurrent cardiovascular symptoms have been identified as one of the hallmarks of long-COVID or post-acute sequelae of SARS-CoV-2 infection (PASC). The purpose of this study was to determine the prevalence and extent of cardiac abnormalities in patients referred for cardiac MRI due to clinical evidence of PASC. To investigate this, two tertiary care hospitals identified all patients who were referred for cardiac MRI under the suspicion of PASC in a 2-year period and retrospectively included them in this study.
Patients with previously known cardiac diseases were excluded. This resulted in a total cohort of 129 patients (63, 51% female; age 41 ± 16 years). The majority of patients (57%) showed normal cardiac results. No patient had active myocarditis or an acute myocardial infarction. However, 30% of patients had evidence of non-ischemic myocardial fibrosis, which exceeds the prevalence in the normal adult population and suggests that a possible history of myocarditis might explain persistent symptoms in the PASC setting.
Source: Halfmann MC, Luetkens JA, Langenbach IL, Kravchenko D, Wenzel P, Emrich T, Isaak A. Cardiac MRI Findings in Patients Clinically Referred for Evaluation of Post-Acute Sequelae of SARS-CoV-2 Infection. Diagnostics. 2023; 13(13):2172. https://doi.org/10.3390/diagnostics13132172 https://www.mdpi.com/2075-4418/13/13/2172 (Full text)

Long COVID and the cardiovascular system-elucidating causes and cellular mechanisms in order to develop targeted diagnostic and therapeutic strategies: a joint Scientific Statement of the ESC Working Groups on Cellular Biology of the Heart and Myocardial and Pericardial Diseases

Abstract:

Long COVID has become a world-wide, non-communicable epidemic, caused by long-lasting multiorgan symptoms that endure for weeks or months after SARS-CoV-2 infection has already subsided. This scientific document aims to provide insight into the possible causes and therapeutic options available for the cardiovascular manifestations of long COVID.

In addition to chronic fatigue, which is a common symptom of long COVID, patients may present with chest pain, ECG abnormalities, postural orthostatic tachycardia, or newly developed supraventricular or ventricular arrhythmias. Imaging of the heart and vessels has provided evidence of chronic, post-infectious perimyocarditis with consequent left or right ventricular failure, arterial wall inflammation, or microthrombosis in certain patient populations.

Better understanding of the underlying cellular and molecular mechanisms of long COVID will aid in the development of effective treatment strategies for its cardiovascular manifestations. A number of mechanisms have been proposed, including those involving direct effects on the myocardium, microthrombotic damage to vessels or endothelium, or persistent inflammation.

Unfortunately, existing circulating biomarkers, coagulation, and inflammatory markers, are not highly predictive for either the presence or outcome of long COVID when measured 3 months after SARS-CoV-2 infection. Further studies are needed to understand underlying mechanisms, identify specific biomarkers, and guide future preventive strategies or treatments to address long COVID and its cardiovascular sequelae.

Source: Selvakumar J, Havdal LB, Drevvatne M, Brodwall EM, Lund Berven L, Stiansen-Sonerud T, Einvik G, Leegaard TM, Tjade T, Michelsen AE, Mollnes TE, Lund-Johansen F, Holmøy T, Zetterberg H, Blennow K, Sandler CX, Cvejic E, Lloyd AR, Wyller VBB. Prevalence and Characteristics Associated With Post-COVID-19 Condition Among Nonhospitalized Adolescents and Young Adults. JAMA Netw Open. 2023 Mar 1;6(3):e235763. doi: 10.1001/jamanetworkopen.2023.5763. PMID: 36995712; PMCID: PMC10064252. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064252/ (Full text)

Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection

Abstract:

Background: Long COVID is associated with multiple symptoms and impairment in multiple organs. Cross-sectional studies have reported cardiac impairment to varying degrees by varying methodologies. Using cardiac MR (CMR), we investigated a 12-month trajectory of abnormalities in Long COVID.

Objectives: To investigate cardiac abnormalities 1-year post-SARS-CoV-2 infection.

Methods: 534 individuals with Long COVID underwent CMR (T1/T2 mapping, cardiac mass, volumes, function and strain) and multiorgan MRI at 6 months (IQR 4.3-7.3) since first post-COVID-19 symptoms. 330 were rescanned at 12.6 (IQR 11.4-14.2) months if abnormal baseline findings were reported. Symptoms, questionnaires and blood samples were collected at both time points. CMR abnormalities were defined as ≥1 of low left or right ventricular ejection fraction (LVEF), high left or right ventricular end diastolic volume, low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac segments. Significant change over time was reported by comparison with 92 healthy controls.

Results: Technical success of multiorgan and CMR assessment in non-acute settings was 99.1% and 99.6% at baseline, and 98.3% and 98.8% at follow-up. Of individuals with Long COVID, 102/534 (19%) had CMR abnormalities at baseline; 71/102 had complete paired data at 12 months. Of those, 58% presented with ongoing CMR abnormalities at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms or clinical outcomes. At baseline, low LVEF was associated with persistent CMR abnormality, abnormal GLS associated with low quality of life and abnormal T1 in at least three segments was associated with better clinical outcomes at 12 months.

Conclusion: CMR abnormalities (left ventricular or right ventricular dysfunction/dilatation and/or abnormal T1mapping), occurred in one in five individuals with Long COVID at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers could not identify CMR abnormalities in Long COVID.

Source: Fernandez AR, Wamil M, Telford A, Carapella V, Borlotti A, Monteiro D, Thomaides-Brears H, Kelly M, Dennis A, Banerjee R, Robson M, Brady M, Lip GYH, Bull S, Heightman M, Ntusi N, Banerjee A. Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection. Open Heart. 2023 Feb;10(1):e002241. doi: 10.1136/openhrt-2022-002241. PMID: 36822818; PMCID: PMC9950586. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950586/ (Full text)

Myalgic encephalomyelitis: postviral fatigue and the heart

Note: This letter appeared in the November 11, 1989 issue of the British Medical Journal.

 

SIR, The controversial subject of myalgic encephalomyelitis has surfaced once more,(1) and I would like to contribute to the debate about its viral origins.

Persistent virus infections impair the specialised functions of cells. These include the synthesis of specific products such as heavy and light myosin chains, melanin, hormones, and immune functions.(2) Evidence of persistent enterovirus infection has been found in both dilated cardiomyopathy,(3-5) an organic disease discussed at a recent symposium,(3) and the more controversial myalgic encephalomyelitis.(6,7)

In murine myocarditis induced by Coxsackie viruses, more severe and lasting disease is associated with immunopathological processes, which include virus specific, cross reactive, and autoimmune reactions.(3, 8, 9) In Coxsackie viral myocarditis and cardiomyopathy of humans the antibodies that cross react with Coxsackie B antigens are reported.(3) Serum samples from patients with.cardiomyopathy may react with cardiac ,B adrenoreceptors, with mitochondrial ADP/ATP carriers, and with cell surface protein of the calcium channel causing calcium overload of myocytes and consequent dysfunction.(3) Thus a complex pattern of pathogenic mechanisms is emerging to explain dilated cardiomyopathy, which was formerly considered to be idiopathic but is now recognised as a late sequel of a proportion of cardiac infections with certain enteroviruses, particularly those of the Coxsackie B group. This does not exclude the possible role of other viruses-for example, arboviruses where these are prevalent-as initiators of such pathogenic processes.

It seems likely that similar immunological and metabolic disturbances in myalgic encephalomyelitis may also result from chronic infection, usually with enteroviruses, providing the organic basis of the postviral fatigue syndrome.(10) This condition is characterised by severe fatiguability and recuperation through rest. The myocardium, however, cannot rest-except terminally. Does “postviral dilated cardiomyopathy” represent the result of postviral fatigue syndrome of the unresting heart?

~NORMAN R GRIST Communicable Diseases (Scotland) Unit, Ruchill Hospital, Glasgow G20 9NB

 

References

1 Harris F, Taitz LS. Damaging diagnoses of myalgic encephalitis in children. BrMedj 1989;299:790. (23 September.)

2 Southern P, Oldstone MBA. Medical consequences of persistent viral infection. N Englj Med 1986;314:359-67.

3 Schultheiss HP, ed. New concepts in viral heart disease. Berlin: Springer, 1988.

4 Bowles NE, Richardson PJ, Olsen EGJ, Archard LC. Detection of Coxsackie-B-virus-specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy. Lancet 1986;i: 1120-3.

5 Kandolf R, Kirschner P, Amies D, et al. Enteroviral heart disease: diagnosis by in situ hybridization. In: Schultheiss HP, ed. New concepts in viral heart disease. Berlin: Springer, 1988:337-48.

6 Yousef GE, Mann GF, Smith DG, et al. Chronic enterovirus infection in patients with postviral fatigue syndrome. Lancet 1988;i: 146-50.

7 Archard LC, Bowles NE, Behan PO, Bell EJ, Doyle D. Postviral fatigue syndrome: persistence of enterovirus RNA in muscle and elevated creatinine kinase. J R Soc Med 1988;81:326-9.

8 Huber SA. The role of immune mechanisms in pathogenesis. In: Bendinelli M, Friedman H, eds. Coxsackieviruses, a general update. New York: Plenum, 1988:103-16.

9 Beisel KW, Rose NR. Relationship of coxsackievirus to cardiac autoimmnunity. In: Bendinelli M, Friedmann H, eds. Coxsackievinruses, a general update. New York: Plenum, 1988:271-92.

10 Behan PO, Behan WMH, Bell EJ. The post-viral fatigue syndrome-an analysis of the findings in 50 cases. J Infect 1985;10:21 1-22.

 

Source:  N. R. Grist. Myalgic encephalomyelitis: postviral fatigue and the heart. BMJ. 1989 Nov 11; 299(6709): 1219. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1838100/pdf/bmj00258-0049b.pdf