cardiac autoimmnunity – American ME and CFS Society

Abstract:

Severe cases of COVID-19 are characterized by an inflammatory burst, which is accompanied by multiorgan failure. The elderly population has higher risk for severe or fatal outcome for COVID-19. Inflammatory mediators facilitate the immune system to combat viral infection by producing antibodies against viral antigens. Several studies reported that the pro-inflammatory state and tissue damage in COVID-19 also promotes autoimmunity by autoantibody generation. We hypothesized that a subset of these autoantibodies targets cardiac antigens.

Here we aimed to detect anti-cardiac autoantibodies in severe COVID-19 patients during hospitalization. For this purpose, 104 COVID-19 patients were recruited, while 40 heart failure patients with dilated cardiomyopathy and 20 patients with severe aortic stenosis served as controls. Patients were tested for anti-cardiac autoantibodies, using human heart homogenate as a bait. Follow-up samples were available in 29 COVID-19 patients. Anti-cardiac autoantibodies were detected in 68% (71 out of 104) of severe COVID-19 patients.

Overall, 39% of COVID-19 patients had anti-cardiac IgG autoantibodies, while 51% had anti-cardiac autoantibodies of IgM isotype. Both IgG and IgM anti-cardiac autoantibodies were observed in 22% of cases, and multiple cardiac antigens were targeted in 38% of COVID-19 patients. These anti-cardiac autoantibodies targeted a diverse set of myocardial proteins, without apparent selectivity. As controls, heart failure patients (with dilated cardiomyopathy) had similar occurrence of IgG (45%, p = 0.57) autoantibodies, while significantly lower occurrence of IgM autoantibodies (30%, p = 0.03). Patients with advanced aortic stenosis had significantly lower number of both IgG (11%, p = 0.03) and IgM (10%, p < 0.01) type anti-cardiac autoantibodies than that in COVID-19 patients. Furthermore, we detected changes in the anti-cardiac autoantibody profile in 7 COVID-19 patients during hospital treatment.

Surprisingly, the presence of these anti-cardiac autoantibodies did not affect the clinical outcome and the prevalence of the autoantibodies did not differ between the elderly (over 65 years) and the patients younger than 65 years of age. Our results demonstrate that the majority of hospitalized COVID-19 patients produce novel anti-cardiac IgM autoantibodies. COVID-19 also reactivates resident IgG autoantibodies. These autoantibodies may promote autoimmune reactions, which can complicate post-COVID recuperation, contributing to post-acute sequelae of COVID-19 (long COVID).

Source: Fagyas M, Nagy B Jr, Ráduly AP, Mányiné IS, Mártha L, Erdősi G, Sipka S Jr, Enyedi E, Szabó AÁ, Pólik Z, Kappelmayer J, Papp Z, Borbély A, Szabó T, Balla J, Balla G, Bai P, Bácsi A, Tóth A. The majority of severe COVID-19 patients develop anti-cardiac autoantibodies. Geroscience. 2022 Sep 16:1–14. doi: 10.1007/s11357-022-00649-6. Epub ahead of print. PMID: 36112333; PMCID: PMC9483490. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9483490/ (Full text)

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