Haruyuki Kinoshita,Takashi Kurashige,Takahiro Fukuda,Masashi Morita,Shiori Maeda,Munehiro Kanegawa,Yoji Sumimoto,Kenji Masada,Takashi Shimonaga,Hiroshi Sugino
The impact that myocarditis for post-acute COVID-19 syndrome may be dermatomyositis-like myocarditis: A case report
SARS-CoV-2,COVID-19,Long COVID-19-associated myocarditis,Post-acute COVID-19 syndrome,Fulminant myocarditis,Human myxovirus resistance protein 1 (MxA),Dermatomyositis
Myocarditis is often reported as a complication of COVID-19 infection or post-vaccination, but there are few reports of “myocarditis for Post-acute COVID-19 syndrome”, and many unknowns still remain. Apart from that, an association between COVID-19 infection and dermatomyositis has also been reported. We describe the clinical presentation of acute myocarditis in a patient who had developed COVID-19 syndrome one-month earlier. A healthy 49-year-old man experienced typical COVID-19 symptoms. Thirty-two days later, he was admitted because of fever and severe fatigue, chest pain and bradycardia. Blood tests showed major inflammation. PCR for SARS-CoV-2 on nasopharyngeal swab (ID NOW™) was positive, but diagnosed as a previous infection due to a high CT value. Because of haemodynamic worsening with both an increase in cardiac troponin I and NT-pro BNP levels and reduced wall motion on echocardiography, acute myocarditis was suspected. Myocardial biopsy revealed severe lymphocytic infiltration and interstitial edema between myocardial fibers. These findings led to the diagnosis of fulminant myocarditis. Interestingly, myocardium was also stained with human myxovirus resistance protein 1 (MxA). We consider that there may be an aspect of “dermatomyositis-like myocarditis with SARS-CoV-2” in our case. This is the first case of fulminant myocarditis for Post-acute COVID-19 syndrome in which diagnosis of active myocarditis was proven by pathological examination following myocardial biopsy and strong association with dermatomyositis was suggested pathologically.
The impact that myocarditis for post-acute COVID-19 syndrome may be dermatomyositis-like myocarditis: A case report

Myocarditis is often reported as a complication of COVID-19 infection or post-vaccination, but there are few reports of “myocarditis for Post-acute COVID-19 syndrome”, and many unknowns still remain. Apart from that, an association between COVID-19 infection and dermatomyositis has also been reported. We describe the clinical presentation of acute myocarditis in a patient who had developed COVID-19 syndrome one-month earlier. A healthy 49-year-old man experienced typical COVID-19 symptoms. Thirty-two days later, he was admitted because of fever and severe fatigue, chest pain and bradycardia. Blood tests showed major inflammation. PCR for SARS-CoV-2 on nasopharyngeal swab (ID NOW™) was positive, but diagnosed as a previous infection due to a high CT value. Because of haemodynamic worsening with both an increase in cardiac troponin I and NT-pro BNP levels and reduced wall motion on echocardiography, acute myocarditis was suspected. Myocardial biopsy revealed severe lymphocytic infiltration and interstitial edema between myocardial fibers. These findings led to the diagnosis of fulminant myocarditis. Interestingly, myocardium was also stained with human myxovirus resistance protein 1 (MxA). We consider that there may be an aspect of “dermatomyositis-like myocarditis with SARS-CoV-2” in our case. This is the first case of fulminant myocarditis for Post-acute COVID-19 syndrome in which diagnosis of active myocarditis was proven by pathological examination following myocardial biopsy and strong association with dermatomyositis was suggested pathologically.

A novel coronavirus (SARS-CoV-2) was confirmed in Wuhan, China in December 2019 and subsequently spread throughout the world. In March 2020, the World Health Organization (WHO) declared a pandemic, and a SARS-CoV-2 infection was named Coronavirus Disease (COVID-19). While the clinical symptoms of COVID-19 are mainly respiratory symptoms, there are also reports of cardiac complications such as myocardial damage and ventricular arrhythmia [1]. This case is the first report of a diagnosis of fulminant myocarditis in which cardiomyocytes were positive for human myxovirus resistance protein 1 (MxA) staining, with a complete atrioventricular block, and cardiogenic shock by myocardial biopsy of a Post-acute COVID-19 syndrome patient.

A 49-year-old man with diabetes, Graves' disease, dyslipidemia, and hypertension had a fever and was diagnosed with a COVID-19 infection by PCR test. Since his symptoms were mild, he was treated at home and recovered after 10 days of home care. Thirty-two days later, he had a fever again and was diagnosed with COVID-19 infection by a nearby doctor and continued to feel sick and lose appetite. Four days later, he was transferred to our emergency center with chest pain, dyspnea, and body aches. His blood pressure was not palpable, heart rate was 36 beats/min, respiratory rate was 30/min, oxygen saturation was 90% on room air, and body temperature was 35 °C. Physical examination revealed marked sweating and peripheral coldness, but no other significant findings. His blood gas showed 11.5 mmol/L for lactate. WBC 6.1 × 109/L (neutrophils 61.6%, eosinophils 0.3%, lymphocytes 34%), hemoglobin 173 g/L, PLT 6.7 × 109/L, blood creatinine 291μmol/L, C-reactive protein 50,600 μmol/L, D-dimer was 6.6 × 103 μg/L, cTnI 37,096 ng/L, NT-pro 1958 pmol/L (Table 1), and COVID-19 PCR was positive (ID NOW ™/Abbott). In ECG, there was AV block, inversion of the T wave in Ⅱ Ⅲ aVf and ST elevation and QS pattern waveforms in V1–V3, thus raising concern about myocardial ischemia (Fig. 1A). Transthoracic echocardiography revealed diffuse hypokinesis wall motion of the left ventricle with a left ventricular, although the posterior inferior wall region showed significant wall motion abnormalities. Since his respiratory condition did not deteriorate, he was not intubated, and his blood pressure gradually improved with a massive infusion of fluids. However, since bradycardia due to complete A-V block continued, the patient was taken to the catheter lab, and a temporary pacemaker was inserted from the right internal jugular vein. An IABP was inserted through the right femoral artery, and subsequent coronary angiography revealed normal coronary artery disease. At this point, the differential diagnosis was acute myocarditis after COVID-19 infection or other myocarditis. With massive infusion, catecholamines, temporary pacing, and IABP support, his cyclic dynamics became stable without serious arrhythmias, and he had a myocardial biopsy and was admitted to the ICU. Immediately after admission to the ICU, sudden VT and Vf were observed (Fig. 1B), so CPR, endotracheal intubation, and V-A ECMO were started. The PCR CT value was found to be 40.8, and his COVID-19 infection was diagnosed as a previous infection rather than an acute infection. However, since the patient's circulation remained unstable, he was transferred to a university hospital on the same day. Despite subsequent use of a percutaneous transluminal left ventricular assist device (Impella CP) implantation at the same institution, the patient developed progressive sepsis and left ventricular function did not improve, and he died on the nineth day of the illness. Myocardial biopsy showed disarried myocardial cell arrangement and myocyte shedding and some fatty degeneration, with marked proliferation of interstitium, suggesting macrophage-dominated interstitial edema with T lymphocytes and a high inflammatory infiltrate (Fig. 2A–C). No giant cells, eosinophils or vascular thrombi were observed. Interestingly, we found notable perifascicular staining patterns of human myxovirus resistance protein 1 (MxA) (Fig. 2D).

This is the first case of myocarditis for Post-acute COVID-19 syndrome in which positive staining for human myxovirus resistance protein 1 (MxA) was proven for the first time [2]. MxA is a representative protein induced by type 1 interferon and is an excellent diagnostic marker for dermatomyositis [3]. Zhang et al. reported that women diagnosed with COVID-19-associated myositis were positive for anti-small ubiquitinlike modifier-1–activating enzyme (anti–SAE1) antibodies, one of the dermatomyositis-specific antibodies [4]. Nishino et al. suggest that patients with COVID-19-associated myositis should undergo anti-SAE antibody test and immunohistochemical testing with MxA, which is a diagnostic marker induced by dermatomyositis and synthesized by type 1 IFN [5]. Holzer et al. also reported that the production of dermatomyositis-specific autoantibodies, such as anti-MDA5 antibodies, anti-NXP2 antibodies, as well as anti-Mi2 antibodies and anti-TIF1γ antibodies, were closely related to a COVID-19 infection [6]. In particular, it has been reported that the anti-MDA5 antibody titer in patients with COVID-19 infection is higher than that in normal persons, and the relationship between a COVID-19 infection and dermatomyositis autoantibodies is close, and since JAK inhibitors are expected to be therapeutic agents in both severe COVID-19 patients and dermatomyositis (the JAK inhibitor tofacitinib is now being used in a clinical trial for dermatomyositis: ClinicalTrials.gov Identifier: NCT0300264) [7,8]. COVID-19-associated myocarditis is considered “immune-mediated, requires prompt diagnosis and treatment as it can be life threatening and may be associated with long-term cardiac and neurologic sequelae” and it has been described as a “multisystem inflammatory syndrome (MIS) associated with SARS-CoV-2 featuring Kawasaki-like disease” [9]. But we also considered that there may be an aspect of “immune-mediated type 1 interferon-associated myocarditis with SARS-CoV-2” or “dermatomyositis-like myocarditis with SARS-CoV-2” in our case. Although it is difficult to make a judgment based on this case alone, considering previous reports of COVID-19-associated myocarditis and the positive MxA findings of the myocardial biopsy of this case (which was shortly after onset and without mechanical stress), we expect that dermatomyositis autoantibodies (DMSA) such as anti-SAE1, anti-Mi2, anti-MDA5, anti-SAE antibodies, anti-TIF1γ antibodies, and anti-NXP-2 antibodies are also tested to predict COVID severity, in addition to MxA staining of myocardial tissue. And regarding COVID-19-associated myocarditis, we hope future research will examine treatment strategies for dermatomyositis such as JAK inhibitors.Key PointsQuestion: There are still many unknowns about myocarditis for Post-acute COVID-19 syndrome.Findings: Myocardial biopsy in our case showed no giant cells, eosinophils or vascular thrombi were observed and notable perifascicular staining patterns of human myxovirus resistance protein 1 (MxA).Meaning: This is the first case of fulminant myocarditis for Post-acute COVID-19 syndrome in which diagnosis of active myocarditis was proven by pathological examination following myocardial biopsy and strong association with dermatomyositis was suggested pathologically.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.