Acute myocarditis associated with secondary cerebral edema in a patient with Covid-19: Case report



Female patient, 44 years old, admitted with symptoms of COVID-19. She presented elevation of cardiac troponin I, as well as diffuse hypokinesia in transthoracic echocardiography, which suggested the diagnosis of myocarditis. Next, a skull tomography showed diffuse cerebral edema and tonsilar herniation, and the patient evolved with brain death


In December 2019 a series of pneumonia cases of unknown etiology, but with characteristics similar to a viral picture, emerged in Wuhan, Hubei Province, China.(1,2) Researchers identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the causer of this infection, which was named COVID-19. Patients infected with SARS-CoV-2 usually present with fever, cough, and dyspnea over a period of 2 to 14 days, and may develop pneumonia.(2,3) Like other coronaviruses, SARS-CoV-2 uses the Angiotensin-converting enzyme II (ACE2) receptor for ligand binding before entering the cell by receptor-mediated endocytosis.(4) The ACE2 receptor is a membrane protein present on cardiomyocytes, type 2 pneumocytes, astrocytes, and other cells. (5,6)

In addition to causing damage to the respiratory system, SARS-CoV-2 can trigger cardiac and brain injury. (7,8) The mechanisms of damage to these two systems are not fully understood and are probably multifactorial. (6) In some cases of myocardial injury, SARS-CoV-2 particles have been identified in the myocardium, reinforcing the hypothesis that cardiotoxicity occurs. (9,10) Regarding the brain, studies suggest that SARS-CoV-2 can infect it directly, reaching the brain parenchyma through the blood and through the olfactory system. (11) Moreover, the hyperinflammatory state triggered by COVID-19(12) promotes vascular inflammation, plaque instability, myocardial inflammation, electrolyte imbalance and hypercoagulation state, (13,14) contributing to the occurrence of myocardial and brain injury.(6)

Recent studies indicate that a considerable number of patients diagnosed with COVID-19 present myocardial injury, and this condition is associated with higher mortality rates(2,10) and more severe disease outcomes. (10) Cases of myocarditis are rare in patients diagnosed with COVID-19, but when they occur fulminantly they are associated with fatal outcomes in these patients.(11) Therefore, in-depth studies of cases of myocarditis in patients infected with SARS-CoV-2 are necessary.

Case Report

A 44-year-old female sought medical attention with a clinical picture of dry cough, dyspnea on moderate effort, odynophagia, prostration, and myalgia. On admission, the patient had a temperature of 37.1°C (afebrile), blood pressure of 128/79 mmHg, heart rate of 94 bpm, and oxygen saturation (O2) of 96%, and the only alteration found on physical examination was crackling rales in both lung bases. She had a history of dyslipidemia, for which she was taking statins, and was also overweight (body mass index - BMI: 27.68 kg/cm2). The patient had been diagnosed with COVID-19 4 days before, by means of the reverse-transcriptase polymerase chain reaction (RT-PCR) test. On the 1st day of hospitalization, a chest CT scan showed acute inflammatory pulmonary changes, which were compatible with COVID-19 viral pneumonia, affecting about 50% of the lung parenchyma. Laboratory tests showed a cardiac troponin I level of 4.8pg/mL (reference value: less than 11.6pg/mL), C-reactive protein of 71.5mg/L (reference value: less than 5mg/L), and normal blood cell counts. On day 2, the patient evolved with Acute Respiratory Failure, and an orotracheal intubation procedure was performed. Then a transthoracic echocardiography found a left ventricular ejection fraction of 44%, diffuse hypokinesia and increased left ventricular dimensions, suggestive of myocarditis. On day 6, the patient was improving, with an O2 saturation of 93%, mild acidosis, and permissive hypercapnia on arterial blood gas. She evolved with hemodynamic instability due to circulatory shock (mean arterial pressure 55mmHg and heart rate 125bpm), and the dose of vasoactive drugs was increased.  He also presented fixed midriatic pupils and absence of corneal eyelid reflex. On that day, the cardiac troponin I level found was 11,576.6pg/mL (reference value: less than 11.6pg/mL), which was considered the highest since day 1 (Figure 1). The patient underwent a skull CT scan which showed reduced differentiation between white and gray substances in the cerebral hemispheres, being suggestive of diffuse cerebral edema, associated with expansive effect and tonsillar herniation. The electrocardiogram performed showed no signs of myocardial ischemia and sinus tachycardia (Figure 2). Thus, the patient was under suspicion of brain death, and the sedation was turned off and the hemodynamic, respiratory, and cardiologic surveillance was maintained. The patient did not undergo the Cardiovascular Magnetic Resonance exam due to the worsening of her health condition. On the 7th day the patient died.


In addition to pulmonary involvement, SARS-CoV-2 infection can impair myocardial function, triggering cases of acute myocarditis.  Myocarditis, an inflammatory disease of the myocardium, is one of the manifestations of myocardial injury. Viral infections - such as enteroviroses and adenoviroses - are common causes of this condition, which causes focal or global myocardial inflammation, necrosis, and in some cases ventricular dysfunction.(15) The diagnosis of myocarditis is based on several parameters, since this condition can manifest from a subclinical disease to sudden death. The symptoms of myocarditis usually present as chest pain, palpitations, fatigue, and syncope; however, in many cases additional tests are required. Increased markers of myocardial necrosis, nonspecific ST segment and T wave changes in the electrocardiogram, global hypokinesia and pericardial effusion in the echocardiogram, as well as histological changes in the biopsy are used as criteria for the diagnosis of myocarditis.(16,17) Moreover, in the absence of evidence of coronary artery disease, increased cardiac troponin I levels may suggest the occurrence of myocarditis, since this marker has high specificity for the diagnosis of myocarditis. (17) The pathogenesis of this involvement may reflect a process of viral replication and dissemination through the blood or lymphatic system of the respiratory tract. Moreover, it may be associated with the infectious process triggered by SARS-CoV-2, which characteristically induces an exaggerated inflammatory response capable of causing myocardial injury. (18) Furthermore, during pulmonary infection, fever and tachycardia increase oxygen demand by cardiac tissue. However, gas exchange impaired by continuous blood flow to lung regions of low ventilation causes a ventilation-perfusion mismatch resulting in blood hypoxemia, and consequently in worsening oxygenation of cardiac tissue. (19)

Yokoo et al.,(7) presented the case of a patient over 80 years old with a history of hypertension and ischemic stroke. Laboratory tests showed high levels of troponin T, electrocardiogram showed no signs of ischemia, and echocardiogram showed an ejection fraction of 35%. This patient underwent a cardiovascular MRI that revealed areas of delayed enhancement with ischemia in the left ventricular base septal wall, in addition to diffuse hypokinesia and impaired global systolic function. (7) Cases of myocarditis associated with COVID-19 have been reported from young to old. Paul et al., (20) described the case of a 35-year-old patient who was overweight as the only cardiovascular risk. In the electrocardiogram of this patient, alterations in repolarization were detected, and laboratory tests showed elevated level of cardiac troponin I of high sensitivity. Cardiac magnetic resonance imaging showed subepicardial enhancement predominantly in the lateral and inferior wall, a typical finding of myocarditis.(20) The two cases described presented patients with pre-existing cardiovascular risk, however, acute myocarditis associated with COVID-19 can also manifest in patients without cardiovascular risk factors. Inciardi et al.,(21) published a case of acute myocarditis in a patient without cardiovascular risk, who presented high-sensitivity troponin T elevation, besides diffuse hypokinesia and reduced ventricular ejection on transthoracic echocardiogram. In this sense, repolarization changes on electrocardiogram, cardiac troponin elevation, as well as detection of left ventricular diastolic impairment on echocardiogram are indicative of myocarditis associated with COVID-19.(21,22)

Patients with cardiac injury associated with SARS-CoV-2 infection have an acute manifestation of COVID-19 with greater severity, characterized by elevated levels of C-reactive protein and creatinine, as well as more intense pulmonary involvement, similar to the patient in this case.(21) The mortality rate is also influenced by the myocardial injury associated with COVID-19, being higher than 50% among patients with cardiac injury in comparison to 5% among those without it, indicating that it is associated with more severe clinical outcomes of COVID-19.(22,23)

In the present reported case, in addition to myocarditis, the patient presented diffuse cerebral edema. Several mechanisms are proposed for the neurological complications induced by COVID-19. The first hypothesis is based on the hematogenous or axonal retrograde pathway with viral accumulation in endothelial cells, smooth muscle cells, pericytes, inflammatory cells, neurons or glia cells. Brain damage may also be related to pneumonia caused by SARS-CoV-2, because when the virus passes through the lung parenchyma, it triggers exaggerated accumulation of neutrophils, increased vascular permeability, and formation of diffuse, interstitial exudates leading to hypoxemia. In the brain, hypoxia promotes increased anaerobic metabolism, promoting vasodilation and cerebral edema.(24) In this sense, the cerebral involvement of the patient in this case probably occurred due to severe hypoxia, which was also associated with the occurrence of circulatory shock. Furthermore, the pneumonia caused by the SARS-CoV-2 infection causes an exaggerated inflammatory response known as "cytokine storm”.(2) This hyperinflammatory state appears in advanced stages of severe COVID-19, causing damage to several organs.(25) The increased levels of cytokines cause destabilization of plaques, which may cause plaque rupture and thus trigger cardiac and cerebral injury. (25,26)

Another point to be analyzed is the presence of dyslipidemia as a comorbidity in the case patient. A meta-analysis of several studies highlighted the existence of a relationship between the presence of dyslipidemia and severe outcomes of COVID-19.(27) After the occurrence of a viral infection, macrophages may interact with cholesterol in atherosclerotic plaques or become involved in inflammasome activation, increasing the secretion of proinflammatory cytokines.(28) Thus, the presence of dyslipidemia may cause endothelial dysfunction and increase the risk of cardiovascular complications. (29)


In addition to causing respiratory complications, SARS-CoV-2 infection can impair cardiac and cerebral function. Acute myocarditis, a manifestation of myocardial injury, is associated with more severe outcomes of COVID-19 and may lead to poor cerebral perfusion culminating in edema and brain death. Furthermore, dyslipidemia has a high influence on the progression of COVID-19 and its presence is related to more severe disease outcomes.



There are no conflicts of interest


The study "Acute myocarditis associated with secondary cerebral edema in a patient with COVID-19" was approved by the ethics committee of Pontifical Catholic University of Paraná, with approval number 30188020.7.1001.0020. The patient's next of kin provided informed consent to publish the clinical data. All protocols were followed according to institutional guidelines.


  1. Lu H, Stratton CW, Tang YW. Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle. J Med Virol. 2020;92(4):401-2.
  2. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Jan 30;395(10223):497-506.
  3. Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, Griffin JM, Masoumi A, et al. COVID-19 and Cardiovascular Disease. Circulation. 2020;141(20):1648-55. Review.
  4. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-280.e8.
  5. Xiong TY, Redwood S, Prendergast B, Chen M. Coronaviruses and the cardiovascular system: acute and long-term implications. Eur Heart J. 2020;41(19):1798-800.
  6. Suri JS, Puvvula A, Biswas M, Majhail M, Saba L, Faa G, et al. COVID-19 pathways for brain and heart injury in comorbidity patients: A role of medical imaging and artificial intelligence-based COVID severity classification: A review. Comput Biol Med. 2020;124:103960. Review.
  7. Yokoo P, Fonseca EK, Sasdelli Neto R, Ishikawa WY, Silva MM, Yanata E, et al. COVID-19 myocarditis: a case report. einstein (Sao Paulo). 2020;18:eRC5876.
  8. Solomon IH, Normandin E, Bhattacharyya S, Mukerji SS, Keller K, Ali AS, et al. Neuropathological Features of Covid-19. N Engl J Med. 2020;383(10):989-92.
  9. Yao XH, Li TY, He ZC, Ping YF, Liu HW, Yu SC, et al. [A pathological report of three COVID-19 cases by minimally invasive autopsies]. Zhonghua Bing Li Xue Za Zhi. 2020;49(5):411-7.
  10. Hartmann C, Miggiolaro A, Motta Junior JS, Carstens LB, Paula CB. Grobe SF, et al. The Pathogenisis of COVID-19 Myocardial Injury: an Immunohistochemical Study of Postmortem Biopsies. 11.   Garg R. Spectrum of Neurological Manifestations in Covid-19: A Review. Neurol India [Internet]. 2020 May 1 [cited 2020 Dec 4];68(3):560. Available from:
  11. Kang Y, Chen T, Mui D, Ferrari V, Jagasia D, Scherrer-Crosbie M, et al. Cardiovascular manifestations and treatment considerations in COVID-19. Heart. 2020;106(15):1132-41. Review.
  12. Prabhu SD. Cytokine-induced modulation of cardiac function. Cir Res. 2004;95(12):1140-53. Review.
  13. Levi M, Van Der Poll T, Büller HR. Bidirectional relation between inflammation and coagulation. Circulation. 2004;109(22):2698-704. Review.
  14. Esfandiarei M, McManus BM. Molecular biology and pathogenesis of viral myocarditis. Annu Rev Pathol. 2008;3(1):127-55. Review.
  15. Felker GM, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK, Baughman KL, et al. Echocardiographic findings in fulminant and acute myocarditis. J Am Coll Cardiol. 2000;36(1):227-32.
  16. Cooper LT. Myocarditis. N Engl J Med. 2009;360(15):1526-38.
  17. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420-2.
  18. Musher DM, Rueda AM, Kaka AS, Mapara SM. The association between pneumococcal pneumonia and acute cardiac events. 2007;45(2):158-65.
  19. Paul JF, Charles P, Richaud C, Caussin C, Diakov C. Myocarditis revealing COVID-19 infection in a young patient. Eur Heart J Cardiovasc. 2020;21(7):776. Review.
  20. Inciardi RM, Lupi L, Zaccone G, Italia L, Raffo M, Tomasoni D, et al. Cardiac Involvement in a Patient with Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):819-24.
  21. Figueiredo Neto JA, Marcondes-Braga FG, Moura LZ, Figueiredo AM, Figueiredo VM, Mourilhe-Rocha R, et al. Coronavirus disease 2019 and the myocardium.Arq Bras Cardiol. 2020;114(6)1051-7. Review.
  22. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of Cardiac Injury with Mortality in Hospitalized Patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020;5(7):802-10.
  23. Zhang H, Baker A. Recombinant human ACE2: acing out angiotensin II in ARDS therapy. Crit Care. 2017;21(1):305.
  24. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-4.
  25. Schoenhagen P, Tuzcu EM, Ellis SG. Plaque vulnerability, plaque rupture, and acute coronary syndromes: (Multi)-Focal manifestation of a Systemic disease process. Circulation. 2002;106(7):760-2
  26. Choi GJ, Kim HM, Kang H. The Potential Role of Dyslipidemia in COVID-19 Severity: an Umbrella Review of Systematic Reviews. J Lipid Atheroscler. 2020;9(3):435-48.
  27. Tall AR, Yvan-Charvet L. Cholesterol, inflammation and innate immunity. Nat Rev Immunol. 201515(2):104-16. Review.
  28. Kim JA, Montagnani M, Chandrasekran S, Quon MJ. Role of lipotoxicity in endothelial dysfunction. Heart Fail ; 20128(4):589-607.