==== Front Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.39905 Cardiology Infectious Disease A Rare Case of Fulminant Myocarditis Caused by COVID-19 and Influenza B Co-infection Muacevic Alexander Adler John R Mirza Noreen 1 Mirza Mariam 2 Rayad Mohammad Nabil 1 Ahmad Amin Zaid 3 Suleiman Addi 3 1 Internal Medicine, Saint Michael’s Medical Center, Newark, USA 2 Internal Medicine, St. George’s University School of Medicine, True Blue, GRD 3 Cardiology, Saint Michael’s Medical Center, Newark, USA Noreen Mirza nsmirza4@gmail.com 3 6 2023 6 2023 15 6 e399053 6 2023 Copyright © 2023, Mirza et al. 2023 Mirza et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from https://www.cureus.com/articles/154091-a-rare-case-of-fulminant-myocarditis-caused-by-covid-19-and-influenza-b-co-infection Coronavirus disease 2019 and influenza B can have similar presentations and are self-limited in most cases. They are rarely associated with fatal cardiovascular complications. Coronavirus and influenza B-induced myocarditis is a rare but reversible cause of cardiogenic shock. Early detection plus administration of antiviral agents and supportive care with mechanical circulatory support in the form of an intra-aortic balloon pump can be a lifesaving measure in myocarditis. covid-19 pocus in critical care and mechanical circulatory support (vv and va ecmo) iabp intra-aortic balloon pump (iabp) influenza virus type a and b viral-induced myocarditis influenza b covid-induced myocarditis fulminant myocarditis ==== Body pmcIntroduction Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has changed the face of medicine resulting in more than 230 million confirmed cases of the disease since December 2021 [1]. This disease has varying clinical presentations, with the most common organ involved being the lung [2]. Patients with underlying cardiovascular conditions are seen to have prognostic consequences [2,3]. Only a few cases of COVID-19-related myocarditis have been described in the literature [4-6]. Most of these cases are related to messenger RNA (mRNA) vaccinations in the younger population [7]. Influenza infection is highly transmissible between individuals [8]. It commonly presents with upper respiratory symptoms and is self-limiting in most cases; however, it may progress to acute respiratory distress syndrome and myocarditis [8]. Influenza A is more frequently associated with the development of myocarditis [9]. Myocarditis is an inflammatory disease of the heart that can manifest as cardiac arrhythmias, chest pain, and heart failure. Heart failure can progress to cardiocirculatory failure causing fulminant myocarditis [9]. Here, we present a rare case of a previously healthy male patient with COVID-19 and influenza B-induced fulminant myocarditis requiring an intra-aortic balloon pump (IABP). Case presentation A 45-year-old male with an alcohol and tobacco use history presented to the emergency department after he was found confused and lying on the street. He complained of exertional shortness of breath without orthopnea or paroxysmal nocturnal dyspnea. He denied chest pain or presyncope. The patient was unvaccinated against COVID-19 or influenza. On examination, his temperature was 98.9°F, heart rate was 130 beats per minute, blood pressure was 144/111 mmHg, respiratory rate was 20 breaths per minute, and he was saturating 97% on room air. Additionally, there were bilateral bibasilar crackles in the lungs and trace lower extremity edema bilaterally. Initial laboratory data are shown below in Table 1. Table 1 Initial laboratory data on the day of admission. BUN = blood urea nitrogen; AST = aspartate transaminase; ALT = alanine transaminase; CK = creatinine kinase; WBC = white blood cell; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; NAA = nucleic acid amplification; RSV = respiratory syncytial virus   Admission labs Reference range Sodium 138 mmol/L 136–145 mmol/L Potassium 4.0 mmol/L 3.5–5.3 mmol/L Bicarbonate 20 mmol/L 20–31 mmol/L Chloride 103 mmol/L 98–110 mmol/L Anion gap 11 <12 B-natriuretic peptide 187 pg/mL 0–100 pg/mL High-sensitivity troponin 1,777 ng/L <78 ng/L BUN 44 mg/dL 6–24 mg/dL Creatinine 3.7 mg/dL 0.6–1.2 mg/dL Lactic acid 2.1 mmol/L 0–2.0 mmol/L C-reactive protein 9.4 mg/dL 0.0–0.8 mg/dL Procalcitonin 5.05 ng/mL <0.5 ng/mL Total bilirubin 2.1 mg/dL 0.2–1.2 mg/dL AST 128 U/L 10–36 U/L ALT 59 U/L 9–46 U/L Alkaline phosphatase 100 U/L 40–115 U/L Total CK 288 U/L 38–176 U/L Complete blood count WBC count 14,400 cells/µL 4,400–11,000 cells/µL Hemoglobin 10.1 g/dL 13.5–17.5 g/dL Platelet count 140,000 cells/µL 150,000–450,000 cells/µL SARS antigen Positive Negative SARS-CoV-2 by NAA Positive Negative Rapid influenza B Ag Positive Negative RSV screen Negative Negative An electrocardiogram (ECG) on admission showed sinus tachycardia with a normal axis and no acute ST-T-wave changes (seen in Figure 1); however, a subsequent ECG 16 hours later showed sinus rhythm with T-wave inversions (seen in Figure 2). Figure 1 Electrocardiogram on the day of admission showing sinus tachycardia with no ST or T-wave changes. Figure 2 Electrocardiogram 16 hours after admission showing sinus rhythm with T-wave inversions in the anterolateral leads. Echocardiogram showed a severely reduced left ventricular ejection fraction (LVEF) of 30-35% with severe hypokinesis of the mid and apical left ventricle (LV), as seen in Videos 1-3. Video 1 Apical four-chamber view. Video 2 Parasternal short-axis view. Video 3 Parasternal long-axis view. The patient was empirically started on antibiotics with ceftriaxone and doxycycline. He was started on antiviral therapy with oseltamivir and was given remdesivir. After the patient developed ECG changes and his troponins continued trending upwards peaking at 1,876 ng/L, the decision was made to start acute coronary syndrome protocol with a therapeutic heparin drip, aspirin, Brilinta, and atorvastatin. The patient then underwent cardiac catheterization that showed non-obstructive 60% stenosis in the distal right coronary artery with negative physiologic testing, as seen in Figure 3. Cardiac catheterization was otherwise unremarkable in the other coronary arteries, as seen in Figure 4. Figure 3 Coronary angiogram of the right coronary artery: large size, dominant vessel, and mildly calcific mid 60% lesion with a negative instantaneous wave-free ratio of 0.96. Figure 4 Coronary angiogram showing left anterior descending artery, left circumflex artery, and left main coronary artery with no significant stenosis. During the procedure, the patient’s blood pressure dropped requiring vasopressors. The patient underwent IABP insertion for hemodynamic support in light of findings of severe LV dysfunction with hypotension. The patient’s ejection fraction and hemodynamic status improved over a few days and the IABP was removed. Discussion Myocarditis typically resolves on its own; however, some cases may progress to severe conditions, including myocardial infarction, heart failure, and arrhythmias [10]. Myocarditis in COVID-19 has been hypothesized to be related to a cytokine storm [10]. The virus is able to gain access to human cells by attaching its spike protein to the membrane protein called angiotensin-converting enzyme 2 (ACE2). The spike protein is then cleaved at the S1/S2 and S2 sites so binding to ACE2 may occur [11]. TMPRSS2, a serine protein, is responsible for the cleavage of the S1/S2 site. ACE2 is present in cardiomyocytes allowing SARS-CoV-2 to infect the human heart [10]. When the virus enters cardiomyocytes, its accessory proteins may impede stress granule formation allowing for viral replication. Antigen-presenting cells (APCs) can prime naive T-lymphocytes which travel to the cardiomyocytes and cause myocardial inflammation through cell-mediated cytotoxicity. During the cytokine storm syndrome, proinflammatory cytokines are released into the bloodstream which boosts T-lymphocyte activation, resulting in further cytokine production and causing a feedback loop of damage to the myocardium [10]. Influenza A is a more common cause of myocarditis, and the pathogenesis behind myocarditis in influenza is still unknown. It is hypothesized to be due to direct myocardial injury by the influenza virus and heightened levels of host cell immunity due to increased expression of matrix metalloproteinases, trypsin, and cytokines such as tumor necrosis factor [12]. The cytokines result in an overproduction of nitric oxide which leads to myocardial ATP depletion due to the inhibition of complexes I and II of the electron transport chain [12]. There is also an imbalance between levels of Bax versus anti-apoptotic protein B-cell lymphoma 2 leading to the induction of cardiomyocyte apoptosis [12]. Coronavirus and influenza viruses share common clinical manifestations, including respiratory symptoms, usually fever, cough, fatigue, and myalgia, and are typically spread through respiratory droplets or aerosols [13]. Co-infection of both viruses is a rare phenomenon and is typically seen with influenza A but not as often with influenza B [13]. The severity of clinical symptoms in the presence of a positive influenza test should raise the clinical suspicion of co-infection with COVID-19, as was seen in our patient [13]. In a UK-based study regarding co-infection of COVID-19 and influenza, it was found that viral co-infection was associated with higher rates of mortality and invasive mechanical ventilation [14]. Another study published in 2020 from China found that concurrent infection of both viruses caused patients to have higher risks of inferior health outcomes [15]. A limited number of cases have been published in the literature regarding co-infection, and the most common laboratory findings that have been seen in co- infection include leukopenia, elevated C-reactive protein, elevated levels of liver transaminases, and lymphopenia [13]. The most frequent complications of co-infection include acute respiratory distress syndrome and acute liver injury [13]. There has also been one report of stress-induced cardiomyopathy precipitated by COVID-19 infection and influenza A co-infection [16]. Myocarditis treatment is focused on both hemodynamic and respiratory support [17]. In terms of hemodynamic management, it begins with medication management with vasopressors and inotropes [17]. However, more severe cases of myocarditis may require the use of an IABP, extracorporeal membrane oxygenation, or ventricle assist device [17]. An IABP allows for circulatory support by increasing systolic blood pressure while reducing cardiac afterload and myocardial oxygen demands [17]. IABP used within the first 24 hours of presentation has a reduced risk of mortality from myocarditis [17]. Myocarditis can progress to fulminant acute heart failure and cardiogenic shock. Early treatment with IABP restores hemodynamic stability by improving LV function and reducing LV volume and pressure and overall improves survival [18]. IABP is associated with an increase in LVEF by about 8% which is an important determinant of survival [18]. Conclusions This case highlights a rare presentation of COVID-19 and influenza co-infection-induced fulminant myocarditis where patients can have improved LVEF within a few days with mechanical support devices such as IABP. Human Ethics Consent was obtained or waived by all participants in this study The authors have declared that no competing interests exist. ==== Refs References 1 Coinfection with SARS-CoV-2 and influenza A virus increases disease severity and impairs neutralizing antibody and CD4(+) T cell responses J Virol Kim EH Nguyen TQ Casel MA 0 96 2022 https://doi.org/10.1128/jvi.01873-21 2 Mechanisms of SARS-CoV-2 transmission and pathogenesis Trends Immunol Harrison AG Lin T Wang P 1100 1115 41 2020 33132005 3 Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19) JAMA Cardiol Guo T Fan Y Chen M 811 818 5 2020 https://doi.org/10.1001/jamacardio.2020.1017 32219356 4 First case of COVID-19 complicated with fulminant myocarditis: a case report and insights Infection Zeng JH Liu YX Yuan J 773 777 48 2020 https://doi.org/10.1007/s15010-020-01424-5 32277408 5 Coronavirus fulminant myocarditis treated with glucocorticoid and human immunoglobulin Eur Heart J Hu H Ma F Wei X Fang Y 206 42 2021 32176300 6 Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection Eur Heart J Sala S Peretto G Gramegna M 1861 1862 41 2020 https://doi.org/10.1093/eurheartj/ehaa286 32267502 7 Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December 2020 to August 2021 JAMA Oster ME Shay DK Su JR 331 340 327 2022 https://doi.org/10.1001/jama.2021.24110 35076665 8 Acute respiratory distress syndrome and acute myocarditis developed in a previously healthy adult with influenza B BMC Pulm Med Chang HL Hsu JF Tsai YM Lin SY Kuo HF Yang CJ 1 16 2016 https://doi.org/10.1186/s12890-015-0163-3 26728359 9 When the heart gets the flu: fulminant influenza B myocarditis: a case-series report and review of the literature J Crit Care Hékimian G Jovanovic T Bréchot N 61 64 47 2018 https://doi.org/10.1016/j.jcrc.2018.06.001 29929152 10 Recognizing COVID-19-related myocarditis: the possible pathophysiology and proposed guideline for diagnosis and management Heart Rhythm Siripanthong B Nazarian S Muser D 1463 1471 17 2020 https://doi.org/10.1016/j.hrthm.2020.05.001 32387246 11 SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor Cell Hoffmann M Kleine-Weber H Schroeder S 271 280 181 2020 https://doi.org/10.1016/j.cell.2020.02.052 32142651 12 Up-regulation of ectopic trypsins in the myocardium by influenza A virus infection triggers acute myocarditis Cardiovasc Res Pan HY Yamada H Chida J 595 603 89 2011 https://doi.org/10.1093/cvr/cvq358 21084314 13 Are coinfections with COVID-19 and influenza low or underreported? 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