key: cord-0817907-ix8itwlj authors: Roest, Stefan; Brugts, Jasper J.; van Kampen, Jeroen J.A.; von der Thüsen, Jan H.; Constantinescu, Alina A.; Caliskan, Kadir; Hirsch, Alexander; Manintveld, Olivier C. title: COVID-19-related myocarditis post-heart transplantation date: 2021-04-20 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2021.04.013 sha: e7829ae54f91f15d7b145e536042aceeee5d3f36 doc_id: 817907 cord_uid: ix8itwlj We describe the first heart transplantation recipient with acute biventricular heart failure symptoms caused by a post-myocarditis state late after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No other viral pathogens could be detected, computed tomography angiography did not show cardiac allograft vasculopathy, and myocardial biopsy demonstrated no clinically relevant rejection. Subsequent cardiovascular magnetic resonance imaging revealed extensive epicardial delayed enhancement without myocardial edema. Heart failure medication was initiated and an implantable cardioverter defibrillator was implanted, (partially) recovering the ejection fraction. Further studies are needed to investigate the number of heart transplant recipients with myocardial damage after a SARS-CoV-2 infection. The Coronavirus disease 2019 (COVID-19) pandemic continues with 122.5 million cases and over 2.7 million deaths reported by the World Health Organization on the 23 rd of March 2021 (WHO, 2021) . The virus has more impact on immunocompromised patients such as cancer patients (Belsky, 2021 , Jindal, 2020 , stem cell transplant patients (Belsky, 2021 , HIV patients (Patel, 2021) , solid organ transplant recipients (Belsky, 2021) including heart transplant patients (Marcondes-Braga, 2021). We present a case of COVID-19-related postmyocarditis state on MRI late after initial infection in a HT recipient. A 50 years old patient six years post-HT (due to a dilated cardiomyopathy) who was scheduled for an annual check-up in March 2020 called the outpatient clinic with complaints of fever (38.5 degrees Celsius), dyspnea and malaise. The patient was seen at the emergency room and admitted with desaturation (92%) and bilateral crepitations in the basal lung fields. A chest Computed Tomography (CT) demonstrated lung abnormalities with a high suspicion (CO-RADS 5) (Prokop, 2020) for a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (severity score 15). The nasopharyngeal swab tested positive for SARS-CoV-2 RNA by real time polymerase chain reaction (RT-PCR). The mycophenolate mofetil was temporarily stopped and the prednisone dosage increased, while tacrolimus was continued. Furthermore, the patient received chloroquine (600 mg loading dosage and 300 mg 12 hours later followed by 300 mg chloroquine twice daily with a total treatment duration of 5 days). During admission no were normal indicating no acute rejection (Vermes, 2018) . The images did not match with abnormalities seen in stress cardiomyopathy (Eitel, 2011) . The CMR findings were most likely the result of a post-myocarditis state without signs of active myocarditis based on the modified Lake Louis criteria (Ferreira, 2018 The patient was initiated with heart failure medication and an implantable cardioverterdefibrillator was implanted due to non-sustained ventricular tachycardias. At discharge the NT-proBNP had dropped to 49 pmol/L. Two months after discharge, the ejection fraction had partially recovered (LVEF 46%). The first report on HT patients and COVID-19 originated from China (Wuhan) describing a cohort at the beginning of the pandemic. In this period, no patient had been tested positive for SARS-CoV-2 (Ren, 2020). However, after this first publication, several single-center studies J o u r n a l P r e -p r o o f were published on solid organ transplant recipients in general and specifically HT patients with COVID-19 (Hoek, 2020 , Iacovoni, 2020 , Singhvi, 2020 . These reports demonstrated a wide range of infection severity (from asymptomatic to ventilator support and even vasopressor support) and varying clinical outcome. Even a HT recipient needing retransplantation was reported (Soquet, 2020) . These findings demonstrate that follow-up in patients who develop symptoms related to COVID-19 is essential. In a recent Spanish study, 2.1% of the patients with a SARS-CoV-2 infection without previous history of chronic heart failure, acute heart failure was diagnosed (Rey, 2020) . The authors argued that due to the restrictive use of non-invasive imaging, these numbers could be an underestimation. Unfortunately, no additional imaging was performed to determine the cause of the acute heart failure due to lack of resources (Rey, 2020) . Furthermore, another case report recently published demonstrated a patient with myocarditis late after COVID-19 (Nicol, 2020) . These findings emphasize the need for close monitoring of cardiac function in the follow-up of patients who have been suffering from SARS-CoV-2. Recently, a case report was published on a pediatric HT patient who recovered from a SARS-CoV-2 infection, but developed de novo DSAs afterwards (Russell, 2020) . Although this is a single case, treating physicians should always think of acute rejection due to de novo DSAs when a patient has an impaired cardiac function. In another study from Brazil that looked at long-term outcomes in HT patients, the mortality rate was 27.5%, an acute rejection period was seen in 10% and an impaired left ventricular function with unknown cause in 12.5% of patients (Marcondes-Braga, 2021). We believe additional imaging should be performed when a clinically significant rejection cannot be proven in a HT patient with an impaired heart function post-SARS-CoV-2 infection, preferably CMR to clarify the cause of the left ventricular dysfunction. Another study demonstrated a wide range of abnormalities on CMR after a SARS-CoV-2 infection in an unselected (relatively low cardiovascular risk) patient population (Puntmann, 2020) . In 78 out of the 100 patients, CMR revealed cardiac involvement and even ongoing myocardial inflammation in 60 patients after the infection resolvement (Puntmann, 2020) . These abnormalities were independent of infection severity. In three patients with severe abnormalities, endomyocardial biopsies were performed. None of the biopsies detected viral genome as was the case in our patient (Puntmann, 2020) . In another study, 26 competitive athletes who had a SARS-CoV-2 infection with no or only mild symptoms had a CMR after quarantine (Rajpal, 2021) . In these low-risk patients, 4 (15%) had signs of myocarditis, confirming that even in these athletes, a relatively large group suffers from myocardial damage (Rajpal, 2021) . Given the fact that a significant number of these athletes demonstrated abnormalities on CMR, we believe that HT recipients who have suffered from COVID-19 should undergo cardiac evaluation. At least patients who present with a decrease in cardiac function, pericardial effusion or raised troponins should have a CMR to determine post-COVID-19 damage. In conclusion, HT patients who develop dysfunction of the allograft after a SARS-CoV-2 infection should be screened for both acute rejection, DSAs and cardiac allograft vasculopathy. However, if no substrate for the allograft dysfunction is found, additional testing with CMR should be performed to look for myocardial damage due to SARS-CoV-2-related myocarditis. None. 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