key: cord-1031412-ocpu7bd5 authors: Gnecchi, Massimiliano; Moretti, Francesco; Bassi, Emilio Maria; Leonardi, Sergio; Totaro, Rossana; Perotti, Luciano; Zuccaro, Valentina; Perlini, Stefano; Preda, Lorenzo; Baldanti, Fausto; Bruno, Raffaele; Visconti, Luigi Oltrona title: Myocarditis in a 16-year-old boy positive for SARS-CoV-2 date: 2020-06-25 journal: Lancet DOI: 10.1016/s0140-6736(20)31307-6 sha: c7d641e6065d738b1f6aaa5a9dfd6a923b48fff2 doc_id: 1031412 cord_uid: ocpu7bd5 nan . Control electrocardiogram recorded during the chest pain episode occurred the first night of hospitalization (hospital day one, 10:15 pm). No significant differences were present compared with the previous trace. Cine-SSFP (systole) Figure S7 . Cine-steady-state free precession images of four and three chambers long-axis view in end-diastolic and end-systolic phase show normal volumes and wall thickness and preserved biventricular systolic function. T2 mapping Figure S8 . Cardiac magnetic resonance T2 mapping sequences demonstrating the presence of patchy oedema of the lateral wall. T2w STIR T2 mapping T1w LGE Figure S9 . Cardiac magnetic resonance images of short axis projection of the basal (top panels) and mid segments are reported. T2w-STIR images show subepicardial band-like high signal demonstrating the presence of oedema at the level of inferior and infero-lateral walls, and patchy oedema pattern involving the whole lateral wall. T2 mapping sequences confirm the presence of oedema in the same segments. Finally, the late gadolinium sequences reveal high intensity signal indicating necrosis with the same distribution and localization. Creatinine (mg/dL) 0·73 -1·18 0·87 0·84 ·· ·· 0·89 0·96 1·02 1·11 Urea (mg/dL) 10·0 -50·0 32·0 30·0 ·· ·· 42·0 44·0 43·0 50·0 Glucose (mg/dL) 76·0 -110·0 106·0 91·0 ·· ·· 124·0 80·0 ·· 71·0 Lactate dehydrogenase (mU/mL) 125·0 -220·0 276·0 ·· 281·0 275·0 246·0 248·0 253·0 229·0 C-reactive protein (mg/dL) <0·5 3·25 6·20 3·33 1·67 0·95 ·· 0·40 0·29 Procalcitonin (ng/mL) 0·00 -0·50 The treating physicians were responsible for the patient's data management and data protection with the aim of improving treatment and safety. Clinical specimens for SARS-CoV-2 testing were collected by using a sterile flexible nasopharyngeal nylon flocked premoistened swab (FLOQSwabs™, Copan Italia, Brescia, Italy) dipped in three mL universal transport medium (UTM™, Copan Italia, Brescia, Italy). Total nucleic acids (DNA/RNA) were extracted from 200 μL of UTM™ using the QI-Asymphony® instrument with QIAsymphony® DSP Virus/Pathogen Midi Kit (Complex 400 protocol) according to the manufacturer's instructions (QIAGEN, Qiagen, Hilden, Germany). Specific real-time reverse transcriptase-polymerase chain reaction targeting RNA-dependent RNA polymerase and E genes were used to detect the presence of SARS-CoV-2 according to WHO guidelines 1 and Corman et al. protocols 2 . Late Gadolinium Enhancement (LGE) Cardiac Magnetic Resonance (CMR) images were obtained using a 1.5T scanner (Magnetom Aera, Siemens Medical System, Erlangen, Germany) with a phased array cardiac coil and electrocardiogram gating. Cine magnetic resonance images were acquired in two-chamber, four-chamber and three-chamber planes, then in short-axis with contiguous eight mm thick slices, from valve plane to ventricular apex, to assess ventricular function and cardiac kinesis. Both T2-weighted short-tau inversion recovery (T2w-STIR) and T2 mapping images were performed to assess myocardial oedema using the same planes. Then, 0·1 mmol/kg of Gadolinium-DTPA (Gadovist; Bayer Schering Pharma, Berlin, Germany) was then administered and after ten minutes LGE images were obtained with a breath-hold 2-D segmented phase sensitive IR sequence, setting the acquisition window to mid-end diastole and using an inversion time between 240 and 300 milliseconds to null normal myocardium signal. All CMR images were analysed using the CMR2 software (Circle Cardiovascular Imaging, Calgary, Alberta, Canada), manually drawing both endocardial and epicardial borders in the end-diastolic and end-systolic short-axis cine-steady-state free precession (SSFP) images. T2w-STIR images were visually assessed and all segments with signal intensity exceeding two standard deviations compared to normal myocardium were considered positive for oedema. The T2 mapping values of segments positive on T2w-STIR were obtained and compared to non-oedematous segments. LGE was considered present in areas with signal intensity exceeding five standard deviation compared to normal myocardium signal. The number of patients impacted by the ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to increase on a daily basis [3] [4] [5] [6] [7] . The majority of COVID-19 cases have mild symptoms and benign prognosis, but some evolve to severe clinical cases that can frequently be fatal. Although COVID-19 mainly affects the respiratory system, cardiac damage documented by elevation in cardiac troponin occurs in up to 28% of hospitalized COVID-19 adults and is negatively associated with mortality 8, 9 . Surprisingly, cardiac involvement has also been described in a consistent percentage of paediatric patients, an observation that has important diagnostic and therapeutic implications 10 . While type 1 and 2 myocardial infarctions are expected to represent the most frequent causes of troponin elevation in adult patients, acute myocarditis is probably the leading cause of cardiac damage in the youngest patients, although so far there are no reported cases on this matter. It is known that viral infections are the most frequent cause of acute myocarditis 11, 12 and other betacoronaviruses have already been associated with myocarditis 13 . A few cases of documented acute myocarditis in an adult COVID patient have also been recently reported 14, 15 . Here, we describe the first documented case of acute myocarditis as an isolated clinical manifestation in a paediatric patient positive for SARS-CoV-2 infection. The mechanism through which this virus may cause myocardial damage is still unknown. It has been shown that SARS-CoV-2 infection of a variety of cell lines, including lung, bronchus, kidney, liver and colon cells, depends on the metallopeptidase Angiotensin-Converting Enzyme 2 (ACE2) 16 , that is highly expressed in the heart 13 . It therefore seems reasonable to suppose that SARS-CoV-2 may infect cardiomyocytes though ACE2 interaction and directly lead to cell death. It is also possible that cardiac damage is caused by an autoimmune reaction to self-antigens previously hidden to the immune system 11, 17 . More studies are needed to unravel the prevalence and the pathophysiology of myocarditis in COVID-19 patients. Diagnostic detection of 2019-nCoV by real-time RT-PCR Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR A Novel Coronavirus from Patients with Pneumonia in China Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Clinical Characteristics of Coronavirus Disease 2019 in China Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases Update on Myocarditis Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19) Myocarditis in a patient with COVID-19: a cause of raised troponin and ECG changes SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor We thank all the healthcare professionals involved in the management of the epidemic, the members of the COVID-19 IRCCS San Matteo Pavia Task Force, the patient and his family. The authors are grateful to Vanessa Marchesi, PhD, and Vanessa Cuccu, MS, for expert editorial support.