key: cord-0963413-058as96u
authors: Impellizzeri, Andrea; Suma, Nicole; Palermo, Francesco; Sansonetti, Angelo; Armillotta, Matteo; Stefanizzi, Andrea; Amicone, Sara; Angeli, Francesco; Fabrizio, Michele; Bergamaschi, Luca; Paolisso, Pasquale; Rinaldi, Andrea; Foà, Alberto; Fedele, Damiano; Catalano, Costantina; Bertelli, Michele; Galiè, Nazzareno; Pizzi, Carmine
title: 742 Myocarditis after SARS-CoV-2 vaccine: is that so simple?
date: 2021-12-08
journal: Eur Heart J Suppl
DOI: 10.1093/eurheartj/suab135.038
sha: 8ecf39fb31376784c263a4bb446f176388564ca0
doc_id: 963413
cord_uid: 058as96u

SARS-CoV-2 vaccination is associated with potential side effects, particularly following second vaccine dose. Recent case series have reported a potential association between SARS-CoV-2 vaccination and acute myocarditis, predominantly in young males. We hereby describe a previously healthy 17-year-old man, with no past cardiac history, who presented to the emergency department with persistent chest pain and fever (up to 38 °C). The patient had received the first dose of Cominarty (BioNTech/Pfizer) vaccine 10 days before symptom onset and reported flu-like symptoms and conjunctivitis involving both eyes one week before administration of the first vaccine dose. On that occasion, no COVID test was performed and the patient was treated with anti-inflammatory drugs and antibiotic eye drops. On admission, laboratory tests were performed (Troponin-I Δ 19 500–23 270 ng/l. CRP 23 mg/dl, ESR 43 s, WBC 17 570 cell/mm(3)) as well as COVID-19 PCR, Serological tests and Autoimmune disorders panel all resulting negative. CT coronary angiogram did not reveal any spontaneous coronary artery dissection or anomalous origin of coronary arteries and Calcium Score was 0. Transthoracic echocardiography showed a depressed LVEF (36%) with concomitant posterior and inferior wall as well as posterior and anterior basal interventricular septum hypokinesia. Endomyocardial biopsy revealed multifocal lymphocytic myocarditis with sub-endomyocardial and interstitial fibrosis. CMR was also performed (1-week after presentation) demonstrating mildly depressed systolic function (LVEF 47%), with hypokinesia of the posterior and inferior wall, increased signal intensity on T2 maps (58 ms, n.v. <55 ms), prolonged native T1 values (1083 ms, n.v. <1030 ms) as well as subepicardial and intramyocardial LGE enhancement of infero-lateral segments reflecting intercellular fibrosis. Thereafter, the patient was discharged with medical therapy including ACE-inhibitor, colchicine, and ibuprofen. Given the close proximity between SARS-CoV-2 vaccine administration and the absence of other predisposing conditions, the aetiology of myocarditis was attributed to the vaccine. In addition, as the patient suffered from flu-like symptoms and conjunctivitis 1 week before the vaccine, a previous paucisymptomatic SARS-CoV-2 infection was suspected and anti-SARS-Coronavirus Nucleocapsid Protein antibody test revealed high antibody levels with low IgG avidity. Given that myocarditic symptoms evolved after complete Sars-Cov2 symptom resolution, our first hypothesis is that the infection is unlikely to be the cause of acute myocarditis in this patient. Indeed, current literature on COVID-related myocarditis reports close temporal association between respiratory symptoms and myocarditis onset. In support to our hypothesis, recent trials have reported that myocarditis more frequently occurs following administration of mRNA vaccines especially in male adolescents and young adults like our patient. However, cardiac side effects typically occur after full vaccination and symptoms appear within three days following the second dose, which does not fully apply to this case. Notwithstanding this, more recent studies have reported myocarditis even after first vaccination dose in patients with previous COVID-19 infection, analogously to the case described. This case suggests a complex interaction between immunological factors and covid infection/vaccination with potential significant implications on the cardiovascular system. From current literature, much uncertainty remains regarding time interval criteria for reliable post-vaccination myocarditis diagnosis, hence large-scale clinical trials are needed to address this issue.

Aims: Most patients who had COVID-19 are still symptomatic after many months post infection, but the long-term outcomes are not yet well-defined. The aim of our prospective/retrospective study was to define the cardiac sequelae of COVID-19 infection. Methods and results: This monocentric cohort study included 160 consecutive patients (64 females, 60 þ 12 years) who had been discharged from the ward or from the outpatient clinic after a diagnosis of COVID-19 and subsequently referred for a follow-up visit. Clinical features as well as lab and instrumental data about the acute phase of the disease, such as haemodynamic instability (HI), cardiac biomarkers, Ddimer, C-reactive protein (CRP), high resolution CT (HRCT) score along with information about the follow-up visit, including ECG and Conventional and Doppler Tissue Echocardiographic (DTE) parameters, were recorded. The median follow-up time after symptom onset was 5 months. At follow-up visit, the majority of the patients reported dyspnoea and asthenia. Moreover, echocardiography showed morphofunctional changes of both right (RV) and left (LV) ventricles, such as RV dilation, increased pressure in the pulmonary circulation, and by-ventricular systolic-diastolic dysfunction. When examined using multivariate analysis, independent of age, sex, and co-morbidities, RV and LV changes were significantly associated (P < 0.05) with HRCT score and HI and with CRP, respectively. Conclusions: Our results suggest that COVID-19 may impact RV and LV differently. Notably, the extent of the pneumonia and HI may affect RV, whereas the inflammatory status may influence LV. A long-term follow-up is warranted to refine and customize the most appropriate therapeutic strategies. Aims: Sex-differences have been demonstrated in the acute phase of COVID-19 infection; females (f) were found to be less prone to develop a severe disease than males (M), but few studies have assessed sex-differences in Long-COVID-19 syndrome. Methods and results: The aim of this prospective/retrospective study was to characterize the long-term consequences of this infection from a sex-perspective. For this purpose, we enrolled 223 patients (89 F and 134 M) who experienced a SARS-CoV-2 infection. In the acute phase of the illness, females reported more frequently than males: weakness, dysgeusia, anosmia, thoracic pain, palpitations, diarrhoea, and myalgia without significant differences in breathlessness, cough, and sleep disturbance. After a mean follow-up time of 5 months after the acute phase, females were significantly more likely than males to report weakness, thoracic pain, palpitations, and sleep disturbance but not myalgia and cough. At the multivariate logistic regression, women were statistically significantly likely to experience persistent symptoms such as dyspnoea, fatigue, chest pain, and palpitations. On the contrary, myalgia, cough and sleep disturbance were not influenced by sex. Conclusions: We demonstrated that females were more symptomatic than males not only in the acute phase but also at follow-up. Sex was found to be an important determinant of Long-COVID syndrome because it is a significant predictor of persistent symptoms in females, such as dyspnoea, fatigue, chest pain, and palpitations. Our results suggest the need for long-term follow-up of these patients from a sexperspective in order to implement early preventive and personalized therapeutic strategies.

742 Myocarditis after SARS-CoV-2 vaccine: is that so simple?

Andrea Impellizzeri, Nicole Suma, Francesco Palermo, Angelo Sansonetti, Matteo Armillotta, Andrea Stefanizzi, Sara Amicone, Francesco Angeli, Michele Fabrizio, Luca Bergamaschi, Pasquale Paolisso, Andrea Rinaldi, Alberto Foà, Damiano Fedele, Costantina Catalano, Michele Bertelli, Nazzareno Galiè, and Carmine Pizzi Policlinico S. Orsola (Bologna), Italy SARS-CoV-2 vaccination is associated with potential side effects, particularly following second vaccine dose. Recent case series have reported a potential association between SARS-CoV-2 vaccination and acute myocarditis, predominantly in young males. We hereby describe a previously healthy 17-year-old man, with no past cardiac history, who presented to the emergency department with persistent chest pain and fever (up to 38 C). The patient had received the first dose of Cominarty (BioNTech/Pfizer) vaccine 10 days before symptom onset and reported flu-like symptoms and conjunctivitis involving both eyes one week before administration of the first vaccine dose. On that occasion, no COVID test was performed and the patient was treated with anti-inflammatory drugs and antibiotic eye drops. On admission, laboratory tests were performed (Troponin-I D 19 500-23 270 ng/l. CRP 23 mg/dl, ESR 43 s, WBC 17 570 cell/mm 3 ) as well as COVID-19 PCR, Serological tests and Autoimmune disorders panel all resulting negative. CT coronary angiogram did not reveal any spontaneous coronary artery dissection or anomalous origin of coronary arteries and Calcium Score was 0. Transthoracic echocardiography showed a depressed LVEF (36%) with concomitant posterior and inferior wall as well as posterior and anterior basal interventricular septum hypokinesia. Endomyocardial biopsy revealed multifocal lymphocytic myocarditis with sub-endomyocardial and interstitial fibrosis. CMR was also performed (1-week after presentation) demonstrating mildly depressed systolic function (LVEF 47%), with hypokinesia of the posterior and inferior wall, increased signal intensity on T2 maps (58 ms, n.v. <55 ms), prolonged native T1 values (1083 ms, n.v. <1030 ms) as well as subepicardial and intramyocardial LGE enhancement of infero-lateral segments reflecting intercellular fibrosis. Thereafter, the patient was discharged with medical therapy including ACE-inhibitor, colchicine, and ibuprofen. Given the close proximity between SARS-CoV-2 vaccine administration and the absence of other predisposing conditions, the aetiology of myocarditis was attributed to the vaccine. In addition, as the patient suffered from flu-like symptoms and conjunctivitis 1 week before the vaccine, a previous paucisymptomatic SARS-CoV-2 infection was suspected and anti-SARS-Coronavirus Nucleocapsid Protein antibody test revealed high antibody levels with low IgG avidity. Given that myocarditic symptoms evolved after complete Sars-Cov2 symptom resolution, our first hypothesis is that the infection is unlikely to be the cause of acute myocarditis in this patient. Indeed, current literature on COVID-related myocarditis reports close temporal association between respiratory symptoms and myocarditis onset. In support to our hypothesis, recent trials have reported that myocarditis more frequently occurs following administration of mRNA vaccines especially in male adolescents and young adults like our patient. However, cardiac side effects typically occur after full vaccination and symptoms appear within three days following the second dose, which does not fully apply to this case. Notwithstanding this, more recent studies have reported myocarditis even after first vaccination dose in patients with previous COVID-19 infection, analogously to the case described. This case suggests a complex interaction between immunological factors and covid infection/vaccination with potential significant implications on the cardiovascular system. From current literature, much uncertainty remains regarding time interval criteria for reliable post-vaccination myocarditis diagnosis, hence large-scale clinical trials are needed to address this issue.

Aims: Cardiovascular sequelae in COVID-19 survivors remain largely unclear and can potentially go unrecognized. Reports on follow-up focused on cardiovascular evaluation after hospital discharge are currently scarce. Aim of this prospective study was to assess cardiovascular sequelae in previously hospitalized COVID-19 survivors. Methods and results: The study was conducted at 'Sapienza' University of Rome-Policlinico 'Umberto I'. After 2 months from discharge, n ¼ 230 COVID-19 survivors underwent a follow-up visit at a dedicated 'post-COVID Outpatient Clinic'. A cardiovascular evaluation including electrocardiogram (ECG), Troponin and echocardiography was performed. Further tests were requested when clinically indicated. Medical history, symptoms, arterial-blood gas, blood tests, chest computed tomography, and treatment of both in-hospital and follow-up evaluation were recorded. A 1-year telephone follow-up was performed. A total of 36 (16%) COVID-19 survivors showed persistence or delayed onset of cardiovascular disease at 2-months follow-up visit. Persistent condition was recorded in 62% of survivors who experienced an in-hospital cardiovascular disease. Delayed cardiovascular involvement included: myocarditis, pericarditis, ventricular disfunction, new onset of systemic hypertension and arrhythmias. At 1-year telephone follow-up, 105 (45%) survivors reported persistent symptoms, with dyspnoea and fatigue being the most frequent. 60% of survivors showed persistent chest CT abnormalities and among those 28% complained of persistent cardiopulmonary symptoms at long term follow-up. Conclusions: Our preliminary data showed persistent or delayed onset of cardiovascular involvement (16%) at short-term follow-up and persistent symptoms (45%) at long-term follow-up. These findings suggest the need for monitoring COVID-19 survivors.

288 The effects of cardiovascular diseases and treatment on clinical course of hospitalized COVID-19 patients

All patients underwent a cardiovascular evaluation including troponin, electrocardiogram (ECG), and echocardiogram. Data on medical history, pre-existing CVD, CV risk factors, and therapy were collected. Admission to the Intensive Care Unit (ICU) or Cardiac Intensive Care Unit (CICU), as well as the development of new-onset CVD, were considered as endpoint of the study. Among n ¼ 229 patients enrolled, 22 (10%) died. Nearly half of patients (112, 49%) were admitted to the ICU/CICU. The presence of prior ischaemic heart disease nearly doubled the probability of hospitalization in the ICU

Conclusions: Our study found that hospitalized COVID-19 patients who have at least one CV risk factor or pre-existing CVD had a greater likelihood of being admitted to the ICU/CICU and experiencing new onset CVD

Cardiac injury following immunization with mRNA SARS-CoV-2 vaccines

Massimo Vincenzo Bonfantino 1

3 Cardiology Unit

Aims: Cardiac involvement as myocarditis and/or pericarditis is now recognized as a rare but possible adverse event following SARS-CoV-2 mRNA vaccines. In this brief report we describe a series of four subjects: three of them with myocarditis and one with pericarditis probably due to hypersensitivity and developed in temporal association with COVID-19 mRNA vaccination. Methods and results: During last summer, we observed a series of four young Caucasian male [median (range) age, 25 (18-32) years] presenting to the Emergency Department with severe acute chest pain within few days after second dose COVID-19 mRNA vaccine administration [median (range), 3 (2-5) days]. All of these were previously healthy and fitness males. All patients had abnormal electrocardiogram (EKG) and three of them had elevated high sensitive cardiac I troponin (hs-cTnI) levels. These latter three were diagnosed as having myocarditis and undergone cardiac magnetic resonance imaging (CMR). None had acute or prior COVID-19 or pulmonary disease on chest X-ray. Moreover, ischaemic injury, other infections, adverse drug reactions or any autoimmune diseases were excluded by appropriate tests. All patients underwent ecocardiography which showed preserved ejection fraction and no wall motion abnormalities and it excluded coronary origin abnormalities in each patient. The hospital course was uneventful for all four patients and they were discharged within few days of hospitalization [median (range), 6 (3-8) days] after a conservative treatment. The four patients met CDC criteria for probable myocarditis and pericarditis. To date, it is recognized a possible clinical correlation between cardiac injury and SARS-CoV-2 mRNA vaccination. The following elements support this hypothesis: (i) short time lapse between vaccine administration and symptoms onset;