key: cord-1012251-p3ibcsfj
authors: Ammirati, Enrico; Cavalotti, Cristina; Milazzo, Angela; Pedrotti, Patrizia; Soriano, Francesco; Schroeder, Jan W.; Morici, Nuccia; Giannattasio, Cristina; Frigerio, Maria; Metra, Marco; Camici, Paolo G.; Oliva, Fabrizio
title: Temporal Relation Between Second Dose BNT162b2 mRNA Covid-19 Vaccine and Cardiac involvement in a Patient with Previous SARS-COV-2 Infection
date: 2021-04-05
journal: Int J Cardiol Heart Vasc
DOI: 10.1016/j.ijcha.2021.100778
sha: 388bbd11dc0e64c132a8f8a6671fbb838d21d9f7
doc_id: 1012251
cord_uid: p3ibcsfj

nan

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Coronavirus disease (COVID)-19 caused by severe acute respiratory syndrome coronarvirus (SARS-COV)-2 infection has been demonstrated to be associated with cardiac injury [1] [2] [3] . Cases of acute myocarditis have been reported, even in patients with COVID-19 in the absence of significant lung involvement, suggesting a viral triggered immune-mediated injury [4] . The modified RNA vaccines, the BNT162b2 and mRNA-1273, that encode the prefusion SARS-COV-2 spike glycoprotein, have shown to confer 94-95% protection against COVID-19 with a safe profile [5, 6] . Although these vaccines can counteract the COVID-19 pandemic, there is apprehension for patients who experienced previous SARS-COV-2 infection, as these subjects have not been tested in the trials [5] . Systemic reactogenicity, leading to systemic adverse events often occurred after dose 2 and within 2 days after vaccination [5] . The present report describes a case of cardiac infection with fever lasting for 3 days and cough for 1 week, but he did not complain of chest pain or dyspnea. He was not hospitalized, and he took only acetaminophen. Nasopharyngeal swabs by real-time reverse-transcriptase-polymerase-chain-reaction (rRT-PCR) assay, had been persistently positive for 1 month while he did not undergo any blood tests during that period.

One month later, anti-SARS-COV-2 serology demonstrated presence of IgG anti S1 and S2

proteins (titer of 60 AU/mL with positive threshold above 15).

On arrival at the emergency department arterial blood pressure was 165/95 mmHg, heart rate 81 beats per minute, oxygen saturation 99% while breathing ambient air and body temperature 36.2°C. Electrocardiogram (ECG) showed sinus rhythm, and minimal ST elevation on precordial leads, with peaked T waves. The chest x-ray was unremarkable (Supplemental Figure 1A -B).

Laboratory tests revealed elevated levels of biomarkers of myocardial necrosis, i.e. highsensitivity (hs) troponin T 289 ng/L, and C-reactive protein 2.9 mg/L with normal blood cell counts, without evidence of peripheral eosinophilia ( Table 1) . Urgent coronary angiography carried out to rule out an acute coronary syndrome (Figure 1A-1B) . Cardiac ventriculography showed preserved global left ventricular function. Chest pain resolved spontaneously within 4 hours of admission. The patient was therefore transferred to the cardiology ward with a diagnosis of suspected acute myocarditis. He underwent nasopharyngeal swabbing and the specimens were tested for common respiratory viruses by RT-PCR and resulted all negative. As expected,

anti-SARS-COV-2 serology revealed a high-titer of IgG anti S1 and S2 proteins (titer >400 AU/mL), and positive anti-nucleocapsid antibodies due to previous exposure. Hs-troponin T and CK-MB Ventricular arrhythmias can occur as consequence of an inflammatory cardiac injury [8, 9] , and they were frequently observed in patients with COVID19 and cardiac injury [3] . Two deaths were documented during the trial and were judged as unrelated, although in one case a cardiac arrest occurred [5] . No reports of acute myocarditis were observed in the BNT162b2 mRNA and mRNA-1273 trials. Acute myocarditis can be underestimated in clinical trials. Myocarditis must be actively searched as observed in anticancer agent studies involving immune checkpoints inhibitors [10, 11] . The expected long-term prognosis of the patient we reported is good [12] .

Acute myocarditis can occur following vaccination [13] , and smallpox vaccination has been frequently associated with eosinophilic myocarditis [14] . In the present case, no peripheral eosinophilia and no signs suggesting a hypersensitivity reaction (rush and fever) were observed, thus eosinophilic myocarditis appears unlikely. As a potential explanation of myocarditis, it is possible that molecular mimicry between viral proteins of SARS-CoV-2 and cardiac structures can explain at least partially the high incidence of cardiac injury observed during COVID-19. Thus, in predisposed individuals, also an immune response against the viral spike glycoprotein could confer a risk for immune-mediated organ injury. Alternatively, the cardiac injury could derive from a nonspecific inflammatory response secondary to vaccination [15] . Hypothetically, both mechanisms might explain the observed acute myocarditis. In conclusion, our case report suggests that pharmacovigilance on cardiac injury could be considered, especially with suspected or confirmed previous history of COVID-19 aimed to actively search for acute myocarditis when chest pain or discomfort is reported.

No Author had potential conflicts of interest involving the work under consideration for publication. EA received honoraria for participation to advisory board from Kiniksa Pharmaceutical in the last 3 years. Furthermore, anti-ANA, -ENA and -nDNA tests were negative, rheumatoid factor, and complement C3 and C4 levels were within the normal ranges. Figure 1 

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