key: cord-0830003-w9sfxkgw authors: Riedel, Patrícia Gabriela; Sakai, Vitoria Fedrizzi; Castro Cardoso Toniasso, Sheila de; Brum, Maria Carlota Borba; Fernandes, Fernando Schmidt; Pereira, Robson Martins; Baldin, Camila Pereira; Baldin, Cícero de Campos; Takahasi, Anderson Yudi; Sakai, Hugo; Kresky, Ana Maria Rocha; Macedo, Damasio Trindade; Merlo, Álvaro Roberto Crespo; Rohde, Luis Eduardo Paim; Joveleviths, Dvora title: Heart failure secondary to myocarditis after SARS-CoV-2 reinfection: a case report date: 2021-10-21 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2021.10.031 sha: 5f13aacb0a87acf4db457feb333533bf9112fc68 doc_id: 830003 cord_uid: w9sfxkgw Introduction: Cardiac involvement in COVID-19 can range from mild damage to severe myocarditis. The precise mechanism by which COVID-19 causes myocardial injury is still unknown. Myocarditis following administration of COVID-19 vaccines, especially those based on mRNA, has also been described. However, no reports of heart failure following reinfection with COVID-19 in patients immunized with an inactivated vaccine have been identified. Case description: Male, 47-year-old, of African descent, construction worker, with type II diabetes, with a history of infection by SARS-CoV-2 in December 2020 and May 2021, confirmed by RT-PCR. Received two doses of an inactivated vaccine against COVID-19. Between the two COVID-19 episodes with positive RT-PCR he had two episodes of bacterial lung infection. After the second episode of SARS-CoV-2 infection, he was diagnosed with severe heart failure as a sequelae of myocarditis. Conclusion: It is essential to do a proper follow-up after infection by SARS-CoV-2, since even with proper immunization, there is a possibility that the patient was reinfected and had severe cardiac sequelae as a consequence, and the hypothesis of an etiology associated with the use of an inactivated vaccine against COVID-19 with a potential immune enhancement mechanism following re-infection with SARS-CoV-2 cannot be rejected. Introduction: Cardiac involvement in COVID-19 can range from mild damage to severe myocarditis. The precise mechanism by which COVID-19 causes myocardial injury is still unknown. Myocarditis following administration of COVID-19 vaccines, especially those based on mRNA, has also been described. However, no reports of heart failure following reinfection with COVID-19 in patients immunized with an inactivated vaccine have been identified. Case description: Male, 47-year-old, of African descent, construction worker, with type II diabetes, with a history of infection by in December 2020 and May 2021, confirmed by RT-PCR. Received two doses of an inactivated vaccine against COVID-19. Between the two COVID-19 episodes with positive RT-PCR he had two episodes of bacterial lung infection. After the second episode of SARS-CoV-2 infection, he was diagnosed with severe heart failure as a sequelae of myocarditis. Conclusion: It is essential to do a proper follow-up after infection by SARS-CoV-2, since even with proper immunization, there is a possibility that the patient was reinfected and had severe cardiac sequelae as a consequence, and the hypothesis of an etiology associated with the use of an inactivated vaccine against COVID-19 with a potential immune enhancement mechanism following re-infection with SARS-CoV-2 cannot be rejected. Keywords: COVID-19, SARS-CoV-2, myocarditis, heart failure, vaccine Cardiac involvement in COVID-19 can range from mild damage to severe myocarditis. SARS-CoV-2 binds with high affinity to the human angiotensin-converting enzyme receptor 2 (ACE 2), which is expressed in the entire body, including the heart. Severe systemic manifestations, such as myocarditis, have been reported in association with the coronavirus disease 2019 (COVID-19) (Kerneis et al., 2020; Hamming et al., 2004) . Some COVID-19 patients have persistent tachycardia, sustained asymptomatic hypotension, and bradycardia (Huang et al., 2020) . Higher mortality has been demonstrated in patients with COVID-19; specifically, in patients who had acute myocarditis and acute myocardial infarction (AMI), as well as rapid-onset heart failure ). The precise mechanism by which COVID-19 causes myocardial injury is still unknown. However, it is suspected that the main mechanisms involved in the myocardial lesions are direct damage to cardiomyocytes caused by systemic inflammation, myocardial interstitial fibrosis, exaggerated cytokine response by Type-1 and Type-2 T-helper cells, destabilization of coronary plaque, hypoxia and interferonmediated immune responses (Babapoor-Farrokhran et al., 2020) . There is concern about possible cases of myocarditis associated with vaccine administration. Myocarditis following administration of COVID-19 vaccines, especially those based on mRNA, has also been described (CDC, 2021) . However, no reports of heart failure following reinfection with COVID-19 in patients immunized with an inactivated vaccine have been identified .The incidence of myocarditis and pericarditis, to date, regardless of the type of vaccine applied is low, having been reported in a previous study as 2-3 cases of myocarditis/pericarditis per million doses applied ( Cai C et al, 2021) . Male, 47 years old, of African descent, construction worker, with type II diabetes, with a history of infection by SARS-CoV-2 with confirmed diagnosis by RT-PCR (reverse transcriptase reaction followed by polymerase chain reaction) on December 10, 2020, when presented mild flu-like symptoms (cough, rhinitis and myalgia). On February 10, 2021, he presented bronchopneumonia, identified by a chest X-ray and was treated with the antibiotics azithromycin and amoxicillin with clavulanic acid, his symptoms improved, and RT-PCR was not performed. He received the first dose of the Sinovac immunizing agent, an inactivated vaccine against COVID-19, on In June 2, 2021, he presented tiredness and fatigue on minimal exertion, associated with feelings of suffocation and orthopnea that had started two days before, requiring hospitalization. An echocardiogram identified diffuse hypokinesia, ejection fraction of 15%, severe pulmonary arterial hypertension (PASP 71 mmHg), exercise testing with non-sustained polymorphic ventricular tachycardia. During hospitalization, he presented 52 pg/mL troponin I, dilated and hypokinetic LV and RV in cardiac MRI, biatrial dilation, mitral and tricuspid insufficiency, late enhancement of non-ischemic aspect, in addition to negative serology for Chagas disease, syphilis and viral diseases. He evolved with clinical improvement, persisting with fatigue and dyspnea on moderate exertion, is still being followed up in an outpatient clinic, with a diagnosis of heart failure probably secondary to myocarditis sequelae, following immunization with an inactivated SARS-CoV-2 virus vaccine associated with a probable reinfection. Figure 1 depicts the case history timeline. Myocarditis is an inflammation of the myocardium which can be caused by a variety of infectious (viruses, bacteria and protozoa) and non-infectious diseases (Bozkurt et al., 2021) . There are case reports of myocarditis and pericarditis following vaccination with mRNA COVID-19 immunizing agent, mostly in male adolescents, after a few days of vaccination against COVID-19 and, more often, after the second dose, just like what occurred with our patient (CDC, 2021). Among the adverse effects after the SARS-COV2 vaccine, the most frequent were: pain, fatigue and headache, in addition to edema, fever, joint pain, muscle pain ( Cai et al, 2021) Study demonstrated that no serious adverse events were reported within 28 days after application of inactivated live virus vaccine (Xia S et al,2021; Saeed et al, 2021 . Previous diagnosis of COVID-19 may provide a protective factor for a new COVID-19 infection (Toniasso et al., 2021) . However, this patient, even with a previous COVID-19 infection, when developing symptoms after the second dose of the SARS-CoV-2 vaccine, raises interesting possibilities about a potential immune enhancement mechanism following previous immune exposure (Shaw et al., 2021) . In addition, this report, with myocarditis and severe heart failure, involving the COVID-19 inactivated virus vaccine associated with probable reinfection, is not yet described in the literature, thus reinforcing the need for better knowledge of the natural history of COVID-19 and its sequelae (Boff et al, 2020) . Studies report that almost all patients with vaccinerelated myocarditis had a resolution of the signs and symptoms and showed improvement, in addition to improved diagnostic and imaging markers with or without treatment (Singh et al., 2021) . However, this was not observed in our patient, who suffers from cardiac sequelae with severe heart failure. The case reported reinforces the importance of an adequate interdisciplinary follow-up after SARS-CoV-2 infection with greater surveillance and evaluation of the adverse event after immunization, because even with adequate immunization, there is a possibility that the patient has been reinfected, presenting severe cardiac sequelae. The etiological hypothesis for this case of myocarditis and heart failure may be related to the patient's previous history of diabetes mellitus (risk factor for myocarditis) aggravated by the use of the inactivated vaccine against COVID-19 as a potential mechanism of immune reinforcement after recurrent infection with SARS -CoV-2. The researchers declare that they have no conflicts of interest. The study was financial support was provided by the Research Incentive Fund (FIPE) of Hospital de Clínicas de Porto Alegre. The study was approved by the Research Ethics Committee of Hospital de Clínicas de Porto Alegre. Title: Heart failure secondary to myocarditis after SARS-CoV-2 reinfection: a case report Rio Grande do Sul 2350, Brazil. Email: djoveleviths@hcpa.edu.br a-Medical student at Hospital de Clínicas de Porto Alegre Rio Grande do Sul, Brazil. c-Physician at the Cardiology Medicine Service at Hospital de Clínicas de Porto Alegre Myocardial injury and COVID-19: possible mechanisms COVID-19: concern about interrupting social isolation of healthcare workers and professionals. What should be done with the results of the available COVID-19 diagnostic tests? Myocarditis with COVID-19 mRNA Vaccines A comprehensive analysis of the efficacy and safety of COVID-19 vaccines Myocarditis and Pericarditis Following mRNA COVID-19 Vaccination Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. 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