Monkeypox: Myocarditis attributable to monkeypox virus infection in US
The US CDC have issued a warning concering two cases of possible cases of myocarditis in patients infected with monkeypox.
The clinical course of human monkeypox is milder than that of smallpox in immunocompetent hosts. However, severe complications have been identified, including pneumonitis, encephalitis, eyesight-threatening keratitis, secondary bacterial infections, acute kidney injury, and myocarditis. Thornhill et al. recently reported 2 cases of self-limited myocarditis in patients with monkeypox that resolved within 7 days without major complications; 1 patient had a history of HIV with a normal CD4 cell count. Similarly, the patients in our report improved 10–12 days after illness onset; 1 patient received tecovirimat, an inhibitor of the orthopoxvirus VP37 envelope-wrapping protein that prevents the formation of egress-competent enveloped virions and has been shown to decrease circulating viral DNA in a nonhuman primate model.
Many viruses have been associated with myocarditis. The most common pathophysiology of viral myocarditis is lymphocytic myocarditis associated with myonecrosis that occurs 10–14 days postinfection; illness can be either self-limiting or result in fulminant myocarditis. In some cases, viral myocarditis can progress to a noninfectious chronic phase, characterized by myocardial fibrosis, cardiac dysfunction, and dilated cardiomyopathy.
Myocardial involvement of orthopox infections was initially reported when myocarditis was observed after smallpox vaccination with replicating vaccinia-based vaccines in young military recruits. The pathophysiology of orthopox-induced myocarditis remains unknown. However, an autoimmune-mediated phenomenon has been postulated because of the absence of direct viral infection of the myocytes observed on histopathologic examination of samples from vaccinees with myocarditis (10). Most cases are mild and self-limited; major sequelae, such as dilated cardiomyopathy, are rare.
Hemorrhagic smallpox, the most severe manifestation of variola major, is characterized by rapid onset fever, rash, and disseminated intravascular coagulation. Anatomopathologic studies in hemorrhagic smallpox patients showed myocardial and endocardial hemorrhages. In a macaque model of hemorrhagic smallpox, histopathologic tests at day 6 or 7 postexposure showed acute lymphohistiocytic myocarditis with myocardiocyte degeneration and hemorrhage, primarily driven by direct viral myocardial injury and mediated by CD14 monocytes, chemotactic cytokines, and interleukin 6. Therefore, we hypothesize that direct myocardial infiltration associated with monkeypox viremia may also result in myocarditis and that antiviral agents could play a role in treatment.
CDC: Myocarditis Attributable to Monkeypox Virus Infection in 2 Patients, United States, 2022
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