Successful treatment of fulminant neonatal enteroviral myocarditis in monochorionic diamniotic twins with cardiopulmonary support, intravenous immunoglobulin and pocapavir

Abstract

Neonatal cardiogenic shock most commonly occurs due to critical congenital heart disease, sepsis, metabolic disorder or arrhythmias. In particular, enterovirus infections are common in the neonatal period, and patients can present with fulminant myocarditis. Early recognition is imperative due to its high morbidity and mortality without prompt and aggressive treatment. We present the successful treatment of fulminant neonatal enteroviral myocarditis in a pair of monochorionic diamniotic twins with cardiopulmonary support, intravenous immunoglobulin and pocapavir, an enteroviral capsid inhibitor. The twins took an almost exact parallel hospital course, including day of extracorporeal membrane oxygenation (ECMO) cannulation, day of ECMO decannulation, improvement of cardiac function, discharge and status at follow-up. While it was difficult to assess the relative contribution of each intervention, our case shows promise in the use of pocapavir for treatment of severe enteroviral infections. Remarkably, both twins demonstrated remarkable recovery within 2 weeks, underscoring that early aggressive cardiopulmonary support, and potentially pocapavir, contributed to their recovery.

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions

“…In the past two decades, B19V and HHV6 have been more frequently detected in EMB samples from patients with myocarditis than enteroviruses or adenoviruses, and approximately 30% of patients have multiple viral infections 10 , 14 . In infants, a high number of cases of acute enterovirus myocarditis has been observed in the past 5 years 15 – 17 . In general, the detection frequency of the viruses associated with inflammatory cardiomyopathy has changed over time, partly influenced by the evaluation of a broader repertoire of viruses (Fig.…”

“…Trial participants with enterovirus-positive myocarditis or adenovirus-positive myocarditis (as assessed with EMB) showed viral clearance after treatment with IFNβ 26 , 260 , but IFNβ therapy was not associated with viral DNA clearance in patients with B19V-positive myocarditis 146 , 260 . The antiviral drugs pocapavir and pleconaril as well as IVIG therapy are effective in neonates with enteroviral myocarditis 15 – 17 . In patients with latent infection with Epstein–Barr virus, cytomegalovirus or HHV6, the use of anti-herpesvirus drugs is an option to reduce viral copy numbers 261 .…”

Antifungal Triazole Posaconazole Targets an Early Stage of the Parechovirus A3 Life Cycle

“…Members of a class of antienteroviral compounds known as capsid inhibitors exert their antiviral effect by inserting into the hydrophobic pocket in the virus canyon and replacing a lipid pocket factor, thereby preventing virus uncoating (29)(30)(31). Recently completed clinical trials of capsid inhibitors pleconaril and pocapavir have demonstrated safety and efficacy (32,33), and studies using pocapavir as a treatment for enterovirus infection in neonates have shown some success (34)(35)(36). Recently, a novel early-stage capsid inhibitor, 4-dimethylaminobenzoic acid (4EDMAB), was shown to inhibit replication of coxsackievirus B3 (CVB3) with a mechanism targeting the capsid outside the typical binding pocket (37).…”

Genetic Basis of Myocarditis: Myth or Reality?

“…Reasons to suspect a genetic susceptibility in infectious myocarditis may derive from twin studies (usually newborn or children) [16][17][18], familial clustering suggesting genetic determinants or predisposing genetic factors [19][20][21], and rare Mendelian diseases [22,23] as well as endemic infections linked to both pathogen and population genetic make-up [24]. The topic must be discussed with caution so as not to transform infectious diseases into genetic ones, especially as the distinction between genetic susceptibility from exclusive environmental factors that might aggregate within families can be difficult.…”