Influenza myocarditis in paediatric patients

Abstract Acute myocarditis is a rare but potentially fatal disease. Endomyocardial biopsy and histologic examination are key to an accurate diagnosis. Despite being an uncommon cause, Influenza A and B viruses are a well-documented aetiology. Myocarditis may complicate about 0 to 10% of influenza virus infections (0.4 to 5% in paediatric cases). The clinical presentation varies widely, from ischemic-like chest pain to fulminant myocarditis with acute hemodynamic compromise, requiring mechanical circulatory support, with high mortality in the acute phase. We report a series of paediatric patients with myocarditis due to Influenza virus, to emphasize the importance of considering this uncommon aetiology.

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Influenza A (H3N2) Induced Fulminant Myocarditis Requiring Mechanical Circulatory Support

JACC: Case Reports ◽

10.1016/j.jaccas.2019.06.006 ◽

2019 ◽

Vol 1 (2) ◽

pp. 133-137

Author(s):

John Hollowed ◽

Ali Nsair

Keyword(s):

Influenza A ◽

Mechanical Circulatory Support ◽

Fulminant Myocarditis ◽

Circulatory Support

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Fulminant myocarditis in a COVID-19 positive patient treated with mechanical circulatory support – a case report

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytaa523 ◽

2020 ◽

Author(s):

Joanna-Maria Papageorgiou ◽

Henrik Almroth ◽

Mattias Törnudd ◽

Henriëtte van der Wal ◽

Georgia Varelogianni ◽

...

Keyword(s):

Respiratory Failure ◽

Mechanical Circulatory Support ◽

Clinical Presentation ◽

Low Voltage ◽

Troponin T ◽

Left Ventricular ◽

Fulminant Myocarditis ◽

Circulatory Support ◽

Positive Polymerase Chain Reaction ◽

First Case

Abstract Background Coronavirus disease 2019 (COVID-19) spreading from Wuhan, Hubei province in China, is an expanding global pandemic with significant morbidity and mortality. Even though respiratory failure is the cardinal form of severe COVID-19, concomitant cardiac involvement is common. Myocarditis is a challenging diagnosis due to heterogeneity of clinical presentation, ranging from mild symptoms to fatal arrhythmia and cardiogenic shock (CS). The aetiology is often viral and endomyocardial biopsy (EMB) is the gold standard for definite myocarditis. However, the diagnosis is often made on medical history, clinical presentation, magnetic resonance imaging, and blood tests. Case summary We present a 43-year-old man with mixed connective tissue disease treated with hydroxychloroquine who rapidly developed CS 4 days from symptom onset with fever and cough, showing positive polymerase chain reaction nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. While computed tomography of the thorax was normal, high-sensitivity troponin T was elevated and electrocardiogram showed diffuse ST elevation and low voltage as signs of myocardial oedema. Echocardiography showed severe depression of left ventricular function. The myocardium recovered completely after a week with mechanical circulatory support (MCS). EMB was performed but could neither identify the virus in the cardiomyocytes, nor signs of inflammation. Still the most probable aetiology of CS in this case is myocarditis as a sole symptom of COVID-19. Discussion COVID-19 patients in need of hospitalization present commonly with respiratory manifestations. We present the first case of fulminant myocarditis rapidly progressing to CS in a COVID-19 patient without respiratory failure, successfully treated with inotropes and MCS.

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Myocarditis Associated with Influenza A H1N1pdm2009

Influenza Research and Treatment ◽

10.1155/2012/351979 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 17

Author(s):

Akira Ukimura ◽

Hidetoshi Satomi ◽

Yukimasa Ooi ◽

Yumiko Kanzaki

Keyword(s):

Influenza A ◽

Case Reports ◽

Acute Myocarditis ◽

Influenza Pandemic ◽

Influenza Infection ◽

Clinical Severity ◽

Fulminant Myocarditis ◽

Circulatory Support ◽

Influenza Pandemics ◽

2009 Influenza Pandemic

Acute myocarditis is a well-known complication of influenza infection. The frequency of myocardial involvement in influenza infection varies widely, with the clinical severity ranging from asymptomatic to fulminant varieties. The worst cases can result in death due to impaired cardiac function, although such fulminant myocarditis associated with influenza infection is rare, as shown by previous papers. Following the 2009 influenza pandemic, we reported on the clinical features of a cohort of 15 patients in Japan with H1N1pdm2009 myocarditis. In our subsequent survey of the literature for case reports or series of patients with myocarditis associated with H1N1pdm2009, we identified 58 detailed cases. We discuss here the high prevalence of fulminant myocarditis (36/58, 62%) among patients reported to have myocarditis associated with H1N1pdm2009. Mechanical circulatory support was required in 17 of the patients with fulminant myocarditis, 13 of whom recovered. We stress the need for increased awareness of influenza-associated myocarditis; such knowledge will facilitate earlier diagnosis and treatment of this fatal complication during future influenza pandemics.

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Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses

Scientific Reports ◽

10.1038/s41598-020-79590-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

James D. Allen ◽

Ted M. Ross

Keyword(s):

Influenza Virus ◽

Immune Responses ◽

Influenza A ◽

Seasonal Influenza ◽

Influenza Viruses ◽

Next Generation ◽

Virus Infections ◽

Wild Type ◽

Influenza Hemagglutinin ◽

H3n2 Influenza

AbstractWhile vaccines remain the best tool for preventing influenza virus infections, they have demonstrated low to moderate effectiveness in recent years. Seasonal influenza vaccines typically consist of wild-type influenza A and B viruses that are limited in their ability to elicit protective immune responses against co-circulating influenza virus variant strains. Improved influenza virus vaccines need to elicit protective immune responses against multiple influenza virus drift variants within each season. Broadly reactive vaccine candidates potentially provide a solution to this problem, but their efficacy may begin to wane as influenza viruses naturally mutate through processes that mediates drift. Thus, it is necessary to develop a method that commercial vaccine manufacturers can use to update broadly reactive vaccine antigens to better protect against future and currently circulating viral variants. Building upon the COBRA technology, nine next-generation H3N2 influenza hemagglutinin (HA) vaccines were designed using a next generation algorithm and design methodology. These next-generation broadly reactive COBRA H3 HA vaccines were superior to wild-type HA vaccines at eliciting antibodies with high HAI activity against a panel of historical and co-circulating H3N2 influenza viruses isolated over the last 15 years, as well as the ability to neutralize future emerging H3N2 isolates.

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Exacerbation of Influenza Virus Infections in Mice by Intranasal Treatments and Implications for Evaluation of Antiviral Drugs

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01664-12 ◽

2012 ◽

Vol 56 (12) ◽

pp. 6328-6333 ◽

Cited By ~ 15

Author(s):

Donald F. Smee ◽

Mark von Itzstein ◽

Beenu Bhatt ◽

E. Bart Tarbet

Keyword(s):

Influenza Virus ◽

Influenza A ◽

H1n1 Virus ◽

Antiviral Agent ◽

Virus Production ◽

Lung Pathology ◽

Virus Infections ◽

Challenge Dose ◽

Virus Challenge ◽

Time To Death

ABSTRACTCompounds lacking oral activity may be delivered intranasally to treat influenza virus infections in mice. However, intranasal treatments greatly enhance the virulence of such virus infections. This can be partially compensated for by giving reduced virus challenge doses. These can be 100- to 1,000-fold lower than infections without such treatment and still cause equivalent mortality. We found that intranasal liquid treatments facilitate virus production (probably through enhanced virus spread) and that lung pneumonia was delayed by only 2 days relative to a 1,000-fold higher virus challenge dose not accompanied by intranasal treatments. In one study, zanamivir was 90 to 100% effective at 10 mg/kg/day by oral, intraperitoneal, and intramuscular routes against influenza A/California/04/2009 (H1N1) virus in mice. However, the same compound administered intranasally at 20 mg/kg/day for 5 days gave no protection from death although the time to death was significantly delayed. A related compound, Neu5Ac2en (N-acetyl-2,3-dehydro-2-deoxyneuraminic acid), was ineffective at 100 mg/kg/day. Intranasal zanamivir and Neu5Ac2en were 70 to 100% protective against influenza A/NWS/33 (H1N1) virus infections at 0.1 to 10 and 30 to 100 mg/kg/day, respectively. Somewhat more difficult to treat was A/Victoria/3/75 virus that required 10 mg/kg/day of zanamivir to achieve full protection. These results illustrate that treatment of influenza virus infections by the intranasal route requires consideration of both virus challenge dose and virus strain in order to avoid compromising the effectiveness of a potentially useful antiviral agent. In addition, the intranasal treatments were shown to facilitate virus replication and promote lung pathology.

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In Vivo Influenza Virus-Inhibitory Effects of the Cyclopentane Neuraminidase Inhibitor RWJ-270201

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.3.749-757.2001 ◽

2001 ◽

Vol 45 (3) ◽

pp. 749-757 ◽

Cited By ~ 77

Author(s):

Robert W. Sidwell ◽

Donald F. Smee ◽

John H. Huffman ◽

Dale L. Barnard ◽

Kevin W. Bailey ◽

...

Keyword(s):

Influenza Virus ◽

Hong Kong ◽

Influenza A ◽

Arterial Oxygen Saturation ◽

Virus Titer ◽

Neuraminidase Inhibitor ◽

Arterial Oxygen ◽

Virus Infections ◽

Inhibitory Effects ◽

Lung Consolidation

ABSTRACT The cyclopentane influenza virus neuraminidase inhibitor RWJ-270201 was evaluated against influenza A/NWS/33 (H1N1), A/Shangdong/09/93 (H3N2), A/Victoria/3/75 (H3N2), and B/Hong Kong/05/72 virus infections in mice. Treatment was by oral gavage twice daily for 5 days beginning 4 h pre-virus exposure. The influenza virus inhibitor oseltamivir was run in parallel, and ribavirin was included in studies with the A/Shangdong and B/Hong Kong viruses. RWJ-270201 was inhibitory to all infections using doses as low as 1 mg/kg/day. Oseltamivir was generally up to 10-fold less effective than RWJ-270201. Ribavirin was also inhibitory but was less tolerated by the mice at the 75-mg/kg/day dose used. Disease-inhibitory effects included prevention of death, lessening of decline of arterial oxygen saturation, inhibition of lung consolidation, and reduction in lung virus titers. RWJ-270201 and oseltamivir, at doses of 10 and 1 mg/kg/day each, were compared with regard to their effects on daily lung parameters in influenza A/Shangdong/09/93 virus-infected mice. Maximum virus titer inhibition was seen on day 1, with RWJ-270201 exhibiting the greater inhibitory effect, a titer reduction of >104 cell culture 50% infective doses (CCID50)/g. By day 8, the lung virus titers in mice treated with RWJ-270201 had declined to 101.2 CCID50/g, whereas titers from oseltamivir-treated animals were >103CCID50/g. Mean lung consolidation was also higher in the oseltamivir-treated animals on day 8. Both neuraminidase inhibitors were well tolerated by the mice. RWJ-270201 was nontoxic at doses as high as 1,000 mg/kg/day. These data indicate potential for the oral use of RWJ-270201 in the treatment of influenza virus infections in humans.

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