Coinfection of Parvovirus B19 with Influenza A/H1N1 Causes Fulminant Myocarditis and Pneumonia. An Autopsy Case Report

Parvovirus-B19 (PVB19) is a frequent causative agent of myocarditis. For unclear reasons, viral reactivation can cause acute myocarditis, a leading cause of sudden death in the young. Influenza A/H1N1(2009) virus (IAV/H1N1) is known for causing flu/pneumonia, but the heart is rarely involved. Co-infections of cardiotropic viruses are rarely reported and the mechanisms of viral interactions remain unknown. A 5-year old girl had a flu-like syndrome, when she suddenly presented with a respiratory distress and cardiac arrest. At autopsy, the lungs were found haemorrhagic. Lungs’ histology showed severe bronchiolitis, diffuse haemorrhagic necrosis, and mononuclear inflammation. In the heart, a moderate inflammation was found with no necrosis. IAV/H1N1 was detected in nasal and tracheal swabs, lungs, and the heart. The viral load was high in the lungs, but low in the heart. PVB19 was detected in the heart with a high viral load. Viral co-infection increases the risk of severe outcome but the mechanisms of interaction between viruses are poorly understood. In our case, viral loads suggested a reactivated PVB19-induced acute myocarditis during an IAV/H1N1 pneumonia. Viral interactions may involve an IAV/H1N1-induced cytokine storm, with a fulminant fatal outcome. Clinically, our case shows the importance of investigating inflammatory pathways as therapeutic targets.

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Faculty Opinions recommendation of Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1040866.490920 ◽

2006 ◽

Author(s):

James Crowe

Keyword(s):

Viral Load ◽

Influenza A ◽

Fatal Outcome ◽

High Viral Load ◽

Human Influenza

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Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia

Nature Medicine ◽

10.1038/nm1477 ◽

2006 ◽

Vol 12 (10) ◽

pp. 1203-1207 ◽

Cited By ~ 1207

Author(s):

Menno D de Jong ◽

Cameron P Simmons ◽

Tran Tan Thanh ◽

Vo Minh Hien ◽

Gavin J D Smith ◽

...

Keyword(s):

Viral Load ◽

Influenza A ◽

Fatal Outcome ◽

High Viral Load ◽

Human Influenza

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Faculty Opinions recommendation of Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1040866.497053 ◽

2006 ◽

Author(s):

Tim Uyeki

Keyword(s):

Viral Load ◽

Influenza A ◽

Fatal Outcome ◽

High Viral Load ◽

Human Influenza

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A patient who survived 2009 influenza A/H1N1-associated fulminant myocarditis with percutaneous cardiopulmonary support (PCPS)

Nihon Kyukyu Igakukai Zasshi ◽

10.3893/jjaam.21.804 ◽

2010 ◽

Vol 21 (9) ◽

pp. 804-810

Author(s):

Noriyuki Hattori ◽

Yasumasa Morita ◽

Mayuh Katoh ◽

Nobuaki Shikama ◽

Naoki Ishio ◽

...

Keyword(s):

Influenza A ◽

Fulminant Myocarditis ◽

Percutaneous Cardiopulmonary Support ◽

Cardiopulmonary Support ◽

Influenza A H1n1

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Convalescent Plasma Treatment Reduced Mortality in Patients With Severe Pandemic Influenza A (H1N1) 2009 Virus Infection

Clinical Infectious Diseases ◽

10.1093/cid/ciq106 ◽

2011 ◽

Vol 52 (4) ◽

pp. 447-456 ◽

Cited By ~ 299

Author(s):

Ivan FN Hung ◽

Kelvin KW To ◽

Cheuk-Kwong Lee ◽

Kar-Lung Lee ◽

Kenny Chan ◽

...

Keyword(s):

Intensive Care ◽

Viral Load ◽

Treatment Group ◽

Respiratory Tract ◽

Plasma Treatment ◽

Pandemic Influenza ◽

Influenza A ◽

Control Group ◽

Severity Scores ◽

Influenza A H1n1

Background. Experience from treating patients with Spanish influenza and influenza A(H5N1) suggested that convalescent plasma therapy might be beneficial. However, its efficacy in patients with severe pandemic influenza A(H1N1) 2009 virus (H1N1 2009) infection remained unknown. Methods. During the period from 1 September 2009 through 30 June 2010, we conducted a prospective cohort study by recruiting patients aged ≥18 years with severe H1N1 2009 infection requiring intensive care. Patients were offered treatment with convalescent plasma with a neutralizing antibody titer of ≥1:160, harvested by apheresis from patients recovering from H1N1 2009 infection. Clinical outcome was compared with that of patients who declined plasma treatment as the untreated controls. Results. Ninety-three patients with severe H1N1 2009 infection requiring intensive care were recruited. Twenty patients (21.5%) received plasma treatment. The treatment and control groups were matched by age, sex, and disease severity scores. Mortality in the treatment group was significantly lower than in the nontreatment group (20.0% vs 54.8%; P = .01). Multivariate analysis showed that plasma treatment reduced mortality (odds ratio [OR], .20; 95% confidence interval [CI], .06-.69; P = .011), whereas complication of acute renal failure was independently associated with death (OR, 3.79; 95% CI, 1.15-12.4; P = .028). Subgroup analysis of 44 patients with serial respiratory tract viral load and cytokine level demonstrated that plasma treatment was associated with significantly lower day 3, 5, and 7 viral load, compared with the control group (P < .05). The corresponding temporal levels of interleukin 6, interleukin 10, and tumor necrosis factor α (P < .05) were also lower in the treatment group. Conclusions. Treatment of severe H1N1 2009 infection with convalescent plasma reduced respiratory tract viral load, serum cytokine response, and mortality.

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Virus-Associated Hemophagocytic Syndrome Contributes to Fatal Outcome In Critical Ill Patients with 2009 Influenza A (H1N1) Infection.

Blood ◽

10.1182/blood.v116.21.3795.3795 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3795-3795

Author(s):

Gernot Beutel ◽

Olaf Wiesner ◽

Matthias Eder ◽

Jan T. Kielstein ◽

Carsten Hafer ◽

...

Keyword(s):

Organ Failure ◽

Critically Ill ◽

Critically Ill Patients ◽

Influenza A ◽

Hemophagocytic Syndrome ◽

Fatal Outcome ◽

Multiple Organ ◽

H1n1 Infection ◽

Viral Shedding ◽

Influenza A H1n1

Abstract Abstract 3795 Introduction: Virus-associated hemophagocytic syndrome (VAHS) is a severe complication of various viral infections often resulting in multiple organ failure syndrome and death. Based on previous experience with seasonal (H3N2) and avian (H5N1) infections the 2009 influenza A (H1N1) virus offers the potency of VAHS-development resulting in an aggressive and life-threatening disease. Most patients infected by the novel human influenza A (H1N1) experienced a mild clinical course; however some patients become critically ill with respiratory failure requiring intensive care and ventilator support. Multiple organ failure was one of the leading causes of death suggesting that patients with severe influenza A (H1N1) infection may develop a virus-associated hemophagocytic syndrome (VAHS). Methods: To evaluate frequency, clinical course and outcome of VAHS in critically ill patients a prospective observational study was performed at a single center intensive care unit in Hannover, Germany. Collected data include demographics, comorbid conditions, viral shedding, diagnosis of VAHS, illness progression, treatments and survival. VAHS was suspected when patients developed fever, cytopenia affecting at least two lineages, hepatitis or splenomegaly, hemophagocytosis in bone marrow samples and/or increased serum levels of sIL-2R and ferritin. Diagnosis of VAHS was made according to established HLH-diagnostic criteria. Primary outcome variables were the development of VAHS and VAHS-associated mortality. Results: Between October 5, 2009 and January 4, 2010 twenty five consecutive critically ill patients with RT-PCR confirmed 2009 influenza A (H1N1) infection and respiratory failure were identified. VAHS developed in nine out of 25 (36%) patients. Treatment of VAHS was started in 6 out of the 9 patients; three patients showed terminal disease and were no longer considered candidates for treatment with etoposide and dexamethasone. Despite VAHS-directed therapy, 5 out of the 6 patients died from uncontrolled progress leading to multiorgan failure. Overall, 8 out of the nine patients (89%) with confirmed VAHS died. In contrast, the mortality rate in the remaining 16 patients without VAHS was 25% (p=0.004). Patients were young (median, 45 [IQR, 35–56] years), however 18 (72%) presented one or more risk factors for a severe course of influenza illness. All 25 patients received mechanical ventilation for severe acute respiratory distress syndrome and refractory hypoxemia with duration of mechanical ventilation of median (IQR) 19 (13-26) days. Additionally 17 patients (68%) required extracorporeal membrane oxygenation for median (IQR) 10 (6-19) days. Oseltamivir and zanamivir were used as antiviral treatment in 24 patients (96%) for a median (IQR) of 7 (4-10) days and in 15 patients (60%) for a median (IQR) of 7 (5-12) days, respectively. The median (IQR) duration of viral shedding from disease-onset to the last positive H1N1 RT-PCR was 19 (14-26) days. In patients without VAHS the median (IQR) viral shedding time was 15 (12-22) days as opposed to 21 (14-26) days (p=0.13) in patients with VAHS. Conclusion: The present case series confirms previous post mortem analysis that severe influenza A (H1N1) infection is an important contributor to the development of VAHS in critically ill patients. Development of VAHS was associated with fatal outcome showing rapid clinical deterioration and multi organ failure syndrome and either contributes greatly to, or is itself causative of death in this patient population. Our findings are preliminary but potentially have important implications for future management of patients with influenza A (H1N1) disease as well as other severe virus infections which can induce secondary hemophagocytic syndromes. Disclosures: No relevant conflicts of interest to declare.

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Clinical manifestations, therapy and outcome of pandemic influenza a (H1N1) 2009 in hospitalized patients

Vojnosanitetski pregled ◽

10.2298/vsp1103248m ◽

2011 ◽

Vol 68 (3) ◽

pp. 248-256 ◽

Cited By ~ 2

Author(s):

Dragan Mikic ◽

Darko Nozic ◽

Miroslav Kojic ◽

Svetlana Popovic ◽

Dejan Hristovic ◽

...

Keyword(s):

Risk Factors ◽

Respiratory Failure ◽

Acute Respiratory Failure ◽

Antiviral Therapy ◽

Pandemic Influenza ◽

Influenza A ◽

Laboratory Tests ◽

Fatal Outcome ◽

Severe Illness ◽

Influenza A H1n1

Background/Aim. Increasing number of epidemiological and clinical studies to date showed that the pandemic influenza A (H1N1) 2009, by its characteristics, significantly differs from infection caused by seasonal influenza. Therefore, the information about clinical spectrum of manifestations, risk factors for severe form of the disease, treatment and outcome in patients with novel flu are still collected. Methods. A total of 98 patients (mean age 32 ? 15 years, range 14-88 years) with the signs and symptoms of novel influenza were treated in the Clinic for Infectious and Tropical Diseases, Military Medical Academy. There were 74 (75.5%) patients with suspected influenza A (H1N1) 2009, 10 (10.2%) with the likelihood and 14 (14.3%) with the confirmed influenza. In all the patients we registered the basic demographic data, risk factors for severe disease, symptoms and signs of influenza, laboratory tests and chest radiography. We analyzed antiviral therapy use and disease outcome (survived, died). Results. The average time from the beginning of influenza A (H1N1) to the admission in hospital was 3 days (0-16 days) and from the moment of hospitalization to the Intensive Care Unit (ICU) admission was 2 days (0-5 days). There were 49 (50.0%) patients, 20-29 years of age and 5 (5.1%) patients older than 65. A total of 21 (21.4%) patients were with underlying disease, 18 (18.4%) were obese, 19 (19.4%) were cigarette smokers. All of the patients had fever, 81 (82.6%) cough, while dyspnea and diarrhea were registered in ? of the patients. In more than 75% of the patients laboratory tests were within normal limits. The realtime polymerase chain reaction (PCR) test for identification of influenza A (H1N1) 2009 was positive in 14 (77.8%), while pneumonia was verified in 30 (30.7%) of the patients. Six (6.1%) patients, mean age of 45 ? 14 years (31-59 years) were admitted to the ICU, of whom five (5.1%) had Adult Respiratory Distress Syndrome (ARDS). Risk factors were registered more frequently in the patients with acute respiratory failure (14.2% vs 4.9%, p < 0.05). A total of 67 (68.4%) patients received oseltamivir, 89 (90.1%) was applied to antibiotics and 64 (65.3%) were treated with a combined therapy. Antiviral therapy was applied to 43 (43.3%) patients in the first 48 hours from the onset of the disease, of whom only one (3.4%) developed ARDS. Fatal outcome was noted in 2.0% of the patients (2 of 98 patients) and in 33.3% of the patients treated in the ICU. Conclusion. Novel influenza A (H1N1) is most commonly manifested as a mild acute respiratory disease, which usually affects young healthy adults. A small number of the patients develop severe illness with acute respiratory failure and death. Patients seem to have benefit from antiviral therapy especially in first 48 hours.

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Performance of laboratory diagnostics for the detection of influenza A(H1N1)v virus as correlated with the time after symptom onset and viral load

Journal of Clinical Virology ◽

10.1016/j.jcv.2009.11.022 ◽

2010 ◽

Vol 47 (2) ◽

pp. 182-185 ◽

Cited By ~ 38

Author(s):

Peter K.C. Cheng ◽

Kitty K.Y. Wong ◽

Gannon C. Mak ◽

Ann H. Wong ◽

Anita Y.Y. Ng ◽

...

Keyword(s):

Viral Load ◽

Symptom Onset ◽

Influenza A ◽

Laboratory Diagnostics ◽

Influenza A H1n1

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TNFA and IL10 Polymorphisms and IL-6 and IL-10 Levels Influence Disease Severity in Influenza A(H1N1)pdm09 Virus Infected Patients

Genes ◽

10.3390/genes12121914 ◽

2021 ◽

Vol 12 (12) ◽

pp. 1914

Author(s):

Kalichamy Alagarasu ◽

Himanshu Kaushal ◽

Pooja Shinde ◽

Mahadeo Kakade ◽

Urmila Chaudhary ◽

...

Keyword(s):

Disease Severity ◽

Influenza A ◽

Severe Disease ◽

Fatal Outcome ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Mild Disease ◽

Pdm09 Virus ◽

Potential Biomarker ◽

Influenza A H1n1

Cytokines are key modulators of immune response, and dysregulated production of proinflammatory and anti-inflammatory cytokines contributes to the pathogenesis of influenza A(H1N1)pdm09 virus infection. Cytokine production is impacted by single nucleotide polymorphisms (SNPs) in the genes coding for them. In the present study, SNPs in the IL6, TNFA, IFNG, IL17A, IL10, and TGFB were investigated for their association with disease severity and fatality in influenza A(H1N1)pdm09-affected patients with mild disease (n = 293) and severe disease (n = 86). Among those with severe disease, 41 patients had fatal outcomes. In a subset of the patients, levels of IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17 were assayed in the plasma for their association with severe disease. The frequency of TNFA rs1800629 G/A allele was significantly higher in severe cases and survived severe cases group compared to that of those with mild infection (OR with 95% for mild vs. severe cases 2.95 (1.52–5.73); mild vs. survived severe cases 4.02 (1.84–8.82)). IL10 rs1800896-rs1800872 G-C haplotype was significantly lower (OR with 95% 0.34 (0.12–0.95)), while IL10 rs1800896-rs1800872 G-A haplotype was significantly higher (OR with 95% 12.11 (2.23–76.96)) in fatal cases group compared to that of the mild group. IL-6 and IL-10 levels were significantly higher in fatal cases compared to that of survived severe cases. IL-6 levels had greater discriminatory power than IL-10 to predict progression to fatal outcome in influenza A(H1N1)pdm09 virus-infected patients. To conclude, the present study reports the association of TNFA and IL10 SNPs with severe disease in Influenza A(H1N1)pdm09 virus-infected subjects. Furthermore, IL-6 levels can be a potential biomarker for predicting fatal outcomes in Influenza A(H1N1)pdm09 virus infected subjects.

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