Lung Transplantation as a way to Escape Pneumonia in Patients with COVID-19: Lessons from ARDS and Influenza.

In this era, the novel Coronavirus, referred to as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a life-threatening virus with a high mortality rate (4.2%) and with no absolute treatment as of yet, may ultimately result in acute respiratory distress syndrome (ARDS). ARDS is one of the fatal complications, highlighted by pulmonary infiltration and severe hypoxemia. This condition can be developed from primary lung inflammation caused by various viruses, particularly influenza viruses, some of the most common human pathogens. Due to this issue, many studies explored several approaches for ARDS treatment. Lung transplantation has been claimed as an efficient cure for severe ARDS and Influenza, which can also be offered for treating critical lung complications of SARS-CoV-2. Thereupon, to the best of our knowledge for the first time, we aimed to review all available data about capability of lung transplantation for the treatment of critically ill patients with ARDS, Influenza, and SARS-CoV-2.

Early Use of Anti-influenza Medications in Hospitalized Children With Tracheostomy.

BACKGROUND: Early administration of anti-influenza medications is recommended for all children hospitalized with influenza. We investigated whether early use of anti-influenza medications is associated with improved outcomes in children with tracheostomy hospitalized with influenza. METHODS: We performed a multicenter retrospective cohort study through the Pediatric Health Information System database for patients aged 30 days to 19 years who were discharged between October 1, 2007, and September 30, 2015 with diagnostic codes for both influenza and tracheostomy. Our primary predictor was receipt of anti-influenza medications on hospital day 0 or 1. We used propensity score matching to adjust for confounding by indication. Primary outcomes were length of stay (LOS) and 30-day all-cause revisit rate (emergency department visit or hospital admission). RESULTS: Of 1436 discharges screened, 899 met inclusion criteria. The median admission age was 5 years (interquartile range: 2-10). The majority had multiple complex chronic conditions (median 3; interquartile range: 3-4) and technology dependence, such as gastrostomy tube (73.6%). After matching 772 unique admissions by propensity score, LOS was shorter for the cohort receiving early anti-influenza medications (6.4 vs 7.5 days; P = .01) without increase in revisit rate (27.5% vs 24.1%; P = .28). More than 80% in both cohorts received empirical antibiotics, and the duration of antibiotic therapy was similar (5.0 vs 5.6 days; P = .11). CONCLUSIONS: Early use of anti-influenza medications in children with tracheostomy hospitalized with influenza is associated with shorter LOS, but these children continue to receive antibiotics despite identification and treatment of their viral infections.

Transplanting the pulmonary virome: Dynamics of transient populations.

BACKGROUND: Lung transplantation provides a unique opportunity to investigate the dynamics of the human pulmonary virome that is transplanted within the donor lungs. The pulmonary virome comprises both "resident" and "transient" viruses. In this study we aimed to analyze the dynamics of the "transient" members. METHODS: We conducted a single-center, prospective, longitudinal investigation of community-acquired respiratory viruses detected in nasopharyngeal swabs, swabs of explanted and donor lungs, and serial bronchoalveolar lavages post-transplant. RESULTS: Fifty-two consecutive lung transplant recipients were recruited (bilateral:heart‒lung:bilateral lung-liver = 48:2:2) (age [mean ± SD] 48 ± 15 years, range 20 to 63 years; 27 males and 25 females). Follow-up was 344 ± 120 (range 186 to 534) days. Seventeen of 45 explanted lungs were positive for influenza A and/or B (A = 14, B = 2, A+B = 1), despite recipient vaccination and negative nasal swabs, and 4 of 45 had human rhinovirus and 2 of 45 parainfluenza. Donor swabs showed influenza (A = 1, B = 1) and rhinovirus (n = 3). Day 1 lavage showed influenza A (n = 28), rhinovirus (n = 9), and parainfluenza (n = 1). Forty-seven of 52 recipients had a positive lavage for virus (38 of 47 on multiple lavages). Influenza persisted for 59 ± 38 (range 4 to 147) days in 27 of 52, and 14 had a single isolate. Rhinovirus persisted for 95 ± 84 (range 22 to 174) days in 13 of 52, and 13 had a single isolate. Analysis of 118 paired transbronchial biopsies and lavage demonstrated no association between viruses and acute cellular rejection (Fisher's exact test, 2 tailed, p = 1.00). CONCLUSIONS: Using a sensitive uniplex polymerase chain reaction we found that the transplanted pulmonary virome often includes community-acquired respiratory viruses, including influenza, which are variably persistent but not associated with acute rejection.

Pharmacokinetics of Oral and Intravenous Oseltamivir Treatment of Severe Influenza B Virus Infection Requiring Organ Replacement Therapy.

BACKGROUND AND OBJECTIVES: Patients with severe influenza virus infection, multi-organ failure and organ replacement therapy may absorb and metabolize neuraminidase inhibitors differently. Systematic pharmacokinetic/pharmacodynamic clinical trials are currently lacking in this high-risk group. Inadequate dosing increases the risk of treatment failure and drug resistance, especially in severely ill patients with elevated virus loads. This study aims to explore the impact of organ replacement therapy on oseltamivir drug concentrations. METHODS: Serial pharmacokinetic/pharmacodynamic measurements and Sieving coefficients were assessed in two patients with severe influenza B infection requiring organ replacement therapy. RESULTS: Patient #1, a 9-year-old female with severe influenza B virus infection, biventricular assist device, and continuous veno-venous hemodiafiltration, received 75 mg oral oseltamivir twice-daily for 2 days, then intravenous oseltamivir with one-time renoprotective dosing (40 mg), followed by regular intravenous administration of 100 mg twice-daily. Plasma oseltamivir carboxylate concentrations were stable initially, but only regular administration of 100 mg resulted in virus load decline and clinical improvement. Patient #2, a 28-year-old female with influenza B virus infection requiring extracorporeal membrane oxygenation, received 75 mg oral oseltamivir twice-daily, resulting in erratic oseltamivir blood concentrations. In both patients, drug concentrations remained well within safety margins. CONCLUSIONS: In severe cases with multi-organ failure, administration of 100 mg intravenous oseltamivir twice-daily provided reliable drug concentrations, as opposed to renoprotective and oral dosing, thereby minimizing the risk of treatment failure and drug resistance. Evidence-based pediatric dosing recommendations and effective intravenous antiviral treatment modalities are needed for intensive care patients with life-threatening influenza disease.

Clinical Features of Acute and Fulminant Myocarditis in Children　- 2nd Nationwide Survey by Japanese Society of Pediatric Cardiology and Cardiac Surgery.

BACKGROUND: The 1st nationwide survey by the Japanese Society of Pediatric Cardiology and Cardiac Surgery of acute or fulminant myocarditis (AMC/FMC) in children revealed that the survival rate of FMC was only 51.6%. The 2nd nationwide survey was performed to evaluate the recent outcomes of pediatric myocarditis.Methods and Results:Questionnaires regarding patients aged ≤18 years with AMC/FMC during the period from January 2006 to December 2011 were mailed. A total of 221 cases (age 6.5±5.3 years, 116 boys and 105 girls) were reported. There were 145 (65.6%) and 74 cases (33.5%) of AMC/FMC, respectively; the type of myocarditis was not reported in the remaining 2 cases (0.9%). Viruses were identified in 56 cases (25.3%), including coxsackie B in 9 and influenza A in 8. Histopathology by either endomyocardial biopsy or autopsy was obtained in 38 cases (19.2%). Intravenous immunoglobulin was effective in 49 (34.3%) of 143 cases. Steroid therapy was effective in 20 (32.8%) of 61 cases. Mechanical circulatory support was given in 54 cases (24.4%) and 94.2% of them were patients with FMC. The survival rates for the whole study population, acute myocarditis, and FMC were 75.6%, 91.0%, and 48.6%, respectively. CONCLUSIONS: The survival rate of children with myocarditis was almost identical to that of 10 years ago. (Circ J 2016; 80: 2362-2368).

Mapping and ablation of multiple atrial arrhythmias in a patient with persistent atrial standstill after remote viral myocarditis.

This is a case of multiple atrial arrhythmias (atrioventricular node reentry and two different focal atrial tachycardias) originating from the remaining atrial myocardium after global scarring of both atria following a remote viral myocarditis. All the induced arrhythmias were successfully treated with catheter ablation.

[Histologic and ultrastructural studies of the patient died of highly pathogenic H5N1 avian influenza virus infection in China].

OBJECTIVE: To explore histopathologic and ultrastructural characteristics of human avian influenza (AI) infection and related etiological pathogenesis. METHODS: Postmortem lung and heart samples were collected from the patient who died of avian influenza virus infection on November 29, 2003 in China. Light and electron microscopy, immunohistochemistry and histochemistry were used to investigate the pathological changes. RESULTS: The main pathological findings included extensive pulmonary consolidation, hemorrhage, pulmonary edema and local hemorrhagic infarct. The lamina of alveoli and bronchioles were abundantly filled with protein-rich fluid, erythrocytes, fibrin and cell debris admixed with many neutrophilis, macrophages, lymphocytes and a few of monokaryon and multinuclear giant cells. Hyaline membranes were formed. Local pulmonary tissues were heavily damaged by hemorrhage and necrosis. Alveolar septum was disintegrated. Mesenchymal edema with a few of macrophages infiltration of heart was found. Electron microscopy showed the avian influenza A virus-like particles (type C and type A) of 80 - 120 nm diameter and envelopes in the cytoplasm of pneumocytes and endothelial cells. CONCLUSIONS: Fatal pneumonia associated with highly pathogenic avian influenza A virus (H5N1) infection leads to extensive pulmonary consolidation, edema and marked hemorrhagic necrosis and inflammation. Electron microscopy can identify avian influenza A virus-like particles. The findings may offer an important theoretical basis for clinical diagnosis and treatment.

Rhabdomyolysis and lower extremity compartment syndrome due to influenza B virus.

Rhabdomyolysis is an unusual complication following infection with influenza B virus. We recently managed a young boy who presented with severe rhabdomyolysis and bilateral lower extremity compartment syndrome due to infection with influenza B virus.