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Objectives: To measure the prevalence of viral infections, length of stay (LOS), and outcome in children admitted to the pediatric intensive care unit (PICU) during the period preceding the COVID-19 pandemic in a MERS-CoV endemic country. Methods: A retrospective chart review of children 0–14 years old admitted to PICU with a viral infection. Results: Of 1736 patients, 164 patients (9.45%) had a positive viral infection. The annual prevalence trended downward over a three-year period, from 11.7% to 7.3%. The median PICU LOS was 11.6 days. Viral infections were responsible for 1904.4 (21.94%) PICU patient-days. Mechanical ventilation was used in 91.5% of patients, including noninvasive and invasive modes. Comorbidities were significantly associated with intubation (P-value = 0.025). Patients infected with multiple viruses had median pediatric index of mortality 2 (PIM 2) scores of 4, as compared to 1 for patients with single virus infections (p < 0.001), and a median PICU LOS of 12 days, compared to 4 in the single-virus group (p < 0.001). Overall, mortality associated with viral infections in PICU was 7 (4.3%). Patients with viral infections having multiple organ failure were significantly more likely to die in the PICU (p = 0.001). Conclusion: Viral infections are responsible for one-fifth of PICU patient-days, with a high demand for mechanical ventilation. Patients with multiple viral infections had longer LOS, and higher PIM 2 scores. The downward trend in the yearly rate of PICU admissions for viral infections between the end of the MERS-CoV outbreak and the start of the COVID-19 pandemic may suggest viral interference that warrants further investigations. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases
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Mast cells (MCs) are a part of the innate immune system and express receptors for microbial and viral pathogens characteristic of this system. The pathological role of MCs has been demonstrated for a number of highly virulent viral infections. The role of MCs and their Fc receptors for IgE in the immediate-type hypersensitivity reactions and in immunocomplex reactions is well-known, although the role of MCs and their Fc receptors for IgG (Fc gamma R) in immunocomplex processes is much less studied. Antibody-dependent enhancement syndrome (ADE) has been observed in a number of viral infections and is associated with greater secondary infection. ADE is enhanced by virus-specific antibodies, which are not involved in the virus penetration into the cell but are capable of forming immune complexes. The role of MCs in ADE is well-established for dengue infection, RSV infection and coronavirus (CoV) infection. The involvement of IgG-mediated mast cell responses in other human viral infections including Coronavirus disease 2019 (COVID-19) is poorly understood. Recently discovered mast cell activation disease is considered one of the causes of severe post -infectious complications in COVID-19. If the role of MCs in the pathogenesis of severe viral infections, including ADE in recurrent viral infection is clarified, these cells and the products they release may serve as promising targets for such therapeutic agents as histamine receptor blockers or membrane stabilizers to prevent possible complications.
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SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: COVID-19 has affected over 200 million people worldwide. Clinicians continue to observe unusual manifestations of this disease. In an attempt to improve our understanding of COVID-19 pneumonia, we present the details of one patient who developed large bilateral pulmonary cysts. CASE PRESENTATION: A 40-year-old woman with no known medical problems presented with the chief complaint of fever, nausea, vomiting, generalized weakness followed by difficulty breathing that developed over a few days. Her vital signs on admission included temperature 98.4° F, heart rate 104 beats/minute, respiratory rate 48 breaths/minute, O2 saturation 88 percent on 15 liters of oxygen through a non-rebreather mask, and Body Mass Index 42 kg/m2. The patient tested positive for COVID-19. Computed tomography (CT) of the chest to rule out a pulmonary embolism showed bilateral extensive ground-glass opacities and reticular and nodular opacities. She was intubated for acute hypoxic respiratory failure. Twenty days into the hospital admission, she was noted to have a bulla in the right lower lobe. A repeat CT chest on day 45 revealed an increase in the number and size of cysts bilaterally. Patient was discharged to rehab and later readmitted for worsening respiratory status. This time she tested positive for human metapneumovirus. A CT chest showed increase in the size of the right sided lung cysts;the left sided lung cysts had resolved. DISCUSSION: The first COVID-19 related pulmonary cystic lesions were reported in May 2020(1). Since then, several reports have now established a relationship between an infection and cyst formation. The most common distribution is peripheral in the lower lobes. The pathogenesis remains uncertain, but several mechanisms have been proposed. Microthrombi in the pulmonary circulation could lead to ischemia and subsequent remodeling of interstitial matrix and bronchial obstruction with distal hyperinflation due to check valve mechanism. (1,2). Hamad et al. propose that pneumatoceles are formed by air leaked in to the interstitium which causes stripping and separation of a thin layer of lung parenchyma with further injury to the small blood vessels and bronchioles. The rate of barotrauma in non-COVID-19 related ARDS is 0.5%;the rate in COVID-19 ARDS is 15% (3). This suggests a close relation between COVID-19 pneumonia and subsequent development of pulmonary cysts. Our patient had no preexisting pulmonary disease and was noted to have pulmonary cysts after being on mechanical ventilation for almost 2 weeks. The patient later contracted the human metapneumovirus infection and CT showed that the right-sided lung cysts had become bigger in size. However, the left-sided cysts which had a maximum diameter of 4.8 cm had resolved. CONCLUSIONS: We need to follow patients with COVID 19 induced lung cysts clinically and radiologically to understand the clinical course and best management strategies. Reference #1: Kefu Liu et al. COVID 19 with cystic features on Computed tomography;Medicine (Baltimore) 2020May;99(18): e20175. PMCID: PMC7486878 Reference #2: Galindo J, Jimenez L, Lutz J et al. Spontaneous pneumothorax with or without pulmonary cysts, in patients with COVID 19 Pneumonia. Journal of infections in developing countries 2021;15(10);1404-1407 Reference #3: McGuinness G, Zhan C, Rosenberg N, Azour L, Wickstrom M, Mason DM, Thomas KM, Moore WH. Increased incidence of barotrauma in patients with COVID-19 on invasive mechanical ventilation. Radiology. 2020;297(2): E252–E262. doi: 10.1148/radiol.2020202352 DISCLOSURES: No relevant relationships by Arunee Motes No relevant relationships by Kenneth Nugent No relevant relationships by Tushi Singh No relevant relationships by Myrian Vinan Vega
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Background: Acute respiratory infection (ARI) is the leading infectious cause of pediatric death worldwide, comprising 15% of all deaths in children under 5 years old. Human metapneumovirus (HMPV) is a primary cause of ARI, and accounts for a major portion of ARI-related hospitalizations in infants and young children. Although nearly every person is infected with HMPV during early childhood, re-infections occur often, highlighting the difficulty in building long-term immunity. There are no approved vaccines or antiviral therapies. Early host responses to HMPV are poorly characterized, and further understanding could identify important antiviral pathways and potential therapeutic targets. Type I (IFN-α/β) and III interferons (IFN-λ) display antiviral activity against numerous respiratory viruses and are currently being investigated for therapeutic use in several respiratory infections including SARS-CoV-2. However, their roles in HMPV infection remain largely unknown. Our laboratory has previously shown that type I IFN is critical for HMPV pathogenesis, as loss of IFN-α/β signaling reduces lung inflammation and lessens HMPV disease severity in mice. Here, we describe distinct antiviral roles for type I and III IFNs during HMPV infection using an established mouse model. Methods: In vivo studies were conducted using mice lacking either the IFN-α/ β receptor (IFNAR-/-) or IFN-λ receptor (IFNLR-/-). Early immune responses to HMPV strains TN/94-49 and C2-202 were assessed by clinical disease scoring, plaque assay, Luminex immunoassay, and spectral cytometry of mouse lung samples. In vitro studies were performed using CMT 64-61 mouse bronchial epithelial cells. Responses to TN/94-49 and C2-202 were measured by qPCR, plaque assay, and Luminex immunoassay of cell lysates and supernatants. Results: IFNAR-/- mice exhibited lower clinical disease scores, reduced lung levels of inflammatory cytokines IL6, MIP-1α, and MCP-1, and decreased numbers of lung interstitial macrophages during HMPV infection, highlighting their critical role in HMPV immune-mediated pathogenesis. IFNLR-/- mice with intact IFNAR showed moderate clinical disease, higher lung levels of inflammatory cytokines IL-6, MCP-1, and IFN-γ, and increased lung interstitial macrophage recruitment. A reduction in HMPV disease was also recapitulated by IFNAR-neutralizing antibody treatment of IFNLR-/- mice. Interestingly, IFNLR-/- showed higher HMPV viral titers, while IFNAR-/- mice showed no differences or slightly lower viral titers, compared to wild-type mice. Moreover, IFN-λ pre-treatment of infected CMT 64-61 cells reduced HMPV viral titers and decreased supernatant levels of inflammatory cytokines IL-6, IL-1β, TNFα, and MCP-1. Conclusion: These findings suggest that type I IFN is necessary for HMPV pathogenesis, while type III IFN is critical for limiting HMPV replication in the lungs but does not contribute to HMPV inflammatory disease. This work uncovers key functional differences between type I and III IFNs during HMPV infection, an important feature of innate immune responses to HMPV that may be utilized to inform treatment.
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AIM: We sought to describe the aetiology, demographics and outcomes of patients with pneumonia undergoing venovenous extracorporeal membrane oxygenation (VV-ECMO) in Aotearoa New Zealand. METHODS: Retrospective observational study. RESULTS: Between January 2004 and August 2020, 133 patients underwent VV-ECMO for pneumonia. This VV-ECMO cohort is representative of the geographic and ethnic distribution of the population of Aotearoa New Zealand. Six-month survival was 85/133 (64%). A primary viral aetiology was identified in 63/133 cases (47%) with bacterial co-infection present in 34/63 viral pneumonias (54%). Primary bacterial pneumonia was identified in 48/133 cases (36%). Twenty-three (17%) of 133 patients developed necrotising pneumonia. The most commonly identified microorganisms were influenza A, Staphylococcus aureus and Streptococcus pneumoniae. Infection with Staphylococcus aureus or Streptococcus species was strongly associated with necrotising pneumonia (OR 10.18, 95% CI 3.52–37.13, P<0.0001). Necrotising pneumonia was more common in Māori and Pacific Peoples than in other ethnic groups (OR 3.08, 95% CI 1.16–7.96, P=0.02). DISCUSSION: Outcomes from VV-ECMO for pneumonia in Aotearoa New Zealand are comparable to large international series. Although the use of VV-ECMO was matched to the ethnic distribution of the population of Aotearoa New Zealand, Māori may have reduced access because they have higher rates of pneumonia than non-Māori.