Respiratory viral infections in the lower respiratory tract failure (Literature review)

The sharp increase in viral pneumonia against the background of the pandemic of the new coronavirus infection SARS-CoV-2 requires more attention to the study of the role of viruses in damage to the lower respiratory tract, including their etiological significance in the development of community-acquired pneumonia. Modern possibilities of laboratory diagnostics make it possible not only to identify and study respiratory viruses, but also to help differentiate active viral infections as a cause of lower respiratory tract disease from virus carriers. The review describes the epidemiological and clinical features of the most relevant or less studied pneumotropic viral infections in children (respiratory syncytial, adenovirus, bocavirus, metapneumovirus), including their role in the etiology of pneumonia in children. Understanding the viral etiology of pneumonia in children will reduce the antibacterial load, which will help to reduce the side effects of chemotherapy and slow the emergence of antimicrobialresistant bacterial strains.

Weight Status and Risk of Inpatient Admission for Children With Lower Respiratory Tract Disease

OBJECTIVES To identify associations between weight category and hospital admission for lower respiratory tract disease (LRTD), defined as asthma, community-acquired pneumonia, viral pneumonia, or bronchiolitis, among children evaluated in pediatric emergency departments (PEDs). METHODS We performed a retrospective cohort study of children 2 to <18 years of age evaluated in the PED at 6 children’s hospitals within the PEDSnet clinical research network from 2009 to 2019. BMI percentile of children was classified as underweight, healthy weight, overweight, and class 1, 2, or 3 obesity. Children with complex chronic conditions were excluded. Mixed-effects multivariable logistic regression was used to assess associations between BMI categories and hospitalization or 7- and 30-day PED revisits, adjusted for covariates (age, sex, race and ethnicity, and payer). RESULTS Among 107 446 children with 218 180 PED evaluations for LRTD, 4.5% had underweight, 56.4% had healthy normal weight, 16.1% had overweight, 14.6% had class 1 obesity, 5.5% had class 2 obesity, and 3.0% had class 3 obesity. Underweight was associated with increased risk of hospital admission compared with normal weight (odds ratio [OR] 1.76; 95% confidence interval [CI] 1.69–1.84). Overweight (OR 0.87; 95% CI 0.85–0.90), class 1 obesity (OR 0.88; 95% CI 0.85–0.91), and class 2 obesity (OR 0.91; 95% CI 0.87–0.96) had negative associations with hospital admission. Class 1 and class 2, but not class 3, obesity had small positive associations with 7- and 30-day PED revisits. CONCLUSIONS We found an inverse relationship between patient weight category and risk for hospital admission in children evaluated in the PED for LRTD.

Safety and Tolerability of an Ad26.RSV.preF-based Vaccine in a Phase 2b Study in Older Adults

Respiratory syncytial virus (RSV) may cause severe lower respiratory tract disease in older adults and there is currently no approved vaccine. We assessed the safety and reactogenicity of an Ad26.RSV.preF-based vaccine in a randomized, double-blind, placebo-controlled Phase 2b proof-of-concept trial in adults aged ≥65 years (CYPRESS; NCT03982199). Prior to the RSV season, participants were randomized 1:1 to receive an Ad26.RSV.preF-based vaccine or placebo. Solicited adverse events (AEs; fatigue, headache, nausea, myalgia, fever, injection site reactions) and unsolicited AEs were assessed from time of vaccination to Day 8 and Day 29, respectively, in a safety subset of 695 participants (vaccine, n=348; placebo, n=347). All participants were followed for serious AEs (SAEs) until the end of the RSV season or 6 months after vaccination, whichever occurred later. A total of 5728 participants were randomized and received vaccine or placebo (n=2891 in each group). In the safety subset, the frequency of solicited AEs and Grade ≥3 solicited AEs was 51.4% and 3.2% in the vaccine group and 20.2% and 0.6% in the placebo group, respectively. The most frequent solicited AEs in the vaccine group were fatigue, myalgia, headache, and injection site pain/tenderness. The rates of unsolicited AEs and Grade ≥3 unsolicited AEs were similar between the vaccine (16.7% and 1.7%) and placebo (14.4% and 1.4%) groups. In the overall study population, the rate of SAEs was similar between groups (vaccine, 4.6%; placebo, 4.7%); none were considered related to the vaccine. The Ad26.RSV.preF-based vaccine was safe and well tolerated in adults aged ≥65 years.

LB14. Efficacy and Immunogenicity of an Ad26.RSV.preF-based Vaccine in the Prevention of RT-PCR-confirmed RSV-mediated Lower Respiratory Tract Disease in Adults Aged ≥65 Years: A Randomized, Placebo-controlled, Phase 2b Study

Background Respiratory syncytial virus (RSV) can cause serious lower respiratory tract disease (LRTD) in older adults. Despite a high burden of disease, there is currently no licensed vaccine for RSV. Here, we report the primary efficacy and immunogenicity results from a Phase 2b proof-of-concept trial of an Ad26.RSV.preF-based vaccine for the prevention of RSV-mediated LRTD in adults aged ≥65 years. Methods CYPRESS (NCT03982199) is a randomized, double-blind, placebo-controlled Phase 2b trial. Adults ≥65 years of age were randomized 1:1 prior to the RSV season to receive an Ad26.RSV.preF-based vaccine or placebo. Symptoms of acute respiratory infection (ARI) were collected through an RSV-specific patient-reported Respiratory Infection Intensity and Impact Questionnaire (RiiQ) and/or by a clinician assessment until the end of the RSV season. The primary endpoint was the first occurrence of RT-PCR-confirmed RSV-mediated LRTD according to any of 3 case definitions: (1) ≥3 symptoms of lower respiratory tract infection (LRTI), (2) ≥2 symptoms of LRTI, or (3) ≥2 symptoms of LRTI or ≥1 symptom of LRTI with ≥1 systemic symptom. The secondary endpoint was the first occurrence of any RT-PCR-confirmed RSV-mediated ARI. Immunogenicity assessments were performed in a subset of approximately 200 participants. Results A total of 5782 participants (2891 in each study arm) received study treatment (92.5% white, 57.7% female, median age 71 years). Vaccine efficacy was 80% (94.2% CI, 52.2–92.9%), 75% (50.1–88.5%), and 69.8% (43.7–84.7%) for case definition 1, 2, and 3, respectively (all P values < 0.001). Efficacy for any RSV-mediated ARI was 69.8% (95% CI, 42.7–85.1%). In the vaccine arm of the immunogenicity subset, geometric mean fold increase in antibody titers 14 days after vaccination was 13.5 for RSV neutralizing antibodies and 8.6 for RSV prefusion F-specific binding antibodies. Median frequency of RSV-F-specific INFγ T-cells increased from 34 to 444 SFC/106 PBMC 14 days after vaccination in the vaccine arm; no relevant changes were observed in the placebo arm. Conclusion In CYPRESS, the Ad26.RSV.preF-based vaccine was highly effective against RSV-mediated LRTD through the first RSV season and elicited robust humoral and cellular immune responses in adults aged ≥65 years. Disclosures Ann R. Falsey, MD, AstraZeneca (Individual(s) Involved: Self): Grant/Research Support; BioFire Diagnostics (Individual(s) Involved: Self): Grant/Research Support; Janssen (Individual(s) Involved: Self): Grant/Research Support; Merck, Sharpe and Dohme (Individual(s) Involved: Self): Grant/Research Support; Novavax (Individual(s) Involved: Self): Other Financial or Material Support, Paid DSMB member; Pfizer (Individual(s) Involved: Self): Grant/Research Support Kristi Williams, PhD, Janssen R&D US (Employee) Efi Gymnopoulou, MSc, Janssen Infectious Diseases BV (Employee) Arangassery Rosemary Bastian, PhD, Janssen Vaccines & Prevention BV (Employee) Joris Menten, n/a, Janssen Infectious Diseases BV (Employee) Els De Paepe, MSc, Janssen Infectious Diseases BV (Employee) Hilde de Boer, MSc, Janssen-Cilag (Employee) Sjoukje Vandenberghe, n/a, Janssen Infectious Diseases BV (Employee) Eric Chan, PhD, Janssen Global Services, LLC (Employee) Jerald Sadoff, MD, Johnson & Johnson (Employee, Shareholder) Macaya Douoguih, MD, MPH, Janssen (Employee) Benoit Callendret, PhD, Janssen Vaccines & Prevention BV (Employee) Christy Comeaux, MD, Janssen Vaccines & Prevention BV (Employee) Esther Heijnen, MD, Janssen Vaccines & Prevention BV (Employee)

Early Detection of ARI Disease and First Aid in Children with Fever Seizures at Posyandu Cadres at Kantil Depok, Sleman

Background: Acute Respiratory Infection (ARI) is one of the problems of death in children in developing countries. ARI is an upper or lower respiratory tract disease, usually contagious, which can cause a wide spectrum of disease that ranges from asymptomatic disease or mild infection to severe and deadly disease.Objective: Yandu cadres can improve knowledge, attitudes and skills in handling ARI and febrile seizures in children, so as to optimize growth and development in children optimally.Methods: socialization and simulation of the handling of ARI and febrile seizures in children through cadres. Cadres were given material about ARI and febrile seizures, followed by interactive activities about the steps taken to overcome/handle ARI and febrile seizures in children. The cadres were divided into three groups and accompanied by one trainer.Results: the cadres stated that they understood, and seemed capable of handling febrile seizures in children.Suggestion: The existence of counseling and training to parents/mothers about ARI and handling febrile seizures in children, providing first aid kits and simple medicines for handling febrile seizures at Posyandu, also in families who have children and often experience febrile seizures under the supervision of a doctor, it is necessary the existence of socialization in physical form contains the importance of handling febrile seizures in children.

Early Detection of ARI Disease and First Aid in Children with Fever Seizures at Posyandu Cadres at Kantil Depok, Sleman

Background: Acute Respiratory Infection (ARI) is one of the problems of death in children in developing countries. ARI is an upper or lower respiratory tract disease, usually contagious, which can cause a wide spectrum of disease that ranges from asymptomatic disease or mild infection to severe and deadly disease.Objective: Yandu cadres can improve knowledge, attitudes and skills in handling ARI and febrile seizures in children, so as to optimize growth and development in children optimally.Methods: socialization and simulation of the handling of ARI and febrile seizures in children through cadres. Cadres were given material about ARI and febrile seizures, followed by interactive activities about the steps taken to overcome/handle ARI and febrile seizures in children. The cadres were divided into three groups and accompanied by one trainer.Results: the cadres stated that they understood, and seemed capable of handling febrile seizures in children.Suggestion: The existence of counseling and training to parents/mothers about ARI and handling febrile seizures in children, providing first aid kits and simple medicines for handling febrile seizures at Posyandu, also in families who have children and often experience febrile seizures under the supervision of a doctor, it is necessary the existence of socialization in physical form contains the importance of handling febrile seizures in children.

COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey

This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0–80.3) for allogeneic, and 60.6 years (7.7–81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2–292.7) in allogeneic and 24.6 months (−0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.

Lower respiratory tract disease (LRTD) in patients with cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) study.

6563 Background: Immunodeficiency in patients (pts) with cancer can lead to the progression of common respiratory viral infections to lower respiratory tract disease (LRTD) with potentially high mortality. Understanding risk factors of SARS-CoV-2 related LRTD in pts with cancer is imperative for the development of preventive measures. Methods: We examined all patients aged 18 years or older with cancer and laboratory-confirmed SARS-CoV-2 infection reported between March 16, 2020 and February 6, 2021 in the international CCC19 registry. We examined frequency of LRTD (pneumonia, pneumonitis, acute respiratory distress syndrome, or respiratory failure), demographic and clinicopathologic factors associated with LRTD, and 30-day and overall mortality in pts with and without LRTD. Results: Of 7,289 pts with a median follow-up time of 42 (21-90) days, 2187 (30%) developed LRTD. Pts of older age (65 yrs or older), male sex, pre-existing comorbidities, baseline immunosuppressants, baseline corticosteroids, and ECOG performance status of 2 or more had substantially higher rates of LRTD compared to those without these risk factors (Table). We did not observe differences in LRTD rates between pts of different racial/ethnic groups, smoking history, hypertension, obesity, cancer status, timing or type of anti-cancer therapy. LRTD was more likely in pts with thoracic malignancy (39%), hematological malignancy (39%) compared to those with other solid tumors (27%). The majority of pts (86%) had symptomatic presentation; however, 8% of pts with asymptomatic presentation developed LRTD. 30-day and overall mortality rates were significantly higher in pts with LRTD than those without LRTD (31% vs. 4% and 38% vs. 6%, P < 0.05). Conclusions: COVID-19 related LRTD rate is high and associated with worse mortality rates in pts with cancer. The majority of risk factors associated with LRTD demonstrate underlying immunodeficiency or lung structural damage as a driving force in this population. Identifying pts at high-risk for developing LRTD can help guide clinical management, improve pt outcomes, increase the cost-effectiveness of antiviral therapy, and direct future clinical trial designs for vaccine or antiviral agents.[Table: see text]

Acute Upper Limb Arterial Thrombosis associated with COVID-19: A Case Report

COVID-19 is a viral respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Majority of the cases present with upper or lower respiratory tract disease. Common complications of the disease include cytokine storm and acute respiratory distress syndrome. The disease is also found to be associated with an increased incidence of thromboembolism. However, data and literature regarding this dreadful complication are limited. Here, we present a case report of arterial thrombosis in COVID-19 which led to ischemia and gangrene of the fingers.