On reporting interferon research.

Current research and future needs in allergic rhinitis and asthma

Viral respiratory tract infections increase platelet reactivity and activation: an explanation for the higher rates of myocardial infarction and stroke during viral illness

Data regarding the effects of coronavirus disease 2019 (COVID-19) on host-microbiome alteration and subsequent effects on susceptibility and clinical course of COVID-19, especially in atopic patients, are currently limited. Here, we review the studies regarding the microbiome of atopic patients with other respiratory infections and discuss the potential role of probiotics as therapeutic targets for COVID-19 to decrease its susceptibility and severity of COVID-19. Respiratory tract virus infection affects the gut and airway microbiome structures and host's immune function. Diverse factors in atopic diseases affect the airway and gut microbiome structures, which are expected to negatively influence host health. However, response to respiratory virus infection in atopic hosts depends on the preexisting microbiome and immune responses. This may explain the inconclusiveness of the effects of COVID-19 on the susceptibility, morbidity, and mortality of patients with atopic diseases. Beneficial probiotics may be a therapeutic adjuvant in COVID-19 infection as the beneficial microbiome can decrease the viral load in the early phase of respiratory virus infection and improve the morbidity and mortality. Application of probiotics can be a potential adjuvant treatment in respiratory virus infection to improve host immune responses and disturbed microbiome structures in atopic patients. Further related studies involving COVID-19 are warranted in near future.

Respiratory seasonal viral infections remain one of the most important issues in community medicine. The heterogeneity of etiological agents and the characteristics of the hosts airway antiviral defenses account for the complex management of these infections. The clinical consequence of this picture is that, despite the widespread use of vaccination as the primary prevention strategy, the rates of acute respiratory complications remain still high. In addition, they determine post-infectious fatigue and organ dysfunction. Inflammation and oxidative stress are the principal pathogenic mechanisms responsible for clinical complications during respiratory seasonal viral infections. Nowadays, a growing body of evidence indicates that adjunctive nutritional support can contribute to relieve the symptoms during the acute and subacute phases of respiratory viral infections. We assess the data in the literature regarding the combination of L-Arginine and Liposomal Vitamin C as adjuvant treatment for respiratory seasonal viral infections. The database of the National Library of Medicine (PubMed) was searched using the keywords "L-Arginine, Vitamin C, dietary supplements, seasonal respiratory viral infections". The treatment of symptoms during acute and post-acute respiratory viral infections requires an integrated approach that includes vitamins and nutritional supplementation. The combination of L-Arginine and Liposomal Vitamin C seems to represent a nutritional support able to mitigate symptoms occurring during the acute or post-acute phase of infection.

Viral respiratory infections are one of the leading causes of morbidity and mortality, especially in children, elderly and immunocompromised patients. The inclusion of post-mortem studies to diagnose the infection causing mortality could be beneficial in specifying new pathogens and determining strategies for treatment and prevention.The aim of this study was to research viral etiology by applying multiplex real-time polymerase chain reaction (Rt-PCR) method in autopsy cases who have been considered to have a respiratory infection and to assess whether the viruses detected are the primary cause of the infection and whether they have any contributory effect on the mortality together with histopathological evidence. In this study, we included a total of 834 cases consisting of sudden death cases from infantile-pediatric age group and autopsy cases from > 18 year age group with suspected respiratory tract infection in our laboratory between January 2013 and May 2017. Of 834 cases, 468 (56.1%) were male and 366 (43.9%) were female, there were 191 (22.9%) cases between 0-1 months, 593 (71.1%) cases between 1 month-18 years, and 50 (6%) cases in the > 18 years age group. In 728 of 834 (87.3%) cases nasopharyngeal/tracheal swab samples and in 106 (12.7%) of them paraffin-embedded lung tissue samples were studied by the use of "FTD Respiratory 21 (Fast-Tract Diagnostics Luxemburg)" kit, with multiplex Rt-PCR method. The post-mortem samples were evaluated for human rhinovirus (HRV), parainfluenza viruses (PIV) (1, 2, 3, 4), influenza virus type A and B (INF-A, INF-B), enterovirus (EV), human bocavirus (HBoV), adenovirus (AdV), human coronavirus (HCoV 229,63,HKU,43), human metapneumovirus A ve B (HMPV-A/B), parechovirus, respiratory syncytial virus (RSV A/B) and Mycoplasma pneumoniae. In our study, at least one respiratory virus was detected by Rt-PCR in 379 (45.4%) of total 834 cases, whereas no viral agent was identified in 455 (54.6%) of the cases. One viral agent was detected in 278 (33.3%), two viral agents were detected in 83 (9.94%) and three viral agents were detected in 18 (2.16%) cases. Overall, the most common viral agent was HRV 110 (13.2%) followed by AdV 39 (4.7%) and RSV A/B 33 (4%). In pediatric cases the rate of positive results for respiratory viruses was 31.8% and in adult group it was 20% (p= 0.032). The most common virus detected among children was HRV and INF-A in adult group. In 101 (12.1%) cases infections caused by two or three agents were diagnosed. Infections with two causative agents were detected as 2.6% (5/191) in 0-1 month age group, 13% (77/593) in 1 month-18 year age group and 2% (1/50) in > 18 age group. The most frequently observed co-infections with double causative agents were HRV and INF-B, HRV and PIV, HRV and HBoV, HRV and AdV combinations. Infections with three causative agents were detected completely among 1 month-18 year age [3% (18/593)] group. In our study, 318 (38.1%) cases had no signs of infection in the postmortem histopathological examination of the lung tissues, while the most common finding was lobular pneumonia/purulent bronchitis in 233 (28%) cases and the second was interstitial pneumonia in 168 (20.1%) cases. When all cases were evaluated in terms of infection, positive results were detected in 469 (56.2%) cases. As a result; postmortem microbiological diagnosis with autopsy and histopathological detection of the patients who are thought to have respiratory tract infection will also determine the infectious agents causing death.

Background Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract illnesses (LRI) worldwide, particularly affecting high-risk groups such as cancer patients, solid organ transplant (SOT) recipients, older adults, and those with significant comorbidities. The Advisory Committee on Immunization Practices (ACIP) recommends vaccinating adults aged ≥75 years, and those aged 60-74 at greater risk for severe RSV disease (1). Recently, they proposed expanding this recommendation to at-risk patients aged 50-59 (2). Our study aims to investigate outcomes of RSV infection and identify risk factors for complications in various populations.Table 1:Baseline characteristics and clinical outcomes of patients with RSV-related respiratory viral infection by underlying conditions.aData are no. (%) unless otherwise specified; bn=528; cn=419; dn=435; en=159; fn=298; gn=332; hn=263; in=512; jn=520; kn=443; ln=379=; mn=214.*In post-hoc analysis, the comparisons between the cancer and the non-cancer/SOT groups, and the SOT and non-cancer/SOT groups were statistically significant (p < 0.05).**The HCT indication was primary immunodeficiency disorder.***Coinfections included rhinovirus (n=18), endemic human coronavirus (n=9), SARS-CoV-2 (n=8), parainfluenza virus (n=3), adenovirus (n=1), influenza virus (n=3), CMV pneumonitis (n=2), Pseudomonas aerogenes (n=10), Streptococcus pneumonia (n=4), Stenotrophomonas melophilia (n=3), Haemophilus influenza (n=3), staphylococcus aureus (MSSA) (n=4), staphylococcus aureus (MRSA) (n=1), Legionella pneumophila (n=1), Nocardia (n=1), Escherichia coli (n=1), Aspergillus (n=4), Zygomycete (n=1), Pneumocystis jirovecii (n=1) .Abbreviations: ALL, acute lymphocytic leukemia; AML, acute myeloid leukemia; BiPAP, bilevel positive airway pressure; BITE, Bispecific T cell Engager; BMI, body mass index; CAR-T, chimeric antigen receptor T-cell therapy; CKD, chronic kidney disease; CLL, chronic lymphocytic leukemia; CMML, Chronic myelomonocytic leukemia; CML, Chronic myeloid leukemia; HCT, hematopoietic stem cell transplantation; HFNC, high-flow nasal cannula; HIV, human immunodeficiency virus; HM, haematologic malignancy; ICU, intensive care unit; IQR, intra-quartile range; IVIG, intravenous immunoglobulin; LRI, lower respiratory tract infection; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasms; RSV, respiratory syncytial virus; RVI, respiratory virus infection; SOT, solid organ transplantation; SD, standard deviation; TIA, transient ischemic attack; URI, upper respiratory tract infection.Table 2a:Multivariable analysis (logistic regression) for risk factors of lower respiratory tract infection. Table 2b: Multivariable analysis (logistic regression) for risk factors of 30-day all-cause mortality.Abbreviations: aOR, adjusted odds ratio; LRI, lower respiratory tract infection; RVI, respiratory viral infection; SOT, solid organ transplantation; 95% CI, 95% confidence interval. Methods We conducted an international multicenter retrospective observational study including adults with RSV infection across six centers in the USA, the Netherlands, Israel, and Taiwan from October 2018 to April 2024. Patients were categorized based on underlying conditions: cancer, SOT recipients, and those without either. Primary outcomes included LRI and 30-day all-cause and RSV-related mortality.Figure 1:RSV infection outcomes stratified by age groupsAbbreviations: LRI, lower respiratory tract infection; RSV, respiratory syncytial virus; SOT, solid organ transplantation. * In the SOT group, only one patient was aged over 80. This patient progressed to LRI and died from another etiology after 19 days of follow-up.Figure 2:30-day all-cause mortality according to the underlying condition type and the infection site.Abbreviations: LRI, lower respiratory tract infection; RVI, respiratory virus infection; SOT, solid organ transplantation; URI, upper respiratory tract infection Results We analyzed 562 patients: 425 (75.6%) with cancer, mainly hematologic malignancies (HMs), and 53 (9.4%) SOT recipients (Table 1). Most patients without either cancer or SOT (84 patients, 15.0%) had significant comorbidities, with 73.8% having a Charlson comorbidity index (CCI) ≥4. Overall LRI rates were 46.8% (48.9% in cancer patients, 35.8% in SOT recipients, and 42.9% in others), with 30-day mortality of 8.0% (7.3% in cancer patients, 11.3% in SOT recipients, and 9.5% in others). LRI and mortality by age group and underlying condition are presented in Figure 1. Independent risk factors for LRI were older age, higher CCI, HMs, smoking, recent steroid use, lymphopenia, and elevated creatinine levels, but the type of underlying condition was not independently associated with LRI (Table 2a). Independent risk factors for 30-day mortality were SOT (compared to cancer), metastatic solid malignancy, nosocomial infection, neutropenia, respiratory co-infection, and LRI (Table 2b, Figure 2). Conclusion The study highlights significant morbidity and mortality from RSV in patients with cancer and SOT recipients, as well as in patients without these conditions who are over 50 years of age. Disclosures Jonathan Hand, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Ferring: Grant/Research Support|Innoviva: Advisor/Consultant|Janssen: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Scynexis: Grant/Research Support|The Antibiotic Resistance Leadership Group (ARLG): Grant/Research Support|The Antibiotic Resistance Leadership Group (ARLG): Honoraria Lior Nesher, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Honoraria|F2G: Grant/Research Support|GSK: Advisor/Consultant|GSK: Honoraria|Medison: Advisor/Consultant|Moderna: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|Takeda: Honoraria Roy F. Chemaly, MD, MPH, FIDSA, FACP, FESCMID, ADMA Biologics: Advisor/Consultant|AiCuris: Advisor/Consultant|AiCuris: Grant/Research Support|Ansun Biopharma: Advisor/Consultant|Ansun Biopharma: Grant/Research Support|Assembly Bio: Advisor/Consultant|Astellas: Advisor/Consultant|Eurofins Viracor: Advisor/Consultant|Eurofins Viracor: Grant/Research Support|Genentech: Grant/Research Support|Gilead: Advisor/Consultant|InflaRX: Advisor/Consultant|IntegerBio: Advisor/Consultant|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck/MSD: Advisor/Consultant|Merck/MSD: Grant/Research Support|Moderna: Advisor/Consultant|Oxford Immunotec: Advisor/Consultant|Pfizer: Advisor/Consultant|Shionogi: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Tether: Advisor/Consultant

Viral acute respiratory infections represent a significant cause of morbidity and mortality across all ages, especially in patients with chronic underlying conditions. Although recognized anecdotally, the risks of viral infection to those children with chronic underlying conditions rendering them technology dependent, or to those children with neuromuscular disorders, have not been well studied. Studies of children with underlying conditions that result in technology dependence and those with neuromuscular disorders who required hospitalization for respiratory syncytial virus infection are reviewed. Additionally surveys of physician perceptions toward risk factors for severe viral illness and prevention in this population of patients are reported. Possible mechanisms to explain the increased risk of disease severity with viral respiratory infections are explored as well. Current or recent use of supplemental oxygen is associated with more severe disease in children with chronic underlying conditions, especially bronchopulmonary dysplasia. Supplemental oxygen use may be a marker for several factors known to increase the severity of viral respiratory illnesses. Children with neuromuscular weakness are also likely to experience more severe disease, most likely resulting from compromised airway clearance. Although the number of children who are technology-dependent or have severe neuromuscular weakness is small, their risk of severe disease after viral respiratory infection may be similar to that of premature infants or other high risk groups. A better understanding of the factors responsible for severe viral disease in these children would help create better strategies for treatment and prevention.

Chapter 32. Applications of Recombinant DNA Technology of Interest to Medicinal Chemists

Objective: During the coronavirus disease 2019 (COVID-19) pandemic, these globally implemented nonpharmacological interventions (NPIs) have altered the circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as other respiratory viruses in the community. To evaluate the impact of NPIs on the incidence and severity of viral respiratory tract infection (RTI) in newborns during and after the COVID-19 pandemic. Methods: The study was performed as a retrospective design between 2020-2023. Newborns with signs of upper or lower RTI who had undergone real-time polymerase chain reaction (RT-PCR) testing were included. The study was divided into 3 periods by considering the intervals when NPIs were strictly applied (period 1), relaxed (period 2), and removed (period 3). The incidence, viral diversity, and clinical severity of neonates with viral RTI were compared between the periods. Results: During the study 109 viral agents were detected in 100 neonates. The percentage of RTI cases was significantly lower in period 1 (5% vs 41% and 54% in periods 1, 2, 3 respectively, p: 0.001). A total of 9 different viral agents were isolated from neonates with decreasing frequency, including respiratory syncytial virus (RSV) (35%), rhinovirus/enterovirus (31%), SARS-CoV-2 (13%), parainfluenza virus (PIV) (7.2%) and other viruses (13.8%). In the first period, the infant with RSV was not present. RSV was detected at the highest rate in period 3, although there was no significant difference between periods. RSV peaks were detected in November and December in period 2 and 3. Rhinovirus/enterovirus was detected in all study periods with similar percentages. The percentages requiring non-invasive mechanical ventilation, inhaled budesonide, and inhaled salbutamol were significantly higher in period 3. Conclusion: The incidence of viral RTI (especially RSV) increased significantly after the removal of NPIs in period 3, viral RTI was more severe in this period. RSV-associated RTI peaks in newborns shifted a few months earlier in post-pandemic period.

Introduction: Emerging importance of the rhinovirus

Most studies focusing on respiratory infections in immunocompromised children have been addressed to bacterial etiology. However, respiratory virus infections in this population can also lead to severe disease. The objective of this study is to evaluate the clinical significance of respiratory virus infections in children with cancer or human immunodeficiency virus (HIV) infection. Retrospective study conducted in a teaching hospital in Madrid. Medical records from children <or=14 years diagnosed with cancer or with HIV infection were reviewed. We analyzed demographic characteristics, clinical syndromes associated with the infection, need for hospitalization, treatment prescribed, and outcome. Fifty-three respiratory viral infections were identified: 26 (20%) in 129 HIV-infected children and 27 (12%) in 218 children with cancer. Twenty (38%) of the respiratory infections were nosocomial. Causal viruses were: respiratory syncytial virus, 43%; influenza A, 26%; adenovirus, 13%; parainfluenza virus, 13%; and influenza B, 4%. Thirty-three children were hospitalized: 14 (54%) with HIV infection and 19 (70%) receiving anticancer chemotherapy. Pneumonia occurred in 11 (34%) of the 33 hospitalized children. Four (21%) of the 19 hospitalized children with cancer, but none of the HIV-infected children, were admitted to the Pediatric Intensive Care Unit (P=0.096). Two children with cancer died. Common respiratory virus infections in children with cancer or HIV infection have a relevant morbidity. The fact that 40% of these infections are hospital-acquired emphasizes the need for isolation and preventive measures.

ABSTRACTDuring respiratory-virus infection, excessive lymphocyte activation can cause pathology both in acute infection and in exacerbations of chronic respiratory diseases. The costimulatory molecule CD161 is expressed on lymphocyte subsets implicated in promoting respiratory inflammation, including Th2, Th17, mucosally associated invariant T (MAIT) cells, and type 2 innate lymphoid cells. We asked whether the CD161 ligand LLT1 could be expressed on respiratory epithelial cells following respiratory-virus infection as a mechanism by which respiratory-virus infection could promote activation of proinflammatory lymphocytes. In response to respiratory syncytial virus (RSV) infection, expression of LLT1 was upregulated in the BEAS-2B respiratory epithelial cell line and primary human bronchial epithelial cells. Imaging studies revealed that LLT1 expression increased in both RSV-infected and cocultured uninfected cells, suggesting that soluble factors produced during infection stimulate LLT1 expression. TLR3 and TLR2/6 ligands led to a rapid increase in LLT1 mRNA in respiratory epithelial cells, as did the proinflammatory cytokines type I interferons, interleukin 1β (IL-1β), and tumor necrosis factor alpha (TNF-α), which are produced early in respiratory-virus infection. Immunohistochemistry confirmed the increase in LLT1 protein on the epithelial cell surface, and live-cell confocal microscopy demonstrated accumulation of epithelial LLT1 at synapses formed with CD161+ T lymphocytes. LLT1 expression by the respiratory epithelium in response to respiratory-virus infection and inflammatory cytokines represents a novel link between innate immunity and lymphocyte activation. As a regulator of CD161+ proinflammatory lymphocytes, LLT1 could be a novel therapeutic target in inflammation caused by respiratory-virus infection.IMPORTANCE The immune response to respiratory-virus infection is essential for clearing the pathogen but, if excessive, can lead to tissue damage and obstruction of the airways. How viral infection activates immune cells in the lungs is not fully understood. Here, we show that LLT1 can be expressed in lung cells in response to infection. LLT1 triggers CD161, a receptor on inflammatory immune cells. This mechanism may promote activation of immune cells in the lungs in viral infection and could be a novel target for therapies aimed at reducing lung inflammation.

Chapter 13 - Evolution and Genetic Engineering

BackgroundWe aimed to investigate the effects of ambient respiratory viral infections in the general population on rheumatoid arthritis (RA) development.MethodsData of weekly incident RA (2012–2013) were obtained from the Korean National Health Insurance claims database, and those of weekly observations on eight respiratory viral infections were obtained from the Korea Centers for Disease Control and Prevention database. We estimated the percentage change in incident RA associated with ambient mean respiratory viral infections using a generalized linear model, after adjusting for time trend, air pollution, and meteorological data.ResultsA total of 24,117 cases of incident RA (mean age 54.7 years, 18,688 [77.5%] women) were analyzed. Ambient respiratory viral infections in the population were associated with a higher number of incident RA over time, and its effect peaked 6 or 7 weeks after exposure. Among the 8 viruses, parainfluenza virus (4.8% for 1% respiratory viral infection increase, 95% CI 1.6 to 8.1, P = .003), coronavirus (9.2%, 3.9 to 14.8, P < .001), and metapneumovirus (44%, 2.0 to 103.4, P = .038) were associated with increased number of incident RA. The impact of these respiratory viral infections remained significant in women (3.8%, 12.1%, and 67.4%, respectively, P < .05) and in older patients (10.7%, 14.6%, and 118.2%, respectively, P < .05).ConclusionsAmbient respiratory viral infections in the population were associated with an increased number of incident RA, especially in women and older patients, suggesting that respiratory viral infections can be a novel environmental risk factor for the development of RA.

Büyükkapu-Bay S, Kebudi R, Görgün Ö, Meşe S, Zülfikar B, Badur S. Respiratory viral infection`s frequency and clinical outcome in symptomatic children with cancer: A single center experience from a middle-income country. Turk J Pediatr 2018; 60: 653-659. In developing countries, acute respiratory tract infections are a significant cause of morbidity and mortality in children, particularly in pediatric cancer patients. A majority of these illnesses are precipitated by viral infections. In our country, studies were conducted on the single respiratory viral infection in a pediatric hematology-oncology unit; however, the analysis of respiratory viral infections in children with cancer is lacking. The present study aimed to provide analysis of multiple respiratory viral infections and clinical outcome in children with cancer who receive chemotherapy and show signs and symptoms of respiratory tract infections. During January, 2014 and January, 2015 children with cancer under treatment who presented with respiratory tract infections were assessed for viruses by using multiplex real-time reverse transcription polymerase chain reaction (rRT-PCR). Specimens were collected by nasal swabbing at in-patient and out-patient clinics. Overall, 72 samples of respiratory tract infection episodes, collected from children with cancer were evaluated with the simultaneous detection of 20 respiratory viruses. A respiratory viral pathogen was obtained in 56.9% samples. Rhinovirus (24.3%) and co-infection with two viruses (19.5%) were the most frequently isolated pathogens. There were four (9.6%) samples of severe pneumonia. Patients with febrile neutropenic episodes and pneumonia were hospitalized and treated with broad-spectrum antibiotics. Other non-neutropenic and mild respiratory tract infections were treated with supportive care as outpatient procedures. There were no deaths. Because there are no effective antiviral agents for certain respiratory viruses, infection control and early diagnosis are crucial in preventing the spread of infection. Clinical findings and serological results of viral respiratory tract infections help us to accurately determine the treatment approach and avoid the unnecessary use of antibiotics.