Respiratory infections such as Coronavirus disease 2019 are a substantial worldwide health challenge, frequently resulting in severe sickness and death, especially in susceptible groups. Conventional drug development for respiratory infections faces obstacles such as extended timescales, substantial expenses, and the rise of resistance to current treatments. Drug repurposing is a potential method that has evolved to quickly find and reuse existing medications for treating respiratory infections. Drug repurposing utilizes medications previously approved for different purposes, providing a cost-effective and time-efficient method to tackle pressing medical needs. This chapter summarizes current progress and obstacles in repurposing medications for respiratory infections, focusing on notable examples of repurposed pharmaceuticals and their probable modes of action. The text also explores the significance of computational approaches, high-throughput screening, and preclinical investigations in identifying potential candidates for repurposing. The text delves into the significance of regulatory factors, clinical trial structure, and actual data in confirming the effectiveness and safety of repurposed medications for respiratory infections. Drug repurposing is a valuable technique for quickly increasing the range of treatments for respiratory infections, leading to better patient outcomes and decreasing the worldwide disease burden.

Haemophilus influenzae serotype a (Hia) has recently emerged as an important cause of invasive disease in the North American Arctic and Sub-Arctic regions, mainly affecting young Indigenous children. In this study, we addressed the question of whether the prevalence of Hia and all H. influenzae in the nasopharynx differed between paediatric populations from regions with high versus low incidence of invasive Hia disease. Nasopharyngeal specimens from children with acute respiratory tract infections (ARTI) collected for routine diagnostic detection of respiratory viruses were analysed with molecular-genetic methods to identify and serotype H. influenzae. In Nunavut, a region with a high incidence of invasive Hia disease, all H. influenzae and particularly Hia were found in the nasopharynx of 60.6% and 3.0% children. In Southern Ontario (Hamilton region), where Hia invasive disease is rare, the frequencies of all H. influenzae and Hia detection were 38.5% and 0.6%, respectively. In both cohorts, non-typeable H. influenzae was prevalent (57.0% and 37.9%, respectively). Considering that Hia is an important cause of severe invasive disease in Nunavut children, 3% prevalence of Hia among children with ARTI can reflect continuing circulation of the pathogen in the Northern communities that may result in invasive disease outbreaks.

The upper respiratory tract (URT) is home to a diverse range of microbial species. Respiratory infections disturb the microbial flora in the URT, putting people at risk of secondary infections. The potential dangers and clinical effects of bacterial and fungal coinfections with SARS-CoV-2 support the need to investigate the microbiome of the URT using clinical samples. Mass spectrometry (MS)-based metaproteomics analysis of microbial proteins is a novel approach to comprehensively assess the clinical specimens with complex microbial makeup. The coronavirus that causes severe acute respiratory syndrome (SARS-CoV-2) is responsible for the COVID-19 pandemic resulting in a plethora of microbial coinfections impeding therapy, prognosis, and overall disease management. In this chapter, the corresponding workflows for MS-based shotgun proteomics and metaproteomic analysis are illustrated.

UNASSIGNED: Young farm animals are susceptible to opportunistic infections which may cause economic losses due to mortality and poor weight gain. The development of antimicrobial resistance and the desire to improve therapy efficacy and safety are the reasons to seek for new antibacterial drugs ensuring rapid recovery with minimum adverse events.
UNASSIGNED: To estimate the efficacy of DOKSI AVZ 500 in respiratory pathologies in young pigs.
UNASSIGNED: The study was conducted in 65-70-day-old Yorkshire piglets with signs of bacterial respiratory pathologies. The animals were treated with the test drug for 3 or 5 days. The reference group received TETRAMAX 500 which is similar to the test drug in terms of chemical structure, mechanism of action, and activity spectrum. The animal\'s status was assessed using clinical examination, clinical blood count, and bacteriological tests.
UNASSIGNED: Both test and reference drugs were well tolerated and ensured the animal recovery within about 4 days. The recovery was accompanied by normalization of hematological parameters and flora composition. The bacterium associated with the disease development, Streptococcus suis, was virtually completely eliminated in all groups. No adverse events were noted. After the treatment, all the animals readily gained weight and live market quality.
UNASSIGNED: DOKSI AVZ 500 was a highly efficient therapy for respiratory pathologies caused by the resident opportunistic flora in piglets. It has also shown noninferiority vs. TETRAMAX 500 in terms of all the health-related parameters and thus can be recommended for introduction in veterinary practice in pig farms.

OBJECTIVE: To analyze the effects and tolerability of physiotherapeutic methods with optical radiation (phototherapy) in acute respiratory diseases (ARD) on the basis of the modern scientific literature data and the results of doctors and patients survey.
METHODS: An analysis of regulatory sources and modern scientific literature on the subject of research, survey of 200 patients with ARD and 100 primary care physicians of the Central Federal District on their sociomedical status and awareness of phototherapeutic treatment methods were conducted.
RESULTS: Phototherapy in ARD have demonstrated chromogenic, immunostimulating, photosensitizing, vitamin-forming, trophostimulating, anti-inflammatory, analgesic, desensitizing, bactericidal and mycocidal, metabolic, coagulo-correcting therapeutic effects. Patients and doctors have been insufficiently aware of phototherapy methods and used them in practice relatively rare. A significant proportion of patients had ARD risk factors, namely teamwork, tobacco smoking and chronic diseases.
CONCLUSIONS: 1. The therapeutic effects of all types of phototherapy in acute respiratory infections are interrelated with their etiopathogenesis. 2. Patients and doctors are insufficiently informed and relatively rarely use phototherapy methods. 3. A significant proportion of patients have risk factors for acute respiratory infections: teamwork (88%), tobacco smoking (68%) and chronic diseases (52%).
UNASSIGNED: Проанализировать эффекты и переносимость физиотерапевтических методов оптической природы (фототерапии) при острых респираторных заболеваниях (ОРЗ) на основании данных современной научной литературы и результатов опроса врачей и пациентов.
UNASSIGNED: Проведены анализ нормативных источников и современной научной литературы по теме исследования, анкетирование 200 пациентов с ОРЗ и 100 врачей первичного звена здравоохранения Центрального федерального округа относительно их медико-социального статуса и информированности о фототерапевтических методах лечения.
UNASSIGNED: Фототерапия при ОРЗ продемонстрировала пигментообразующий, иммуностимулирующий, фотосенсибилизирующий, витаминообразующий, трофостимулирующий, противовоспалительный, анальгетический, десенсибилизирующий, бактерицидный и микоцидный, метаболический, коагулокорригирующий лечебные эффекты. Пациенты и врачи оказались недостаточно осведомлены о методах фототерапии и относительно редко применяли их в своей практике. Значительная часть пациентов имели факторы риска ОРЗ: работу в коллективах, курение табака и хронические заболевания.
UNASSIGNED: 1. Лечебные эффекты всех видов фототерапии при ОРЗ взаимосвязаны с их этиопатогенезом. 2. Пациенты и врачи недостаточно осведомлены и относительно редко применяют фототерапевтические методы. 3. Значительная часть пациентов имеют факторы риска ОРЗ: работу в коллективах (88%), курение табака (68%) и хронические заболевания (52%).

Viral tropism is most commonly linked to receptor use, but host cell protease use can be a notable factor in susceptibility to infection. Here we review the use of host cell proteases by human viruses, focusing on those with primarily respiratory tropism, particularly SARS-CoV-2. We first describe the various classes of proteases present in the respiratory tract, as well as elsewhere in the body, and incorporate the targeting of these proteases as therapeutic drugs for use in humans. Host cell proteases are also linked to the systemic spread of viruses and play important roles outside of the respiratory tract; therefore, we address how proteases affect viruses across the spectrum of infections that can occur in humans, intending to understand the extrapulmonary spread of SARS-CoV-2.

The epidemiology of different respiratory viral infections is believed to be affected by prior viral infections in addition to seasonal effects. This PROSPERO-registered systematic review identified 7388 studies, of which six met our criteria to answer the question specifically. The purpose of this review was to compare the prevalence of sequential viral infections in those with previously documented positive versus negative swabs. The pooled prevalence of sequential viral infections over varying periods from 30-1000 days of follow-up was higher following a negative respiratory viral swab at 0.15 than following a positive swab at 0.08, indicating the potential protective effects of prior respiratory viral infections. However, significant heterogeneity and publication biases were noted. There is some evidence, albeit of low quality, of a possible protective effect of an initial viral infection against subsequent infections by a different virus, which is possibly due to broad, nonspecific innate immunity. Future prospective studies are needed to validate our findings.

This study aimed to determine the incidence and etiological, seasonal, and genetic characteristics of respiratory viral coinfections involving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Between October 2020 and January 2024, nasopharyngeal samples were collected from 2277 SARS-CoV-2-positive patients. Two multiplex approaches were used to detect and sequence SARS-CoV-2, influenza A/B viruses, and other seasonal respiratory viruses: multiplex real-time polymerase chain reaction (PCR) and multiplex next-generation sequencing. Coinfections of SARS-CoV-2 with other respiratory viruses were detected in 164 (7.2%) patients. The most common co-infecting virus was respiratory syncytial virus (RSV) (38 cases, 1.7%), followed by bocavirus (BoV) (1.2%) and rhinovirus (RV) (1.1%). Patients ≤ 16 years of age had the highest rate (15%) of mixed infections. Whole-genome sequencing produced 19 complete genomes of seasonal respiratory viral co-pathogens, which were subjected to phylogenetic and amino acid analyses. The detected influenza viruses were classified into the genetic groups 6B.1A.5a.2a and 6B.1A.5a.2a.1 for A(H1N1)pdm09, 3C.2a1b.2a.2a.1 and 3C.2a.2b for A(H3N2), and V1A.3a.2 for the B/Victoria lineage. The RSV-B sequences belonged to the genetic group GB5.0.5a, with HAdV-C belonging to type 1, BoV to genotype VP1, and PIV3 to lineage 1a(i). Multiple amino acid substitutions were identified, including at the antibody-binding sites. This study provides insights into respiratory viral coinfections involving SARS-CoV-2 and reinforces the importance of genetic characterization of co-pathogens in the development of therapeutic and preventive strategies.

Following an interseasonal rise in mainly pediatric respiratory syncytial virus (RSV) cases in Germany in 2021, an exceptionally high number of adult cases was observed in the subsequent respiratory season of 2022/2023. The aim of this study was to compare the clinical presentation of RSV infections in the pre- and post-SARS-CoV-2 pandemic periods. Additionally, the local epidemiology of the RSV fusion protein was analyzed at a molecular genetic and amino acid level. RSV detections in adults peaked in calendar week 1 of 2023, 8 weeks earlier than the earliest peak observed in the three pre-pandemic seasons. Although the median age of the adult patients was not different (66.5 vs. 65 years), subtle differences between both periods regarding comorbidities and the clinical presentation of RSV cases were noted. High rates of comorbidities prevailed; however, significantly lower numbers of patients with a history of lung transplantation (p = 0.009), chronic kidney disease (p = 0.013), and immunosuppression (p = 0.038) were observed in the 2022/2023 season. In contrast, significantly more lower respiratory tract infections (p < 0.001), in particular in the form of pneumonia (p = 0.015) and exacerbations of obstructive lung diseases (p = 0.008), were detected. An ICU admission was noted for 23.7% of all patients throughout the study period. Sequence analysis of the fusion protein gene revealed a close phylogenetic relatedness, regardless of the season of origin. However, especially for RSV-B, an accumulation of amino acid point substitutions was noted, including in antigenic site Ø. The SARS-CoV-2 pandemic had a tremendous impact on the seasonality of RSV, and the introduction of new vaccination and immunization strategies against RSV warrants further epidemiologic studies of this important pathogen.

Recombination events in human adenovirus (HAdV) have led to some new highly pathogenic or infectious types. It is vital to monitor recombinant HAdVs, especially in children with acute respiratory tract infections (ARIs). In the retrospective study, HAdV positive specimens were collected from pediatric patients with ARIs during 2015 to 2021, then typed by sequence analysis of the penton base, hexon and fiber gene sequence. For those with inconsistent typing results, a modified method with species-specific primer sets of a fiber gene sequence was developed to distinguish co-infections of different types from recombinant HAdV infections. Then, plaque assays combined with meta-genomic next-generation sequencing (mNGS) were used to reveal the HAdV genomic characteristics. There were 466 cases positive for HAdV DNA (2.89%, 466/16,097) and 350 (75.11%, 350/466) successfully typed with the most prevalent types HAdV-B3 (56.57%, 198/350) and HAdV-B7 (32.00%, 112/350), followed by HAdV-C1 (6.00%, 21/350). Among 35 cases (7.51%, 35/466) with inconsistent typing results, nine cases were confirmed as co-infections by different types of HAdVs, and 26 cases as recombinant HAdVs in six genetic patterns primarily clustered to species C (25 cases) in pattern 1-5, or species D (1 case) in pattern 6. The novel recombinant HAdV of species D was identified with multiple recombinant events among HAdV-D53, HAdV-D64, and HAdV-D8, and officially named as HAdV-D115. High-frequency recombination of HAdVs in six genetic recombination patterns were identified among children with ARIs in Beijing. Specifically, there is a novel Adenovirus D human/CHN/S8130/2023/115[P22H8F8] designed as HAdV D115.