Method to Assess Immunosenescent CD8+ T Cells in Respiratory Viral Infections.

Immunosenescence is a well-characterized phenomenon that occurs with increasing age in all immune and somatic cells. In order to best study immunosenescence, it is imperative to develop methods to accurately identify immunosenescent cells. Elderly patients are known to have impaired immune responses to respiratory viruses, and it is hypothesized that this is due, in part, to immunosenescent, terminally exhausted CD8+ T cells. To test this hypothesis, we developed an aged mouse model and a flow cytometry protocol using the Cytek® Aurora to assess the CD8+ T-cell response during respiratory viral infection and identify immunosenescent CD8+ T cells. This protocol and our aged mouse model have great potential to be incredibly valuable for future studies elucidating how to rejuvenate and possibly reverse immunosenescent CD8+ T cells, which could improve the immune response to respiratory viruses in this at-risk population.

Sex differences in the impact of lower respiratory tract infections on older adults' health trajectories: a population-based cohort study.

BACKGROUND: Lower respiratory tract infections (LRTIs) are a major global health concern, particularly among older adults, who have an increased risk of poorer health outcomes that persist beyond the acute infectious episode. We aimed to investigate the mid-term (up to 7 years) and long-term (up to 12 years) effects of LRTIs on the objective health status trajectories of older adults, while also considering potential sex differences. METHODS: Cohort data of adults aged ≥ 60 years from the Swedish National study of Aging and Care in Kungsholmen (SNAC-K) collected between 2001 and 2016 was analyzed. Information on LRTIs was obtained from the Swedish National Patient Register, and objective health status was assessed using the Health Assessment Tool (HAT) which incorporates indicators of mild and severe disability, cognitive and physical functioning, and multimorbidity. The LRTI-exposed and -unexposed participants were matched using propensity score matching based on an expansive list of potential confounders. Mixed linear models were used to analyze the association between LRTIs and changes in HAT scores. RESULTS: The study included 2796 participants, 567 of whom were diagnosed with a LRTI. LRTIs were independently associated with an excess annual decline of 0.060 (95% CI: -0.107, -0.013) in the HAT score over a 7-year period. The associations were stronger among males, who experienced an excess annual decline of 0.108 (95% CI: -0.177, -0.039) in up to 7-years follow-up, and 0.097 (95% CI: -0.173, -0.021) in up to 12-years follow-up. The associations were not statistically significant among females in either follow-up period. CONCLUSION: LRTIs, even years after the acute infectious period, seem to have a prolonged negative effect on the health of older adults, particularly among males. Preventative public health measures aimed at decreasing LRTI cases among older adults could help in preserving good health and functioning in old age.

Doxycycline with or without famciclovir for infectious ophthalmic and respiratory disease: a prospective, randomized, masked, placebo-controlled trial in 373 kittens.

OBJECTIVES: The aim of this study was to prospectively evaluate in a randomized, triple-masked, placebo-controlled trial, outcomes for kittens with ocular manifestations of infectious upper respiratory disease (IURD) treated with an ophthalmic and oral antibiotic only vs those also treated with famciclovir. METHODS: Kittens were stratified into three age (1 to <4, 4 to <8 or 8-12 weeks) and two disease severity ('mild' [total disease score 1-11] or 'severe' [total disease score 12-23]) groups and randomized to receive approximately 5 mg/kg doxycycline either with placebo (group D) or with approximately 90 mg/kg famciclovir (group DF) PO q12h. Caregivers scored clinical signs once daily for 21 days. Ophthalmic examinations and scoring by veterinarians were completed on days 1 and 21. Ophthalmic and clinical resolution were defined as scores of zero for all ocular signs and all ocular and respiratory signs, respectively. Ophthalmic and clinical recovery were defined by absence of active inflammation. RESULTS: For kittens with mild disease, those in group D were slower than those in group DF to achieve clinical recovery (P = 0.049) and clinical resolution (P = 0.030), but not ophthalmic recovery (P = 0.064) or ophthalmic resolution (P = 0.089). Kittens with mild disease and receiving famciclovir achieved predicted 75% clinical resolution 4-5 days earlier than kittens with mild disease and receiving doxycycline alone, and kittens with severe disease (regardless of treatment group). Significantly fewer kittens in group DF developed corneal disease than in group D (P = 0.016). All five kittens whose clinical signs worsened sufficiently to be removed from the study were in group D. CONCLUSIONS AND RELEVANCE: The addition of famciclovir to standard antibiotic treatment may reduce corneal disease, length of stay and time to adoption for shelters and rescue groups, thereby increasing capacity for care. Early administration of famciclovir in kittens exhibiting mild ocular manifestations of IURD may be preferable to delaying this treatment until the disease progresses to a severe stage.

Serum Levels of Selected Cytokines and Chemokines and IgG4 in Children With Recurrent Respiratory Tract Infections.

Background: Respiratory tract infections are a common health problem. Cytokines/chemokines play a critical role in the regulation of the immune system. Their defective production may predispose to recurrent respiratory tract infections (RRIs), and an excessive immune response may lead to chronic inflammation and cause damage to the respiratory tract. Another biomarker of respiratory infections may be immunoglobulin-IgG4. Its meaning has still been little explored. We wanted to assess the suitability of the levels of biomarkers tested: interleukin (IL)-17A, IL-18, IL-23, normal T cells expressed and secreted (RANTES), and induced protein (IP)-10, as well as immunoglobilun G4 (IgG4) to predict recurrent infections. Methods: The study group (SG) included a total of 130 children (68 girls, 62 boys) between 3 and 17 years of age with RRI. The control group (CG) included 86 healthy children with no symptoms of inflammatory or allergic diseases (44 girls and 42 boys) of the same age. Blood samples were collected in fasting state and then serum samples were frozen and stored until biomarker assay. Results: Serum RANTES, IL-18, IL-23, and IgG4 concentration were higher in all children with recurrent infections vs. those in the CG (p < 0001). Serum levels of IL-17A and IP-10 were also significantly higher in the SG than in the CG, but only in the youngest children. Among the six serum markers, RANTES demonstrated the highest area under the receiver operating characteristic curve (area under curve) value (0.998, 95% confidence interval [CI]: 0.98-1.0, p < 0.001) for the diagnosis of RRIs, followed by IL-23 (0.99, 95% CI 0.966-0,999, p < 0.001) and IL-18 (0.957, 95% CI 0.921-0.980, p < 0.001). Conclusions: RANTES, IL-23, and IL-18 could be strong predictors of respiratory infections recurrence in children.

Empirical assessment of the enrichment-based metagenomic methods in identifying diverse respiratory pathogens.

Probe-based nucleic acid enrichment represents an effective route to enhance the detection capacity of next-generation sequencing (NGS) in a set of clinically diverse and relevant microbial species. In this study, we assessed the effect of the enrichment-based sequencing on identifying respiratory infections using tiling RNA probes targeting 76 respiratory pathogens and sequenced using both Illumina and Oxford Nanopore platforms. Forty respiratory swab samples pre-tested for a panel of respiratory pathogens by qPCR were used to benchmark the sequencing data. We observed a general improvement in sensitivity after enrichment. The overall detection rate increased from 73 to 85% after probe capture detected by Illumina. Moreover, enrichment with probe sets boosted the frequency of unique pathogen reads by 34.6 and 37.8-fold for Illumina DNA and cDNA sequencing, respectively. This also resulted in significant improvements on genome coverage especially in viruses. Despite these advantages, we found that library pooling may cause reads mis-assignment, probably due to crosstalk issues arise from post-capture PCR and from pooled sequencing, thus increasing the risk of bleed-through signal. Taken together, an overall improvement in the breadth and depth of pathogen coverage is achieved using enrichment-based sequencing method. For future applications, automated library processing and pooling-free sequencing could enhance the precision and timeliness of probe enrichment-based clinical metagenomics.

Can switching from cigarettes to heated tobacco products reduce consequences of pulmonary infection?

RATIONALE: While tobacco industry data suggests that switching from combustible cigarettes to heated tobacco products (HTPs), like IQOS, may reduce the users' exposure to respiratory toxicants, it is not known if using HTPs impacts the outcomes of acute respiratory infections. OBJECTIVES: Does switching from cigarettes to HTPs improve responses to pulmonary infection. METHODS: We conducted experiments in which 3 groups of mice were pre-exposed to cigarette smoke for 8 weeks, followed by 8-week exposure to (1) HTPs (tobacco product switching), (2) air (smoking cessation), or (3) continued exposure to cigarette smoke. Pulmonary bacterial clearance and surrogate markers of lung damage were assessed as study outcomes. MAIN RESULTS: Significantly compromised clearance of bacteria from the lungs post-acute challenge occurred in both the switching group and in mice continuously exposed to cigarette smoke. Bacterial clearance, inflammatory T-cell infiltration into the lungs, and albumin leak improved at 12 h post-acute challenge in the switching group compared to mice continuously exposed to cigarette smoke. Bacterial clearance, total lung immune-cell infiltration, inflammatory T-cell infiltration into the lungs, the content of total proteins in the BAL, and albumin leak measured post-acute challenge were compromised in the switching group compared to mice in the cessation group. Switching from cigarettes to HTPs did not improve lung myeloperoxidase and neutrophil elastase levels (markers for lung inflammation and damage), which, however, were significantly reduced in the cessation group. CONCLUSIONS: This study reveals only a modest improvement in respiratory infection outcomes after switching exposure from cigarettes to HTPs and significantly compromised outcomes compared to a complete cessation of exposure to all tobacco products.

"She mimicked the manipulations on my hand": fostering embodied care among children with recurrent acute respiratory tract infections in Southern China.

INTRODUCTION: When young children experience recurrent respiratory infections, caregivers face the challenge of preventing new episodes whilst maintaining close rapport with their children. Pediatric massage, such as pediatric Tuina, entails soft massage of the skin, administered by trained providers. This non-pharmaceutical measure is used to prevent new respiratory infections in China. The aim of this study is to deepen our understanding of caregivers' experiences and perceptions of providing pediatric Tuina treatment to their children with recurrent respiratory tract infections. METHODS: A qualitative study, based on semi-structured interviews, was conducted in accordance with the Consolidated Criteria for Reporting Qualitative Research checklist. Sixteen mothers from Southern China, whose children had received pediatric Tuina for recurrent respiratory tract infections, participated online. Analysis was conducted according to the principles of reflexive thematic analysis, using the NVivo qualitative research software. RESULTS: The overarching theme was "Fostering embodied care with children". Caregivers assessed pediatric Tuina by hearing others' experiences of pediatric Tuina, as well as observing the manipulations on their child's body and their bodily reactions during pediatric Tuina sessions. Caregivers also closely observed children's bodily changes after pediatric Tuina sessions. Embodied attachment between children and adults was nurtured through the pediatric Tuina. Compared to other treatments or medical consultations, children were more relaxed and more involved in embodied care, which involved direct skin touching and verbal communication from the pediatric Tuina provider. Children also took the initiative to bring pediatric Tuina into their family life, by asking caregivers to perform it on them and mimicking the manipulations on the caregivers' hand. CONCLUSIONS: Pediatric Tuina served as a means of interaction between children and adults, fostering an embodied care on both a physical and emotional level. Beyond its potentially preventive effect on recurrent respiratory tract infections, pediatric Tuina could be a support for parents of children with recurrent or chronic disease at home.

Functional evaluation of TMEM176B and its predictive role for severe respiratory viral infection through integrated analysis of single-cell and bulk RNA-sequencing.

Transmembrane protein 176B (TMEM176B), localized mainly on the endosomal membrane, has been reported as an immune regulatory factor in malignant diseases. However, the biological function of this molecule remains undetermined during respiratory viral infections. To investigate the functions and prognostic value of this gene, six gene sets were selected from the Gene Expression Omnibus database for research. First, the function of TMEM176B and its co-expressed genes were evaluated at different levels (cell, peripheral blood, lung tissue). Afterwards, a machine learning algorithm was utilized to analyze the relationship between TMEM176B and its interacting genes with prognosis. After importance evaluation and variable screening, a prognostic model was established. Finally, the reliability of the model was further verified through external data sets. In vitro experiments were conducted to validate the function of TMEM176B. TMEM176B and its co-expressed genes are involved in multiple processes such as inflammasome activation, myeloid immune cell development, and immune cell infiltration. Machine learning further screened 27 interacting gene modules including TMEM176B as prognostic models for severe respiratory viral infections, with the area under the ROC curve (AUCs) of 0.986 and 0.905 in derivation and external validation sets, respectively. We further confirmed that viral load as well as NLRP3 activation and cell death were significantly enhanced in TMEM176B-/- THP-1-differentiated macrophages via in vitro experiments. Our study revealed that TMEM176B is involved in a wide range of biological functions in respiratory viral infections and has potential prognostic value, which is expected to bring new insights into the clinical management of severe respiratory viral infection hosts.

Clinical symptoms, comorbidities and health outcomes among outpatients infected with the common cold coronaviruses versus influenza virus.

BACKGROUND: Common cold coronaviruses (ccCoVs) and influenza virus are common infectious agents causing upper respiratory tract infections (RTIs). However, clinical symptoms, comorbidities, and health effects of ccCoV infection remain understudied. METHODS: A retrospective study evaluated 3,935 outpatients with acute upper RTI at a tertiary teaching hospital. The presence of ccCoV and influenza virus was determined by multiplex molecular assay. The demographic, clinical symptoms, and health outcomes were compared between patients with ccCoV (n = 205) and influenza (n = 417) infections. Multivariable logistic regression was employed to evaluate predictors and health outcomes over a one-year follow-up. RESULTS: Sore throat, nasal discharge, headache, and myalgia were more predominant in ccCoV infection; fever was common in influenza. Most patients reported moderate symptoms severity (49.8% ccCoV, 56.1% influenza). Subsequent primary care visits with symptoms of RTI within a year were comparable for both infections (27.3% ccCoV vs. 27.6% influenza). However, patients with influenza reported increased primary care visits for non-RTI episodes and all-cause hospital admission. Baseline comorbidities were associated with increased primary care visits with symptoms of RTI in either ccCoV (adjusted odds ratio [aOR] 2.5; 95% confidence interval [CI] 1.1-5.9; P = 0.034) or influenza (OR 1.9; 95% CI 1.1-3.1; P = 0.017) infections, due probably to the dysregulation of the host immune response following acute infections. In patients infected with influenza infection, dyslipidemia was a predictor for subsequent primary care visits with symptoms of RTI (unadjusted OR 1.8; 95% CI 1.0-3.0; P = 0.040). CONCLUSIONS: Both influenza and ccCoV infection pose significant disease burden, especially in patients with comorbidities. The management of comorbidities should be prioritized to mitigate poor health outcomes in infected individuals.

Genomic characteristics of human respiratory syncytial virus from children in China during 2017-2020.

Acute lower respiratory tract infections (ALRTIs) are a leading cause of mortality in young children worldwide due to human respiratory syncytial virus (RSV). The aim of this study was to monitor genetic variations in RSV and provide genomic data support for RSV prevention and control. A total of 105 complete RSV genome sequences were determined during 2017-2020. Phylogenetic analysis showed that all of the RSVA sequences were of genotype ON1, and all of the RSVB sequences were of genotype BA9. Notably, a phylogenetic tree based on the whole genome had more branches than a tree based on the G gene. In comparison to the RSV prototype sequences, 71.43% (50/70) of the ON1 sequences had five amino acid substitutions (T113I, V131N, N178G, H258Q, and H266L) that occurred simultaneously, and 68.57% (24/35) of the BA9 genotype sequences had 12 amino acid substitutions, four of which (A131T, T137I, T288I, and T310I) occurred simultaneously. In the F gene, there were 19 amino acid substitutions, which were mainly located in the antigenic sites Ø, II, V, and VII. Other amino acid substitutions were found in the NS1, NS2, P, SH, and L proteins. No significant evidence of recombination was found in any of the sequences. These findings provide important data that will be useful for prevention, control, and vaccine development against RSV.

Common viral respiratory infections in children with cancer during the COVID-19 pandemic: a multicenter study from Türkiye.

BACKGROUND: Microbiologic confirmation of respiratory tract infections gained importance during the coronavirus disease 2019 (COVID-19) pandemic. This study retrospectively evaluated seasonal distribution, clinical presentation, and complications of respiratory viral infections (RVIs) other than COVID-19 in children with cancer during and after the pandemic lockdown. METHODS: Two hundred and sixty-five inpatient and outpatient RVI episodes in 219 pediatric cancer patients confirmed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) panels from 13 centers were enrolled. RESULTS: Eighty-six (32.5%) of the total 265 episodes occurred in 16 months corresponding to the lockdowns in Türkiye, and the remaining 67.5% in 10 months thereafter. Human rhinovirus/enterovirus (hRE) (48.3%) was the most common agent detected during and after lockdown. Parainfluenza virus (PIV) (23.0%), influenza virus (9.8%), and respiratory syncytial virus (RSV) (9.1%) were the other common agents. The 28.7% of episodes were lower respiratory tract infections (LRTIs), and complications and mortality were higher than upper respiratory tract infections (URTIs) (25.0% vs 5.3%). Bacteremia was identified in 11.5% of culture-drawn episodes. Treatment delay in one-third and death within four weeks after RVI in 4.9% of episodes were observed. CONCLUSION: During the pandemic, fewer episodes of RVIs occurred during the lockdown period. Respiratory viruses may cause complications, delays in treatment, and even death in children with cancer. Therefore, increased awareness of RVIs and rapid detection of respiratory viruses will benefit the prevention and, in some cases, abrupt supportive and some antiviral treatment of RVI in children with cancer.

[Comparative assessment of the clinical effectiveness of direct-acting antiviral drugs in outpatient patients with acute respiratory viral infections].

AIM: To evaluate the clinical effectiveness, safety and compare the incidence of hospitalization during treatment with antiviral drugs with a direct mechanism of action (riamilovir and umifenovir) in people with acute respiratory viral infections (ARVI) in an outpatient setting. MATERIALS AND METHODS: The study included 150 outpatients with ARVI aged 18-27 years: 50 patients received riamilovir 250 mg 3 times a day for 5 days, the second group included 50 patients who received umifenovir 200 mg 4 times a day for 5 days, 50 individuals received only pathogenetic treatment. RESULTS: The use of direct-acting antiviral drugs was characterized by the least severity of pain and aches in the body, general weakness, and in the group of patients receiving riamilovir, the lowest severity of rhinitis, cough, and the lowest morning body temperature were recorded compared to other groups. In riamilovir group reduction in the duration of the disease was observed. The lowest frequency of ARVI pathogens detection was observed on the 6th day in riamilovir group. Outpatient treatment with riamilovir was accompanied by a minimal number of cases of the disease requiring hospitalization. CONCLUSION: The use of direct antiviral drugs contributes to the rapid relief of ARVI symptoms in patients receiving medical care on an outpatient basis. The antiviral drug riamilovir showed the most pronounced effectiveness (clinical and laboratory).

Respiratory viral infections in bone marrow transplant patients: insights from a tertiary care hospital in Rawalpindi, Pakistan.

OBJECTIVE: To determine the incidence of respiratory viral infections in bone marrow transplant patients. METHODS: The prospective, descriptive, cross-sectional study was conducted at a tertiary care hospital in Rawalpindi, Pakistan, from September 2019 to August 2020, and comprised respiratory specimens from recipients of haematopoietic stem cell transplant. The specimens were collected in viral transport medium, and were then taken to the Department of Virology. Multiplex polymerase chain reaction was performed on the specimens to ascertain the incidence and prevalence of respiratory viruses. Data was analysed using SPSS 24. RESULTS: Of the 85 subjects, 53(62.35%) were males and 32(37.65%) were females. The overall median age was 20.0 years (interquartile range: 11.0-32.0 years). Respiratory viral infections were detected in 31(36.4%) specimens. Among them, human rhinovirus was detected in 12(38.7%) cases, respiratory syncytial virus in 5(16.1%), influenza A/H3 in 4(13%), human parainfluenza virus-1 in 3(9.7%), adenovirus in 2(6.4%), human parainfluenza virus-3 in 1(3.2%), human parainfluenza virus-4 in 1(3.2%) and human metapneumovirus in 1(3.2%) case. There were 2(6.4%) cases of co-infection. CONCLUSIONS: More than one-third recipients of haematopoietic stem cell transplant were found to have respiratory viral infections, highlighting the importance of employing multiplex respiratory polymerase chain reaction in early diagnosis and treatment of such infections.

IFN-γ primes bone marrow neutrophils to acquire regulatory functions in severe viral respiratory infections.

Neutrophil subsets endowed with regulatory/suppressive properties are widely regarded as deleterious immune cells that can jeopardize antitumoral response and/or antimicrobial resistance. Here, we describe a sizeable fraction of neutrophils characterized by the expression of programmed death-ligand 1 (PD-L1) in biological fluids of humans and mice with severe viral respiratory infections (VRI). Biological and transcriptomic approaches indicated that VRI-driven PD-L1+ neutrophils are endowed with potent regulatory functions and reduced classical antimicrobial properties, as compared to their PD-L1- counterpart. VRI-induced regulatory PD-L1+ neutrophils were generated remotely in the bone marrow in an IFN-γ-dependent manner and were quickly mobilized into the inflamed lungs where they fulfilled their maturation. Neutrophil depletion and PD-L1 blockade during experimental VRI resulted in higher mortality, increased local inflammation, and reduced expression of resolving factors. These findings suggest that PD-L1+ neutrophils are important players in disease tolerance by mitigating local inflammation during severe VRI and that they may constitute relevant targets for future immune interventions.

Incidence of serious respiratory tract infections and associated characteristics in a population exposed to immunosuppressive therapies: a register-based population study.

BACKGROUND: Immunosuppressive therapies are associated with a risk of infections. Nevertheless, their incidence in this population remains unclear. This study aims to determine the incidence of serious respiratory tract infections (SRI) in a population exposed to immunosuppressive therapies. METHODS: Data from a representative sample of the French healthcare claims from 01/01/2014 to 12/31/2019 were analyzed. Exposure to immunosuppressive therapy was defined by the dispensation of drugs through community pharmacies or in hospitals. SRI diagnosis was based on ICD-10 codes from hospitalization records. A cohort analysis was performed to estimate standardized SRI incidence rates. A nested case-control analysis within this cohort was used to study the characteristics associated with SRI. RESULTS: We identified 24,122 individuals exposed to immunosuppressive therapies, among which 1,559 developed SRI, resulting in a standardized incidence rate of 1,398 per 100,000 person-years. In this population, the risk of SRI was associated with a history of cancer (OR 2.68, 95% Confidence Intervals (CI) 2.24-3.21; p < 0.001), chronic respiratory disease (2.62, 95%CI 2.17-3.16; p < 0.001), end-stage renal failure (2.38, 95%CI 1.37-4.13; p = 0.003), neurodegenerative diseases (1.52, 95%CI 1.07-2.17; p = 0.026), diabetes (1.44, 95%CI 1.14-1.82; p < 0.001), psychiatric diseases (1.27, 95%CI 1.06-1.52; p < 0.001), and cardiovascular diseases (1.26, 95%CI 1.04-1.52; p = 0.002). Compared to corticosteroids alone, the risk of SRI was lower in individuals treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) only (0.44, 95%CI 0.25-0.78; p < 0.001). CONCLUSION: In the population exposed to immunosuppressive therapies, a history of chronic disease is associated with an increased risk of SRI. This risk is lower in those receiving csDMARD alone than corticosteroids alone.

Pediatric respiratory infectious emergencies: clinical profiles and outcomes.

Infectious diseases are among the most frequent causes of hospital admission and a substantial contributor to morbidity and mortality. These diseases pose a persistent concern, particularly within the pediatric population, where delays or inappropriate management can result in serious harm. Additionally, infectious diseases contribute to overcrowding in pediatric emergency departments (EDs). This study aimed to explore the epidemiology, clinical presentation, diagnostics, outcome, and social and behavioral impacts of infectious diseases on child health. We conducted a retrospective, single-hospital study at a tertiary care center that is publicly funded and owned to serve the entire community. Pediatric patients with at least one or more chief complaints related to the respiratory system or infectious etiology were included. Data analysis was performed using SPSS to assess relationships between variables. A total of 15,106 patients were included, with a mean age of 3.80 years. The largest age group was toddlers (42.8%). Most cases (71.9%) were classified as urgent (Priority 3). Regarding patient outcomes, 76.1% were discharged after receiving appropriate treatment in the ED, and 22.9% required admission for further management. Nearly 38% of patients presented with a single complaint. Fever was the most frequent complaint across all groups. In summary, this study provides insights into the presentation of pediatric respiratory infectious diseases in the emergency room. The study revealed that toddlers were the most affected age group, with fever and cough being the common symptoms.

Seasonality and Co-Detection of Respiratory Viral Infections Among Hospitalised Patients Admitted With Acute Respiratory Illness-Valencia Region, Spain, 2010-2021.

BACKGROUND: Respiratory viruses are known to represent a high burden in winter, yet the seasonality of many viruses remains poorly understood. Better knowledge of co-circulation and interaction between viruses is critical to prevention and management. We use > 10-year active surveillance in the Valencia Region to assess seasonality and co-circulation. METHODS: Over 2010-2021, samples from patients hospitalised for acute respiratory illness were analysed using multiplex real-time PCR to test for 9 viruses: influenza, respiratory syncytial virus (RSV), parainfluenza virus (PIV), rhino/enteroviruses (HRV/ENV), metapneumovirus (MPV), bocavirus, adenovirus, SARS-CoV-2 and non-SARS coronaviruses (HCoV). Winter seasonal patterns of incidence were examined. Instances of co-detection of multiple viruses in a sample were analysed and compared with expected values under a crude model of independent circulation. RESULTS: Most viruses exhibited consistent patterns between years. Specifically, RSV and influenza seasons were clearly defined, peaking in December-February, as did HCoV and SARS-CoV-2. MPV, PIV and HRV/ENV showed less clear seasonality, with circulation outside the observed period. All viruses circulated in January, suggesting any pair had opportunity for co-infection. Multiple viruses were found in 4% of patients, with more common co-detection in children under 5 (9%) than older ages. Influenza co-detection was generally observed infrequently relative to expectation, while RSV co-detections were more common, particularly among young children. CONCLUSIONS: We identify characteristic patterns of viruses associated with acute respiratory hospitalisation during winter. Simultaneous circulation permits extensive co-detection of viruses, particularly in young children. However, virus combinations appear to differ in their rates of co-detection, meriting further study.

Respiratory pathogen analysis in pediatric inpatients unraveled the infection pattern of Mycoplasma pneumoniae post the COVID-19 pandemic.

Background: To counteract the COVID-19 pandemic, nonpharmaceutical interventions (NPIs) were implemented globally, exerting a profound influence on a wide spectrum of infectious diseases, encompassing respiratory tract infections (RTIs). Subsequent to the easing of NPIs, China experienced a significant outbreak of Mycoplasma pneumoniae (MP). Methods: Over a decade from 2015 to 2024, our study scrutinized 12 common infectious diseases among pediatric children. Etiologically diagnostic data and clinical outcome metrics of children with RTIs, tested for 13 pathogens, were analyzed to evaluate changes during and after the pandemic compared to pre-pandemic periods, with a notable emphasis on age profile and coinfection patterns of MP. Results: Among 57,471 hospitalized children, 23,178 were diagnosed with infectious diseases. Under NPIs, most respiratory infections declined compared to pre-pandemic levels, rebounding by 69.64% in 2023. While the infection rate of common respiratory pathogens decreased, cases of respiratory syncytial virus increased during the period of extensive NPI implementation. In 2023, pediatric intensive care unit durations for these pathogens increased, suggesting greater severity of illness compared to 2019. MP exhibited the highest infection rate (31.38% average), with a notable outbreak post-pandemic due to severity increase in <3 year olds and rise among older children. NPIs reduced MP coinfections and mitigated their severity, while exerting a significant influence on bacterial coinfections with MP over the span of 5 years, in contrast to their impact on viral pathogens. Conclusion: NPIs effectively curb transmission of respiratory infections by most pathogens, resulting in increased average age of MP infections and altered patterns of coinfection post-pandemic.