Emerging Paradigms in Type 2 Immunity.

A principal purpose of type 2 immunity was thought to be defense against large parasites, but it also functions in the restoration of homeostasis, such as toxin clearance following snake bites. In other cases, like allergy, the type 2 T helper (Th2) cytokines and cells present in the environment are detrimental and cause diseases. In recent years, the recognition of cell heterogeneity within Th2-associated cell populations has revealed specific functions of cells with a particular phenotype or gene signature. In addition, here we discuss the recent data regarding heterogeneity of type 2 immunity-related cells, as well as their newly identified role in a variety of processes ranging from involvement in respiratory viral infections [especially in the context of the recent COVID-19 (coronavirus disease 2019) pandemic] to control of cancer development or of metabolic homeostasis.

Mucosal plasma cells are required to protect the upper airway and brain from infection.

While blood antibodies mediate protective immunity in most organs, whether they protect nasal surfaces in the upper airway is unclear. Using multiple viral infection models in mice, we found that blood-borne antibodies could not defend the olfactory epithelium. Despite high serum antibody titers, pathogens infected nasal turbinates, and neurotropic microbes invaded the brain. Using passive antibody transfers and parabiosis, we identified a restrictive blood-endothelial barrier that excluded circulating antibodies from the olfactory mucosa. Plasma cell depletions demonstrated that plasma cells must reside within olfactory tissue to achieve sterilizing immunity. Antibody blockade and genetically deficient models revealed that this local immunity required CD4+ T cells and CXCR3. Many vaccine adjuvants failed to generate olfactory plasma cells, but mucosal immunizations established humoral protection of the olfactory surface. Our identification of a blood-olfactory barrier and the requirement for tissue-derived antibody has implications for vaccinology, respiratory and CNS pathogen transmission, and B cell fate decisions.

Mechanism and spectrum of inhibition of a 4'-cyano modified nucleotide analog against diverse RNA polymerases of prototypic respiratory RNA viruses.

The development of safe and effective broad-spectrum antivirals that target the replication machinery of respiratory viruses is of high priority in pandemic preparedness programs. Here, we studied the mechanism of action of a newly discovered nucleotide analog against diverse RNA-dependent RNA polymerases (RdRps) of prototypic respiratory viruses. GS-646939 is the active 5'-triphosphate metabolite of a 4'-cyano modified C-adenosine analog phosphoramidate prodrug GS-7682. Enzyme kinetics show that the RdRps of human rhinovirus type 16 (HRV-16) and enterovirus 71 incorporate GS-646939 with unprecedented selectivity; GS-646939 is incorporated 20-50-fold more efficiently than its natural ATP counterpart. The RdRp complex of respiratory syncytial virus and human metapneumovirus incorporate GS-646939 and ATP with similar efficiency. In contrast, influenza B RdRp shows a clear preference for ATP and human mitochondrial RNA polymerase does not show significant incorporation of GS-646939. Once incorporated into the nascent RNA strand, GS-646939 acts as a chain terminator although higher NTP concentrations can partially overcome inhibition for some polymerases. Modeling and biochemical data suggest that the 4'-modification inhibits RdRp translocation. Comparative studies with GS-443902, the active triphosphate form of the 1'-cyano modified prodrugs remdesivir and obeldesivir, reveal not only different mechanisms of inhibition, but also differences in the spectrum of inhibition of viral polymerases. In conclusion, 1'-cyano and 4'-cyano modifications of nucleotide analogs provide complementary strategies to target the polymerase of several families of respiratory RNA viruses.

The impact of trained immunity in respiratory viral infections.

Epidemic peaks of respiratory viruses that co-circulate during the winter-spring seasons can be synchronous or asynchronous. The occurrence of temporal patterns in epidemics caused by some respiratory viruses suggests that they could negatively interact with each other. These negative interactions may result from a programme of innate immune memory, known as trained immunity, which may confer broad protective effects against respiratory viruses. It is suggested that stimulation of innate immune cells by a vaccine or a pathogen could induce their long-term functional reprogramming through an interplay between metabolic and epigenetic changes, which influence the transcriptional response to a secondary challenge. During the coronavirus disease 2019 pandemic, the circulation of most respiratory viruses was prevented by non-pharmacological interventions and then resumed at unusual periods once sanitary measures were lifted. With time, respiratory viruses should find again their own ecological niches. This transition period provides an opportunity to study the interactions between respiratory viruses at the population level.

Agnostic Sequencing for Detection of Viral Pathogens.

The advent of next-generation sequencing (NGS) technologies has expanded our ability to detect and analyze microbial genomes and has yielded novel molecular approaches for infectious disease diagnostics. While several targeted multiplex PCR and NGS-based assays have been widely used in public health settings in recent years, these targeted approaches are limited in that they still rely on a priori knowledge of a pathogen's genome, and an untargeted or unknown pathogen will not be detected. Recent public health crises have emphasized the need to prepare for a wide and rapid deployment of an agnostic diagnostic assay at the start of an outbreak to ensure an effective response to emerging viral pathogens. Metagenomic techniques can nonspecifically sequence all detectable nucleic acids in a sample and therefore do not rely on prior knowledge of a pathogen's genome. While this technology has been reviewed for bacterial diagnostics and adopted in research settings for the detection and characterization of viruses, viral metagenomics has yet to be widely deployed as a diagnostic tool in clinical laboratories. In this review, we highlight recent improvements to the performance of metagenomic viral sequencing, the current applications of metagenomic sequencing in clinical laboratories, as well as the challenges that impede the widespread adoption of this technology.

Respiratory Viral Infections from 2015 to 2022 in the HIVE Cohort of American Households: Incidence, illness characteristics, and seasonality.

BACKGROUND: Viral respiratory illnesses are the most common acute illnesses experienced and generally follow a predicted pattern over time. The SARS-CoV-2 pandemic interrupted that pattern. METHODS: The HIVE (Household Influenza Vaccine Evaluation) study was established in 2010 to follow a cohort of Southeast Michigan households over time. Initially focused on influenza, surveillance was expanded to include other major respiratory pathogens, and, starting in 2015, the population was followed year-round. Symptoms of acute illness were reported, and respiratory specimens were collected and tested to identify viral infections. Based on the known population being followed, virus-specific incidence was calculated. RESULTS: From 2015 to 2022, 1755 participants were followed in HIVE for 7785 person-years with 7833 illnesses documented. Before the pandemic, rhinovirus (RV) and common cold human coronaviruses (HCoVs) were the viruses most frequently identified, and incidence decreased with increasing age. Type A influenza was next but with comparable incidence by age. Parainfluenza and respiratory syncytial viruses were less frequent overall, followed by human metapneumoviruses. Incidence was highest in young children, but infections were frequently documented in all age groups. Seasonality followed patterns established decades ago. The SARS-CoV-2 pandemic disrupted these patterns, except for RV and, to a lesser extent, HCoVs. In the first two years of the pandemic, RV incidence far exceeded that of SARS-CoV-2. CONCLUSION: Longitudinal cohort studies are important in comparing the incidence, seasonality, and characteristics of different respiratory viral infections. Studies documented the differential effect of the pandemic on the incidence of respiratory viruses in addition to SARS-CoV-2.

The Activation of the RIG-I/MDA5 Signaling Pathway upon Influenza D Virus Infection Impairs the Pulmonary Proinflammatory Response Triggered by Mycoplasma bovis Superinfection.

Concurrent infections with multiple pathogens are often described in cattle with respiratory illness. However, how the host-pathogen interactions influence the clinical outcome has been only partially explored in this species. Influenza D virus (IDV) was discovered in 2011. Since then, IDV has been detected worldwide in different hosts. A significant association between IDV and bacterial pathogens in sick cattle was shown in epidemiological studies, especially with Mycoplasma bovis. In an experimental challenge, IDV aggravated M. bovis-induced pneumonia. However, the mechanisms through which IDV drives an increased susceptibility to bacterial superinfections remain unknown. Here, we used the organotypic lung model precision-cut lung slices to study the interplay between IDV and M. bovis coinfection. Our results show that a primary IDV infection promotes M. bovis superinfection by increasing the bacterial replication and the ultrastructural damages in lung pneumocytes. In our model, IDV impaired the innate immune response triggered by M. bovis by decreasing the expression of several proinflammatory cytokines and chemokines that are important for immune cell recruitment and the bacterial clearance. Stimulations with agonists of cytosolic helicases and Toll-like receptors (TLRs) revealed that a primary activation of RIG-I/MDA5 desensitizes the TLR2 activation, similar to what was observed with IDV infection. The cross talk between these two pattern recognition receptors leads to a nonadditive response, which alters the TLR2-mediated cascade that controls the bacterial infection. These results highlight innate immune mechanisms that were not described for cattle so far and improve our understanding of the bovine host-microbe interactions and IDV pathogenesis. IMPORTANCE Since the spread of the respiratory influenza D virus (IDV) infection to the cattle population, the question about the impact of this virus on bovine respiratory disease (BRD) remains still unanswered. Animals affected by BRD are often coinfected with multiple pathogens, especially viruses and bacteria. In particular, viruses are suspected to enhance secondary bacterial superinfections. Here, we use an ex vivo model of lung tissue to study the effects of IDV infection on bacterial superinfections. Our results show that IDV increases the susceptibility to the respiratory pathogen Mycoplasma bovis. In particular, IDV seems to activate immune pathways that inhibit the innate immune response against the bacteria. This may allow M. bovis to increase its proliferation and to delay its clearance from lung tissue. These results suggest that IDV could have a negative impact on the respiratory pathology of cattle.

Persistence of human respiratory viral RNA in wastewater-settled solids.

Wastewater-based epidemiology has emerged as a valuable tool for monitoring respiratory viral diseases within communities by analyzing concentrations of viral nucleic-acids in wastewater. However, little is known about the fate of respiratory virus nucleic-acids in wastewater. Two important fate processes that may modulate their concentrations in wastewater as they move from household drains to the point of collection include sorption or partitioning to wastewater solids and degradation. This study investigated the decay kinetics of genomic nucleic-acids of seven human respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV), human coronavirus (HCoV)-OC43, HCoV-229E, HCoV-NL63, human rhinovirus (HRV), and influenza A virus (IAV), as well as pepper mild mottle virus (PMMoV) in wastewater solids. Viruses (except for PMMoV) were spiked into wastewater solids and their concentrations were followed for 50 days at three different temperatures (4°C, 22°C, and 37°C). Viral genomic RNA decayed following first-order kinetics with decay rate constants k from 0 to 0.219 per day. Decay rate constants k were not different from 0 for all targets in solids incubated at 4°C; k values were largest at 37°C and at this temperature, k values were similar across nucleic-acid targets. Regardless of temperature, there was limited viral RNA decay, with an estimated 0% to 20% reduction, over the typical residence times of sewage in the piped systems between input and collection point (<1 day). The k values reported herein can be used directly in fate and transport models to inform the interpretation of measurements made during wastewater surveillance.IMPORTANCEUnderstanding whether or not the RNA targets quantified for wastewater-based epidemiology (WBE) efforts decay during transport between drains and the point of sample collection is critical for data interpretation. Here we show limited decay of viral RNA targets typically measured for respiratory disease WBE.

The role of ion dissolution in metal and metal oxide surface inactivation of SARS-CoV-2.

Anti-viral surface coatings are under development to prevent viral fomite transmission from high-traffic touch surfaces in public spaces. Copper's anti-viral properties have been widely documented, but the anti-viral mechanism of copper surfaces is not fully understood. We screened a series of metal and metal oxide surfaces for anti-viral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19). Copper and copper oxide surfaces exhibited superior anti-SARS-CoV-2 activity; however, the level of anti-viral activity was dependent on the composition of the carrier solution used to deliver virus inoculum. We demonstrate that copper ions released into solution from test surfaces can mediate virus inactivation, indicating a copper ion dissolution-dependent anti-viral mechanism. The level of anti-viral activity is, however, not dependent on the amount of copper ions released into solution per se. Instead, our findings suggest that degree of virus inactivation is dependent on copper ion complexation with other biomolecules (e.g., proteins/metabolites) in the virus carrier solution that compete with viral components. Although using tissue culture-derived virus inoculum is experimentally convenient to evaluate the anti-viral activity of copper-derived test surfaces, we propose that the high organic content of tissue culture medium reduces the availability of "uncomplexed" copper ions to interact with the virus, negatively affecting virus inactivation and hence surface anti-viral performance. We propose that laboratory anti-viral surface testing should include virus delivered in a physiologically relevant carrier solution (saliva or nasal secretions when testing respiratory viruses) to accurately predict real-life surface anti-viral performance when deployed in public spaces.IMPORTANCEThe purpose of evaluating the anti-viral activity of test surfaces in the laboratory is to identify surfaces that will perform efficiently in preventing fomite transmission when deployed on high-traffic touch surfaces in public spaces. The conventional method in laboratory testing is to use tissue culture-derived virus inoculum; however, this study demonstrates that anti-viral performance of test copper-containing surfaces is dependent on the composition of the carrier solution in which the virus inoculum is delivered to test surfaces. Therefore, we recommend that laboratory surface testing should include virus delivered in a physiologically relevant carrier solution to accurately predict real-life test surface performance in public spaces. Understanding the mechanism of virus inactivation is key to future rational design of improved anti-viral surfaces. Here, we demonstrate that release of copper ions from copper surfaces into small liquid droplets containing SARS-CoV-2 is a mechanism by which the virus that causes COVID-19 can be inactivated.

Natural variability of TRAIL, IP-10, and CRP in healthy adults - The "HERACLES" study.

A novel host-protein score (called MMBV) helps to distinguish bacterial from viral infection by combining the blood concentrations of three biomarkers: tumour necrosis factor related apoptosis inducing ligand (TRAIL), interferon gamma induced protein 10 (IP-10), and C-reactive protein (CRP). These host biomarkers are differentially expressed in response to bacterial versus viral acute infection. We conducted a prospective study, with a time series design, in healthy adult volunteers in the Netherlands. The aim was to determine the variability of TRAIL, IP-10, and CRP and the MMBV score in healthy adults across time. Up to six blood samples were taken from each healthy volunteer over a period of up to four weeks. In 77 healthy participants without recent or current symptoms, MMBV scores (maximal) were bacterial in 1.3 % and viral (or other non-infectious etiology) in 93.5 % of participants. There was little variation in the mean concentrations of TRAIL (74.5 pg/ml), IP-10 (113.6 pg/ml), and CRP (1.90 mg/L) as well as the MMBV score. The variability of biomarker measurement was comparable to the precision of the measurement platform for TRAIL, IP-10, and CRP. Our findings establish the mean values of these biomarkers and MMBV in healthy individuals and indicate little variability between and within individuals over time, supporting the potential utility of this novel diagnostic to detect infection-induced changes.

Viral coinfection in hospitalized patients during the COVID-19 pandemic in Southern Brazil: a retrospective cohort study.

PURPOSE: Since the worldwide spread of SARS-CoV-2, different strategies have been followed to combat the pandemic and limit virus transmission. In the meantime, other respiratory viruses continued to circulate, though at decreased rates. METHODS: This study was conducted between June and July 2022, in a hospital in the metropolitan region of Rio Grande do Sul state, in the southernmost state of Brazil. The 337 hospitalized patients included those with respiratory symptoms without delimitation of age. Reverse transcription-quantitative real-time polymerase chain reaction detected 15 different respiratory viruses and confirmed coinfections in the samples. Different statistical tests were applied to evaluate the association between associations of clinical characteristics and coinfection. RESULTS: Sampling corresponds to 337 selected and 330 patients analyzed. The principal clinical outcome found was hospital discharge in 309 (94%) cases, while 21 (6%) resulted in death. The principal viral agents related to coinfections were Human rhinovirus, Human enterovirus, and Respiratory syncytial virus. The most frequent viral agent detected was SARS-CoV-2, with 60 (18%) infections, followed by 51 (15%) cases of Respiratory syncytial virus B (15%) and 44 (13%) cases of Human rhinovirus 1. Coinfection was mainly observed in children, while adults and the elderly were more affected by a single infection. Analyzing COVID-19 vaccination, 175 (53%) were unvaccinated while the remainder had at least one dose of the vaccine. CONCLUSIONS: This study presents information to update the understanding of viral circulation in the region. Furthermore, the findings clarify the behavior of viral infections and possible coinfections in hospitalized patients, considering different ages and clinical profiles. In addition, this knowledge can help to monitor the population's clinical manifestations and prevent future outbreaks of respiratory viruses.

Targeting SARS-CoV-2 by synthetic dual-acting thiol compounds that inhibit Spike/ACE2 interaction and viral protein production.

The SARS-CoV-2 life cycle is strictly dependent on the environmental redox state that influences both virus entry and replication. A reducing environment impairs the binding of the spike protein (S) to the angiotensin-converting enzyme 2 receptor (ACE2), while a highly oxidizing environment is thought to favor S interaction with ACE2. Moreover, SARS-CoV-2 interferes with redox homeostasis in infected cells to promote the oxidative folding of its own proteins. Here we demonstrate that synthetic low molecular weight (LMW) monothiol and dithiol compounds induce a redox switch in the S protein receptor binding domain (RBD) toward a more reduced state. Reactive cysteine residue profiling revealed that all the disulfides present in RBD are targets of the thiol compounds. The reduction of disulfides in RBD decreases the binding to ACE2 in a cell-free system as demonstrated by enzyme-linked immunosorbent and surface plasmon resonance (SPR) assays. Moreover, LMW thiols interfere with protein oxidative folding and the production of newly synthesized polypeptides in HEK293 cells expressing the S1 and RBD domain, respectively. Based on these results, we hypothesize that these thiol compounds impair both the binding of S protein to its cellular receptor during the early stage of viral infection, as well as viral protein folding/maturation and thus the formation of new viral mature particles. Indeed, all the tested molecules, although at different concentrations, efficiently inhibit both SARS-CoV-2 entry and replication in Vero E6 cells. LMW thiols may represent innovative anti-SARS-CoV-2 therapeutics acting directly on viral targets and indirectly by inhibiting cellular functions mandatory for viral replication.

Exosome-mediated regulation of inflammatory pathway during respiratory viral disease.

Viruses have developed many mechanisms by which they can stimulate or inhibit inflammation and cause various diseases, including viral respiratory diseases that kill many people every year. One of the mechanisms that viruses use to induce or inhibit inflammation is exosomes. Exosomes are small membrane nanovesicles (30-150 nm) released from cells that contain proteins, DNA, and coding and non-coding RNA species. They are a group of extracellular vesicles that cells can take up to produce and mediate communication. Intercellular effect exosomes can deliver a broad confine of biological molecules, containing nucleic acids, proteins, and lipids, to the target cell, where they can convey therapeutic or pathogenic consequences through the modulation of inflammation and immune processes. Recent research has shown that exosomes can deliver entire virus genomes or virions to distant target cells, then the delivered viruses can escape the immune system and infect cells. Adenoviruses, orthomyxoviruses, paramyxoviruses, respiratory syncytial viruses, picornaviruses, coronaviruses, and rhinoviruses are mostly related to respiratory diseases. In this article, we will first discuss the current knowledge of exosomes. We will learn about the relationship between exosomes and viral infections, and We mention the inflammations caused by viruses in the airways, the role of exosomes in them, and finally, we examine the relationship between the viruses as mentioned earlier, and the regulation of inflammatory pathways that play a role in causing the disease.

Development and validation of a rapid five-minute nucleic acid extraction method for respiratory viruses.

BACKGROUND: The rapid transmission and high pathogenicity of respiratory viruses significantly impact the health of both children and adults. Extracting and detecting their nucleic acid is crucial for disease prevention and treatment strategies. However, current extraction methods are laborious and time-consuming and show significant variations in nucleic acid content and purity among different kits, affecting detection sensitivity and efficiency. Our aim is to develop a novel method that reduces extraction time, simplifies operational steps, and ensures high-quality acquisition of respiratory viral nucleic acid. METHODS: We extracted respiratory syncytial virus (RSV) nucleic acid using reagents with different components and analyzed cycle threshold (Ct) values via quantitative real-time polymerase chain reaction (qRT-PCR) to optimize and validate the novel lysis and washing solution. The performance of this method was compared against magnetic bead, spin column, and precipitation methods for extracting nucleic acid from various respiratory viruses. The clinical utility of this method was confirmed by comparing it to the standard magnetic bead method for extracting clinical specimens of influenza A virus (IAV). RESULTS: The solution, composed of equal parts glycerin and ethanol (50% each), offers an innovative washing approach that achieved comparable efficacy to conventional methods in a single abbreviated cycle. When combined with our A Plus lysis solution, our novel five-minute nucleic acid extraction (FME) method for respiratory viruses yielded superior RNA concentrations and purity compared to traditional methods. FME, when used with a universal automatic nucleic acid extractor, demonstrated similar efficiency as various conventional methods in analyzing diverse concentrations of respiratory viruses. In detecting respiratory specimens from 525 patients suspected of IAV infection, the FME method showed an equivalent detection rate to the standard magnetic bead method, with a total coincidence rate of 95.43% and a kappa statistic of 0.901 (P < 0.001). CONCLUSIONS: The FME developed in this study enables the rapid and efficient extraction of nucleic acid from respiratory samples, laying a crucial foundation for the implementation of expedited molecular diagnosis.

Detection of community-acquired respiratory viruses during COVID-19 pandemic in subtropical region in Japan.

PURPOSE: Coronavirus disease 2019 (COVID-19) pandemic changed the dynamics of other community-acquired respiratory viruses (CARVs), however, information regarding the frequency of CARV detection during COVID-19 pandemic in subtropical regions is limited. Additionally, studies comparing the diagnostic accuracy between multiplex and monoplex PCR for the diagnosis of COVID-19 are scarce. METHODS: We evaluated samples collected from patients suspected of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Okinawa, a subtropical climate in Japan, from March 2020 to March 2021. For SARS-CoV-2, results obtained from monoplex (NIID method) and multiplex (Allplex™ SARS-CoV-2 Assay) PCR were compared. RESULTS: In total, 744 samples were collected and 238 viruses were detected in 205 specimens, of which 22 showed viral co-infection. Viral co-infection was more common in patients aged 10 and under than in older patients (p = 0.0054). For CARV, 142 viruses were detected in 127 specimens (17.1%), and human rhinovirus (HRV) was most common. Overall concordance rate for two SARS-CoV-2 assays was 94.1%; 7 and 37 specimens were detected only by NIID and Allplex™ SARS-CoV-2 Assay, respectively. The median cycling threshold values of the 44 samples that were only positive for either the NIID or Allplex™ SARS-CoV-2 Assay were 37.91 for E gene, 38.13 for RdRp/S gene, 38.21 for N gene and 39.16 for N2 gene. CONCLUSION: HRV was continuously detected during COVID-19 pandemic in the subtropical region and viral co-infection was more common in younger patients. For the diagnosis of COVID-19, multiplex PCR was more reliable, especially in samples with low viral load.

Old foes following news ways?-Pandemic-related changes in the epidemiology of viral respiratory tract infections.

INTRODUCTION: Following lockdown periods and restricting public health measures in response to the COVID-19 pandemic, respiratory tract infections (RTIs) rose significantly worldwide. This led to an increased burden on children's hospitals compromising medical care of acutely and chronically ill children. We characterized changes in the epidemiological pattern of circulating respiratory viral infections. METHODS: We assessed the number of patients with RTIs and the annual distribution of virus detections between 2019 and 2022 based on 4809 clinical samples (4131 patients) from a German pediatric tertiary care-center. We investigated the impact of lockdown periods on spectra of circulating respiratory viruses, pattern of coinfections, age, and seasonality of infections. RESULTS: A fourfold increase in the number of respiratory virus detections was observed in 2022 vs 2019 with numbers doubling in 2022 (vs 2021). In 2022, seasonal patterns of circulating virus, particularly Adeno and seasonal Coronavirus were far less pronounced compared to previous years, in fact almost disappeared for Rhinoviruses.". SARS-CoV-2, Parainfluenza- and human Metapneumovirus detections increased significantly in 2022 (2019 vs 2022, p < 0.01). Coinfections with multiple viruses occurred more frequently since 2021 compared to pre-pandemic years, especially in younger children (2019 vs 2022, p < 0.01). CONCLUSION: Compared to pre-pandemic years, we observed a dramatic increase in pediatric RTIs with an incrementing spectrum of viruses and a predominance in Rhino/Enterovirus infections - leading to a high rate of hospital admissions, particularly in conjunction with other viruses. This caused an acute shortage in medical care and may also be followed by an increase of virus-triggered secondary chronic respiratory diseases like asthma-rendering a burden on the health system.

Respiratory viral co-infections in patients with COVID-19 and associated outcomes: A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to critically assess the published literature related to community-acquired viral co-infections and COVID-19 and to evaluate the prevalence, most identified co-pathogens, and relevant risk factors. Furthermore, we aimed to examine the clinical features and outcomes of co-infected compared to mono-infected COVID-19 patients. We systematically searched PubMed, Web of Science, Embase, Scopus, and The Cochrane Library for studies published from 1 November 2019 to 13 August 2021. We included patients of all ages and any COVID-19 severity who were screened for respiratory viral co-infection within 48 h of COVID-19 diagnosis. The main outcome was the proportion of patients with a respiratory viral co-infection. The systematic review was registered to PROSPERO (CRD42021272235). Out of 6053 initially retrieved studies, 59 studies with a total of 16,643 SARS-CoV-2 positive patients were included. The global pooled prevalence was 5.01% (95% CI 3.34%-7.27%; I2  = 95%) based on a random-effects model, with Influenza Viruses (1.54%) and Enteroviruses (1.32%) being the most prevalent pathogens. Subgroup analyses showed that co-infection was significantly higher in paediatric (9.39%) than adult (3.51%) patients (p-value = 0.02). Furthermore, co-infected patients were more likely to be dyspnoeic and the odds of fatality (OR = 1.66) were increased. Although a relatively low proportion of COVID-19 patients have a respiratory viral co-infection, our findings show that multiplex viral panel testing may be advisable in patients with compatible symptoms. Indeed, respiratory virus co-infections may be associated with adverse clinical outcomes and therefore have therapeutic and prognostic implications.

Viral etiology of febrile respiratory syndrome among patients in Liaoning Province, China.

BACKGROUND: Febrile respiratory syndrome (FRS) is often associated with viral infections. The aim of this study was to identify the viral pathogens responsible for FRS in Liaoning Province, China. METHODS: We tested eight respiratory viruses, namely, influenza virus (IFV), rhinovirus (RV), human adenovirus (HAdV), human bocavirus (HBoV), human parainfluenza virus (HPIV), human coronavirus (HCoV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV), using reverse transcription-polymerase chain reaction (RT-PCR). Statistical analyses were performed using SPSS version 25.0, and the data were plotted using RStudio 4.2.1 software. RESULTS: IFV was the most frequently identified pathogen, followed by RV, HAdV, HBoV, HPIV, HCoV, RSV, and HMPV. RSV/HBoV coinfection occurred most frequently among the mixed cases. The rate of respiratory virus detection was highest in children under one year of age and decreased significantly with age. Seasonal trends showed a peak in virus detection during the winter months. CONCLUSIONS: IFV is the leading cause of FRS in Liaoning Province, China, with single-virus infections prevailing over coinfections. Observations indicate a differential virus detection rate across age groups and seasons, highlighting the need for focused preventive strategies to mitigate the transmission of respiratory viruses, particularly among susceptible populations in the colder season.

Near-source passive sampling for monitoring viral outbreaks within a university residential setting.

Wastewater-based epidemiology (WBE) has proven to be a powerful tool for the population-level monitoring of pathogens, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For assessment, several wastewater sampling regimes and methods of viral concentration have been investigated, mainly targeting SARS-CoV-2. However, the use of passive samplers in near-source environments for a range of viruses in wastewater is still under-investigated. To address this, near-source passive samples were taken at four locations targeting student hall of residence. These were chosen as an exemplar due to their high population density and perceived risk of disease transmission. Viruses investigated were SARS-CoV-2 and its variants of concern (VOCs), influenza viruses, and enteroviruses. Sampling was conducted either in the morning, where passive samplers were in place overnight (17 h) and during the day, with exposure of 7 h. We demonstrated the usefulness of near-source passive sampling for the detection of VOCs using quantitative polymerase chain reaction (qPCR) and next-generation sequencing (NGS). Furthermore, several outbreaks of influenza A and sporadic outbreaks of enteroviruses (some associated with enterovirus D68 and coxsackieviruses) were identified among the resident student population, providing evidence of the usefulness of near-source, in-sewer sampling for monitoring the health of high population density communities.

Epidemic profile of common respiratory viruses in association SARS CoV-2 among SARI and ARI-two year study.

BACKGROUND: COVID-19/SARS CoV-2 continue to pose a threat to human health and placed millions of livelihoods at risk. Surveillance for the other circulating seasonal viruses during this pandemic is necessary to understand the manifestations of the CoV-2 pandemic and their incidence. METHODS: A detailed study survey was performed on subjects with acute respiratory infections (ARI) and severe acute respiratory infection (SARI) in the King Institute of Preventive Medicine and Research, Chennai from April 2020 to March 2022. A total of 1480 patients presenting with either SARI (41.8%) or ARI (58.1%) were screened for SARS CoV-2 and other respiratory viruses. The SARS CoV-2 real-time PCR was carried out using ICMR-approved kits and other respiratory viruses were detected using the commercially available real-time kit. RESULTS: Out of the 620 SARI patients, 198 (31.9%) were positive for SARS CoV-2 RNA. Out of the 860 ARI patients, 352 (40.9%) were positive for SARS CoV-2 RNA. Among the 550 patients positive for SARS CoV-2, 7 (1.2%) were positive coexistent with other respiratory viruses. Among the 930 patients with negative SARS CoV-2, 222 (23.8%) were positive for other common respiratory viruses (p = 0.001). Influenza viruses (36.9%) predominated followed by RSV (31.9%) and Parainfluenza virus (13.5%). CONCLUSION: This study suggests that viral coinfections are significantly higher among SARS CoV-2 negative individuals (23.8 vs. 1.2%). It is possibly due to viral interference and the competitive advantage of SARS CoV-2 in modulating the host immunity. Continuous surveillance is necessary for understanding the viral co-infection mechanisms.