Including Influenza Virus Research Articles

Highly sensitive and selective detection of SARS-CoV-2 spike protein S1 using optically-active nanocomposite-coated melt-blown masks.

Detection of viruses, including coronavirus (SARS-CoV-2), via facile, fast, and optical methods is highly important to control pandemics. In this regard, optically-active nanomaterials and nanoparticles (NPs) are a wise choice due to their long-term stability, ease of functionalization, and modifications. In this work, a nanocomposite based on NiFe layered double hydroxide (LDH) and ZIF-67 metal-organic framework (MOF) was designed and synthesized, and decorated on the surface of the melt-blown mask. The developed nanocomposite has a fluorescence emission at 625nm. The selectivity of the nanocomposite towards the SARS-CoV-2 spike protein S1 was increased by adding CuO NPs. The limit of detection (LOD) of 1.5nM and 24.5nM against SARS-CoV-2 spike protein S1 was recorded by NiFe LDH@ZIF-67@CuO nanocomposite, and NiFe LDH@ZIF-67@CuO decorated on the surface of melt-blown. Also, in the presence of potential competitors and other types of pathogens, including Influenza virus types A and B, Staphylococcus aureus bacteria, and even cations/macromolecules, the fluorescence intensity changes had more than 40% difference.

The Role of Inflammation in the Pathogenesis of Viral Respiratory Infections.

Viral respiratory infections (VRIs) are a leading cause of morbidity and mortality worldwide, making them a significant public health concern. During infection, respiratory viruses, including Influenza virus, SARS-CoV-2, and respiratory syncytial virus (RSV), trigger an antiviral immune response, specifically boosting the inflammatory response that plays a critical role in their pathogenesis. The inflammatory response induced by respiratory viruses can be a double-edged sword since it can be initially induced to be antiviral and protective/reparative from virus-induced injuries. Still, it can also be detrimental to host cells and tissues. However, the mechanisms that differentiate the complex crosstalk between favorable host inflammatory responses and harmful inflammatory responses are poorly understood. This review explores the complex interplay between viral pathogens and the host immune response, mainly focusing on the role of inflammation in the pathogenesis of VRIs. We discuss how inflammation can both contain and exacerbate the progression of viral infections, highlighting potential therapeutic targets and emerging drugs for modulating the aberrant inflammatory responses during VRIs.

Inhibitors of dihydroorotate dehydrogenase synergize with the broad antiviral activity of 4′-fluorouridine

RNA viruses present a constant threat to human health, often with limited options for vaccination or therapy. Notable examples include influenza viruses and coronaviruses, which have pandemic potential. Filo- and henipaviruses cause more limited outbreaks, but with high case fatality rates. All RNA viruses rely on the activity of a virus-encoded RNA-dependent RNA polymerase (RdRp). An antiviral nucleoside analogue, 4'-Fluorouridine (4'-FlU), targets RdRp and diminishes the replication of several RNA viruses, including influenza A virus and SARS-CoV-2, through incorporation into nascent viral RNA and delayed chain termination. However, the effective concentration of 4'-FlU varied among different viruses, raising the need to fortify its efficacy. Here we show that inhibitors of dihydroorotate dehydrogenase (DHODH), an enzyme essential for pyrimidine biosynthesis, can synergistically enhance the antiviral effect of 4'-FlU against influenza A viruses, SARS-CoV-2, henipaviruses, and Ebola virus. Even 4'-FlU-resistant mutant influenza A virus was re-sensitized towards 4'-FlU by DHODH inhibition. The addition of uridine rescued influenza A virus replication, strongly suggesting uridine depletion as a mechanism of this synergy. 4'-FlU was also highly effective against SARS-CoV-2 in a hamster model of COVID. We propose that the impairment of endogenous uridine synthesis by DHODH inhibition enhances the incorporation of 4'-FlU into viral RNAs. This strategy may be broadly applicable to enhance the efficacy of pyrimidine nucleoside analogues for antiviral therapy.

The effects of weather and mobility on respiratory viruses before and during the COVID-19 pandemic

Abstract Background The flu season is caused by a combination of different pathogens, including influenza viruses, which cause the flu, and non-influenza respiratory viruses, that cause common colds or influenza-like illness. These viruses exhibit similar dynamics and, given that outbreaks occur mostly in the winter and there is almost no circulation during the summer, in temperate regions, meteorological conditions have historically been regarded as a principal modulator of their epidemiology. However, after the emergence of SARS-CoV2, in late 2019, the dynamics of these respiratory viruses were strongly perturbed worldwide: some infections displayed near-eradication, while others experienced temporal shifts or occurred “off-season”. This disruption raised questions regarding the dominant role of weather while also providing an unique opportunity to investigate the roles of other determinants in their epidemiological dynamics. Methods Weather, mobility and epidemiological surveillance data was collected for Influenza, RSV, hCOV and hMPV, from Canada and the USA, from 2016 to 2023. Statistical analysis and modeling were employed to test the effects of weather and mobility on viral dynamics, before and during the COVID-19 pandemic. Results Using Beta Regressions, we found that whereas in the pre-COVID-19 pandemic period, weather had a strong effect, in the pandemic period, this effect was strongly reduced post-pandemic with mobility playing a more significant role. Conclusions These results, together with previous studies, dispute the general belief that respiratory viral dynamics are mostly dictated by weather and indicate that behavioral changes resulting from the non-pharmacological interventions implemented to control SARS-CoV2, played a key role. This disruption of past dynamical equilibrium raises important questions regarding the factors that modulate them, particularly in a context of climate change. Key messages • We took advantage of the disruption caused by COVID-19 to study dynamics of other respiratory viruses and to disentangle the effects of weather from those of human behavior. • While before 2020 cold temperatures were highly correlated with incidence, afterwards cold weather was no longer a necessary condition and human mobility became central.

Diet-induced obesity affects influenza disease severity and transmission dynamics in ferrets.

Obesity, and the associated metabolic syndrome, is a risk factor for increased disease severity with a variety of infectious agents, including influenza virus. Yet, the mechanisms are only partially understood. As the number of people, particularly children, living with obesity continues to rise, it is critical to understand the role of host status on disease pathogenesis. In these studies, we use a diet-induced obese ferret model and tools to demonstrate that, like humans, obesity resulted in notable changes to the lung microenvironment, leading to increased clinical disease and viral spread to the lower respiratory tract. The decreased antiviral responses also resulted in obese animals shedding higher infectious virus for a longer period, making them more likely to transmit to contacts. These data suggest that the obese ferret model may be crucial to understanding obesity's impact on influenza disease severity and community transmission and a key tool for therapeutic and intervention development for this high-risk population.

Lessons From the Global SARS-CoV-2 Health Emergency for Potential Future Pandemics

Abstract The emergence of novel infectious agents with pandemic potential remains a critical global concern, as underscored by the COVID-19 pandemic. This study investigates the various factors contributing to the risk of new pandemics and proposes a framework for pandemic prevention and mitigation. We review the characteristics of several infectious agents, including influenza viruses, coronaviruses, filoviruses, paramyxoviruses, Lassa fever virus, Crimean-Congo hemorrhagic fever virus, and the yellow fever virus. These agents are discussed in terms of their transmission modes, reservoirs, potential for human-to-human spread, and historical outbreaks. We emphasize the importance of monitoring and early detection of these agents, especially those with localized outbreaks and zoonotic potential. Our analysis highlights the role of human activities in pandemic risk. Factors such as overuse of antibiotics, environmental changes (deforestation, wildlife habitat encroachment), climate change effects on disease vectors, and increasing global connectivity are examined as drivers of disease emergence. Furthermore, we propose a foursome of critical actions for pandemic prevention and response: early detection and rapid containment; restricting the transmission by social distancing, masking, quarantine, and elimination of vector, which are crucial even before the vaccine is available; global vaccine and treatment distribution; and robust health policy implementation. We emphasize the importance of international collaboration, information sharing, and preparedness to effectively combat pandemics. In conclusion, this commentary provides a comprehensive overview of infectious agents with pandemic potential and their associated risks. It calls for proactive measures to prevent and mitigate future pandemics, emphasizing the need for a global strategy that combines early detection, rapid response, and sustained public health infrastructure.

A Complex-Type N-Glycan-Specific Lectin Isolated from Green Alga Halimeda borneensis Exhibits Potent Anti-Influenza Virus Activity.

Marine algal lectins specific for high-mannose N-glycans have attracted attention because they strongly inhibit the entry of enveloped viruses, including influenza viruses and SARS-CoV-2, into host cells by binding to high-mannose-type N-glycans on viral surfaces. Here, we report a novel anti-influenza virus lectin (named HBL40), specific for complex-type N-glycans, which was isolated from a marine green alga, Halimeda borneensis. The hemagglutination activity of HBL40 was inhibited with both complex-type N-glycan and O-glycan-linked glycoproteins but not with high-mannose-type N-glycan-linked glycoproteins or any of the monosaccharides examined. In the oligosaccharide-binding experiment using 26 pyridylaminated oligosaccharides, HBL40 only bound to complex-type N-glycans with bi- and triantennary-branched sugar chains. The sialylation, core fucosylation, and the increased number of branched antennae of the N-glycans lowered the binding activity with HBL40. Interestingly, the lectin potently inhibited the infection of influenza virus (A/H3N2/Udorn/72) into NCI-H292 cells at IC50 of 8.02 nM by binding to glycosylated viral hemagglutinin (KD of 1.21 × 10-6 M). HBL40 consisted of two isolectins with slightly different molecular masses to each other that could be separated by reverse-phase HPLC. Both isolectins shared the same 16 N-terminal amino acid sequences. Thus, HBL40 could be useful as an antivirus lectin specific for complex-type N-glycans.

Simultaneous detection and characterization of common respiratory pathogens in wastewater through genomic sequencing

Genomic surveillance of SARS-CoV-2 has given insight into the evolution and epidemiology of the virus and its variant lineages during the COVID-19 pandemic. Expanding this approach to include a range of respiratory pathogens can better inform public health preparedness for potential outbreaks and epidemics. Here, we simultaneously sequenced 38 pathogens including influenza viruses, coronaviruses and bocaviruses, to examine the abundance and seasonality of respiratory pathogens in urban wastewater. We deployed a targeted bait capture method and short-read sequencing (Illumina Respiratory Virus Oligos Panel; RVOP) on composite wastewater samples from 8 wastewater treatment plants (WWTPs) and one associated hospital site. By combining seasonal sampling with whole genome sequencing, we were able to concurrently detect and characterise a range of common respiratory pathogens, including SARS-CoV-2, adenovirus and parainfluenza virus. We demonstrated that 38 respiratory pathogens can be detected at low abundances year-round, that hospital pathogen diversity is higher in winter vs. summer sampling events, and that significantly more viruses are detected in raw influent compared to treated effluent samples. Finally, we compared detection sensitivity of RT-qPCR vs. next generation sequencing for SARS-CoV-2, enteroviruses, influenza A/B, and respiratory syncytial viruses. We conclude that both should be used in combination; RT-qPCR allowed accurate quantification, whilst genomic sequencing detected pathogens at lower abundance. We demonstrate the valuable role of wastewater genomic surveillance and its contribution to the field of wastewater-based epidemiology, gaining rapid understanding of the seasonal presence and persistence for common respiratory pathogens. By simultaneously monitoring seasonal trends and early warning signs of many viruses circulating in communities, public health agencies can implement targeted prevention and rapid response plans.

Effect of COVID-19 pandemic on influenza; observation of a tertiary level virology laboratory.

The lockdown enforced amid the COVID-19 pandemic has affected the occurrence and trends of various respiratory virus infections, with a particular focus on influenza. Our study seeks to analyze the repercussions of the COVID-19 pandemic on the positivity of the influenza virus throughout a 4-year span, encompassing both the pre-COVID-19 era (2018 and 2019) and the COVID-19 period (2020 and 2021). Data collected from patients clinically diagnosed with Influenza-like Illness and Severe Acute Respiratory Illness (SARI) from January 2018 to December 2021 for influenza virus detection were acquired and analyzed through multiplex RT-qPCR. The statistical analysis was conducted using SPSS (Statistical Package for Social Sciences) Version 21.0 Software. A total of 4464 samples were tested over 4years (2018-2021), with 3201 samples from the pre-COVID era and 1263 samples from the COVID era. Influenza A positivity dropped from 17.7 to 9.57% and Influenza B positivity decreased from 3.74 to 2.61%. Subtyping revealed changes in prevalence for both viruses. Seasonal variations showed more pronounced peaks in the pre-COVID-19 era with reduced activity during lockdown. Influenza A saw a resurgence in August 2021. Throughout the COVID-19 pandemic (2020-2021) SARI cases did not decrease. The positivity rate for Influenza A slightly rose to 7.79% from 4.23% in the COVID period (2020-2021). This increase correlates with heightened hospitalization rates during the pandemic, sparking concerns of potential coinfection with coronavirus and Influenza A. The notable drop in influenza cases in 2020-2021 is likely due to stringent precautions, lockdowns, drug repurposing, and prioritized testing, indicating no reduction in influenza transmission. Increased influenza positivity in SARI patients during COVID-19 highlights a heightened risk of coinfection. Emphasizing solely on COVID-19 may lead to underreporting of other respiratory pathogens, including influenza viruses.

An intranasal influenza virus vector vaccine protects against Helicobacter pylori in mice.

Helicobacter pylori is a human pathogen that infects almost half of the population. Antibiotic resistance in H. pylori threatens health and increases the demand for prophylactic and therapeutic vaccines. Traditional oral vaccine research faces considerable challenges because of the epithelial barrier, potential enterotoxicity of adjuvants, and the challenging conditions of the gastric environment. We developed an intranasal influenza A virus (IAV) vector vaccine based on two live attenuated influenza viruses with modified acidic polymerase protein (PA) genes encoding the A subunit of H. pylori neutrophil-activating protein (NapA), named IAV-NapA, including influenza virus A/WSN/33 (WSN)-NapA and A/Puerto Rico/8/34 (PR8)-NapA. These recombinant influenza viruses were highly attenuated and exhibited strong immunogenicity in mice. Vaccination with IAV-NapA induced antigen-specific humoral and mucosal immune responses while stimulating robust Th1 and Th17 cell immune responses in mice. Our findings suggest that prophylactic and therapeutic vaccination with influenza virus vector vaccines significantly reduces colonization of H. pylori and inflammation in the stomach of mice.IMPORTANCEHelicobacter pylori is the most common cause of chronic gastritis and leads to severe gastroduodenal pathology in some patients. Many studies have shown that Th1 and Th17 cellular and gastric mucosal immune responses are critical in reducing H. pylori load. IAV vector vaccines can stimulate these immune responses while overcoming potential adjuvant toxicity and antigen dosing issues. To date, no studies have demonstrated the role of live attenuated IAV vector vaccines in preventing and treating H. pylori infection. Our work indicates that vaccination with IAV-NapA induces antigen-specific humoral, cellular, and mucosal immunity, producing a protective and therapeutic effect against H. pylori infection in BALB/c mice. This undescribed H. pylori vaccination approach may provide valuable information for developing vaccines against H. pylori infection.

APPROACH TO THE TREATMENT AND PREVENTION OF COVID-19: VIRUS-SPECIFIC NUTRACEUTICALS AND PLANT EXTRACTS

Objective. To conduct an analysis of current sources of literature on clinical symptoms in patients with the COVID-19 coronavirus, and to confirm that some nutraceuticals and plant compounds derived from plant extracts can be used in the treatment of COVID-19.
 Results and discussion. Evidence of the antiviral potential of plant compounds is emerging. Curcumin has antiviral activity against a wide range of viruses, including influenza virus, adenovirus, hepatitis, human papillomavirus (HPV), human immunodeficiency virus (HIV), herpes simplex virus-2 (HSV-2), and Zika viruses. Baicalin and baicalein have been shown to inhibit SARS-CoV in vitro, and scutellarin can bind to the ACE2 receptor to prevent viral invasion. Resveratrol inhibits SARS-CoV-2 replication, reducing cytotoxicity. Melatonin interacts with CD147, the cellular receptor of SARS-CoV-2, which diffuses into cell walls, especially into erythrocytes and endothelium. Glycyrrhizin has demonstrated potential therapeutic benefit in COVID-19 infections through multiple mechanisms. Quercetin exhibits potent immunomodulatory properties by suppressing the expression of several pro-inflammatory cytokines and signalling pathways. Interferons are able to suppress the replication of SARS-type coronaviruses, so they may be useful in the treatment of COVID-19.
 Conclusions. Despite the lack of clinical data, evidence from the literature suggests that some nutraceuticals and plant compounds derived from plant extracts may be used to treat COVID-19. However, the clinical evidence provided is still inconclusive and controversies exist. Given these factors, randomized controlled trials are needed to help combat the COVID-19 pandemic.

Increase in febrile illness among children in mainland China, winter 2023 - 2024

In late 2023, mainland China reportedly saw a rise in respiratory illnesses, primarily among children. Officials from the Chinese Center for Disease Control attributed this increase to the circulation of known pathogens, including influenza viruses, respiratory syncytial virus, SARS-CoV-2, and mycoplasma pneumoniae, to which the population had only limited exposure while strict “zero Covid” measures were enforced in recent years. However, outside observers raised concerns that a novel infectious agent could be circulating, and the World Health Organisation took the unusual step of publicizing a request for further information from Beijing. While no novel pathogen has been identified at the time of writing, this apprehension among the international press, and among some public health experts, is an instructive reminder of how unresolved issues relating to the outbreak of SARS-CoV-2 in late 2019 continue to impact international public health. Such reactions suggest that the political control of epidemiological data in the early stages of the COVID-19 pandemic has had a lasting impact on international collaboration, institutional trust and global health security. Resolving these issues is essential if the world is to be prepared for future infectious disease outbreaks of potential international concern.

Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells

Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of long-acting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary Tcells composed of blood-derived interferon γ (IFNγ)+ conventional Tcells and locally expanded IL-17A+ innate-like Tcells. Single-cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary Tcells and induces clonal expansion of type 17 innate-like Tcells. rhIL-7-hyFc-mediated disease prevention is dependent on IL-17A in both IAV- and SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.

Metagenomic sequencing detects human respiratory and enteric viruses in air samples collected from congregate settings

Innovative methods for evaluating virus risk and spread, independent of test-seeking behavior, are needed to improve routine public health surveillance, outbreak response, and pandemic preparedness. Throughout the COVID-19 pandemic, environmental surveillance strategies, including wastewater and air sampling, have been used alongside widespread individual-based SARS-CoV-2 testing programs to provide population-level data. These environmental surveillance strategies have predominantly relied on pathogen-specific detection methods to monitor viruses through space and time. However, this provides a limited picture of the virome present in an environmental sample, leaving us blind to most circulating viruses. In this study, we explore whether pathogen-agnostic deep sequencing can expand the utility of air sampling to detect many human viruses. We show that sequence-independent single-primer amplification sequencing of nucleic acids from air samples can detect common and unexpected human respiratory and enteric viruses, including influenza virus type A and C, respiratory syncytial virus, human coronaviruses, rhinovirus, SARS-CoV-2, rotavirus, mamastrovirus, and astrovirus.

Analysis of the common respiratory viruses in children with acute respiratory infection in a hospital in Lanzhou City from 2021 to 2022

To explore the situation of 8 common respiratory pathogens in children with acute respiratory infection (ARI) from 2021 to 2022.The retrospective study selected 8 710 ARI patients from September 2021 to August 2022 in the Maternal and Child Health Hospital of Gansu Province as the study object, patients aged 0 to 17 years old, including 5 048 male children and 3 662 female children. Indirect immunofluorescence was used to detect 8 common respiratory pathogens, including influenza virus A (FluA), influenza virus B (FluB), parainfluenza virus (PIV), respiratory syncytial virus (RSV), adenovirus (ADV), Mycoplasma pneumoniae (MP), Chlamydia pneumoniae (CP), and Coxsackie virus group B (CoxB) IgM antibodies. χ2 test was used to analyze the results. The results showed that 1 497 of 8 710 children with ARI were positive, with a positive rate of 17.19%. The detection rate of MP among 8 common respiratory pathogens was 11.34%, accounting for 66.0%, followed by FluB, CoxB, PIV, RSV, ADV, FluA and CP, accounting for 13.83%, 9.55%, 6.01%, 2.61%, 1.47%, 0.40% and 0.13%, respectively. Respiratory tract viruses (FluA, FluB, RSV, ADV, PIV, CoxB) accounted for 33.86%.There were significant differences in the detection rates of PIV, ADV and MP among children of different genders (χ2=6.814, 5.154 and 17.784, P<0.05). The detection rate of school-age children (6-17 years old) was the highest, accounting for 33.27% (184/553). The detection rates of 8 common respiratory pathogens in patients with ARI were higher in spring and winter and lower in summer and autumn. To sum up, from 2021 to 2022, MP and FluB infection were dominant in ARI patients in our hospital. The peak period of 8 common respiratory pathogens was in spring and winter. The physical examination rate of 8 common respiratory pathogens in ARI patients aged 6-17 years old was the highest.

Improved Humoral Immunity and Protection against Influenza Virus Infection with a 3d Porous Biomaterial Vaccine.

New vaccine platforms that activate humoral immunity and generate neutralizing antibodies are required to combat emerging pathogens, including influenza virus. A slurry of antigen-loaded hydrogel microparticles that annealto form a porous scaffold with high surface area for antigen uptake by infiltrating immune cells as the biomaterial degrades is demonstrated to enhance humoral immunity. Antigen-loaded-microgels elicited a robust cellular humoral immune response, with increased CD4+ T follicular helper (Tfh) cells and prolonged germinal center (GC) B cells comparable to the commonly used adjuvant, aluminum hydroxide (Alum). Increasing the weight fraction of polymer material led to increased material stiffness andantigen-specific antibody titers superior to Alum. Vaccinating mice with inactivated influenza virus loaded into this more highly cross-linked formulation elicited a strong antibody response and provided protection against a high dose viral challenge. By tuning physical and chemical properties, adjuvanticity can be enhanced leading to humoral immunity and protection against a pathogen, leveraging two different types of antigenic material: individual protein antigen and inactivated virus. The flexibility of the platform may enable design of new vaccines to enhance innate and adaptive immune cell programming to generate and tune high affinity antibodies, a promising approach to generate long-lasting immunity.

Wastewater Surveillance Data as a Complement to Emergency Department Visit Data for Tracking Incidence of Influenza A and Respiratory Syncytial Virus - Wisconsin, August 2022-March 2023.

Wastewater surveillance has been used to assist public health authorities in tracking local transmission of SARS-CoV-2. The usefulness of wastewater surveillance to track community spread of other respiratory pathogens, including influenza virus and respiratory syncytial virus (RSV), is less clear. During the 2022-23 respiratory diseases season, concentrations of influenza A virus and RSV in wastewater samples in three major Wisconsin cities were compared with emergency department (ED) visits associated with these pathogens. In all three cities, higher concentrations of influenza A virus and RSV in wastewater were associated with higher numbers of associated ED visits (Kendall's tau range=0.50-0.63 for influenza-associated illness and 0.30-0.49 for RSV-associated illness). Detections of both influenza A virus and RSV in wastewater often preceded a rise in associated ED visits for each pathogen, and virus material remained detectable in wastewater for up to 3 months after pathogen-specific ED visits declined. These results demonstrate that wastewater surveillance has the potential to complement conventional methods of influenza and RSV surveillance, detecting viral signals earlier and for a longer duration than do clinical data. Continued use of wastewater surveillance as a supplement to established surveillance systems such as ED visits might improve local understanding and response to seasonal respiratory virus outbreaks.

Increased Fungal Infection Mortality Induced by Concurrent Viral Cellular Manipulations.

Certain respiratory fungal pathogen mono-infections can cause high mortality rates. Several viral pathogen mono-infections, including influenza viruses and coronaviruses including SARS-CoV-2, can also cause high mortality rates. Concurrent infections by fungal pathogens and highly manipulative viral pathogens can synergistically interact in the respiratory tract to substantially increase their mortality rates. There are at least five viral manipulations which can assist secondary fungal infections. These viral manipulations include the following: (1) inhibiting transcription factors and cytokine expressions, (2) impairing defensive protein expressions, (3) inhibiting defenses by manipulating cellular sensors and signaling pathways, (4) inhibiting defenses by secreting exosomes, and (5) stimulating glucocorticoid synthesis to suppress immune defenses by inhibiting cytokine, chemokine, and adhesion molecule production. The highest mortality respiratory viral pandemicsup to now have had substantially boosted mortalities by inducing secondary bacterial pneumonias. However, numerous animal species besides humans are also carriers of endemic infections by viral and multidrug-resistant fungal pathogens. The vast multi-species scope of endemic infection opportunities make it plausible that the pro-fungal manipulations of a respiratory virus can someday evolve to enable a very high mortality rate viral pandemic inducing multidrug-resistant secondary fungal pathogen infections. Since such pandemics can quickly spread world-wide and outrun existing treatments, it would be worthwhile to develop new antifungal treatments well before such a high mortality event occurs.

Interferons as negative regulators of ILC2s in allergic lung inflammation and respiratory viral infections.

Group 2 innate lymphoid cells (ILC2s), characterized by a lack of antigen receptors, have been regarded as an important component of type 2 pulmonary immunity. Analogous to Th2 cells, ILC2s are capable of releasing type 2 cytokines and amphiregulin, thus playing an essential role in a variety of diseases, such as allergic diseases and virus-induced respiratory diseases. Interferons (IFNs), an important family of cytokines with potent antiviral effects, can be triggered by microbial products, microbial exposure, and pathogen infections. Interestingly, the past few years have witnessed encouraging progress in revealing the important role of IFNs and IFN-producing cells in modulating ILC2 responses in allergic lung inflammation and respiratory viral infections. This review underscores recent progress in understanding the role of IFNs and IFN-producing cells in shaping ILC2 responses and discusses disease phenotypes, mechanisms, and therapeutic targets in the context of allergic lung inflammation and infections with viruses, including influenza virus, rhinovirus (RV), respiratory syncytial virus (RSV), and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2).

High body temperature increases gut microbiota-dependent host resistance to influenza A virus and SARS-CoV-2 infection

Fever is a common symptom of influenza and coronavirus disease 2019 (COVID-19), yet its physiological role in host resistance to viral infection remains less clear. Here, we demonstrate that exposure of mice to the high ambient temperature of 36 °C increases host resistance to viral pathogens including influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High heat-exposed mice increase basal body temperature over 38 °C to enable more bile acids production in a gut microbiota-dependent manner. The gut microbiota-derived deoxycholic acid (DCA) and its plasma membrane-bound receptor Takeda G-protein-coupled receptor 5 (TGR5) signaling increase host resistance to influenza virus infection by suppressing virus replication and neutrophil-dependent tissue damage. Furthermore, the DCA and its nuclear farnesoid X receptor (FXR) agonist protect Syrian hamsters from lethal SARS-CoV-2 infection. Moreover, we demonstrate that certain bile acids are reduced in the plasma of COVID-19 patients who develop moderate I/II disease compared with the minor severity of illness group. These findings implicate a mechanism by which virus-induced high fever increases host resistance to influenza virus and SARS-CoV-2 in a gut microbiota-dependent manner.