Acute Influenza Infection Research Articles

Function of tissue-resident helper T cells in chronic lung sequelae following viral pneumonia

Abstract Respiratory viral infections such as influenza and SARS-CoV-2 can lead to the development of chronic lung disease and impaired lung function long-term after the recovery from acute morbidity. However, the mechanisms underlying the development of chronic diseases post-acute respiratory viral infection are largely elusive. Using a model of age-related development of chronic lung disease after acute influenza infection, we found that a population of lung resident PD1HiCD4+ T helper cells (TRH), which exhibit characteristics of both follicular helper T cells and resident memory cells, was greatly increased after primary influenza pneumonia. Furthermore, TRH cells were located near the dysplastic/inflammatory lung parenchyma after the resolution of primary viral pneumonia. Strikingly, genetic ablation of TRH or the blockade of TRH-derived IL-21 signaling diminished chronic lung pathology and improved lung function following viral pneumonia in aged animals. Moreover, TRH cell presence was associated with worse lung function and increased lung pathology in COVID-19 convalescents. Our data suggest that exuberant TRH responses contribute to the development of chronic lung sequelae following viral pneumonia. Additionally, our findings may pave the way to develop novel preventive and/or therapeutic options treating chronic lung diseases following acute viral pneumonia including long COVID.

Abstract 1390: Pulmonary viral infection promotes the awakening of dormant metastatic breast cancer cells in lungs

Abstract Background: Breast cancer is the most common form of cancer and the second cancer-causing death in females. Although remission rates are high if detected early, survival rates drop substantially when breast cancer becomes metastatic. The most common sites of metastatic breast cancer are bone, liver, and lung. Respiratory viral infections inflict illnesses on countless people, as evidenced by annual flu seasons and the latest pandemic caused by SARS-CoV-2. Respiratory viral infections result in increased inflammation with immune cell influx to facilitate viral clearance. Prior studies have shown that inflammation can contribute to dormant cancer cells awakening and outgrowth. However, how respiratory viral infections contribute to breast cancer lung metastasis remains to be unraveled. Methods: MMTV/NEU mouse model of dormant breast cancer was used, with influenza virus as the model respiratory virus. Lungs and bronchoalveolar lavage fluid were harvested for immunohistochemistry, flow cytometry, cytokines, and single-cell RNA-seq analysis. Flatiron Health Database was mined for epidemiological data to assess the risk of breast cancer metastasis to lung with COVID infection. Results: We have shown a dramatic increase in disseminated cancer cell (DCC) awakening in the lungs following influenza and SARS-CoV-2 infections. Influenza infection results in loss of a pro-dormancy mesenchymal phenotype and increased proliferation of DCC in the lungs within days post-infection, with a more than 1000-fold expansion of carcinoma cells over a couple of weeks. Strikingly, by 15 days post-infection, the lesions that expanded from solitary HER2+ DCCs almost homogeneously return to a quiescent state. Our preliminary data indicate that post-infection increases in IL-6 are required for DCC expansion post-influenza. Acute influenza infection also contributed to an accumulation of CD4+ T cells around expanding tumor cells for as long as 28 days after the initial infection. Depletion of CD4+ T cells but not CD8+ cells during infection with influenza virus prevents the expansion of the DCCs in the lung. Co-depletion of CD8 cells with CD4 cells partially restored the DCC burden in the lungs, indicating a role for CD8 cells in eliminating DCCs when released from CD4-mediated suppression. Single-cell RNA-seq analyses of CD8+ T cells with CD4 depletion showed an increased IL2/STAT5, MTORC1, and Ox/Phos activation by 15 dpi. The analyses also showed an immunosuppressive effect by the tumor cells. Finally, analysis of female breast cancer patients who tested positive with SARS-CoV-2 after their initial diagnosis exhibited a hazard ratio of 1.44 (p=0.043) for subsequent diagnosis of metastatic breast cancer in lungs. Conclusions: These studies reveal the potential risks to cancer survivors who experience respiratory viral infections, with mechanistic insight that could lead to novel prevention or intervention strategies. Citation Format: Shi Biao Chia, Bryan Johnson, Meher Boorgula, Varsha Sreekanth, Andrew Goodspeed, Bennett J. Davenport, Junxiao Hu, Dexiang Gao, Michael Papanicolaou, Thomas E. Morrison, Julio A. Aguirre-Ghiso, Mercedes Rincon, James V. DeGregori. Pulmonary viral infection promotes the awakening of dormant metastatic breast cancer cells in lungs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1390.

A pediatric case series of acute ischemic stroke with concurrent influenza

PurposeTo highlight a case series of three pediatric patients who presented with acute ischemic stroke (AIS) in the setting of influenza illness. MethodsRetrospective chart review was performed. ResultsThree patients of ages 23 months (patient 1), 2 years (patient 2), and 4 years (patient 3) presented with acute hemiparesis or focal status epilepticus. Two patients had trisomy 21 and trivial cardiac septal defects, and one was previously healthy. All patients tested positive for influenza within a week of symptoms. Neuroimaging showed AIS involving right deep grey matter and bilateral posterior cortex in patient 1, left parietal lobe in patient 2, and right parietotemporal and deep grey matter in patient 3. Vascular abnormalities were found and included moyamoya syndrome in two patients and focal arteriopathy in one patient. For secondary stroke prevention, patients 2 and 3 were started on clopidogrel initially and later transitioned to aspirin after the resolution of the acute influenza infection. Patient 1 was started on aspirin at diagnosis since he was not acutely ill. ConclusionsThis case series highlights three pediatric patients with AIS with underlying arteriopathy in the setting of influenza infection. Pediatric AIS is a separate entity from adult stroke. There is limited understanding of its underlying pathophysiology. The most common risk factors described in literature for pediatric AIS are arteriopathy and cardiac disorders. Minor infection may be a significant risk factor in a child that is predisposed to vascular insult. There is some evidence in literature to suggest that vaccination against such illnesses may be protective for AIS.

Associations between severe and notifiable respiratory infections during the first trimester of pregnancy and congenital anomalies at birth: a register-based cohort study

BackgroundEvidence regarding the association between acute respiratory infections during pregnancy and congenital anomalies in babies, is limited and conflicting. The aim of this study was to examine the association between acute respiratory infections during the first trimester of pregnancy and congenital anomalies in babies using record linkage.MethodsWe linked a perinatal register to hospitalisation and disease notifications in the Australian state of New South Wales (NSW) between 2001 to 2016. We quantified the risk of congenital anomalies, identified from the babies’ linked hospital record in relation to notifiable respiratory and other infections during pregnancy using generalized Estimating Equations (GEE) adjusted for maternal sociodemographic and other characteristics.ResultsOf 1,453,037 birth records identified from the perinatal register between 2001 and 2016, 11,710 (0.81%) mothers were hospitalised for acute respiratory infection, 2850 (0.20%) had influenza and 1011 (0.07%) had high risk infections (a record of cytomegalovirus, rubella, herpes simplex, herpes zoster, toxoplasmosis, syphilis, chickenpox (varicella) and zika) during the pregnancy. During the first trimester, acute respiratory infection, influenza and high-risk infections were reported by 1547 (0.11%), 399 (0.03%) and 129 (0.01%) mothers. There were 15,644 (1.08%) babies reported with major congenital anomalies, 2242 (0.15%) with cleft lip/ plate, 7770 (0.53%) with all major cardiovascular anomalies and 1746 (0.12%) with selected major cardiovascular anomalies. The rate of selected major cardiovascular anomalies was significantly higher if the mother had an acute respiratory infection during the first trimester of pregnancy (AOR 3.64, 95% CI 1.73 to 7.66). The rates of all major congenital anomalies and all major cardiovascular anomalies were also higher if the mother had an acute respiratory infection during the first trimester of pregnancy, however the difference was no statistically significant. Influenza during the first trimester was not associated with major congenital anomalies, selected major cardiovascular anomalies or all major cardiovascular anomalies in this study.ConclusionThis large population-based study found severe acute respiratory infection in first trimester of pregnancy was associated with a higher risk of selected major cardiovascular anomalies in babies. These findings support measures to prevent acute respiratory infections in pregnant women including through vaccination.

Acute Influenza Infection Promotes Lung Tumor Growth by Reprogramming the Tumor Microenvironment.

One billion people worldwide get flu every year, including patients with non-small cell lung cancer (NSCLC). However, the impact of acute influenza A virus (IAV) infection on the composition of the tumor microenvironment (TME) and the clinical outcome of patients with NSCLC is largely unknown. We set out to understand how IAV load impacts cancer growth and modifies cellular and molecular players in the TME. Herein, we report that IAV can infect both tumor and immune cells, resulting in a long-term protumoral effect in tumor-bearing mice. Mechanistically, IAV impaired tumor-specific T-cell responses, led to the exhaustion of memory CD8+ T cells and induced PD-L1 expression on tumor cells. IAV infection modulated the transcriptomic profile of the TME, fine-tuning it toward immunosuppression, carcinogenesis, and lipid and drug metabolism. Consistent with these data, the transcriptional module induced by IAV infection in tumor cells in tumor-bearing mice was also found in human patients with lung adenocarcinoma and correlated with poor overall survival. In conclusion, we found that IAV infection worsened lung tumor progression by reprogramming the TME toward a more aggressive state.

A view from the floor of the pharmacy: The experience of a severe asthma attack

A view from the floor of the pharmacy: The experience of a severe asthma attack

Upper respiratory tract infections and influenza-like illnesses among healthcare workers: are serological tests useful in monitoring influenza and influenza-like illness?

Healthcare workers (HCWs) are at high risk for exposure to upper respiratory tract infections (URTIs) and influenza-like illnesses (ILIs). The present study aimed to surveil URTIs and ILIs and their impact among the Department of Pediatric Infectious Diseases in Wroclaw employees and evaluate their humoral response to influenza. Thirty-six HCWs participated in the first season and 32 HCWs in the second season during years of the study. The authors carried out a URTI/ILI surveillance, and all HCWs were asked to complete a weekly report during 2 influenza seasons: 2016/2017 (S1) and 2017/2018 (S2). In S1 both IgG and IgM antibodies against influenza A and B were assessed. The HCWs with symptoms of ILI were encouraged to undergo PCR tests for influenza. No significant differences in reporting URTI were found among vaccinated and non-vaccinated HCWs and HCWs and the control group. Depending on the year 5.5-17.2% of HCWs were treated with antibiotics because of URTI. In the study 58.7% of participants in S1 and 66.7% in S2 decide to work despite the URTI symptoms. There was no statistical relationship between the concentration of anti-influenza IgG and the number of URTIs and ILIs reported. Only vaccinated were willing to undergo voluntary influenza testing. The URTI and ILI occur commonly in HCWs, and HCWs contract URTIs as often as the control group. Despite their medical education, HCWs work with the symptoms of infection and overuse antibiotics to treat the URTI. Serology testing is not able to follow the infection's dynamics or identify the people immune to the influenza-like illness. The diagnostic value of IgM antibodies in acute influenza infection is negligible. Vaccinated HCWs are more focused on their health and are more willing to undergo influenza tests. Med Pr. 2022;73(6):441-7.

Leading-edge non-specific prevention of a new coronavirus infection and acute respiratory infections of other etiology

Background. Acute respiratory infections (ARI) in pediatric practice remain one of the most relevant problems, therefore, it is necessary to search for effective prevention schemes in terms of pandemic caused by the new SARS-CoV-2 coronavirus.
 Aim. To evaluate preventive effect of one of the Polyoxidonium drug regimens in respect to SARS, influenza and COVID-19, compared with the absence of drug prophylaxis in children attending children's organized groups.
 Materials and methods. A prospective open comparative cohort study of the effectiveness of Polyoxidonium used as a preventing treatment against acute respiratory viral infections (ARVI), influenza and coronavirus infection in children attending organized groups was carried out. In the 1st group children (n=300) received Polyoxidonium 1/2 tablet of 12 mg once a day for 7 days, then 21 days drug-free interval (3 courses over a period of 3 months), in the 2nd group children (n=300) received Polyoxidonium 1/2 tablet of 12 mg 1 time per day for 10 days, then 4 days drug-free interval (6 courses over a period of 3 months), group 3 (n=300) control children did not receive prophylactic drugs. The effectiveness of prevention regimen was assessed using morbidity rate and changes in sIgA and lysozyme activity in the nasal secretion.
 Results. In the active groups with Polyoxidonium treatment a significant decrease in the number of cases of ARI and COVID-19 was recorded compared with the control group. The beneficial effect of the preventive use of Polyoxidonium on the likelihood of developing ARVI, COVID-19 and their clinical course was more significant in group 2 (p=0.0001) than in group 1. A positive preventive effect of Polyoxidonium on the development of ARVI, COVID-19 and their clinical course in group 1 was noted when compared to the control group (p=0.0001). In group 2, none of the participants developed pneumonia, while in group 1 one case of pneumonia was registered, and in the control group pneumonia was noted in seven children (2.3%); p=0.0327, 0.0078. The use of Polyoxidonium led to a significant increase in local immunity of the mucous membranes of the upper respiratory tract lysozyme and sIgA in groups 1 and 2 [1 group sIgA 0.240.14 g/L (p=0.0085), lysozyme 60.918.53% (p=0.0084); 2 group sIgA 0.240.14 g/L (p=0.0024), lyzozyme 65.016.62% (p=0.0001)].
 Conclusion. The use of Polyoxidonium drug as a preventing care for ARI and COVID-19 meets up to date requirements and can serve as an additional protection line against infection in children in organized groups.

Heart Failure after Laboratory Confirmed Influenza Infection (FLU-HF).

Background:Influenza has been shown to exacerbate heart failure (HF). Importantly, no study to date has examined the relationship between HF hospitalizations (HFH) with laboratory confirmed influenza infections. This study evaluated the association between laboratory confirmed influenza infection and HFH in the two largest hospitals in Saskatchewan, Canada.Methods:We used a retrospective self-controlled case series design to evaluate the association between laboratory-confirmed influenza infection and HFH. We compared the incidence ratio for HFH during the influenza risk interval with the control interval. We defined the influenza risk interval as the seven days after a laboratory confirmed influenza result and the control interval as one year before and after the risk interval.Results:We identified 114 HFH that occurred within one year before and after a positive test result for influenza between April 1, 2010, and April 30, 2018. Of these, 28 (28 admissions per week) occurred during the risk interval and 86 (0.853 admissions per week) occurred during the control interval. The incidence ratio of a HFH during the risk interval as compared with the control interval was 33.53 (95% confidence interval [CI], 21.89 to 51.36). A decline in incidence was observed after day seven; between days 8 to 14 and 14 to 28 incidence ratios was 0.91 (95% CI, 0.13 to 6.52) and 0.91 (95% CI, 0.22 to 3.68) respectively.Conclusion:We have observed a significant association between acute influenza infection and HFH. However, further research with a larger sample size and involving a multicenter setting is warranted.HighlightsInfluenza may contribute and exacerbate heart failure events especially during annual influenza season.Early identification of influenza among patients with heart failure, could lead to earlier treatment with antiviral medication, reduce unnecessary antibiotic use, and tail off the morbidity and mortality.In this study, despite our efficient study design, our sample size was limited to only the two largest hospitals in the province, possibly excluding a significant population in remote areas.

The impact of work in the conditions of the COVID-19 coronavirus pandemic on the emotional burnout of medical workers (according to the MASLACH BURNOUT INVENTORY questionnaire, MBI)

The article presents the results of a study of emotional burnout syndrome in medical professionals using the Maslach Burnout Inventory (MBI) questionnaire, which measures three burnout indicators: emotional exhaustion, depersonalization and personal achievements. A survey of medical workers of COVID-hospitals providing medical care to patients with a new coronavirus infection (n=201) aged 25 to 64 years was conducted; outpatient medical workers working in conditions of an increased epidemic threshold for acute respiratory viral infections, influenza and new coronavirus infection (n=186) aged 25 to 64 years and medical workers of multidisciplinary hospitals providing medical care according to their main profile and periodically identifying patients with COVID-19 disease (n=195) aged 25 to 64 years. The data obtained indicate that all the studied groups of medical workers in the conditions of the coronavirus pandemic have increased indicators of emotional burnout.

Intranasal, not parenteral, vaccination induces the formation of tissue-resident memory CD8 T cells in nasal mucosa that rapidly clear influenza virus infection

Abstract Respiratory tract infections are among the leading causes of death. While current vaccines reduce severe disease, they provide suboptimal mucosal protection (e.g. against influenza virus and SARS-CoV-2). Nasal vaccines offer an advantage by quickly limiting viral shedding, in part by generating tissue-resident memory (Trm) CD8 T cells in the nasal mucosa. But little is known about the molecular requirements for this Trm formation. The common paradigm is that lymphocytes home to tissues after having been imprinted within draining lymph nodes to express a tissue-specific combination of trafficking molecules, and Trm cells form rapidly from this pool. To probe the paradigm of tissue homing to the nasal mucosa, we compared CD8 T cell trafficking following intranasal and intramuscular vaccination. To investigate the trafficking molecules expressed by CD8 T cells and nasal cells we generated a single-cell RNA sequencing profile of the nasal mucosa over the course of an acute influenza infection. We found significantly more CD8 Trm cells in the nasal mucosa following intranasal vaccination that rapidly cleared influenza infection. Notably, CD8 T cells could be “pulled” into the nasal mucosa with an inflammatory stimulus following intramuscular vaccination, suggesting a new strategy for generating nasal CD8 Trm cells. Unlike canonical T cell homing to the gut and skin, nasal CD8 T cell trafficking depended on a4/VCAM1 (not a4b7/MADCAM1 or P and E-Selectin), and CD8 T cells expressed high levels of CXCR3 and CXCR6. This combination of trafficking molecules suggests a distinct multi-step adhesion cascade for CD8 T cell recruitment to the nasal mucosa and provides critical insights to rationally design vaccines for respiratory tract protection. Supported by grants from NIH (R01 AR068383-01, P01 AI 112521) and HMS-AbbVie Alliance

Study of Antibodies to Influenza Neuraminidase N2.

Humoral immunity to influenza neuraminidase (NA) was evaluated among different groups of people including patients with acute influenza infection and healthy people in different age groups using an enzyme linked lectin assay (ELLA). The amino acid composition of NA of seasonal influenza viruses A/Victoria/361/2011(H3N2) and A/Hong Kong/4801/2014(H3N2) differed by 2%, while cross-reacting neuraminidase-inhibiting (NI) antibodies to them in the same serum samples were detected in 10% of cases. Middle-aged patients born from 1977 to 2000 had a high level of hemagglutination-inhibiting (HI) antibodies to A/Hong Kong/4801/2014(H3N2), but almost no NI antibodies, which may indicate that in the case of a change in the hemagglutinin (HA) subtype, this age group will be susceptible to influenza A/H3N2 viruses. Therefore, it could mean there is a need for priority vaccination of this age group with a vaccine against the appropriate strain. It was shown that after intranasal administration of live influenza vaccine (LAIV) for the 2017–2018 season, serum antibody response was not lower compared to that during natural infection. In older people, antibodies to archival A/H2N2 viruses were detected more often than to modern A/H3N2. Since the conversion of antibodies to HA and NA often did not coincide, antibodies to NA can serve as an additional criterion for assessing the immunogenicity of influenza vaccines.

The effect of influenza A (H1N1) pdm09 virus infection on cytokine production and gene expression in BV2 microglial cells

Acute influenza infection has been reported to be associated with neurological symptoms such as influenza-associated encephalopathy (IAE). Although the pathophysiology of this condition remain unclear, neuroinflammation and associated alterations in the central nervous system (CNS) are usually induced. Microglia (MGs), CNS-resident macrophages, are generally the first cells to be activated in response to brain infection or damage. We performed reverse transcriptase droplet digital PCR (RT-ddPCR) and luminex assays to investigate virus proliferation and immune reactions in BV2 MGs infected with influenza A(H1N1)pdm09 virus. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics methods were used to investigate the dynamic change in the protein expression profile in BV2 MGs to gain insight into the CNS response to influenza A (H1N1) pdm09 infection. Our results showed that the influenza A(H1N1)pdm09 virus was replicative and productive in BV2 MG cells, which produced cytokines such as interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. The expression of osteopontin (OPN) in the influenza A (H1N1) pdm09-infected BV2 MGs was upregulated at 16 and 32 h post-infection (hpi) compared to that in the control group, resulting in aggravated brain damage and inflammation. Our study indicates that OPN signalling might provide new insights into the treatment of CNS injury and neurodegenerative diseases in IAE.

Evaluation of Influenza Patients Admitted in 2019–2020 Flu Season

Abstract Objective Influenza viruses are among the most common respiratory pathogens for all age groups, and may cause seasonal outbreaks. The aim of our study was to describe the clinical characteristics of influenza cases in the 2019–2020 flu season and to study the risk factors for hospital admission and complications. Methods This was a retrospective study in 251 children (group 1: nonhospitalized; group 2: hospitalized) with influenza in the 2019–2020 flu season. Data on demographic features, influenza type, complaints, complications, and hospitalization length were collected and recorded. Results Influenza A was detected in 199 (79.3%) patients, and influenza B was detected in 52 (20.7%); 43.4% of patients were girls and 56.6% were boys. The mean age of the patients was 3.91 ± 3.3 years (16 days to 18 years). A total of 52 (20.7%) patients were hospitalized. The age of the patients in group 2 was lower than that in group 1 (3.1 vs. 4.2 years, p = 0.03). Group 2 patients were more likely to have creatine kinase (CK) elevation, febrile seizures, and physical examination abnormalities. Group 2 patients were also more likely to have influenza A. Patients with febrile seizures, chronic diseases, abnormal physical examination findings, developed complications, and additional drug use apart from oseltamivir in the treatment were also more likely to require hospitalization. Conclusion Infants and children with chronic diseases, history of febrile seizures, complications, and the use of drugs other than antiviral drugs should be carefully evaluated in case they need hospitalization. Increasing vaccination rates, initiation of antiviral treatment for selected patients, and close monitoring of patients in risk groups can decrease morbidity and mortality. Myalgias are a common complaint in patients with acute influenza infection. Previous studies suggest CK measurement be part of the work-up for the hospitalized patient with acute influenza infection.

115. Variable Use of Diagnostic Codes for Acute Respiratory Infections Across Emergency Departments and Urgent Care Clinics in an Integrated Healthcare System: Implications for Accuracy of Antibiotic Stewardship Metrics

BackgroundAntibiotic stewardship initiatives can leverage metrics that make peer-peer comparisons. A commonly used metric measures how frequently a clinician prescribes antibiotics for acute respiratory infections (ARIs), as defined by diagnostic codes. However, it is unclear if clinicians differ in their use of ARI diagnostic codes. In this study, we evaluated differences in how frequently clinicians code for ARIs and factors that are associated with the use of ARI diagnostic codes in Emergency Department (ED) and Urgent Care (UC) visits across an integrated healthcare system.MethodsWe analyzed a retrospective cohort of all ED and UC patient-visits across 129 Veterans Affairs medical centers during 2016-2018. ARI visits were identified using ICD-10 codes for acute bronchitis, influenza, pharyngitis, sinusitis, and upper respiratory tract infections for clinicians with 100 or more visits. A generalized linear mixed model with a link logit function that accounted for clustering at the clinician and facility-level was used to calculate median odds ratios (OR) and to identify factors associated with increased likelihood of entering an ARI code.ResultsThere were 6,016,499 patient-visits, and 519,389 (8.6%) were coded as an ARI (Table 1). The mean rate of ARI diagnoses across all visits was 8.9% (SD 2.5%) at the facility-level and 7.4% (SD 4.5%) at the clinician-level (Table 2). The median OR was 2.19 (95% CI 2.18, 2.22), suggesting there was between-clinician variation in coding for ARI diagnoses. Visits were significantly more likely to be coded as ARIs if seen by an advanced practice provider (OR=2.36, 95% CI 2.19, 2.54), if a fever was recorded (OR=4.20, 95% CI 4.18, 4.29), and if the visit occurred between December-March (OR=1.97, 95% CI 1.96, 1.98). Approximately 2/5th of the variability (41.4%) in assigning an ARI diagnostic code was explained by differences across individual clinicians. ConclusionThere was substantial variability in how frequently ED and UC clinicians coded a visit as an ARI, and a large proportion of the variability was explained by differences across clinicians. Unmeasured factors could include different approaches to using diagnostic codes. ARI metrics based on diagnostic codes may need to account for differences in clinicians’ coding behavior.Disclosures All Authors: No reported disclosures

Mice with diverse microbial exposure histories as a model for preclinical vaccine testing

Laboratory mice comprise an expeditious model for preclinical vaccine testing; however, vaccine immunogenicity in these models often inadequately translates to humans. Reconstituting physiologic microbial experience to specific pathogen-free (SPF) mice induces durable immunological changes that better recapitulate human immunity. We examined whether mice with diverse microbial experience better model human responses post vaccination. We co-housed laboratory mice with pet-store mice, which have varied microbial exposures, and then assessed immune responses to influenza vaccines. Human transcriptional responses to influenza vaccination are better recapitulated in co-housed mice. Although SPF and co-housed mice were comparably susceptible to acute influenza infection, vaccine-induced humoral responses were dampened in co-housed mice, resulting in poor control upon challenge. Additionally, protective heterosubtypic Tcell immunity was compromised in co-housed mice. Because SPF mice exaggerated humoral and Tcell protection upon influenza vaccination, reconstituting microbial experience in laboratory mice through co-housing may better inform preclinical vaccine testing.

Low pathogenic avian influenza virus infection retards colon microbiota diversification in two different chicken lines

BackgroundA commensal microbiota regulates and is in turn regulated by viruses during host infection which can influence virus infectivity. In this study, analysis of colon microbiota population changes following a low pathogenicity avian influenza virus (AIV) of the H9N2 subtype infection of two different chicken breeds was conducted.MethodsColon samples were taken from control and infected groups at various timepoints post infection. 16S rRNA sequencing on an Illumina MiSeq platform was performed on the samples and the data mapped to operational taxonomic units of bacterial using a QIIME based pipeline. Microbial community structure was then analysed in each sample by number of observed species and phylogenetic diversity of the population.ResultsWe found reduced microbiota alpha diversity in the acute period of AIV infection (day 2–3) in both Rhode Island Red and VALO chicken lines. From day 4 post infection a gradual increase in diversity of the colon microbiota was observed, but the diversity did not reach the same level as in uninfected chickens by day 10 post infection, suggesting that AIV infection retards the natural accumulation of colon microbiota diversity, which may further influence chicken health following recovery from infection. Beta diversity analysis indicated a bacterial species diversity difference between the chicken lines during and following acute influenza infection but at phylum and bacterial order level the colon microbiota dysbiosis was similar in the two different chicken breeds.ConclusionOur data suggest that H9N2 influenza A virus impacts the chicken colon microbiota in a predictable way that could be targeted via intervention to protect or mitigate disease.

Wood smoke particle exposure in mice reduces the severity of influenza infection

Elevated ambient temperatures and extreme weather events have increased the incidence of wildfires world-wide resulting in increased wood smoke particle (WSP). Epidemiologic data suggests that WSP exposure associates with exacerbations of respiratory diseases, and with increased respiratory viral infections. To assess the impact of WSP exposure on host response to viral pneumonia, we performed WSP exposures in rodents followed by infection with mouse adapted influenza (HINI-PR8). C57BL/6 male mice aged 6–8 weeks were challenged with WSP or PBS by oropharyngeal aspiration in acute (single dose) or sub-acute exposures (day 1, 3, 5, 7 and 10). Additional groups underwent sub-acute exposure followed by infection by influenza or heat-inactivated (HI) virus. Following exposures/infection, bronchoalveolar lavage (BAL) was performed to assess for total cell counts/differentials, total protein, protein carbonyls and hyaluronan. Lung tissue was assessed for viral counts by real time PCR. When compared to PBS, acute WSP exposure associated with an increase in airspace macrophages. Alternatively, sub-acute exposure resulted in a dose dependent increase in airspace neutrophils. Sub-acute WSP exposure followed by influenza infection was associated with improved respiratory viral outcomes including reduced weight loss and increased blood oxygen saturation, and decreased protein carbonyls and viral titers. Flow cytometry demonstrated dynamic changes in pulmonary macrophage and T cell subsets based on challenge with WSP and influenza. This data suggests that sub-acute WSP exposure can improve host response to acute influenza infection.

Interferon gamma in the treatment of patients with moderate COVID-19

Interferons are produced in response to the presence of pathogens in cells and are responsible for the proper formation of immune reaction. Preliminary data obtained in studies of properties of recombinant interferon gamma (IFN-γ) that involved patients with community-acquired pneumonia (including bacterial), acute respiratory viral infection (ARVI), influenza and new coronavirus infection have shown promising results.The purpose of the study was to assess the effect of subcutaneous administration of IFN-γ in patients with viral pneumonia on the changes of vital signs and the duration of hospital stay. An open-label, randomized, low-interventional study included patients with moderate new coronavirus infection COVID-19 over 18 years of age of both sexes. IFN-γ 500,000 IU was administered s/c, daily, once a day, during 5 days. IFN-y in addition to complex therapy of the disease resulted in more favorable changes in the stabilization of vital signs, as well as in reduced length of fever and hospital stay by 2 days what allows suggesting a positive effect of this substance on the recovery processes in patients with moderate COVID-19. Special emphasis should be made to the fact that patients who received recombinant IFN- γ experienced no progression of respiratory failure and required no transfer to intensive care unit. This study confirms earlier obtained data on the positive effect of IFN-y on the rate of clinical stabilization and recovery of patients with community-acquired pneumonia and viral infections. Presented results are limited to a small number of patients; further study of drug properties in post-marketing studies is required. Progress in the treatment of patients with moderate COVID-19 by adding recombinant IFN-γ to the complex therapy may reasonably expand the range of existing treatment options for this infection.

Annual influenza vaccination of patients with cardiovascular diseases and changes in hemagglutinin antibody titers: 3-year follow-up data

BACKGROUND: Seasonal influenza vaccination is recommended for patients with cardiovascular diseases. Low vaccination coverage among these patients is due to insufficient knowledge about vaccine efficiency and its regular annual use.
 This work aimed to study the repeated 6-month changes in hemagglutinin antibody titers (AT) for 3 years in patients with cardiac pathology in a comparative study of influenza preventive vaccination.
 MATERIALS AND METHODS: Analysis of ATs obtained based on the hemagglutination-inhibition test (HAI) was performed in 235 of 817 participants in a prospective follow-up. Blood sampling was performed at baseline, before the vaccination, and 6 months after, and at the same term in unvaccinated patients in the 20122013 and 20142015 seasons, respectively. The seropositive and seronegative responses to vaccination or acute respiratory or influenza infection were used, according to the reference values of seroconversion and seroprotection and the fact of seroconversion. Multiple regression analysis with a logarithmic scale was used to assess the vaccine effectiveness indices.
 RESULTS: With vaccination coverage of at least 40% against seasonal influenza within 3 years, the trends of a decrease in seropositive and an increase in seronegative responses in the vaccination group and its reverse nature in the comparison group were determined by traditional analysis. Using logarithmic calculation, an increase in HAI AT seroconversion was revealed over a 3-year follow-up period. It was characterized by a homogeneous serological response at annual vaccination and heterogeneous with a higher serological response in cases without vaccination (p = 0.002 for H1N1 and p = 0.005 for H3N2, respectively). This trend can be determined by a higher and more stable prevaccination level of HAI AT than the same residual level of AT among unvaccinated patients.
 CONCLUSION: During long-term cardiac studies, the logarithmic calculation in interpreting the results of HAI AT overcomes the limitations of the traditional analysis of assessing the efficiency of the annual influenza vaccine. Further serological programs are required to better understand the role of routine seasonal influenza vaccination in preventing morbidity and mortality of patients with cardiovascular diseases.