Epidemiological studies have shown that smoking is associated with increased incidence of severe viral infections leading to hospitalization. Moreover, studies in experimental models have identified impaired antiviral responses and altered inflammatory responses, yet it is unclear how the effects of smoke exposure and influenza A infection interact and how this varies over the course of infection. We hypothesized that smoking would exacerbate innate immune responses against influenza. To test this, female BALB/c mice were exposed to cigarette smoke or air twice a day for 24-28 days and (mock) infected with H3N2 influenza A on day 21 while smoking continued. Three and seven days after infection, changes in immune cell populations, the transcriptome, and viral clearance in lung tissue were analyzed. After influenza A infection, smoke-exposed mice lost significantly more weight than air-exposed controls, indicating that smoking resulted in more severe disease. Immune cell and lung tissue transcriptome analysis revealed that neutrophil infiltration was prolonged and macrophage activation dysregulated after infection of smoke-exposed mice compared to air-exposed controls. Expression of genes in IL-6 and interferon pathways was similarly longer active. In parallel, we observed lower clearance of influenza virus in smoke-exposed mice after infection compared to air-exposed controls, indicating ineffective antiviral responses. Altogether, the data from our mouse model indicate that cigarette smoke exposure prolongs innate immune responses against influenza A. The results from this study help to explain the susceptibility of current smokers to severe influenza A disease.

Background Pediatric respiratory infections, mainly bronchiolitis, are a substantial clinical burden. The most common etiology is respiratory syncytial virus (RSV). Other viruses include human rhinovirus, human metapneumovirus, influenza, adenovirus, coronavirus, and parainfluenza viruses. Objective We aimed to study the epidemiology and clinical characteristics of children with confirmed viral bronchiolitis and flu after the COVID-19 pandemic season and compare the behavior of each virus. Methods This retrospective observation study was done over seven months, from October 2022 to April 2023. All children (0-14) were included in the study if they met the clinical diagnosis of bronchiolitis or flu. Viral etiology is confirmed by PCR, using the respiratory panel available in our center which included the detection of four viruses: COVID-19, RSV, influenza A, and B. Clinical data, lab results, and X-rays were collected and correlated with each viral infection for all admitted patients. Results We recruited 237 children with bronchiolitis and flu symptoms from October 2022 to April 2023. The peak of infections (41%) was in November. Seasonal variations for each virus showed distinct patterns across the year. RSV peaked at the beginning of the season, gradually declining after that. In contrast, influenza A and B maintained a relatively consistent presence throughout the season. Meanwhile, COVID-19 reached its peak during March and April. One hundred forty-four (60%) of the patients were under two years of age. RSV was predominant in 150 patients (63.3%). COVID-19 was only detected in 25 patients (10%), whereas influenza A and B were equally isolated in 31 (13%) patients each. Fifty-one children (21%) were initially sick and required pediatric intensive care unit (PICU) admission, with no deaths reported. Notably, COVID-19 had a milder disease course, a shorter length of stay (LOS) in the hospital (two days) and a shorter duration of illness (five days) compared to other viruses. RSV infection was linked to more profound hypoxia and more sick children with more extended hospital stays. Conclusion Our study showed that, following the pandemic and the release of lockdown measures, there was another peak of upper respiratory tract infections (URTI) and flu, which was more aggressive, primarily due to other viruses, especially RSV. This resurgence was associated with more severe respiratory symptoms and an increased need for hospitalization. Notably, children with COVID-19 were in better condition compared to those with RSV.

UNASSIGNED: Influenza virus infection can cause a range of clinical symptoms, including respiratory failure (RF) and even death. The mechanisms responsible for the most severe forms of the disease are not yet well understood. The objective is to assess the initial immune response upon admission and its potential impact on infection progression.
UNASSIGNED: We conducted a prospective observational study of patients with influenza virus infection who required admission to a tertiary hospital in the 2017/18 and 2018/19 flu seasons. Immune markers, surrogate markers of neutrophil activation, and blood levels of DNase I and Apolipoprotein-H (ApoH) were determined in the first serum sample available during hospital care. Patients were followed until hospital discharge or death. Initially, 792 patients were included. From this group, 107 patients with poor evolution were selected, and a random control group was matched by day of admission.
UNASSIGNED: Patients with poor outcomes had significantly reduced ApoH levels, a soluble protein that regulate both complement and coagulation pathways. In multivariate analysis, low plasma levels of ApoH (OR:5.43; 2.21-13.4), high levels of C- reactive protein (OR:2.73: 1.28-5.4), hyperferritinemia (OR:2.83; 1.28-5.4) and smoking (OR:3.41; 1.04-11.16), were significantly associated with a worse prognosis. RF was independently associated with low levels of ApoH (OR: 5.12; 2.02-1.94), while high levels of IL15 behaved as a protective factor (OR:0.30; 0.12-0.71).
UNASSIGNED: Therefore, in hospitalized influenza patients, a dysregulated early immune response is associated with a worse outcome. Adequate plasma levels of ApoH are protective against severe influenza and RF and High levels of IL15 protect against RF.

[This corrects the article DOI: 10.3389/fimmu.2024.1443096.].

The multiplex molecular diagnostic assays described for severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), influenza A (IAV) and B (IBV) viruses have been mainly based on real-time reaction, which limits their access to many laboratories or diagnostic institutions. To contribute to available strategies and expand access to differential diagnosis, we describe an end-point multiplex RT-PCR targeting SARS-CoV-2, IAV and IBV with simultaneous endogenous control amplification. Initially, we looked for well-established primers sets for SARS-CoV-2, IAV, IBV and RNAse P whose amplicons could be distinguished on agarose gel. The multiplex assay was then standardized by optimizing the reaction mix and cycle conditions. The limit of detection (LoD) was determined using titrated viruses (for SARS-CoV-2 and IAV) and by dilution from a pool of IBV-positive samples. The diagnostic performance of the multiplex was evaluated by testing samples with different RNAse P and viral loads, previously identified as positive or negative for the target viruses. The amplicons of IAV (146 bp), SARS-CoV-2 (113 bp), IBV (103 bp) and RNAse P (65 bp) were adequately distinguished in our multiplex. The LoD for SARS-CoV-2, IAV and IBV was 0.02 TCID50/ml, 0.07 TCID50/ml and 10-3 from a pool of positive samples, respectively. All samples positive for SARS-CoV-2 (n=70, Ct 17.2-36.9), IAV (n=53, Ct 14-34.9) and IBV (n=12, Ct 23.9-31.9) remained positive in our multiplex assay. RNAse P from negative samples (n=40, Ct 25.2-30.2) was also amplified in the multiplex. Overall, our assay is a timely and alternative tool for detecting SARS-CoV-2 and influenza viruses in laboratories with limited access to supplies/equipment.

BackgroundHealthcare personnel (HCP) are at high risk for respiratory infections through occupational exposure to respiratory viruses.AimWe used data from a prospective influenza vaccine effectiveness study in HCP to quantify the incidence of acute respiratory infections (ARI) and their associated presenteeism and absenteeism.MethodsAt the start and end of each season, HCP at two Israeli hospitals provided serum to screen for antibodies to influenza virus using the haemagglutination inhibition assay. During the season, active monitoring for the development of ARI symptoms was conducted twice a week by RT-PCR testing of nasal swabs for influenza and respiratory syncytial virus (RSV). Workplace presenteeism and absenteeism were documented. We calculated incidences of influenza- and RSV-associated ARI and applied sampling weights to make estimates representative of the source population.ResultsThe median age of 2,505 participating HCP was 41 years, and 70% were female. Incidence was 9.1 per 100 person-seasons (95% CI: 5.8-14.2) for RT-PCR-confirmed influenza and 2.5 per 100 person-seasons (95% CI: 0.9-7.1) for RSV illness. Each season, 18-23% of unvaccinated and influenza-negative HCP seroconverted. The incidence of seroconversion or RT-PCR-confirmed influenza was 27.5 per 100 person-seasons (95% CI: 17.8-42.5). Work during illness occurred in 92% (95% CI: 91-93) of ARI episodes, absence from work in 38% (95% CI: 36-40).ConclusionInfluenza virus and RSV infections and associated presenteeism and absenteeism were common among HCP. Improving vaccination uptake among HCP, infection control, and encouraging sick HCP to stay home are important strategies to reduce ARI incidence and decrease the risk of in-hospital transmission.

BACKGROUND: Influenza vaccines are effective in decreasing hospitalizations and mortality related to influenza and its complications. However, the Vaccine Coverage Rate of influenza remains low and multifaceted efforts are required to improve it. The aim of this study was to assess the impact on influenza vaccine perception using a digital tool among outpatients and health care workers (HCWs).
METHODS: A study was performed among outpatients and the HCWs of 23 hospital departments from 4 hospitals affiliated to Lyon university Hospitals (France), between October 2022 and February 2023. By scanning QR (Quick Response) codes, displayed on posters for patients, their companions, as well as in the letters sent to HCWs, users accessed anonymously to a web-application (ELEFIGHT®), which provided information on influenza and invited them to initiate a discussion on influenza prevention with their physicians during the consultation. Patients were also invited to complete a questionnaire regarding their perception of influenza vaccination before and after reading the information on ELEFIGHT®. The retention rate (RR = proportion of people who remain on the page for >2 s), the conversion rate (CR = proportion of people who click on the \"Call-To-Action\" button) and the absolute variation (difference in the perception before/after) and relative variation (absolute change as a percentage of the initial perception) in perception regarding influenza vaccination before and after consulting the application were calculated.
RESULTS: 3791 scans were performed by 3298 patients and/or their companions with a RR of 52% and a CR of 55.1% and 253 scans by 221 HCWs with a RR of 71.2% and a CR of 115.3%. Participants spent an average of 47 s on the application. The questionnaire on influenza vaccination perception was completed by 1533 participants (46.5%); 1390 (90.7%) maintained the same position (neutral, favorable or unfavorable) on this vaccination before and after consulting the application. The relative variations in favor of vaccination were + 7.2% (unfavorable then favorable) and + 19.8% (neutral then favorable).
CONCLUSIONS: This study suggests that a facilitated direct access to medical information through QR codes disseminated in health settings can help nudge people to foster their awareness of influenza and its prevention. Future deployments in a similar context or to other populations could be envisaged. Other vaccine-preventable and/or chronic diseases could also be the target of similar projects as part of public health programs.

Since 2019, the Integrated Biosurveillance Branch of the Armed Forces Health Surveillance Division has conducted an annual forecasting challenge during influenza season to predict short-term respiratory disease activity among Military Health System beneficiaries. Weekly case and encounter observed data were used to generate 1- through 4-week advanced forecasts of disease activity. To create unified combinations of model inputs for evaluation across multiple spatial resolutions, 8 individual models were used to calculate 3 ensemble models. Forecast accuracy compared to the observed activity for each model was evaluated by calculating a weighted interval score. Weekly 1- through 4-week ahead forecasts for each ensemble model were generally higher than observed data, especially during periods of peak activity, with peaks in forecasted activity occurring later than observed peaks. The larger the forecasting horizon, the more pronounced the gap between forecasted peak and observed peak. The results showed that several models accurately predicted COVID-19 cases and respiratory encounters with enough lead time for public health response by senior leaders.

The Department of Defense Global Respiratory Pathogen Surveillance Program conducts continuous surveillance for influenza, severe acute respiratory syndrome 2 (SARS-CoV-2), and other respiratory pathogens at 104 sentinel sites across the globe. These sites submitted 65,475 respiratory specimens for clinical diagnostic testing during the 2021-2022 surveillance season. The predominant influenza strain was influenza A(H3N2) (n=777), of which 99.9% of strains were in clade 3C.2a1b.2a2. A total of 21,466 SARSCoV-2-positive specimens were identified, and 12,225 of the associated viruses were successfully sequenced. The Delta variant predominated at the start of the season, until December 2021, when Omicron became dominant. Most circulating SARS-CoV-2 viruses were subsequently held by Omicron sublineages BA.1, BA.2, and BA.5 during the season. Clinical manifestation, obtained through a self-reported questionnaire, found that cough, sinus congestion, and runny nose complaints were the most common symptoms presenting among all pathogens. Sentinel surveillance can provide useful epidemiological data to supplement other disease monitoring activities, and has become increasingly useful with increasing numbers of individuals utilizing COVID-19 rapid self-test kits and reductions in outpatient visits for routine respiratory testing.

BACKGROUND: The COVID-19 pandemic represented a great stimulus for the adoption of telehealth and many initiatives in this field have emerged worldwide. However, despite this massive growth, data addressing the effectiveness of telehealth with respect to clinical outcomes remain scarce.
OBJECTIVE: The aim of this study was to evaluate the impact of the adoption of a structured multilevel telehealth service on hospital admissions during the acute illness course and the mortality of adult patients with flu syndrome in the context of the COVID-19 pandemic.
METHODS: A retrospective cohort study was performed in two Brazilian cities where a public COVID-19 telehealth service (TeleCOVID-MG) was deployed. TeleCOVID-MG was a structured multilevel telehealth service, including (1) first response and risk stratification through a chatbot software or phone call center, (2) teleconsultations with nurses and medical doctors, and (3) a telemonitoring system. For this analysis, we included data of adult patients registered in the Flu Syndrome notification databases who were diagnosed with flu syndrome between June 1, 2020, and May 31, 2021. The exposed group comprised patients with flu syndrome who used TeleCOVID-MG at least once during the illness course and the control group comprised patients who did not use this telehealth service during the respiratory illness course. Sociodemographic characteristics, comorbidities, and clinical outcomes data were extracted from the Brazilian official databases for flu syndrome, Severe Acute Respiratory Syndrome (due to any respiratory virus), and mortality. Models for the clinical outcomes were estimated by logistic regression.
RESULTS: The final study population comprised 82,182 adult patients with a valid registry in the Flu Syndrome notification system. When compared to patients who did not use the service (n=67,689, 82.4%), patients supported by TeleCOVID-MG (n=14,493, 17.6%) had a lower chance of hospitalization during the acute respiratory illness course, even after adjusting for sociodemographic characteristics and underlying medical conditions (odds ratio [OR] 0.82, 95% CI 0.71-0.94; P=.005). No difference in mortality was observed between groups (OR 0.99, 95% CI 0.86-1.12; P=.83).
CONCLUSIONS: A telehealth service applied on a large scale in a limited-resource region to tackle COVID-19 was related to reduced hospitalizations without increasing the mortality rate. Quality health care using inexpensive and readily available telehealth and digital health tools may be delivered in areas with limited resources and should be considered as a potential and valuable health care strategy. The success of a telehealth initiative relies on a partnership between the involved stakeholders to define the roles and responsibilities; set an alignment between the different modalities and levels of health care; and address the usual drawbacks related to the implementation process, such as infrastructure and accessibility issues.