Background: Influenza-associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. Methods: We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/18 and 2019/20 influenza seasons. All adults with PCR-confirmed influenza infection and treatment on intensive-care unit (ICU) for >24h were included. IAPA was diagnosed according to previously published clinical, radiological and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome which was a composite of in-hospital mortality, ICU length of stay ≥7d, mechanical ventilation ≥7d or extracorporeal membrane oxygenation. Results: 158 patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non-IAPA, p=0.05). Asthma (OR 12.0 (95% CI 2.1-67.2)) and days of mechanical ventilation (OR 1.1 (1.1 – 1.2)) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non-IAPA, p=0.001) and vasoactive support (75% vs. 45%, p=0.03) and had more complications including ARDS (53% vs. 26%, p=0.04), respiratory bacterial infections (65% vs. 37%, p=0.04) and higher ICU-mortality (35% vs. 16.4%, p=0.05). IAPA (OR 28.8 (3.3–253.4)), influenza A (OR 3.3 (1.4-7.8)) and higher SAPS II score (OR 1.07 (1.05—1.10)) were independent predictors of poor outcome. Interpretation: High clinical suspicion, early diagnostics and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA.
Background: Influenza is a persistent public health problem associated with severe morbidity and mortality. Drug use is related to myriad health complications, but the relationship between drug use and severe influenza outcomes is not well understood. The study objective was to evaluate the relationship between drug use and severe influenza-associated outcomes. Methods: Data were collected by the Influenza Hospitalization Surveillance Network (FluSurv-NET) from the 2016-2017 through 2018-2019 influenza seasons. Among persons hospitalized with influenza, descriptive statistics and logistic regression models were used to analyze differences in demographic characteristics, risk and behavioral factors, and severe outcomes (intensive care unit [ICU] admission, mechanical ventilation, or death) between people who used drugs (PWUD), defined as having documented drug use within the past year, and non-PWUD. Results: Among 48,430 eligible hospitalized influenza cases, 2,019 were PWUD and 46,411 were non-PWUD. PWUD were younger than non-PWUD and more likely to be male, non-Hispanic Black or Hispanic/Latino, smoke tobacco, abuse alcohol, and have chronic conditions including asthma, chronic liver disease, chronic lung disease, or immunosuppressive conditions. PWUD had greater odds of ICU admission and mechanical ventilation, but not death compared with non-PWUD. Opioid use specifically was associated with increased risk of ICU admission and mechanical ventilation. Conclusion: PWUD had greater odds of ICU admission and mechanical ventilation than non-PWUD hospitalized with influenza. These results support targeted initiatives to prevent influenza and associated severe outcomes among this population.
Background: Despite the WHO recommendation that pregnant women be prioritised for seasonal influenza vaccination, coverage in the Western Pacific Region remains low. Our goal was to provide additional data for the Western Pacific region about the value of maternal influenza vaccination to pregnant women and their families. Methods: We conducted a 16-year retrospective cohort to evaluate risks associated with influenza-associated maternal acute respiratory infection (ARI) in New Zealand. ARI hospitalisations during the May-September influenza season were identified using select ICD-10-AM primary and secondary discharge codes from chapter J00-J99 (diseases of the respiratory system). Cox proportional hazards models were used to calculate crude and adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results: We identified 822,391 pregnancies among New Zealand residents between 2003 and 2018; 5,095 (0.6%) had >1 associated ARI hospitalisation during the influenza season; these pregnancies were at greater risk of preterm birth (aHR 1.5, 95% CI 1.3-1.7), and low birthweight (aHR 1.7, 95% CI 1.5-2.0) than pregnancies without such hospitalisations. We did not find an association between maternal ARI hospitalisation and fetal death (aHR 1.1, 95% CI 0.6-1.4) during the influenza season. Maternal influenza vaccination was associated with reduced risk of preterm birth (aHR 0.8, 95% CI 0.7-0.9), and low birthweight (aHR 0.9, 95%CI 0.8-0.9), and fetal death (aHR 0.5%, 95% CI 0.3-0.7). Conclusion: In this population-based cohort, being hospitalised for an ARI during the influenza season while pregnant was a risk-factor for delivering a preterm or a low birthweight infant and vaccination reduced this risk.
Objectives: To understand the epidemiological and clinical characteristics of pediatric SARS-CoV-2 infection during the early stage of Omicron variant outbreak in Shanghai. Study designs: This study included local COVID-19 cases<18 years in Shanghai referred to the exclusively designated hospital by the end of March 2022 since emergence of Omicron epidemic. Clinical data, epidemiological exposure and COVID-19 vaccination status were collected. Relative risks (RR) were calculated to assess the effect of vaccination on symptomatic infection and febrile disease. Results: A total of 376 pediatric cases of COVID-19 (median age:6.0±4.2 years) were referred to the designated hospital during the period of March 7-31, including 257 (68.4%) symptomatic cases and 119 (31.6%) asymptomatic cases. Of the 307 (81.6%) children ≥3 years eligible for COVID-19 vaccination, 110 (40.4%) received 2-dose vaccines and 16 (4.0%) received 1-dose vaccine. The median interval between 2-dose vaccination and infection was 3.5 (IQR: 3, 4.5) months (16 days-7 months). Two-dose COVID-19 vaccination reduced the risks of symptomatic infection and febrile disease by 35%(RR 0.65, 95% CI: 0.53-0.79) and 33% (RR 0.64, 95% CI: 0.51-0.81). Two hundred and sixteen (83.4%) symptomatic cases had fever (mean duration:1.7±1.0.8 days), 104 (40.2%) had cough, 16.4% had transient leukopenia; 307 (81.6%) had an epidemiological exposure in household (69.1%) , school (21.8%) and residential area (8.8%). Conclusion: The surge of pediatric COVID-19 cases and multiple transmission model reflect wide dissemination of Omicron variant in the community. Asymptomatic infection is common among Omicron-infected children. COVID-19 vaccination can offer some protection against symptomatic infection and febrile dise
Background: Acute respiratory infections (ARIs) result in millions of illnesses and hundreds of thousands of hospitalizations annually in the US. The responsible viruses include influenza, parainfluenza, human metapneumovirus, coronaviruses, respiratory syncytial virus (RSV), and human rhinoviruses. This study estimated the population-based hospitalization burden of 18 respiratory viruses (RV) over 4 years, from 7/1/2015 to 6/30/2019 among adults ≥18 years of age for Allegheny County (Pittsburgh), Pennsylvania. Methods: We used population-based statewide hospital discharge data, health system electronic medical record (EMR) data for RV tests, census data, and a published method to calculate burden. Results: Among 26,211 eligible RV tests, 67.6% were negative for any virus. The viruses detected were rhinovirus/enterovirus (2,552; 30.1%), influenza A (2,299; 27.1%), RSV (1,082; 12.7%), human metapneumovirus (832; 9.8%), parainfluenza (601; 7.1%), influenza B (565; 6.7%), non-SARS-CoV-2 coronavirus (420; 4.9% 1.5 years of data available), and adenovirus (136; 1.6%). Most tests were among female (58%) and white (71%) patients with 60% of patients ≥65 years, 24% 50-64 years and 16% 18-49 years. The annual burden, ranged from 137-174/100,000 population for rhinovirus/enterovirus; 99-182/100,000 for influenza A; 56-81/100,000 for RSV. Among adults <65 years, rhinovirus/enterovirus hospitalization burden was higher than influenza A; whereas the reverse was true for adults ≥65 years. RV hospitalization burden increased with increasing age. Conclusions: These virus-specific ARI population-based hospital burden estimates showed significant non-influenza burden. These estimates can serve as the basis for several areas of research that are essential for setting funding priorities and guiding public health policy.
Introduction: Case definitions are used to guide clinical practice, surveillance, and research protocols. However, how they identify COVID-19-hospitalised patients is not fully understood. We analysed the proportion of hospitalised patients with laboratory-confirmed COVID-19, in the ISARIC prospective cohort study database, meeting widely used case definitions. Methods: Patients were assessed using the CDC, ECDC, WHO, and UKHSA case definitions by age, region, and time. Case fatality ratios (CFR) and symptoms of those who did and who did not meet the case definitions were evaluated. Patients with incomplete data and non-laboratory-confirmed test-result were excluded. Results: 263,218 of the patients (42%) in the ISARIC database were included. Most patients (90.4%) were from Europe and Central Asia. The proportions of patients meeting the case definitions were 56.8% (WHO), 74.4% (UKHSA), 81.6% (ECDC), and 82.3% (CDC). For each case definition, patients at the extremes of age distribution met the criteria less frequently than those aged 30 to 70 years; geographical and time variations were also observed. Estimated CFRs were similar for the patients that met the case definitions. However, when more patients did not meet the case definition, the CFR increased. Conclusions: The performance of case definitions might be different in different regions and may change over time. Similarly concerning is the fact that older patients often did not meet case definitions. While epidemiologists must balance their analytics with field applicability, ongoing revision of case definitions is necessary to improve patient care through early diagnosis and limit potential nosocomial spread.
Abstract Background. Still now, COVID-19 is a public health concern in both developed and developing countries. Risk perception has been studied in different countries with different population groups. However, there have been few studies conducted risk perception on elderly people and there is no study on elderly people’ in Ethiopia including this study area.This study aimed to assess coronavirus disease low risk perception level and associated factors among the elderly. Methods. To carry out this study among elders in Areka town from 01 August 2021 to 30 August 2021, a community-based cross-sectional study was used. Multi-stage sampling method was applied to select study participants. The data were collected through a structured questionnaire with the mobile application of Open Data Kit mobile(ODK). Results. This study showed that individuals with age range of 65 to 74 [AOR= 4.76, 95% CI (2.35-9.64)], poor practice on preventing coronavirus disease [AOR= 2.39, 95% CI (1.51-3.78), low trust level in medical professionals [AOR=2.44, 95%CI (1.45-4.10)], no history of coronavirus disease [AOR=6.45, 95%CI (2.02-20.58)], poor perceived self-efficacy for preventive practice [AOR=2.25, 95% CI (1.43-3.54)] were identified as associated factors of low risk perception. Conclusions. In the current study area, the perception of risk of coronavirus disease was affected by age, perceived self-efficacy, trust in medical professionals, preventive practice, and history of coronavirus disease. Including Ethiopia, the findings of this study would help for developing countries to generate evidence-based policy decisions for elderly people during COVI-D-19 pandemic and future pandemic(s). Keywords: Associated factors, Coronavirus, Elderly, Ethiopia, Perception
Background Human Metapneumovirus (hMPV) is an important cause of pediatric respiratory infection. We leveraged the Nicaraguan Pediatric Influenza Cohort Study (NPICS) to assess the burden and seasonality of symptomatic hMPV infection in children. Methods NPICS is an ongoing prospective study of children in Managua, Nicaragua. We assessed children for hMPV infection via RT-PCR. We used classical additive decomposition analysis to assess the temporal trends and Generalized Growth Models (GGMs) were used to estimate effective reproduction numbers. Results From 2011-2016 there were 564 hMPV symptomatic infections yielding an incidence rate of 5.74 cases per 100 person-years (95% CI 5.3, 6.2). Children experienced 3,509 Acute Lower Respiratory Infections (ALRIs), of which 160 (4.6%) were associated with hMPV infection. Children under the age of one had 55% of all symptomatic hMPV infections (62/112) develop into hMPV-associated ALRIs and were five times as likely as children over one to have an hMPV-associated ALRI (Rate Ratio 5.5 95% CI 4.1, 7.4 p <0.001). Additionally, symptomatic reinfection with hMPV was common. In total, 87 (15%) of all observed symptomatic infections were reinfections. The seasonality of symptomatic hMPV outbreaks varied considerably. From 2011-2016, four epidemic periods were observed, following a biennial seasonal pattern. The mean ascending phase of the epidemic periods were 7.7 weeks, with an overall mean estimated reproductive number of 1.2 (95% CI 1.1, 1.4). Conclusions Symptomatic hMPV infection was associated with substantial burden among children in the first year of life. Timing and frequency of symptomatic hMPV incidence followed biennial patterns.
Background: Anaphylaxis following influenza vaccination is a rare but serious problem. The underlying immune responses are not well understood. This study elucidated the IgE and IgG antibody responses in healthy children and adolescents following inactivated influenza vaccines (IIVs). Methods: The efficacy and safety of quadrivalent IIV (QIV) and trivalent IIV (TIV) were compared in healthy subjects aged 0-18 years. Serum IIV-specific IgE, IgG and IgG4 levels (sIgE, sIgG, sIgG4) were measured with ImmunoCAP. Hemagglutinin inhibition (HI) assay was performed for each influenza virus subtype. Sera from earlier patients who developed anaphylaxis to different IIVs were similarly tested. Results: A total of 393 subjects were enrolled: 96 were 6 months -2 years old, 100 were 3-5 years old, 100 were 6-12 years old, and 97 were 13-18 years old. No anaphylaxis was observed. Generally, QIV and TIV induced similar antibody responses. IIV-sIgE levels rose significantly after vaccination in the 6m-2y and 3-5y groups, did not change in the 6-12y group, and decreased in the 13-18y group. In contrast, the IIV-sIgG4/sIgE ratio increased significantly after vaccination in all age groups. Sensitized subjects had significantly higher HI titers and IIV-sIgG levels in the youngest age group and higher IIV-sIgG4 levels in all age groups compared with the non-sensitized. The IIV-sIgG4/sIgE ratio in 5 patients with anaphylaxis was significantly lower than in age-matched healthy subjects. Conclusion: IIVs induce IgE sensitization in healthy children, but also robust IgG4 responses that may protect them from anaphylaxis.
Background: The Omicron (lineage B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wales, UK on 3rd December 2021. The aim of the study was to describe the first 1000 cases of the Omicron variant by demographic, vaccination status, travel and severe outcome status and compare this to contemporaneous cases of the Delta variant. Methods: Testing, typing and contact tracing data were collected by Public Health Wales and analysis undertaken by the Communicable Disease Surveillance Centre (CDSC). Risk ratios for demographic factors and symptoms were calculated comparing Omicron cases to Delta cases identified over the same time period. Results: By 14th December 2021, 1000 cases of the Omicron variant had been identified in Wales. Of the first 1000, just 3% of cases had a prior history of travel revealing rapid community transmission. A higher proportion of Omicron cases were identified in individuals aged 20-39 and most cases were double vaccinated (65.9%) or boosted (15.7%). Age adjusted analysis also revealed that Omicron cases were less likely to be hospitalised (0.4%) or report symptoms (60.8%). Specifically a significant reduction was observed in the proportion of Omicron cases reporting anosmia (8.9%). Conclusion: Key findings include a lower risk of anosmia and a reduced risk of hospitalisation in the first 1000 Omicron cases compared to co-circulating Delta cases. We also identify that existing measures for travel restrictions to control importations of new variants identified outside the UK did not prevent the rapid ingress of Omicron within Wales.
Objective: To assess the utility of a test-based approach to shorten isolation of healthcare workers with COVID-19 in the setting of the highly transmissible omicron variant Methods: Between December 24th, 2021, to January 5th, 2022 HCWs who tested positive for SARS-CoV-2 were re-tested at least five days since onset of symptoms. Results: 46 sequential fully COVID-19 vaccinated HCWs who had tested positive for SARS-CoV-2 underwent follow up testing. All the isolates were confirmed as omicron variants and only 4 (8.7%) were negative 5 days or more since onset of symptoms., Conclusions: Implementation of a test-based strategy is logistically challenging, increases costs and did not lead to shorter isolation in our institution.
Pandemic influenza viruses may emerge from animal reservoirs and spread among humans in the absence of cross-reactive antibodies in the human population. Immune response to highly conserved T cell epitopes in vaccines may still reduce morbidity and limit the spread of the new virus even when cross-protective antibody responses are lacking. We used an established epitope content prediction and comparison tool, EpiCC, to assess the potential for emergent H1N1 G4 swine influenza A virus (G4) to impact swine and human populations. We identified and computed the total cross-conserved T cell epitope content in HA sequences of human seasonal and experimental influenza vaccines, swine influenza vaccines from Europe and the United States (US) against G4. The overall T cell epitope content of US commercial swine vaccines was poorly conserved with G4, with an average T cell epitope coverage of 35.7%. EpiCC scores for the comparison between current human influenza vaccines and circulating human influenza strains were also very low. In contrast, the T cell epitope coverage of a recent European swine influenza vaccine (HL03) was 65.8% against G4. Poor T cell epitope cross-conservation between emergent G4 and swine and human influenza vaccines in the US may enable G4 to spread in swine and spillover to human populations in the absence of protective antibody response. One European influenza vaccine, HL03, may protect against emergent G4. This study illustrates the use of the EpiCC tool for prospective assessment of existing vaccine strains against emergent viruses in swine and human populations.
Background: The nucleoprotein (N protein) of respiratory syncytial virus (RSV) is a candidate antigen for new RSV vaccine development. The aim of the present study was to investigate the association between maternal antibody titers against the RSV N protein at birth and the newborns’ risk of developing very-severe lower respiratory tract infection (VS-LRTI). Methods: In this single-center prospective cohort study, 578 infants born during the RSV epidemic season in France were included. Among these, 36 were hospitalized for RSV VS-LRTI. A generalized linear model was used to test the occurrence of a VS-LRTI in function of sex, mode of delivery, parity of the mother, type of pregnancy, date of birth in relation to the peak of the epidemic, and antibody titer against N protein. Results: All cord blood samples had detectable antibodies against N protein. The mean titers were significantly lower in newborns with risk factors for RSV severe LRTI (preterm infants, birth before the peak epidemic, multiparous mother). There was no association between antibody titer against the N protein and a protection against VS-LRTI. Conclusions The present study found that transfer of maternal antibodies against the RSV N protein may not provide a significant immune protection early in infancy. Clinical Trials Registration. NCT04144816.
Background: With the emergence of SARS-CoV-2, influenza surveillance systems in Spain were transformed into a new syndromic sentinel surveillance system. The Acute Respiratory Infection Surveillance System (SiVIRA in Spanish) is based on a sentinel network for Acute Respiratory Infection (ARI) surveillance in Primary care, and a network of sentinel hospitals for Severe ARI (SARI) surveillance in hospitals. Methods: Using a test-negative design and data from SARI admissions notified to SiVIRA between January 1 and October 3, 2021, we estimated COVID-19 VE against hospitalization, by age group, vaccine type, time since vaccination and SARS-CoV-2 variant. Results: VE was 89% (95% CI: 83-93) against COVID-19 hospitalization overall in persons aged 20 years and older. VE was higher for mRNA vaccines, and lower for those aged 80 years and older, with a decrease in protection beyond 3 months of completing vaccination, and a further decrease after 5 months. We found no differences between periods with circulation of Alpha or Delta SARS-CoV-2 variants, although variant-specific VE was slightly higher against Alpha. Conclusions: The SiVIRA surveillance system, with a network of sentinel hospitals in Spain was able to describe clinical and epidemiological characteristics of SARI hospitalizations, monitor the circulation of SARS-CoV-2 and other respiratory viruses, and provide data to measure the effectiveness of COVID-19 vaccination in the population under surveillance. Our results add to evidence of high VE of mRNA vaccines against severe COVID-19 and waning protection with time since vaccination.
We evaluated uptake and factors associated with COVID-19 vaccination among health workers (HWs) in Azerbaijan. Among 1,575 HWs, 73% had received at least one dose and 67% received two doses; all received CoronaVac. Factors associated with vaccination uptake included no previous COVID-19 infection, older age, belief in the vaccine’s safety, previous vaccination for influenza, having patient-facing roles, and good or excellent health by self-assessment. These findings could inform strategies to increase vaccination uptake as the campaign continues.
Background Human Parainfluenza viruses (HPIV) comprise of four members of the genetically distinct genera of Respirovirus (HPIV1&3) and Orthorubulavirus (HPIV2&4), causing significant upper and lower respiratory tract infections worldwide, particularly in children. However, despite frequent molecular diagnosis, they are frequently considered collectively or with HPIV4 overlooked entirely. We therefore investigated clinical and viral epidemiological distinctions of the relatively less prevalent Orthorubulaviruses HPIV2&4 at a regional UK hospital across four autumn/winter epidemic seasons. Methods A retrospective audit of clinical features of all HPIV2 or HPIV4 RT-PCR-positive patients, diagnosed between 1st September 2013 and 12th April 2017 was undertaken, alongside sequencing of viral genome fragments in a representative subset of samples. Results Infection was observed across all age groups, but predominantly in children under nine and adults over 40, with almost twice as many HPIV4 as HPIV2 cases. Fever, abnormal haematology, elevated C-reactive protein and hospital admission were more frequently seen in HPIV2 than HPIV4 infection. Each of the four seasonal peaks of either HPIV2, HPIV4 or both, closely matched that of RSV, occurring in November and December and preceding that of Influenza A. A subset of viruses were partially sequenced, indicating co-circulation of multiple subtypes of both HPIV2&4, but with little variation between each epidemic season or from limited global reference sequences. Conclusions Despite being closest known genetic relatives, our data indicates a potential difference in associated disease between HPIV2 and HPIV4, with more hospitalisation seen in HPIV2 mono-infected individuals, but a greater overall number of HPIV4 cases.
Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory infection and therefore, a major threat to global health. In the Philippines, RSV is the second most common respiratory viral pathogen next to rhinovirus among children with severe pneumonia. Since 2006, national influenza-like illness (ILI) and severe acute respiratory infection (SARI) surveillances have been mainly focused only on influenza viruses. The prevalence and genetic diversity of RSV in the last decades were not completely elucidated. This study determined the epidemiological and molecular characteristics of RSV among (ILI) and (SARI) cases of children in the Philippines. The Philippine National Influenza Centre (PNIC) collected oropharyngeal swab and nasopharyngeal swab samples from patients under the age of five who are presented with ILI and SARI for the period of 2006-2016. These swabs have been examined for RSV subgroup by multiplex real-time qRT-PCR. Sequencing and phylogenetic analyses were used to determine the genotype of RSV samples. A total of 1,036 samples were systematically selected and tested. Of these samples, 122 were RSV-positive at 11.8 % prevalence rate, and 58.2% (71/122) were classified as RSV-A. Six genotypes were identified, which included NA1 (27/122, 22.1%), ON1 (5/122, 4.1%), GA2 (1/122, 0.8%) and GA5 (1/123, 0.8%) for RSV-A; and BA2 (13/122, 10.7%) and BA9 (1/122, 0.8%) for RSV-B. Most RSV-related cases were significantly associated with pneumonia and bronchitis. The pattern of RSV activity in the Philippines resembles the transmission of RSV globally.
Background: In France, each year, influenza viruses are responsible for seasonal epidemics leading to 2-6 million cases. Influenza can cause severe disease that may lead to hospitalization or death. As severe disease may be due to the virus itself or to disease complications, estimating the burden of severe influenza is complex. The present study aimed at estimating the epidemiological and economic burden of severe influenza in France during eight consecutive influenza seasons (2010-2018). Methods: Influenza-related hospitalization and mortality data and patient characteristics were taken from the French hospital information database, PMSI. An ecological approach using cyclic regression models integrating the incidence of influenza syndrome from the Sentinelles Network supplemented the PMSI data analysis in estimating excess hospitalization and mortality (CépiDc – 2010-2015) and medical costs. Results: Each season, the average number of influenza-related hospitalizations was 18,979 (range: 8,627-44,024), with an average length of stay of 8 days. The average number of respiratory hospitalizations indirectly related with influenza (i.e., influenza-associated) was 31,490 (95% CI: 24,542-39,012), with an average cost of \euro141 million (range: 54-217); 70% of these hospitalizations and 77% of their costs concerned individuals ≥ 65 years of age (65+). More than 90% of excess mortality was in 65+ subjects. Conclusions: The combination of two complementary approaches allowed estimation of both influenza-related and associated hospitalizations and deaths and their burden in France, showing the substantial impact of complications. The present study highlighted the major public health burden of influenza and its severe complications, especially in 65+ subjects.