Prevalence of Respiratory Viral Infections in Deceased Persons during the COVID-19 Pandemic Season 2021-2022: A Population-Based Observational Study.

Although the omicron variant of SARS-CoV-2 circulated intensely during the 2021-2022 season, many patients with severe acute respiratory disease tested negative for COVID-19. The aim of this study was to assess the presence of different respiratory viruses in deceased persons. The proportion of deceased persons with respiratory viral infections in the 2021-2022 season in Navarre, Spain, was estimated considering all deaths caused by confirmed COVID-19 according to the epidemiological surveillance and the results of multiplex PCR tests for respiratory viruses performed in a sample of deceased persons with a cause of death other than COVID-19. Of 3578 deaths, 324 (9.1%) were initially reported as caused by pre-mortem confirmed COVID-19. A sample of 242 persons who died by causes other than COVID-19 were tested post-mortem; 64 (26.4%) of them were positive for any respiratory virus: 11.2% for SARS-CoV-2, 5.8% for rhinovirus, 3.7% for human coronavirus, 2.5% for metapneumovirus, 1.7% for respiratory syncytial virus, 1.7% for parainfluenza, 1.2% for influenza, and less than 1% each for adenovirus and bocavirus. Combining both approaches, we estimated that 34.4% of all deceased persons during the study period had a respiratory viral infection and 19.2% had SARS-CoV-2. Only 33.3% (9/27) of SARS-CoV-2 and 5.0% (2/40) of other viruses detected post-mortem had previously been confirmed pre-mortem. In a period with very intense circulation of SARS-CoV-2 during the pandemic, other respiratory viruses were also frequently present in deceased persons. Some SARS-CoV-2 infections and most other viral infections were not diagnosed pre-mortem. Several respiratory viruses may contribute to excess mortality in winter.

Body Mass Index and Risk of Hospitalization or Death Due to Lower or Upper Respiratory Tract Infection.

This study assesses the associations between body mass index and risk of hospitalization for or death due to COVID-19, lower respiratory tract infections, and upper respiratory tract infections.

Assessment of a cellular host response test to risk-stratify suspected COVID-19 patients in the Emergency Department setting.

OBJECTIVE: Assess the IntelliSep Index (ISI) for risk stratification of patients presenting to the Emergency Department (ED) with respiratory symptoms suspected of COVID-19 during the pandemic. METHODS: An observational single-center study of prospective cohort of patients presenting to the ED during the early COVID-19 pandemic with respiratory symptoms and a CBC drawn within 4.5 hours of initial vital signs. A sample of this blood was aliquoted for performance of the ISI, and patients were followed for clinical outcomes. The study required no patient-centered activity beyond standard of care and treating clinicians were unaware of study enrollment and ISI test results. MAIN FINDINGS: 282 patients were included. The ISI ranges 0.1 to 10.0, with three interpretation bands indicating risk of adverse outcome: low (green), 0.1-4.9; intermediate (yellow), 5.0-6.2; and high (red), 6.3-10.0. Of 193 (68.4%) tested for SARS-CoV-2, 96 (49.7%) were positive. The ISI resulted in 182 (64.5%) green, 54 (18.1%) yellow, and 46 (15.6%) red band patients. Green band patients had a 1.1% (n = 2) 3-day mortality, while yellow and red band had 3.7% (n = 2, p > .05) and 10.9% (n = 5, p < .05) 3-day mortalities, respectively. Fewer green band patients required admission (96 [52.7%]) vs yellow (44 [81.5%]) and red (43 [93.5%]). Green band patients had more hospital free days (median 23 (Q1-Q3 20-25) than yellow (median 22 [Q1-Q3 0-23], p < 0.05) and red (median 21 [Q1-Q3 0-24], p < 0.01). SOFA increased with interpretation band: green (2, [Q1-Q3 0-4]) vs yellow (4, [Q1-Q3 2-5], p < 0.001) and red (5, [Q1-Q3 3-6]) p < 0.001). CONCLUSIONS: The ISI rapidly risk-stratifies patients presenting to the ED during the early COVID-19 pandemic with signs or suspicion of respiratory infection.

Boletim Epidemiológico dos Casos de Covid-19 no Estado do Rio de Janeiro 2020 - 2021 / Epidemiological Bulletin of Covid-19 Cases in the State of Rio de Janeiro 2020 - 2021

Esta edição do boletim apresenta a análise do total de casos confirmados de COVID-19 de residentes no estado do Rio de Janeiro e suas nove regiões de saúde, incluindo os casos de Síndrome Gripal (SG) ou casos leves, as internações ou casos de Síndrome Respiratória Aguda Grave (SRAG) e os óbitos, ocorridos desde o início da pandemia em 2020 até 26 de fevereiro de 2022 (8ª Semana Epidemiológica).

Indirect effects of the covid-19 pandemic on childhood infection in England: population based observational study.

OBJECTIVE: To assess the impact of the covid-19 pandemic on hospital admission rates and mortality outcomes for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England. DESIGN: Population based observational study of 19 common childhood respiratory, severe invasive, and vaccine preventable infections, comparing hospital admission rates and mortality outcomes before and after the onset of the pandemic in England. SETTING: Hospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data. POPULATION: Children aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021. MAIN OUTCOME MEASURES: For each infection, numbers of hospital admissions every month from 1 March 2017 to 30 June 2021, percentage changes in the number of hospital admissions before and after 1 March 2020, and adjusted odds ratios to compare 60 day case fatality outcomes before and after 1 March 2020. RESULTS: After 1 March 2020, substantial and sustained reductions in hospital admissions were found for all but one of the 19 infective conditions studied. Among the respiratory infections, the greatest percentage reductions were for influenza (mean annual number admitted between 1 March 2017 and 29 February 2020 was 5379 and number of children admitted from 1 March 2020 to 28 February 2021 was 304, 94% reduction, 95% confidence interval 89% to 97%), and bronchiolitis (from 51 655 to 9423, 82% reduction, 95% confidence interval 79% to 84%). Among the severe invasive infections, the greatest reduction was for meningitis (50% reduction, 47% to 52%). For the vaccine preventable infections, reductions ranged from 53% (32% to 68%) for mumps to 90% (80% to 95%) for measles. Reductions were seen across all demographic subgroups and in children with underlying comorbidities. Corresponding decreases were also found for the absolute numbers of 60 day case fatalities, although the proportion of children admitted for pneumonia who died within 60 days increased (age-sex adjusted odds ratio 1.71, 95% confidence interval 1.43 to 2.05). More recent data indicate that some respiratory infections increased to higher levels than usual after May 2021. CONCLUSIONS: During the covid-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions) and societal strategies (school closures, lockdowns, and restricted travel) were used to reduce transmission of SARS-CoV-2, which also reduced admissions for common and severe childhood infections. Continued monitoring of these infections is required as social restrictions evolve.

Respiratory Syncytial Virus-attributable Deaths in a Major Pediatric Hospital in New South Wales, Australia, 1998-2018.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection and an important contributor to child mortality. In this study, we estimated the frequency and described the clinical features of RSV-attributable deaths in Australian children. METHODS: We conducted a retrospective observational study of RSV-associated deaths in hospitalized children <16 years of age over a 21-year period (1998-2018) in a pediatric tertiary/quaternary referral hospital in New South Wales (NSW), Australia. RSV-associated deaths were identified, reviewed, and classified according to RSV contribution to death. For 'RSV-attributable' deaths, we estimated frequency, case fatality ratio (CFR), and population death rate. We described demographic and clinical features of cases. RESULTS: There were 20 RSV-attributable deaths. RSV was considered the primary cause of death for five cases and a contributory cause for 15 cases. The CFR among hospitalized cases was 0.2% (20/9779). The annual death rate was 0.6 per 10,000 hospitalized children. The population death rate was 1.2 (95% confidence interval 0.5-2.7) per million children <16 years of age in NSW. The median age at death was 28.7 months (interquartile range 8.8-75.0). All children had at least one medical comorbidity. Over half the deaths occurred in children ≥2 years of age (11, 55%). RSV healthcare-associated infection (RSV-HAI) was common (11, 55%). CONCLUSIONS: RSV-attributable death is infrequent in this setting. Deaths occurred exclusively in children with medical comorbidity and a high proportion were RSV-HAI. Children with medical comorbidity, including those ≥2 years of age, should be prioritized for targeted prevention of RSV disease.

Short- and medium-term impacts of strict anti-contagion policies on non-COVID-19 mortality in China.

The effects of coronavirus disease-19 (COVID-19) public health policies on non-COVID-19-related mortality are unclear. Here, using death registries based on 300 million Chinese people and a difference-in-differences design, we find that China's strict anti-contagion policies during the COVID-19 pandemic significantly reduced non-COVID-19 mortality outside Wuhan (by 4.6%). The health benefits persisted and became even greater after the measures were loosened: mortality was reduced by 12.5% in the medium term. Significant changes in people's behaviours (for example, wearing masks and practising social distancing) and reductions in air pollution and traffic accidents could have driven these results. We estimate that 54,000 lives could have been saved from non-COVID-19 causes during the 50 days of strict policies and 293,000 in the subsequent 115 days. The results suggest that virus countermeasures not only effectively controlled COVID-19 in China but also brought about unintended and substantial public health benefits.

Lactate dehydrogenase to albumin ratio as a prognostic factor in lower respiratory tract infection patients.

PURPOSE: To verify the role of lactate dehydrogenase to albumin (LDH/ALB) ratio as an independent prognostic factor for mortality due to the lower respiratory tract infection (LRTI) in the emergency department (ED). METHODS: We reviewed the electronic medical records of patients who were admitted to the ED for the management of LRTI between January 2018 and December 2020. Initial vital signs, laboratory data, and patient severity scores in the ED were collected. The LDH/ALB ratio was compared to other albumin-based ratios (blood urea nitrogen to albumin ratio, C-reactive protein to albumin ratio, and lactate to albumin ratio) and severity scales (pneumonia severity index, modified early warning score, CURB-65 scores), which are being used as prognostic factors for in-hospital mortality. Multivariable logistic regression was performed to identify independent risk factors. RESULTS: The LDH/ALB ratio was higher in the non-survivor group than in the survivor group (median [interquartile range]: 217.6 [160.3;312.0] vs. 126.4 [100.3;165.1], p < 0.001). In the comparison of the area under the receiver operating characteristic curve (AUC) for predicting in-hospital mortality, the AUC of the LDH/ALB ratio (0.808, 95% confidence interval: 0.757-0.842, p < 0.001) was wider than other albumin-based ratios and severity scales, except the blood urea nitrogen to albumin ratio. In the multivariable logistic regression analysis, the LDH/ALB ratio independently affected in-hospital mortality. CONCLUSION: The LDH/ALB ratio may serve as an independent prognostic factor for in-hospital mortality in patients with LRTI.

Tracheotomy as a predictor of remission and demise for juvenile-onset recurrent respiratory papillomatosis.

BACKGROUD: The pros and cons of tracheotomy, as a classic treatment of juvenile-onset recurrent respiratory papillomatosis (JORRP), have gradually been recognized, but the exact impact of tracheotomy on remission and demise is not clear. OBJECTIVES: To investigate the predicting influence of tracheotomy on prognosis for JORRP. MATERIAL AND METHODS: Three hundred forty two patients with JORRP treated in Beijing Tongren Hospital were retrospectively reviewed. The clinical characteristics and prognosis parameters were compared in the group of tracheotomy and non-tracheotomy. RESULTS: The rate of tracheotomy was 24.6% (84/342). Among these patients, 68 (81.0%) developed the tracheal papillomatosis. The onset age of RRP occurred earlier in tracheostomized group, and patients performed tracheotomy needed a greater number of surgeries and developed distal spread more easily (p < .05). The remission rate was significantly lower (35.1 vs. 53.7%) and the mortality higher (13.1 vs. 1.2%) in patients with tracheotomy than non-tracheotomy. Tracheotomy decreased odds of remission (OR = 0.48; 95%CI: 0.28-0.83) and increased odds of demise (OR = 11.98; 95%CI: 3.21-44.65). CONCLUSIONS: The age at diagnosis, the surgical frequency and the medical level of hospital are important factors affecting the occurrence of tracheotomy. Patients who had undergone tracheotomy are prone to possess the low remission rate and high mortality.

Sex differences in innate anti-viral immune responses to respiratory viruses and in their clinical outcomes in a birth cohort study.

The mechanisms explaining excess morbidity and mortality in respiratory infections among males are poorly understood. Innate immune responses are critical in protection against respiratory virus infections. We hypothesised that innate immune responses to respiratory viruses may be deficient in males. We stimulated peripheral blood mononuclear cells from 345 participants at age 16 years in a population-based birth cohort with three live respiratory viruses (rhinoviruses A16 and A1, and respiratory syncytial virus) and two viral mimics (R848 and CpG-A, to mimic responses to SARS-CoV-2) and investigated sex differences in interferon (IFN) responses. IFN-α responses to all viruses and stimuli were 1.34-2.06-fold lower in males than females (P = 0.018 - < 0.001). IFN-ß, IFN-γ and IFN-induced chemokines were also deficient in males across all stimuli/viruses. Healthcare records revealed 12.1% of males and 6.6% of females were hospitalized with respiratory infections in infancy (P = 0.017). In conclusion, impaired innate anti-viral immunity in males likely results in high male morbidity and mortality from respiratory virus infections.

Viral burden and diversity in acute respiratory tract infections in hospitalized children in wet and dry zones of Sri Lanka.

The present study was done to identify the viral diversity, seasonality and burden associated with childhood acute respiratory tract infection (ARTI) in Sri Lanka. Nasopharyngeal aspirates (NPA) of hospitalized children (1 month-5 years) with ARTI were collected in 2 centers (wet and dry zones) from March 2013 to August 2014. Respiratory viral antigen detection by immunofluorescence assay (IFA) was used to identify the infecting viruses. IFA negative 100 NPA samples were tested for human metapeumovirus (hMPV), human bocavirus and corona viruses by polymerase chain reaction. Of the 443 and 418 NPAs, 37.2% and 39.4% were positive for any of the 8 different respiratory viruses tested from two centers studied. Viral co-infection was detected with respiratory syncytial virus (RSV) in both centers. Peak viral detection was noted in the wet zone from May-July 2013 and 2014 and in the dry zone from December-January 2014 suggesting a local seasonality for viral ARTI. RSV showed a clear seasonality with a direct correlation of monthly RSV infections with rainy days in the wet zone and an inverse correlation with temperature in both centers. The case fatality rate was 2.7% for RSV associated ARTI. The overall disability adjusted life years was 335.9 and for RSV associated ARTI it was 241.8. RSV was the commonly detected respiratory virus with an annual seasonality and distribution in rainy seasons in the dry and wet zones of Sri Lanka. Identifying the virus and seasonality will contribute to employ preventive measures and reduce the empirical use of antibiotics in resource limited settings.

Morbi-mortality of lower respiratory tract infections in Spain, 1997-2018 / Morbimortalidad de las infecciones del tracto respiratorio inferior en España, 1997-2018

Background:Lower respiratory tract infections (LRTIs) are one of the leading causes of infectious disease mortality worldwide. The aims of the study were to determine the incidence of hospitalizations due to LRTIs, and to analyze the clinical outcomes of the hospitalized patients. Methods:An observational study of hospitalizations due to LRTIs (pneumonia and acute bronchitis/bronchio-litis) in Spain from 1997 to 2018 was carried out. Data were extracted from the national information system for hospital data. Results:Overall, 3.5 % (IQR: 3.4-3.5 %) of total hospitalizations were caused by LRTIs, with a median incidence of 31.2 (IQR: 27.8-33.0) per 10,000 inhabitants/year. The median incidence was higher for pneumonia than for acute bronchitis/bronchiolitis cases (22.2; IQR: 19.1-23.5 vs. 9.0; IQR: 8.4-9.6 per 10,000 inhabitants/year; p < 0.001) and increased by 65.7 % from 1997 to 2018. A 41.2 % of the hospitalizations due to LRTIs took place amongst people over 74 years. The median length of stay was 8.9 days (IQR: 7.6-10.4) and was higher for hospitalizations due to pneumonia than for acute bronchitis/bronchiolitis (9.5 days; IQR: 8.3-10.6 vs. 5.7; IQR: 5.5-6.2; p < 0,001). In 89.1 % of total hospitalizations due to LRTIs, patients were discharged home. In-hospital mortality was 6.8 %, with 9,380 deaths (IQR: 8,192-10,157) per year. Mortality was higher for pneumonia (9.0 vs. 1.7 %; p < 0.001) and doubled from 1997 to 2018 (5,257 deaths in 1997 and 10,514 in 2018). A 75.5 % of the deaths occurred amongst people over 74 years.Conclusions:LRTIs are associated with a high morbi-mortality in Spain. Effective measures that can contribute towards the prevention and treatment of LRTIs need to be adopted.(AU)

Fundamento: Las infecciones del tracto respiratorio inferior (ITRI) constituyen una de las principales causas de mortalidad por enfermedades infecciosas a nivel mundial. Los objetivos del estudio consistieron en determinar la incidencia de hospitalizaciones por ITRI, y en analizar los resultados clínicos de los pacientes hospitalizados. Métodos: Se llevó a cabo un estudio observacional de las hospitalizaciones por ITRI (neumonía y bronquitis/bronquiolitis aguda) en España entre 1997-2018. Los datos se extrajeron del Registro Español de Atención Sanitaria Especializada. Resultados: El 3,5% (RIC: 3,4-3,5%) del total de hospitalizaciones se debieron a ITRI, con una incidencia mediana de 31,2 (RIC: 27,8-33,0) por cada 10.000 habitantes/año. La mediana de incidencia fue superior para las neumonías que para las bronquitis/bronquiolitis agudas (22,2; RIC: 19,1-23,5 vs. 9,0; RIC: 8,4-9,6 por 10.000 habitantes/año; p<0,001), y entre 1997-2018 aumentó un 65,7%. Un 41,2% de las hospitalizaciones por ITRI ocurrieron en mayores de 74 años. La mediana de duración de las hospitalizaciones por ITRI fue 8,9 días (RIC: 7,6-10,4), superior para neumonías (9,5 días; RIC: 8,3-10,6 vs. 5,7; RIC: 5,5-6,2; p<0,001). En un 89,1% de las hospitalizaciones por ITRI los pacientes fueron dados de alta a domicilio. La mortalidad intrahospitalaria fue 6,8%, con 9.380 fallecimientos anuales (RIC: 8,192-10,157). La mortalidad fue superior para neumonías (9,0 vs. 1,7%; p<0,001) y se duplicó entre 1997 y 2018 (5.257 fallecimientos en 1997 y 10.514 en 2018). El 75,5% de las muertes ocurrieron en mayores de 74 años. Conclusiones: Las ITRI se asocian a una elevada morbimortalidad. Se requieren medidas efectivas para su prevención y tratamiento.(AU)

Viral etiology and outcome of severe lower respiratory tract infections among critically ill children admitted to the PICU / Etiología vírica y desenlace de infecciones de las vías respiratorias bajas entre niños críticamente enfermos ingresados en la UCIP

Objective: To determine the viral etiology of severe lower respiratory tract infections (LRTIs), their clinical significance and prognosis among critically ill children. Design A prospective descriptive study was carried out. Setting Pediatric Intensive Care Unit (PICU) of Istanbul Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkey.PatientsA total of 115 patients hospitalized in the PICU were evaluated for inclusion in the study. Children with underlying comorbidities and those who did not require mechanical ventilation were excluded. Main variables of interest Demographic, clinical, laboratory test and radiographic data were recorded. Results A total of 63 patients were eligible for the study. The most common diagnosis was bronchiolitis (57.1%). Respiratory syncytial virus (RSV) was the most frequent causal virus (36.5%). The most common complication was acute respiratory distress syndrome (ARDS) (28.6%). Multiple viral infection was identified in 20.6% of the patients, the most common in this subgroup being rhinovirus. Patients with bocavirus infection had a higher likelihood of needing invasive mechanical ventilation (IMV) at presentation. Children who died were likely to be <12 months old, have ARDS, hepatitis, pneumomediastinum, multiple viral infection, and required IMV support with an increased duration of MV. Additionally, they were found to have a high Pediatric Risk of Mortality III score, Predicted Death Rate and increased need for inotropic support at admission. Conclusions Our study showed critically ill children with LRTI without known risk factors to have high mortality when aged <12 months, in the presence of multiple agents and when certain complications (ARDS, hepatitis) and X-ray findings were identified.

Objetivo: Determinar la etiología vírica de las infecciones graves de las vías respiratorias bajas (IGVRB), su importancia clínica y su pronóstico en niños críticamente enfermos. Diseño Estudio descriptivo prospectivo. Ámbito Unidad de cuidados intensivos pediátricos (UCIP) del Hospital Universitario y de Investigación Goztepe, Universidad Medeniyet de Estambul, Turquía. Pacientes y participantes Se evaluó a un total de 115 pacientes ingresados en la UCIP para su posible inclusión en el estudio. Se excluyó a los niños con comorbilidades subyacentes y a aquellos que no requerían ventilación mecánica. Variables de interés principales Se registraron los datos demográficos, clínicos, de laboratorio y radiológicos de los pacientes. Resultados Un total de 63 pacientes fueron elegidos para participar en el estudio. El diagnóstico más habitual era bronquiolitis (57,1%). El virus sincitial respiratorio era el más común de los virus (36,5%). La complicación más habitual era el síndrome de dificultad respiratoria aguda (SDRA) (28,6%). Se identificaron múltiples infecciones víricas en el 20,6% de los pacientes, siendo la infección por el rinovirus la más común en este subgrupo. Los pacientes con infección por bocavirus presentaban una mayor probabilidad de necesitar ventilación mecánica invasiva (VMI) en el momento de la presentación. Los niños que murieron tenían una mayor probabilidad de presentar: edad <12 meses, SDRA, hepatitis, neumomediastino, infección multiviral y requerir MVI, con una mayor duración de la VM. Además, se observó que presentaban unos valores más altos de la escala PRISM III (Pediatric Risk of Mortality III) y tasa de mortalidad prevista, además de necesidad apoyo inotrópico en el momento del ingreso. Conclusiones: Nuestro estudio demostró que los niños críticamente enfermos con LRTI sin factores de riesgo conocidos tienen una alta mortalidad cuando tienen menos de 12 meses, en presencia de múltiples agentes ... (AU)

Dynamics of the Upper Respiratory Tract Microbiota and Its Association with Mortality in COVID-19.

Rationale: Alteration of human respiratory microbiota had been observed in coronavirus disease (COVID-19). How the microbiota is associated with the prognosis in COVID-19 is unclear. Objectives: To characterize the feature and dynamics of the respiratory microbiota and its associations with clinical features in patients with COVID-19. Methods: We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 patients with COVID-19 (including 39 deceased patients) and 95 healthy controls from the same geographic area. Meanwhile, the concentration of 27 cytokines and chemokines in plasma was measured for patients with COVID-19. Measurements and Main Results: The upper respiratory tract (URT) microbiota in patients with COVID-19 differed from that in healthy controls, whereas deceased patients possessed a more distinct microbiota, both on admission and before discharge/death. The alteration of URT microbiota showed a significant correlation with the concentration of proinflammatory cytokines and mortality. Specifically, Streptococcus-dominated microbiota was enriched in recovered patients, and showed high temporal stability and resistance against pathogens. In contrast, the microbiota in deceased patients was more susceptible to secondary infections and became more deviated from the norm after admission. Moreover, the abundance of S. parasanguinis on admission was significantly correlated with prognosis in nonsevere patients (lower vs. higher abundance, odds ratio, 7.80; 95% CI, 1.70-42.05). Conclusions: URT microbiota dysbiosis is a remarkable manifestation of COVID-19; its association with mortality suggests it may reflect the interplay between pathogens, symbionts, and the host immune status. Whether URT microbiota could be used as a biomarker for diagnosis and prognosis of respiratory diseases merits further investigation.

Decreasing death rates and causes of death in Icelandic children-A longitudinal analysis.

BACKGROUND: Global death rate in children has been declining during the last decades worldwide, especially in high income countries. This has been attributed to several factors, including improved prenatal and perinatal care, immunisations, infection management as well as progress in diagnosis and treatment of most diseases. However, there is certainly room for further progress. The aim of the current study was to describe the changes in death rates and causes of death in Iceland, a high-income country during almost half a century. METHODS: The Causes of Death Register at The Directorate of Health was used to identify all children under the age of 18 years in Iceland that died during the study period from January 1st, 1971 until December 31st, 2018. Using Icelandic national identification numbers, individuals could be identified for further information. Hospital records, laboratory results and post-mortem diagnosis could be accessed if cause of death was unclear. FINDINGS: Results showed a distinct decrease in death rates in children during the study period that was continuous over the whole period. This was established for almost all causes of death and in all age groups. This reduction was primarily attributed to a decrease in fatal accidents and fewer deaths due to infections, perinatal or congenital disease as well as malignancies, the reduction in death rates from other causes was less distinct. Childhood suicide rates remained constant. INTERPRETATION: Our results are encouraging for further prevention of childhood deaths. In addition, our results emphasise the need to improve measures to detect and treat mental and behavioural disorders leading to childhood suicide.

Mortality in children aged <5 years with severe acute respiratory illness in a high HIV-prevalence urban and rural areas of South Africa, 2009-2013.

BACKGROUND: Severe acute respiratory illness (SARI) is an important cause of mortality in young children, especially in children living with HIV infection. Disparities in SARI death in children aged <5 years exist in urban and rural areas. OBJECTIVE: To compare the factors associated with in-hospital death among children aged <5 years hospitalized with SARI in an urban vs. a rural setting in South Africa from 2009-2013. METHODS: Data were collected from hospitalized children with SARI in one urban and two rural sentinel surveillance hospitals. Nasopharyngeal aspirates were tested for ten respiratory viruses and blood for pneumococcal DNA using polymerase chain reaction. We used multivariable logistic regression to identify patient and clinical characteristics associated with in-hospital death. RESULTS: From 2009 through 2013, 5,297 children aged <5 years with SARI-associated hospital admission were enrolled; 3,811 (72%) in the urban and 1,486 (28%) in the rural hospitals. In-hospital case-fatality proportion (CFP) was higher in the rural hospitals (6.9%) than the urban hospital (1.3%, p<0.001), and among HIV-infected than the HIV-uninfected children (9.6% vs. 1.6%, p<0.001). In the urban hospital, HIV infection (odds ratio (OR):11.4, 95% confidence interval (CI):5.4-24.1) and presence of any other underlying illness (OR: 3.0, 95% CI: 1.0-9.2) were the only factors independently associated with death. In the rural hospitals, HIV infection (OR: 4.1, 95% CI: 2.3-7.1) and age <1 year (OR: 3.7, 95% CI: 1.9-7.2) were independently associated with death, whereas duration of hospitalization ≥5 days (OR: 0.5, 95% CI: 0.3-0.8) and any respiratory virus detection (OR: 0.4, 95% CI: 0.3-0.8) were negatively associated with death. CONCLUSION: We found that the case-fatality proportion was substantially higher among children admitted to rural hospitals and HIV infected children with SARI in South Africa. While efforts to prevent and treat HIV infections in children may reduce SARI deaths, further efforts to address health care inequality in rural populations are needed.

Identification of a novel mortality-associated Helicobacter species in gopher tortoises (Gopherus polyphemus), qPCR test development and validation, and correlation with mortality in a wildlife rehabilitation population.

The genus Helicobacter includes spiral-shaped bacteria in the phylum Proteobacteria, class Epsilonproteobacteria, order Campylobacteriales, that have been associated with disease in animals, including reptiles. Three wild gopher tortoise (Gopherus polyphemus) index cases presented between 2012 and 2019 with nasal discharge, lethargy, and weight loss. Cytological examination of nasal discharge from all 3 tortoises identified marked heterophilic and mild histiocytic rhinitis with abundant extracellular and phagocytized spiral shaped bacteria that stained positive with Warthin-Starry stain. Polymerase chain reaction (PCR) and sequencing of the 16S rRNA gene revealed this to be a novel Helicobacter species. Two tortoises died despite treatment attempts, and the third was moribund and was euthanized. Histological examination of the nasal mucosa (n = 3) showed granulocytic to lymphocytic rhinitis with variable mucosal hyperplasia, erosion, and ulceration; Warthin-Starry staining highlighted the presence of spiral bacteria in the untreated tortoise. Genus-specific primers were designed, and the gyrA and groEL genes were amplified by PCR and sequenced. Phylogenetic analysis shows that this organism and other previously characterized Helicobacter from tortoises form a clade. Development and cross-validation of two qPCR diagnostic assays for the gyrA and groEL genes showed significant correlation of the results of two assays (P < 0.0001). These assays were used to survey nasal wash samples from 31 rehabilitating gopher tortoises. Mortality of tortoises significantly correlated with higher Helicobacter loads detected by qPCR (P = 0.028). Appropriate quarantine protocols for tortoises during rehabilitation should consider this organism. Upper respiratory disease in tortoises may involve complex microbial ecology; factors beyond Mycoplasmopsis (Mycoplasma) agassizii should be taken into account.

Immune Dysregulation and the Increased Risk of Complications and Mortality Following Respiratory Tract Infections in Adults With Down Syndrome.

The risk of severe outcomes following respiratory tract infections is significantly increased in individuals over 60 years, especially in those with chronic medical conditions, i.e., hypertension, diabetes, cardiovascular disease, dementia, chronic respiratory disease, and cancer. Down Syndrome (DS), the most prevalent intellectual disability, is caused by trisomy-21 in ~1:750 live births worldwide. Over the past few decades, a substantial body of evidence has accumulated, pointing at the occurrence of alterations, impairments, and subsequently dysfunction of the various components of the immune system in individuals with DS. This associates with increased vulnerability to respiratory tract infections in this population, such as the influenza virus, respiratory syncytial virus, SARS-CoV-2 (COVID-19), and bacterial pneumonias. To emphasize this link, here we comprehensively review the immunobiology of DS and its contribution to higher susceptibility to severe illness and mortality from respiratory tract infections.

Novel STAT-3 gain-of-function variant with hypogammaglobulinemia and recurrent infection phenotype.

Signal transducer and activator of transcription 3 (STAT-3) gain-of-function (GOF) syndrome is an early-onset monogenic inborn error of immunity characterized by multi-organ autoimmune disorders, growth failure and lymphoproliferation. We describe that STAT-3 GOF syndrome may be presented with hypogammaglobulinemia and recurrent severe upper and lower respiratory tract infections. In addition, the patient had lymphoproliferation, short stature and interstitial lung disease. Chest computerized tomography examinations showed mild bronchiectasis with areas of non-fibrosing alveolar-interstitial disease and maldevelopment of bilateral first ribs. Using Sanger sequencing, we revealed a novel c.508G>C, p.D170H STAT-3 variant affecting the coiled coil domain of STAT-3. Functional studies confirmed that p.D170H was a GOF variant, as shown by increased phosphorylated STAT-3 (pSTAT-3) and STAT-3 transcriptional activity. Our observation suggests that STAT-3 GOF syndrome can manifest in early childhood with hypogammaglobulinemia and recurrent severe respiratory tract infections. We suggest that patients with lymphoproliferation, hypogammaglobulinemia and severe recurrent infections should be screened for STAT-3 variants, even if autoimmune manifestations are missing.