Respiratory Tract Infections In Adults Research Articles

Diagnostic accuracy of point-of-care tests for acute respiratory infection: a systematic review of reviews.

Acute respiratory infections are a common reason for consultation with primary and emergency healthcare services. Identifying individuals with a bacterial infection is crucial to ensure appropriate treatment. However, it is also important to avoid overprescription of antibiotics, to prevent unnecessary side effects and antimicrobial resistance. We conducted a systematic review to summarise evidence on the diagnostic accuracy of symptoms, signs and point-of-care tests to diagnose bacterial respiratory tract infection in adults, and to diagnose two common respiratory viruses, influenza and respiratory syncytial virus. The primary approach was an overview of existing systematic reviews. We conducted literature searches (22 May 2023) to identify systematic reviews of the diagnostic accuracy of point-of-care tests. Where multiple reviews were identified, we selected the most recent and comprehensive review, with the greatest overlap in scope with our review question. Methodological quality was assessed using the Risk of Bias in Systematic Reviews tool. Summary estimates of diagnostic accuracy (sensitivity, specificity or area under the curve) were extracted. Where no systematic review was identified, we searched for primary studies. We extracted sufficient data to construct a 2 × 2 table of diagnostic accuracy, to calculate sensitivity and specificity. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies version 2 tool. Where possible, meta-analyses were conducted. We used GRADE to assess the certainty of the evidence from existing reviews and new analyses. We identified 23 reviews which addressed our review question; 6 were selected as the most comprehensive and similar in scope to our review protocol. These systematic reviews considered the following tests for bacterial respiratory infection: individual symptoms and signs; combinations of symptoms and signs (in clinical prediction models); clinical prediction models incorporating C-reactive protein; and biological markers related to infection (including C-reactive protein, procalcitonin and others). We also identified systematic reviews that reported the accuracy of specific tests for influenza and respiratory syncytial virus. No reviews were found that assessed the diagnostic accuracy of white cell count for bacterial respiratory infection, or multiplex tests for influenza and respiratory syncytial virus. We therefore conducted searches for primary studies, and carried out meta-analyses for these index tests. Overall, we found that symptoms and signs have poor diagnostic accuracy for bacterial respiratory infection (sensitivity ranging from 9.6% to 89.1%; specificity ranging from 13.4% to 95%). Accuracy of biomarkers was slightly better, particularly when combinations of biomarkers were used (sensitivity 80-90%, specificity 82-93%). The sensitivity and specificity for influenza or respiratory syncytial virus varied considerably across the different types of tests. Tests involving nucleic acid amplification techniques (either single pathogen or multiplex tests) had the highest diagnostic accuracy for influenza (sensitivity 91-99.8%, specificity 96.8-99.4%). Most of the evidence was considered low or very low certainty when assessed with GRADE, due to imprecision in effect estimates, the potential for bias and the inclusion of participants outside the scope of this review (children, or people in hospital). Currently evidence is insufficient to support routine use of point-of-care tests in primary and emergency care. Further work must establish whether the introduction of point-of-care tests adds value, or simply increases healthcare costs. This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR159948.

A-315 Cardiac Troponin Concentrations in Pediatric Patients Infected with Respiratory Syncytial Virus

Abstract Background Respiratory syncytial virus (RSV) is associated with considerable morbidity and mortality in pediatric patients. Cardiac troponin I (TnI) has been shown to increase in patients with acute respiratory illness, including COVID-19. The impact of RSV infection on circulating TnI has been formally demonstrated in the literature. The goal of this study was to assess the relationship between TnI and respiratory syncytial virus (RSV) in pediatric patients. Methods A prospective study was conducted at St. Louis Children’s Hospital from October 2023 to February 2024. Patients older than 6 months who presented to the ED and had a CBC ordered within 6 hours of testing positive for RSV on the Biofire® FilmArray® Respiratory Panel were enrolled. Patients with Rhinovirus, Enterovirus, Streptococcus pneumoniae, or Adenovirus infections were included as controls. Remnant EDTA specimens were tested on an Abbott ARCHITECT i2000 for high sensitivity TnI (hs-TnI) with a limit of detection of 1.4 ng/L and a limit of quantitation of 3.5 ng/L. 99% upper reference limits from the CALIPER database on the Abbott of <7 ng/L were used as a threshold for positive results. The electronic medical record (EPIC) was assessed for demographic information and outcomes including length of stay (LOS), intensive care unit (ICU) length of stay, requirement of supplemental oxygen, white blood cell count (WBC), and creatinine. Results A total of 103 patients had RSV and 35 had other respiratory infections (ORI). The average age for the RSV positive group was 2.3 and for the ORI group was 2.4. Males made up 61% of the RSV+ group and 51% of the ORIs. 93 patients in the RSV group were admitted. The median TnI for RSV patients was 1.4 (IQR, 1.2-2.9) and for ORIs was 1.4 (IQR, 1.4-6.8). TnI was measurable in 58% of those with RSV and 54% in ORIs. We next assessed the correlation between hospital LOS and TnI in RSV+ patients, with a Pearson r of 0.42 (95% CI= 0.23-0.58). There was no correlation between WBC and LOS (r=-0.04, 95% CI=-0.25-0.17). There was also no correlation between TnI and WBCs or creatinine. Of admitted patients, 44 (47%) in the RSV group were in the ICU compared to 18 (51.4%) in those with ORIs. RSV+ patients that required ICU treatment had comparable TnI (1.4, IQR, 0.9-3.5) to those that didn’t require ICU stay (1.4, IQR, 0.75-1.5). There was no correlation between ICU LOS and TnI in RSV+ patients (r=-0.08, 95% CI=-0.39-0.24). There was a significant difference in mean TnI concentrations in RSV+ patients that required supplemental oxygen (8.7, 95% CI: 0-19) versus those that did not (1.7, 95% CI: 1.1-2.4). Conclusions There was no difference in TnI in patients hospitalized for RSV relative to ORIs. While TnI concentration was associated with LOS, there were minimally other associations between TnI and outcomes in patients hospitalized with RSV. While TnI elevations are associated with acute respiratory infections in adults, the impact on pediatric patients is not as clear. Future investigation is needed to understand how severe respiratory infections impact pediatric cardiac function.

The optimal antibiotic treatment duration for community-acquired pneumonia in adults diagnosed in general practice in Denmark (CAP-D): an open-label, pragmatic, randomised controlled trial

BackgroundUse of antibiotics is the main driver of antimicrobial resistance which is considered one of the biggest threats to human health. In Denmark, most antibiotics are prescribed in general practice. Acute lower respiratory tract infections, including community-acquired pneumonia (CAP), are among the most frequent indications for antibiotic prescribing. Phenoxymethylpenicillin is established as first-line treatment in general practice in Denmark. However, the treatment duration with phenoxymethylpenicillin is mostly based on traditions. Both 5 and 7 days of treatment is recommended in Danish guidelines, and when asking the general practitioners about what treatment duration, they prescribe the variation is even bigger. Several hospital-based studies have proven short course (≤ 6 days) antibiotic treatment non-inferior to long course (≥ 7 days) treatment of CAP. No evidence exists on the optimal treatment duration for CAP in non-hospitalised patients.This randomised controlled trial aim to investigate the optimal treatment duration with phenoxymethylpenicillin for CAP in adults diagnosed in general practice in Denmark.MethodsThis is an open-label, pragmatic, randomised controlled, five-arm DURATIONS trial. Participants will be recruited from at least 24 general practices in Denmark. Eligible participants are adults, with no pre-existing lung disease, presenting with symptoms of CAP, and in whom the general practitioner finds it relevant to treat with antibiotics. The study will compare treatment with phenoxymethylpenicillin 1.2 MIE q.i.d. in 3, 4, 5, 6, and 7 days.DiscussionThis study will provide evidence for the optimal antibiotic treatment duration of CAP in general practice and inform future guidelines on CAP in all countries using phenoxymethylpenicillin for the treatment of acute respiratory tract infections in adults. The results of this study might also be used to guide treatment recommendations in other countries using phenoxymethylpenicillin.Moreover, a (potential) reduction in antibiotic use might lower the development of antimicrobial resistance, increase patient treatment adherence, reduce risks of adverse events, and lower the economical expTrial registrationClinicalTrials.gov: NCT06295120. Registered 28 February 2024. The Scientific Ethics Committee for the North Denmark Region: N-20230039.

COVID-19 mutations: An overview.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the genus Beta coronavirus and the family of Coronaviridae. It is a positive-sense, non-segmented single-strand RNA virus. Four common types of human coronaviruses circulate globally, particularly in the fall and winter seasons. They are responsible for 10%-30% of all mild upper respiratory tract infections in adults. These are 229E, NL63 of the Alfacoronaviridae family, OC43, and HKU1 of the Betacoronaviridae family. However, there are three highly pathogenic human coronaviruses: SARS-CoV-2, Middle East respiratory syndrome coronavirus, and the latest pandemic caused by the SARS-CoV-2 infection. All viruses, including SARS-CoV-2, have the inherent tendency to evolve. SARS-CoV-2 is still evolving in humans. Additionally, due to the development of herd immunity, prior infection, use of medication, vaccination, and antibodies, the viruses are facing immune pressure. During the replication process and due to immune pressure, the virus may undergo mutations. Several SARS-CoV-2 variants, including the variants of concern (VOCs), such as B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617/B.1.617.2 (Delta), P.1 (Gamma), and B.1.1.529 (Omicron) have been reported from various parts of the world. These VOCs contain several important mutations; some of them are on the spike proteins. These mutations may lead to enhanced infectivity, transmissibility, and decreased neutralization efficacy by monoclonal antibodies, convalescent sera, or vaccines. Mutations may also lead to a failure of detection by molecular diagnostic tests, leading to a delayed diagnosis, increased community spread, and delayed treatment. We searched PubMed, EMBASE, Covariant, the Stanford variant Database, and the CINAHL from December 2019 to February 2023 using the following search terms: VOC, SARS-CoV-2, Omicron, mutations in SARS-CoV-2, etc. This review discusses the various mutations and their impact on infectivity, transmissibility, and neutralization efficacy.

Long-Term Exposure to Air Pollution and Lower Respiratory Infection in Adults: Evidence From Over 16-Years' Follow-Up for Danish National Cohort

Long-Term Exposure to Air Pollution and Lower Respiratory Infection in Adults: Evidence From Over 16-Years' Follow-Up for Danish National Cohort

Enterovirus D68 disease burden and epidemiology in hospital-admitted influenza-like illness, Valencia region of Spain, 2014-2020 influenza seasons.

Enterovirus D68 (EV-D68) is an emerging agent for which data on the susceptible adult population is scarce. We performed a 6-year analysis of respiratory samples from influenza-like illness (ILI) admitted during 2014-2020 in 4-10 hospitals in the Valencia Region, Spain. EV-D68 was identified in 68 (3.1%) among 2210 Enterovirus (EV)/Rhinovirus (HRV) positive samples. Phylogeny of 59 VP1 sequences showed isolates from 2014 clustering in B2 (6/12), B1 (5/12), and A2/D1 (1/12) subclades; those from 2015 (n = 1) and 2016 (n = 1) in B3 and A2/D1, respectively; and isolates from 2018 in A2/D3 (42/45), and B3 (3/45). B1 and B2 viruses were mainly detected in children (80% and 67%, respectively); B3 were equally distributed between children and adults; whereas A2/D1 and A2/D3 were observed only in adults. B3 viruses showed up to 16 amino acid changes at predicted antigenic sites. In conclusion, two EV-D68 epidemics linked to ILI hospitalized cases occurred in the Valencia Region in 2014 and 2018, with three fatal outcomes and one ICU admission. A2/D3 strains from 2018 were associated with severe respiratory infection in adults. Because of the significant impact of non-polio enteroviruses in ILI and the potential neurotropism, year-round surveillance in respiratory samples should be pursued.

Therapeutic effect of honey on acute respiratory infections in adults

Context: In Morocco, acute respiratory infections (ARI) are a frequent cause of consultations in the first level health facilities. Scientific reports indicate that honey has an important biochemical therapeutic activity. Aims: To explore the therapeutic effect of honey on ARI in the Guelmim region of southern Morocco. Methods: This was a prospective clinical study aiming to compare the therapeutic effect of honey in the population that consumes it versus a control population, at the level of the regional hospital and health centers, the period of the study was between September 2022 and March 2023, All the participants were questioned through a questionnaire and the study of their files and monitoring forms. Results: The study population was divided into two equal groups of 417 people each. Honey significantly reduced the overall symptom score at Day 5 (p<0.001) in the honey group compared with the reference group, according to the ANOVA test, the significant variables are age, presence of associated diseases, duration of illness, number of consultations for respiratory episodes and current smoking status, the present study also shows that non consumption of honey OR = 15.09 [10.26-22.17], high symptom score at D1 OR = 3.85 [2.37-5.39], frequency of nocturnal cough OR = 4.26 [1.65-10.9], frequency of diurnal cough OR = 3.34 [1.5-7.4], duration of illness OR = 7.12 [3.4-14.6] and type of cough OR = 1.5 [1.04-2.2] were the determinants of high symptom score at Day 5. Conclusions: Honey was effective in relieving symptoms associated with ARI and may be suggested as an adjuvant treatment in adults.

Alterations of pathogen transmission patterns and attenuated immune stimulation might be the cause of increased adult respiratory infections cases in 2023, results from a multi-center study in mainland China

BackgroundSeveral respiratory infections outbreaks have been observed in mainland China after reduction of non-pharmaceutical interventions. Other countries have seen increases in respiratory infections outside typical seasons post-COVID-19, warranting investigation into underlying causes. MethodsWe established monitoring networks for suspected respiratory infection in 14 tertiary hospitals nationwide. PCR for SARS-CoV-2, influenza A and B were performed on 3708 respiratory specimens and deep sequencing were conducted to identify co-infections or newly emerging microbes in 2023. Viral evolutionary analysis was completed. We retrospectively detected serum antibody level for various respiratory pathogens from 4324 adults without respiratory infections over 7 years to observe its dynamic curves. FindingsSARS-CoV-2 and influenza A were the main pathogens during outbreaks in 2023, bacterial-virus and bacterial-bacterial co-infections were most detected, but community co-infections didn't significantly increase pneumonia incidence. Different SARS-CoV-2 and influenza variants were present in different outbreaks, and no novel pathogens were found. The epidemiological patterns of influenza A, COVID-19 and etc. were altered, exhibiting characteristics of being "staggered" compared to most global regions, and potentially led to "overlapping prevalence". Binding antibody testing showed regular fluctuation, without significant decrease against common respiratory pathogens in adults. Influenza A antibody stimulation was attenuated during the 2023 outbreak. Conclusions"Misaligned" alteration in seasonal respiratory disease patterns possibly caused combined epidemics, leading to cases spike in China, 2023. In adults, antibody levels didn't show significant decline, but reduced immune response to influenza during 2020–2023 emphasizes the need for consistent vaccination during pandemics.

Acute Respiratory Infection in Adults

Acute Respiratory Infection in Adults

Clinical-epidemiological characterization and etiological agents of severe acute respiratory infections in adults in Paraguay

Clinical-epidemiological characterization and etiological agents of severe acute respiratory infections in adults in Paraguay

Respiratory Syncytial Virus Sequelae Among Adults in High-Income Countries: A Systematic Literature Review and Meta-analysis.

Respiratory syncytial virus (RSV) can cause severe respiratory infections in adults; however, information on associated sequelae is limited. This systematic literature review aimed to identify sequelae in adults within 1year following RSV-related hospitalization or resolution of acute infection. Studies were identified from Embase, MEDLINE, LILACS, SciELO, and grey literature. Random-effects meta-analyses using restricted maximum likelihood were used to calculate the proportions and relative risks of sequelae in patients with RSV compared with controls (patients with RSV-negative influenza-like illness, influenza, and parainfluenza) per follow-up period, population, and treatment setting, where possible. Twenty-one relevant studies covering the period from 1990 to 2019 were included. Among the general population, the most frequent clinical sequela was sustained function loss (33.5% [95%CI 27.6-39.9]). Decline in lung function and cardiovascular event or congestive heart failure were also identified. Utilization sequelae were readmission (highest at > 6months after discharge) and placement in a skilled nursing facility. The only subpopulation with data regarding sequelae was transplant patients. Among lung transplant patients, the most frequently reported clinical sequelae were decline in lung function, followed by graft dysfunction and bronchiolitis obliterans syndrome. Pooled relative risks were calculated for the following sequela with controls (primarily influenza-positive patients): cardiovascular event (general population) and pulmonary impairment (hematogenic-transplant patients) both 1.4 (95%CI 1.0-2.0) and for readmission (general population) 1.2 (95%CI 1.1-1.3). Although less data are available for RSV than for influenza or other lower respiratory tract infections, RSV infection among adults is associated with medically important sequelae, with a prevalence similar to other respiratory pathogens. RSV sequelae should be included in disease burden estimates.

Environmental Determinants and Hygiene Habits Related to the Development of Acute Respiratory Infections in Adults Attending P/s OPC, León III Quarter, 2023

Environmental Determinants and Hygiene Habits Related to the Development of Acute Respiratory Infections in Adults Attending P/s OPC, León III Quarter, 2023

Exposure to air pollution and risk of respiratory tract infections in the adult Danish population—a nationwide study

ObjectivesThe association between air pollution and risk of respiratory tract infection (RTI) in adults needs to be clarified in settings with low to moderate levels of air pollution. We investigated this in the Danish population between 2004 and 2016. MethodsWe included 3 653 490 persons aged 18–64 years in a nested case-control study. Exposure was defined as the average daily concentration at the individual's residential address of CO, NOX, NO2, O3, SO2, NH3, PPM2.5, black carbon, organic carbon, mineral dust, sea salt, secondary inorganic aerosols, SO42-, NO3-, NH4+, secondary organic aerosols, PM2.5, and PM10 during a 3-month exposure window. RTIs were defined by hospitalization for RTIs. Incidence rate ratios (IRRs) and 95% CIs were estimated comparing highest with lowest decile of exposure using conditional logistic regression models. ResultsIn total, 188 439 incident cases of RTI were identified. Exposure to most air pollutants was positively associated with risk of RTI. For example, NO2 showed an IRR of 1.52 (CI: 1.48–1.55), and PM2.5 showed an IRR of 1.45 (CI: 1.40–1.50). In contrast, exposure to sea salt, PM10, NH3, and O3 was negatively associated with a risk of RTIs. DiscussionIn this nationwide study comprising adults, exposure to air pollution was associated with risk of RTIs and subgroups hereof. Sea salt, PM10, NH3, and O3 may be proxies for rural areas, as the levels of these species in Denmark are higher near the western coastlines and/or in rural areas with fewer combustion sources.

Revitalizing hope for older adults: The use of the novel Arexvy for immunization against respiratory syncytial virus.

Respiratory syncytial virus (RSV), an RNA virus of the family Paramyxoviridae, is the most common cause of respiratory tract diseases, including upper and lower respiratory tract infections in adults. Researchers worldwide have been working for decades to develop an RSV vaccine that is both safe and cost-effective. This correspondence aims to highlight the recent breakthroughs in the immunization against RSV for older adults (60 years and above), encompassing the newly sanctioned prophylactic agent by the FDA, drawing attention to its side effects that need to be taken care of and providing clear recommendations to maximize the potential influence of these advancements on RSV-related diseases globally. We did a literature search on RSV among older adults and its treatment on PubMed, Google Scholar, ResearchGate and FDA databases within 10 years. Keywords used for our search were; "Respiratory Syncytial Virus," "Older adults," "FDA," "Arexvy," and "Immunization." We found approximately 6000-10,000 lives and 60,000-160,000 hospital admissions among adults aged 65 years and older each year in the world, especially in the United States of America. Currently, there is no vaccine or targeted treatment for RSV for the most affected individuals, that is, the older adults, who are given supportive care. Recently, the USA- Food and Drug Administration (FDA) approved Arexvy (a recombinant subunit RSV vaccine) based on its encouraging results demonstrating acceptable safety and efficacy in a large-scale multi-centered Phase 3 trial. Authorization of Arexvy, although a breakthrough in the field of research, needs to be approached with a blend of optimism tempered by caution. Robust studies, including large-scale randomized controlled trials, prospective cohort studies and systematic reviews and meta-analyses, need to be conducted to ascertain its safety and efficacy.

Household Air Pollution: A Dire Need Of Awareness In Pakistan.

Dear Editor, Household Air Pollution [HAP] has proven to be associated with an increased risk of acquiring asthma, lung cancer, pulmonary tuberculosis, and acute respiratory infections in adults and children, along with Chronic Obstructive Pulmonary Disease [COPD], cerebrovascular disease, ischemic heart disease, low birth weight, and stillbirth [1]. This pollution is caused primarily by the absence of clean fuels, which includes electricity, biogas, natural gas, liquefied petroleum gas (LPG), solar, or alcohol fuels. Owing to the absence of clean fuels, individuals resort to the use of biomass to meet their needs, exposing themselves to the detrimental effects of biomass usage. Unfortunately, Pakistan is one of the worst-faring victims of this predicament. As of 2020, only 49.3% of Pakistanis primarily relied on clean fuels and technologies for cooking [2]. With only 26% of rural areas having access to clean fuels, traditional, inefficient three-stone stoves for biomass combustion are typical in rural areas[2][3]. Such stoves expel poisonous gasses, including Nitrogen oxides, Carbon monoxide, and formaldehyde, in addition to several toxic organic compounds depending on the type of biomass used, all detrimental to human health [4]. In urban areas, especially in winter, widespread gas shortages are prevalent, restricting an unknown number of citizens to biomass combustion for their day-to-day purposes. In both scenarios, the harms of HAP are imminent. Unfortunately, using gas stoves in poorly ventilated areas also shows milder effects of HAP [5]. Alarmingly, despite the adverse impact and the high prevalence of HAP, the matter remains neglected, with only very few studies connecting the above-stated health risks with the Pakistani population, evaluating the burden Pakistan bears because of HAP, and assessing the correct strategies for intervention. Such studies would result in implementing specific research-backed mitigation strategies customized to be specifically applicable to different socioeconomic backgrounds and regions of Pakistan, for example, efficient ventilatory systems relevant to Pakistani houses designed to reduce HAP. In the meantime, examples of general policies include, but are not limited to, television advertisements, awareness drives, and allotting larger budgets towards cleaner fuel provision. For people utilizing primitive three-stone stoves, a plancha stove, comprising simply a stove and a chimney, can also be provided. The usage of such stoves is associated with a significantly reduced exposure to HAP [6]. Individually, when operating stoves for any purpose, it is crucial to prioritize ventilation. ---Continue

Virucidal activity of oral, hand, and surface disinfectants against respiratory syncytial virus

Respiratory syncytial virus (RSV) is known as a major cause of respiratory tract infection in adults and children. Human to human transmission occurs via droplets as well as direct and indirect contact (e.g. contaminated surfaces or hands of medical staff). Therefore, applicable hygiene measures and knowledge about viral inactivation are of utmost importance. Here, we evaluated the virucidal efficacy of oral rinses specifically designed for children, WHO-recommended hand rub formulations and ethanol as well as 2-propanol against RSV in a quantitative suspension test (EN14476). Furthermore, we assessed the stability of RSV on stainless steel discs and investigated its inactivation by different surface disinfectants (EN16777). We observed that all tested oral rinses except one reduced infectious viral titres to the lower limit of quantification. The two WHO-recommended hand rub formulations as well as 30% ethanol and 2-propanol completely abolished the detection of infectious virus. Infectious RSV could still be recovered after several days on stainless steel discs. However, RSV could efficiently be inactivated by all tested surface disinfectants based on alcohol, aldehyde, or hydrogen peroxide. In conclusion, oral rinses, all tested hand rub formulations as well as surface inactivation reagents were sufficient for RSV inactivation in vitro.

Evaluation of SARS-CoV-2 Mother-to-Child Vertical Transmission: Prospective and Observational Study

Abstract Objective The COVID-19 pandemic was declared a pandemic and a global health emergency by the World Health Organization (WHO) on March 11, 2020. COVID-19 infection is the most common cause of life-threatening acute respiratory tract infection in adults and older people but more mildly in the childhood age group. While the pandemic continues, there is no clear information about the vertical transmission of COVID-19 infection from the mother to the baby. Methods In our study, we aimed to examine vertical virus transmission (breast milk, amniotic fluid, placenta) in pregnant women with COVID-19 infection and to examine the demographic, clinical, and laboratory characteristics of these infants. Our prospective and observational study was conducted in our hospital between March 1, 2020 and July 31, 2021. Results During the study period, a total of 24 infants were included. All infants were admitted to the neonatal intensive care unit for postnatal follow-up. The virus was not detected in breast milk or amniotic fluids by the SARS-COV-2 reverse transcription polymerase chain reaction (RT-PCR) test, and no evidence of vertical transmission was found. Conclusion In our study, no life-threatening complication was found in the babies of mothers infected with COVID-19 at birth. Babies born to mothers with COVID-19 infection did not develop any system findings that required specific treatment.

Oral and gut microbial biomarkers of susceptibility to respiratory tract infection in adults: A feasibility study

We conducted a feasibility cohort study which aimed to recruit and retain adults from the community to collect saliva (oral) and stool (gut) samples at three time points, at the start of the study (baseline), during a respiratory tract infection (RTI) and post-RTI. Community RTIs place a huge burden on health care services, and a non-invasive microbial diagnostic tool to predict the most vulnerable to respiratory infection would be ideal. To this aim, we analysed oral-gut baseline samples comparing those who reported RTI symptoms to those who remained healthy throughout the study for microbial biomarkers of respiratory susceptibility. Amplicon sequence variants (ASV) were identified by 16S sequence profiling to reveal oral-gut microbes. Reverse transcriptase-polymerase chain reaction (RT-PCR) was applied to target common respiratory microbes. Two general practices were recruited, and the participant recruitment rate was 1.3%. A total of 40 adult participants were retained, of which 19 acquired an RTI whereas 21 remained healthy. In healthy baseline oral and gut samples, ASVs from participants with RTI symptoms compared to those who remained healthy were similar with a high relative abundance of Streptococcus sp., and Blautia sp., respectively. Linear discriminant analysis effect size (LEfSe) revealed baseline oral microbes differed, indicating participants who suffered RTI symptoms had enhanced Streptococcus sobrinus and Megamonas sp., and depletion of Lactobacillus salivarius, Synergistetes, Verrucomicrobia and Dethiosulfovibrio. Furthermore, a random forest model ranked Streptococcus (4.13) as the highest mean decrease in accuracy (MDA) and RT-PCR showed a higher level of carriage of coagulase-negative Staphylococcus. Baseline core gut microbes were similar in both participant groups whereas LEfSe analysis revealed enhanced Veillonella, Rikenellaceae, Enhydobacteria, Eggerthella and Xanthomonsdales and depleted Desulfobulbus and Coprobacillus. Sutterella (4.73) had a high MDA value. Overall, we demonstrated the feasibility of recruiting and retaining adult participants from the community to provide multiple biological samples for microbial profiling. Our analyses identified potential oral-gut microbial biomarkers of respiratory infection susceptibility in otherwise healthy participants.

Host test based on tumor necrosis factor-related apoptosis-inducing ligand, interferon gamma-induced protein-10 and C-reactive protein for differentiating bacterial and viral respiratory tract infections in adults: diagnostic accuracy study

ObjectivesTo assess the performance of a test (called BV), integrating the blood levels of three immune proteins into a score, to differentiate bacterial from viral infection among adults with suspected lower respiratory tract infection (LRTI). MethodsProspective diagnostic accuracy study, enrolling febrile adults >18 years with LRTI signs or symptoms for less than 7 days presenting to several hospitals' emergency departments in Israel. The main exclusion criterion was immunodeficiency. Reference standard diagnosis (bacterial/viral/indeterminate) was based on three experts independently reviewing comprehensive patient data including follow-up data. BV generated three results: viral infection or other nonbacterial condition (0 ≤ score < 35), equivocal (35 ≤ score ≤ 65) and bacterial infection including co-infection (65 < score ≤ 100). BV performance was assessed against the reference standard with indeterminate reference standard and equivocal BV cases removed. ResultsOf 490 enrolled patients, 415 met eligibility criteria (median age 56 years, interquartile range 35). The reference standard classified 104 patients as bacterial, 210 as viral and 101 as indeterminate. BV was equivocal in 9.6% (30/314). Excluding indeterminate reference standard diagnoses and equivocal BV results, BV's sensitivity for bacterial infection was 98.1% (101/103; 95% confidence interval 95.4–100), specificity 88.4% (160/181; 83.7–93.1) and negative predictive value 98.8% (160/162; 97.1–100). DiscussionBV exhibited high diagnostic performance for febrile adults with suspected LRTI among patients with reference standard diagnoses of bacterial or viral LRTI.

Human Metapneumovirus Reinfection in Aged Mice Recapitulates Increased Disease Severity in Elderly Humans Infected with Human Metapneumovirus.

Human metapneumovirus (HMPV) is a leading cause of respiratory infection in adults >65 y. Nearly all children worldwide are seropositive for HMPV by age 5 y, but reinfections occur throughout life, and there is no licensed vaccine. Recurrent HMPV infection is mild and self-resolving in immunocompetent individuals. However, elderly individuals develop severe respiratory disease on HMPV reinfection that leads to a high risk for morbidity and mortality. In this study, we developed a mouse model to mirror HMPV reinfection in elderly humans. C57BL/6J mice were infected with HMPV at 6-7 wk old, aged in-house, and rechallenged with high-dose virus at 70 wk. Aged rechallenged mice had profound weight loss similar to primary infected mice, increased lung histopathology, and accumulated cytotoxic CD8+CD44+CD62L-CD69+CD103+ memory cells despite having undetectable lung virus titer. When aged mice 14 mo postinfection (p.i.) or young mice 5 wk p.i. were restimulated with HMPV cognate Ag to mimic epitope vaccination, aged mice had an impaired CD8+ memory response. Convalescent serum transfer from young naive or 5 wk p.i. mice into aged mice on day of infection did not protect. Aged mice vaccinated with UV-inactivated HMPV also exhibited diminished protection and poor CD8+ memory response compared with young mice. These results suggest aged individuals with HMPV reinfection have a dysregulated CD8+ memory T cell response that fails to protect and exacerbates disease. Moreover, aged mice exhibited a poor memory response to either epitope peptide or UV-inactivated vaccination, suggesting that aged CD8+ T cell dysfunction presents a barrier to effective vaccination strategies.