Basic host response parameters to classify mortality risk in COVID-19 and community-acquired pneumonia.

Improved phenotyping in pneumonia is necessary to strengthen risk assessment. Via a feasible and multidimensional approach with basic parameters, we aimed to evaluate the effect of host response at admission on severity stratification in COVID-19 and community-acquired pneumonia (CAP). Three COVID-19 and one CAP multicenter cohorts including hospitalized patients were recruited. Three easily available variables reflecting different pathophysiologic mechanisms-immune, inflammation, and respiratory-were selected (absolute lymphocyte count [ALC], C-reactive protein [CRP] and, SpO2/FiO2). In-hospital mortality and intensive care unit (ICU) admission were analyzed as outcomes. A multivariable, penalized maximum likelihood logistic regression was performed with ALC (< 724 lymphocytes/mm3), CRP (> 60 mg/L), and, SpO2/FiO2 (< 450). A total of 1452, 1222 and 462 patients were included in the three COVID-19 and 1292 in the CAP cohort for the analysis. Mortality ranged between 4 and 32% (0 to 3 abnormal biomarkers) and 0-9% in SARS-CoV-2 pneumonia and CAP, respectively. In the first COVID-19 cohort, adjusted for age and sex, we observed an increased odds ratio for in-hospital mortality in COVID-19 with elevated biomarkers altered (OR 1.8, 3, and 6.3 with 1, 2, and 3 abnormal biomarkers, respectively). The model had an AUROC of 0.83. Comparable findings were found for ICU admission, with an AUROC of 0.76. These results were confirmed in the other COVID-19 cohorts Similar OR trends were reported in the CAP cohort; however, results were not statistically significant. Assessing the host response via accessible biomarkers is a simple and rapidly applicable approach for pneumonia.

Adverse outcomes in patients hospitalized with pneumonia at age 60 or more: A prospective multi-centric hospital-based study in India.

BACKGROUND: Limited data exists regarding risk factors for adverse outcomes in older adults hospitalized with Community-Acquired Pneumonia (CAP) in low- and middle-income countries such as India. This multisite study aimed to assess outcomes and associated risk factors among adults aged ≥60 years hospitalized with pneumonia. METHODS: Between December 2018 and March 2020, we enrolled ≥60-year-old adults admitted within 48 hours for CAP treatment across 16 public and private facilities in four sites. Clinical data and nasal/oropharyngeal specimens were collected by trained nurses and tested for influenza, respiratory syncytial virus (RSV), and other respiratory viruses (ORV) using the qPCR. Participants were evaluated regularly until discharge, as well as on the 7th and 30th days post-discharge. Outcomes included ICU admission and in-hospital or 30-day post-discharge mortality. A hierarchical framework for multivariable logistic regression and Cox proportional hazard models identified risk factors (e.g., demographics, clinical features, etiologic agents) associated with critical care or death. FINDINGS: Of 1,090 CAP patients, the median age was 69 years; 38.4% were female. Influenza viruses were detected in 12.3%, RSV in 2.2%, and ORV in 6.3% of participants. Critical care was required for 39.4%, with 9.9% in-hospital mortality and 5% 30-day post-discharge mortality. Only 41% of influenza CAP patients received antiviral treatment. Admission factors independently associated with ICU admission included respiratory rate >30/min, blood urea nitrogen>19mg/dl, altered sensorium, anemia, oxygen saturation <90%, prior cardiovascular diseases, chronic respiratory diseases, and private hospital admission. Diabetes, anemia, low oxygen saturation at admission, ICU admission, and mechanical ventilation were associated with 30-day mortality. CONCLUSION: High ICU admission and 30-day mortality rates were observed among older adults with pneumonia, with a significant proportion linked to influenza and RSV infections. Comprehensive guidelines for CAP prevention and management in older adults are needed, especially with the co-circulation of SARS-CoV-2.

Severe Human Parainfluenza Virus Community- and Healthcare-Acquired Pneumonia in Adults at Tertiary Hospital, Seoul, South Korea, 2010-2019.

The characteristics of severe human parainfluenza virus (HPIV)-associated pneumonia in adults have not been well evaluated. We investigated epidemiologic and clinical characteristics of 143 patients with severe HPIV-associated pneumonia during 2010-2019. HPIV was the most common cause (25.2%) of severe virus-associated hospital-acquired pneumonia and the third most common cause (15.7%) of severe virus-associated community-acquired pneumonia. Hematologic malignancy (35.0%), diabetes mellitus (23.8%), and structural lung disease (21.0%) were common underlying conditions. Co-infections occurred in 54.5% of patients admitted to an intensive care unit. The 90-day mortality rate for HPIV-associated pneumonia was comparable to that for severe influenza virus-associated pneumonia (55.2% vs. 48.4%; p = 0.22). Ribavirin treatment was not associated with lower mortality rates. Fungal co-infections were associated with 82.4% of deaths. Clinicians should consider the possibility of pathogenic co-infections in patients with HPIV-associated pneumonia. Contact precautions and environmental cleaning are crucial to prevent HPIV transmission in hospital settings.

Resurgence of common respiratory viruses in patients with community-acquired pneumonia (CAP)-A prospective multicenter study.

BACKGROUND: Community-acquired pneumonia (CAP) is a major global cause of death and hospitalization. Bacteria or community-acquired viruses (CARVs) cause CAP. COVID-19 associated restrictions effectively reduced the circulation of CARVs. OBJECTIVES: The aim of this study was to analyze the proportion of CARVs in adult patients with CAP from mid-2020 to mid-2023. Specifically, we aimed to compare the rate of influenza virus, SARS-CoV-2, and RSV detections in patients aged 18-59 years and ≥60 years. STUDY DESIGN: We analyze the proportion of 21 community-acquired respiratory viruses (CARVs) and three atypical bacteria (Bordetella pertussis, Legionella pneumophila, and Mycoplasma pneumoniae) in nasopharyngeal swab samples using molecular multiplex methods within the prospective, multicentre, multinational study of the German study Group CAPNETZ. We used stringent inclusion criteria throughout the study. RESULTS: We identified CARVs in 364/1,388 (26.2 %) patients. In detail, we detected SARS-CoV-2 in 210/1,388 (15.1 %), rhino-/enterovirus in 64/1,388 (4.6 %), influenza virus in 23/1,388 (1.6 %) and RSV in 17/1,388 (1.2 %) of all patients. We detected RSV and influenza more frequently in patients ≥60 years, especially in 22/23 compared to the previous season. None of the atypical bacteria were detected. CONCLUSIONS: Beginning in 2023, we demonstrate a re-emergence of CARVs in CAP patients. Effective vaccines or specific antiviral therapies for more than two thirds of the detected viral infections are currently available. High detection rates of vaccine-preventable viruses in older age groups support targeted vaccination campaigns.

Syndromic testing for respiratory pathogens but not National Early Warning Score can be used to identify viral cause in hospitalised adults with lower respiratory tract infections.

BACKGROUND: Community-acquired lower respiratory tract infection (LRTI) is a common reason for hospitalisation. Antibiotics are frequently used while diagnostic microbiological methods are underutilised in the acute setting. OBJECTIVES: We aimed to investigate the relative proportion of viral and bacterial infections in this patient group and explore methods for proper targeting of antimicrobial therapy. METHODS: We collected nasopharyngeal samples prospectively from adults hospitalised with LRTIs during three consecutive winter seasons (2016-2019). Syndromic nasopharyngeal testing was performed using a multiplex PCR panel including 16 viruses and four bacteria. Medical records were reviewed for clinical data. RESULTS: Out of 220 included patients, a viral pathogen was detected in 74 (34%), a bacterial pathogen in 63 (39%), both viral and bacterial pathogens in 49 (22%), while the aetiology remained unknown in 34 (15%) cases. The proportion of infections with an identified pathogen increased from 38% to 85% when syndromic testing was added to standard-of-care testing. Viral infections were associated with a low CRP level and absence of pulmonary infiltrates. A high National Early Warning Score did not predict bacterial infections. CONCLUSIONS: Syndromic testing by a multiplex PCR panel identified a viral infection or viral/bacterial coinfection in a majority of hospitalised adult patients with community-acquired LRTIs.

Impact of viral detection in patients with community-acquired pneumonia: An observational cohort study / Impacto de la detección viral en pacientes con neumonía comunitaria: estudio de cohortes observacional

Purpose The presence of a respiratory virus in patients with community-acquired pneumonia (CAP) may have an impact on the bacterial etiology and clinical presentation. In this study we aimed to assess the role of viral infection in the bacterial etiology and outcomes of patients with CAP. Methods We performed a retrospective study of all adults hospitalized with CAP between November 2017 and October 2018. Patients were classified according to the presence of viral infection. An unvaried and a multivaried analysis were performed to identify variables associated with viral infection and clinical outcomes. Results Overall 590 patients were included. A microorganism was documented in 375 cases (63.5%). A viral infection was demonstrated in 118 (20%). The main pathogens were Streptococcus pneumoniae (35.8%), Staphylococcus aureus (2.9%) and influenza virus (10.8%). A trend to a higher rate of S. aureus (p = 0.06) in patients with viral infection was observed. Patients with viral infection had more often bilateral consolidation patterns (17.8% vs 10.8%, p = 0.04), respiratory failure (59.3% vs 42.8%, p = 0.001), ICU admission (17.8% vs 7%, p = 0.001) and invasive mechanical ventilation (9.3% vs 2.8%, p = 0.003). Risk factors for respiratory failure were chronic lung disease, age >65 years, positive blood cultures and viral infection. Influenza, virus but no other respiratory viruses, was associated with respiratory failure (OR, 3.72; 95% CI, 2.06–6.73). Conclusions Our study reinforces the idea that co-viral infection has an impact in the clinical presentation of CAP causing a more severe clinical picture. This impact seems to be mainly due to influenza virus infection (AU)

Objetivos La presencia de virus respiratorios en pacientes con neumonía adquirida en la comunidad (NAC) puede tener un impacto en la etiología bacteriana y en la presentación clínica. El objetivo de este estudio fue evaluar el papel de la infección viral en la etiología bacteriana y la evolución de los pacientes con NAC. Métodos Realizamos un estudio retrospectivo de todos los adultos hospitalizados con diagnóstico de NAC entre noviembre de 2017 y octubre de 2018. Los pacientes fueron clasificados según la presencia de infección viral. Se realizó un análisis univariado y multivariado para identificar variables asociadas con la infección viral y la evolución clínica. Resultados En total se incluyeron 590 pacientes. Se documentó el microorganismo en 375 casos (63,5%). Se demostró una infección viral en 118 (20%). Los principales patógenos fueron S. pneumoniae (35,8%), S. aureus (2,9%) y virus de la influenza (10,8%). Se observó una tendencia a una mayor tasa de S. aureus (p = 0,06) en pacientes con infección viral. Los pacientes con infección viral tenían con mayor frecuencia patrones de consolidación bilateral (17,8% vs 10,8%; p = 0,04), insuficiencia respiratoria (59,3% vs 42,8%; p = 0,001), ingreso en UCI (17,8% vs 7%; p = 0,001) y necesidad de ventilación mecánica invasiva (9,3% vs 2,8%; p = 0,003). Los factores de riesgo para insuficiencia respiratoria fueron enfermedad pulmonar crónica, edad >65 años, hemocultivos positivos e infección viral. El virus de la influenza, pero ningún otro virus respiratorio, se asoció con insuficiencia respiratoria (OR: 3,72; IC 95%: 2,06-6,73). Conclusiones Nuestro estudio refuerza la idea de que la infección viral tiene un impacto en la presentación clínica de la NAC provocando un cuadro clínico más grave. Este impacto parece deberse principalmente a la infección por el virus de la influenza (AU)

Host protease activity classifies pneumonia etiology.

Community-acquired pneumonia (CAP) has been brought to the forefront of global health priorities due to the COVID-19 pandemic. However, classification of viral versus bacterial pneumonia etiology remains a significant clinical challenge. To this end, we have engineered a panel of activity-based nanosensors that detect the dysregulated activity of pulmonary host proteases implicated in the response to pneumonia-causing pathogens and produce a urinary readout of disease. The nanosensor targets were selected based on a human protease transcriptomic signature for pneumonia etiology generated from 33 unique publicly available study cohorts. Five mouse models of bacterial or viral CAP were developed to assess the ability of the nanosensors to produce etiology-specific urinary signatures. Machine learning algorithms were used to train diagnostic classifiers that could distinguish infected mice from healthy controls and differentiate those with bacterial versus viral pneumonia with high accuracy. This proof-of-concept diagnostic approach demonstrates a way to distinguish pneumonia etiology based solely on the host proteolytic response to infection.

Características radiográficas de la neumonía adquirida en la comunidad en el adulto inmunocompetente hospitalizado según el agente causal / Radiographic characteristics of community-acquired pneumonia in the immunocompetent adult hospitalized according to the etiologic agent

Resumen En la práctica clínica, la radiografía de tórax permite confirmar el diagnóstico y la extensión de la neumonía adquirida en la comunidad (NAC). Objetivos: Examinar las características radiográficas de la NAC según el agente causal y el grado de concordancia interobservador (CI) en la descripción de los hallazgos radiográficos. Métodos: Se evaluaron las radiografías de tórax de 300 pacientes adultos inmunocompetentes hospitalizados por NAC, tres residentes de radiología consignaron el patrón de los infiltrados pulmonares, su localización anatómica y extensión, la presencia de derrame pleural y otros hallazgos radiográficos. Se realizaron cultivos de esputo, hemocultivos, pruebas serológicas y técnicas de biología molecular de hisopado nasofaríngeo para identificar los principales patógenos respiratorios. Resultados: Las manifestaciones clínicas y los hallazgos de la radiografía de tórax fueron similares en las neumonías causadas por diferentes patógenos respiratorios: bacterias clásicas, virus respiratorios y microorganismos atípicos. En las neumonías bacterianas predominó el patrón de relleno alveolar de distribución lobar, en las neumonías vírales y atípicas predominó el patrón intersticial o mixto alvéolo-intersticial con opacidades en vidrio esmerilado. La CI fue satisfactoria (kappa > 0,6) para determinar el patrón principal de los infiltrados pulmonares, su localización anatómica y la presencia de derrame pleural, su localización y extensión. La CI fue moderada (kappa 0,4-0,6) para definir la extensión de la neumonía y detectar signos radiológicos asociados a congestión pulmonar. Conclusión: Los hallazgos de la radiografía de tórax no permitieron identificar con precisión el agente causal de la neumonía, siendo útil en la caracterización de los infiltrados pulmonares y para detectar complicaciones como el derrame paraneumónico.

In a clinical setting the chest radiograph is the reference standard in establishing the diagnosis of community-acquired pneumonia (CAP). Objectives: This study aimed to assess interobserver reliability (IR) of radiographic findings and the relationship to different respiratory pathogens in CAP. Methods: Chest radiographs of 300 immunocompetent adult patients hospitalized with pneumonia, obtained from a database, were reviewed by three residents of radiology without specific clinical information. Main pattern of pulmonary infiltrates, topographic localization, extent of pneumonia, presence of pleural fluid, thickened bronchial walls, lymphadenopathy and air bronchogram were scored. Sputum and blood cultures, serological tests and nasopharyngeal swab for respiratory virus detection by molecular diagnostic techniques were performed to identify the causative pathogen. Results: Clinical manifestations and chest X-ray findings were similar in pneumonias caused by different respiratory pathogens: classic bacteria, respiratory viruses and atypical microorganisms. The alveolar pattern of lobar distribution predominated in bacterial pneumonia; meanwhile, interstitial or mixed alveolar-interstitial pattern with ground glass opacities predominated in viral and atypical pneumonias. IR was fair to good (kappa > 0.6) for determining the main pattern of infiltrates, anatomical location and the presence of pleural effusion, their anatomical location and extension. IR was moderate (kappa 0.4-0.6) for determining the extent of pneumonia and signs of congestive heart failure. Conclusion: Simple features such as main pattern description, anatomical location, identifying the involved lobes and pleural fluid recognition showed fair to excellent interobserver reliability. Chest radiographs was of limited value in predicting the causative pathogen but were of beneficial use to characterize pulmonary infiltrates and to detect complications such as parapneumonic effusion.

Epidemiology and Genetic Analysis of SARS-CoV-2 in Myanmar during the Community Outbreaks in 2020.

We aimed to analyze the situation of the first two epidemic waves in Myanmar using the publicly available daily situation of COVID-19 and whole-genome sequencing data of SARS-CoV-2. From March 23 to December 31, 2020, there were 33,917 confirmed cases and 741 deaths in Myanmar (case fatality rate of 2.18%). The first wave in Myanmar from March to July was linked to overseas travel, and then a second wave started from Rakhine State, a western border state, leading to the second wave spreading countrywide in Myanmar from August to December 2020. The estimated effective reproductive number (Rt) nationwide reached 6-8 at the beginning of each wave and gradually decreased as the epidemic spread to the community. The whole-genome analysis of 10 Myanmar SARS-CoV-2 strains together with 31 previously registered strains showed that the first wave was caused by GISAID clade O or PANGOLIN lineage B.6 and the second wave was changed to clade GH or lineage B.1.36.16 with a close genetic relationship with other South Asian strains. Constant monitoring of epidemiological situations combined with SARS-CoV-2 genome analysis is important for adjusting public health measures to mitigate the community transmissions of COVID-19.

Rapid syndromic PCR testing in patients with respiratory tract infections reduces time to results and improves microbial yield.

Lack of rapid and comprehensive microbiological diagnosis in patients with community acquired pneumonia (CAP) hampers appropriate antimicrobial therapy. This study evaluates the real-world performance of the BioFire FilmArray Pneumonia panel plus (FAP plus) and explores the feasibility of evaluation in a randomised controlled trial. Patients presenting to hospital with suspected CAP were recruited in a prospective feasibility study. An induced sputum or an endotracheal aspirate was obtained from all participants. The FAP plus turnaround time (TAT) and microbiological yield were compared with standard diagnostic methods (SDs). 96/104 (92%) enrolled patients had a respiratory tract infection (RTI); 72 CAP and 24 other RTIs. Median TAT was shorter for the FAP plus, compared with in-house PCR (2.6 vs 24.1 h, p < 0.001) and sputum cultures (2.6 vs 57.5 h, p < 0.001). The total microbiological yield by the FAP plus was higher compared to SDs (91% (162/179) vs 55% (99/179), p < 0.0001). Haemophilus influenzae, Streptococcus pneumoniae and influenza A virus were the most frequent pathogens. In conclusion, molecular panel testing in adults with CAP was associated with a significant reduction in time to actionable results and increased microbiological yield. The impact on antibiotic use and patient outcome should be assessed in randomised controlled trials.

A Tool to Distinguish Viral From Bacterial Pneumonia.

BACKGROUND: Establishing the etiology of community-acquired pneumonia (CAP) in children at admission is challenging. Most of the admitted children with CAP receive antibiotics. We aimed to build and validate a diagnostic tool combining clinical, analytical and radiographic features to differentiate viral from bacterial CAP, and among bacterial CAP, typical from atypical bacteria. METHODS: Design-observational, multi-center, prospective cohort study was conducted in 2 phases. Settings: 24 secondary and tertiary hospitals in Spain. Patients-A total of 495 consecutive hospitalized children between 1 month and 16 years of age with CAP were enrolled. Interventions-A score with 2 sequential steps was built (training set, 70% patients, and validation set 30%). Step 1 differentiates between viral and bacterial CAP and step 2 between typical and atypical bacterial CAP. Optimal cutoff points were selected to maximize specificity setting a high sensitivity (80%). Weights of each variable were calculated with a multivariable logistic regression. Main outcome measures-Viral or bacterial etiology. RESULTS: In total, 262 (53%) children (median age: 2 years, 52.3% male) had an etiologic diagnosis. In step 1, bacterial CAPs were classified with a sensitivity = 97%, a specificity = 48%, and a ROC's area under the curve = 0.81. If a patient with CAP was classified as bacterial, he/she was assessed with step 2. Typical bacteria were classified with a sensitivity = 100%, a specificity = 64% and area under the curve = 0.90. We implemented the score into a mobile app named Pneumonia Etiology Predictor, freely available at usual app stores, that provides the probability of each etiology. CONCLUSIONS: This 2-steps tool can facilitate the physician's decision to prescribe antibiotics without compromising patient safety.

Desmoglein 2 (DSG2) Is A Receptor of Human Adenovirus Type 55 Causing Adult Severe Community-Acquired Pneumonia.

Human adenovirus type 55 (HAdV-B55) is a re-emergent acute respiratory disease pathogen that causes adult community-acquired pneumonia (CAP). Previous studies have shown that the receptor of HAdV-B14, which genome is highly similar with HAdV-B55, is human Desmoglein 2 (DSG2). However, whether the receptor of HAdV-B55 is DSG2 is undetermined because there are three amino acid mutations in the fiber gene between HAdV-B14 and HAdV-B55. Here, firstly we found the 3T3 cells, a mouse embryo fibroblast rodent cell line which does not express human DSG2, were able to be infected by HAdV-B55 after transfected with pcDNA3.1-DSG2, while normal 3T3 cells were still unsusceptible to HAdV-B55 infection. Next, A549 cells with hDSG2 knock-down by siRNA were hard to be infected by HAdV-B3/-B14/-B55, while the control siRNA group was still able to be infected by all these types of HAdVs. Finally, immunofluorescence confocal microscopy indicated visually that Cy3-conjugated HAdV-B55 viruses entered A549 cells by binding to DSG2 protein. Therefore, DSG2 is a major receptor of HAdV-B55 causing adult CAP. Our finding is important for better understanding of interactions between adenoviruses and host cells and may shed light on the development of new drugs that can interfere with these processes as well as for the development of potent prophylactic vaccines.

The impact of the SARS-CoV-2 pandemic on the prevalence of respiratory tract pathogens in patients with community-acquired pneumonia in Germany.

We show a shift in the prevalence of respiratory viral pathogens in community-acquired pneumonia patients during the COVID-19 pandemic. Our data support the efficiency of non-pharmaceutical interventions on virus circulation except for rhinoviruses. The consequences of an altered circulation on subsequent winter seasons remain unclear and support the importance of systematic virological surveillance.

The role of angiopoietin-2 and surfactant protein-D levels in SARS-CoV-2-related lung injury: A prospective, observational, cohort study.

INTRODUCTION: Coronavirus disease-2019 (COVID-19) is a respiratory disease whose clinical manifestation ranges from asymptomatic to severe respiratory failure. The purpose of this study was to investigate the place of serum surfactant-D (SP-D) and angiopoetin-2 (Ang-2) levels in predicting severity of disease in patients diagnosed with COVID-19. METHODS: Sixty-four patients diagnosed with COVID-19 between September 2020 and February 2021, 50 patients diagnosed with community-acquired pneumonia and a 50-member healthy control group were included in the study. Plasma samples and clinical data were collected within 72 h after admission, during hospital stay. Serum SP-D and Ang-2 concentrations were measured using the enzyme-linked immunosorbent assay. RESULTS: SP-D and Ang-2 levels were significantly higher in the mild-moderate pneumonia and severe/critical patient groups compared to the asymptomatic and noncomplicated COVID-19 patients (p < 0.001 for all groups). Serum SP-D and Ang-2 levels of severe-critical COVID-19 patients were significantly higher than CAP patients (p < 0.001). Powerful correlation was present between clinical severity of COVID-19 and SP-D and Ang-2 levels (r = 0.885 p < 0.001 and r = 0.913 p < 0.001, respectively). Cut-off values of 37.7 ng/ml (AUC = 0.763, p < 0.001, 95% confidence interval [CI] = 0.667-0.860) for SP-D and 4208.3 pg/ml (AUC = 0.659, p = 0.004, 95% CI = 0.554-0.763) for Ang-2 were identified as predictors of COVID-19 disease at receiver operating characteristic curve analysis. CONCLUSION: SP-D and Ang-2 are predictive factors in differentiating COVID-19 patients and determining severity of disease. These data may be important for the initiation of treatment in the early stage of the disease in patients with COVID-19.

A prospective observational study of community acquired pneumonia in Kenya: the role of viral pathogens.

BACKGROUND: Lower respiratory tract infections continue to contribute significantly to morbidity and mortality across all age groups globally. In sub-Saharan Africa, many studies of community acquired pneumonia in adults have focused on HIV-infected patients and little attention has been given to risk factors and etiologic agents in an urban area with a more moderate HIV prevalence. METHODS: We prospectively enrolled 77 patients admitted to a 280 bed teaching hospital in Kenya with radiographically confirmed community acquired pneumonia from May 2019 to March 2020. The patients were followed for etiology and clinical outcomes. Viral PCR testing was performed using the FTD respiratory pathogen-21 multiplex kit on nasopharyngeal or lower respiratory samples. Additional microbiologic workup was performed as determined by the treating physicians. RESULTS: A potential etiologic agent(s) was identified in 57% including 43% viral, 5% combined viral and bacterial, 5% bacterial and 4% Pneumocystis. The most common etiologic agent was Influenza A which was associated with severe clinical disease. The most common underlying conditions were cardiovascular disease, diabetes and lung disease, while HIV infection was identified in only 13% of patients. Critical care admission was required for 24, and 31% had acute kidney injury, sometimes in combination with acute respiratory distress or sepsis. CONCLUSION: Viruses, especially influenza, were commonly found in patients with CAP. In contrast to other studies from sub-Saharan Africa, the underlying conditions were similar to those reported in high resource areas and point to the growing concern of the double burden of infectious and noncommunicable diseases.

Metabolomic profiling of microbial disease etiology in community-acquired pneumonia.

Diagnosis of microbial disease etiology in community-acquired pneumonia (CAP) remains challenging. We undertook a large-scale metabolomics study of serum samples in hospitalized CAP patients to determine if host-response associated metabolites can enable diagnosis of microbial etiology, with a specific focus on discrimination between the major CAP pathogen groups S. pneumoniae, atypical bacteria, and respiratory viruses. Targeted metabolomic profiling of serum samples was performed for three groups of hospitalized CAP patients with confirmed microbial etiologies: S. pneumoniae (n = 48), atypical bacteria (n = 47), or viral infections (n = 30). A wide range of 347 metabolites was targeted, including amines, acylcarnitines, organic acids, and lipids. Single discriminating metabolites were selected using Student's T-test and their predictive performance was analyzed using logistic regression. Elastic net regression models were employed to discover metabolite signatures with predictive value for discrimination between pathogen groups. Metabolites to discriminate S. pneumoniae or viral pathogens from the other groups showed poor predictive capability, whereas discrimination of atypical pathogens from the other groups was found to be possible. Classification of atypical pathogens using elastic net regression models was associated with a predictive performance of 61% sensitivity, 86% specificity, and an AUC of 0.81. Targeted profiling of the host metabolic response revealed metabolites that can support diagnosis of microbial etiology in CAP patients with atypical bacterial pathogens compared to patients with S. pneumoniae or viral infections.

Cyclovirus detection in Chilean adults with and without community-acquired pneumonia.

Cycloviruses (CyV) (genus Cyclovirus, family Circoviridae) are nonenveloped DNA viruses. The first report in humans was in 2010 and research has focused only on disease-associated human sample detection. The only HuACyV (CyCV-ChileNPA1, HuACyV10) reported in the Chilean population was in children (3.3%) with an acute respiratory infection. Its detection in respiratory samples from adults, with/without respiratory disease remains unknown. The aim of this study was to detect HuACyV10 in adults with and without respiratory disease. HuACyV10 was studied in nasopharyngeal swabs from 105 hospitalized adults with community-acquired pneumonia (CAP) and 104 adults without respiratory symptoms. Total nucleic acids were extracted, and viral rep and cp gene fragments were amplified by real-time polymerase chain reaction. HuACyV10 was detected in 19.05% adults with CAP and in 0.96% asymptomatic adults, being significantly higher in adult CAP than asymptomatic (n = 1) ones (p = 0.0001). C t values were between 26.7 and 39.6, and the median was 34.1 for rep and 33.8 for the CAP in adults CAP (p = 0.68), and 35.7 and 36.0, respectively, in the asymptomatic case. HuACyV10 detection in CAP adults concentrated in the Autumn-Winter season of the Southern hemisphere. The only asymptomatic adult with HuACyV10 was detected in the Spring-Summer period. In this first report of HuACyV10 in respiratory samples from adults, detection was significantly higher in CAP than in asymptomatic adults. As the sensitivity of both rep and cp genes was similar, both can be applied for detecting HuACyV10. It would be advisable to investigate the pathogenic role of HuACyV10 in adult respiratory infections. ​.

Nucleic Acid-based Testing for Noninfluenza Viral Pathogens in Adults with Suspected Community-acquired Pneumonia. An Official American Thoracic Society Clinical Practice Guideline.

Background: This document provides evidence-based clinical practice guidelines on the diagnostic utility of nucleic acid-based testing of respiratory samples for viral pathogens other than influenza in adults with suspected community-acquired pneumonia (CAP).Methods: A multidisciplinary panel developed a Population-Intervention-Comparison-Outcome question, conducted a pragmatic systematic review, and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: The panel evaluated the literature to develop recommendations regarding whether routine diagnostics should include nucleic acid-based testing of respiratory samples for viral pathogens other than influenza in suspected CAP. The evidence addressing this topic was generally adjudicated to be of very low quality because of risk of bias and imprecision. Furthermore, there was little direct evidence supporting a role for routine nucleic acid-based testing of respiratory samples in improving critical outcomes such as overall survival or antibiotic use patterns. However, on the basis of direct and indirect evidence, recommendations were made for both outpatient and hospitalized patients with suspected CAP. Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was not addressed in the literature at the time of the evidence review.Conclusions: The panel formulated and provided their rationale for recommendations on nucleic acid-based diagnostics for viral pathogens other than influenza for patients with suspected CAP.

Community-Acquired Neonatal SARS-CoV-2 Infection Associated with Neurological Symptoms in Colombia.

INTRODUCTION: The SARS-CoV-2/COVID-19 may produce neurological manifestations, including its occurrence in children, and newborns, which has been little reported so far in newborns with COVID-19. CASE: We present a case in Colombia, of community-acquired neonatal infection of SARS-CoV-2, with suggestive symptoms, such as fever, and showing neurological findings, such as drowsiness, poor suction and mild hypotonia for a short time. DISCUSSION: The clinical manifestations of SARS-COV-2 in neonates are beginning to be described in detail. We report a case of SARS-COV-2-associated neurological compromise in a newborn, with features of drowsiness, poor suction and hypotonia.

Hypergraph learning for identification of COVID-19 with CT imaging.

The coronavirus disease, named COVID-19, has become the largest global public health crisis since it started in early 2020. CT imaging has been used as a complementary tool to assist early screening, especially for the rapid identification of COVID-19 cases from community acquired pneumonia (CAP) cases. The main challenge in early screening is how to model the confusing cases in the COVID-19 and CAP groups, with very similar clinical manifestations and imaging features. To tackle this challenge, we propose an Uncertainty Vertex-weighted Hypergraph Learning (UVHL) method to identify COVID-19 from CAP using CT images. In particular, multiple types of features (including regional features and radiomics features) are first extracted from CT image for each case. Then, the relationship among different cases is formulated by a hypergraph structure, with each case represented as a vertex in the hypergraph. The uncertainty of each vertex is further computed with an uncertainty score measurement and used as a weight in the hypergraph. Finally, a learning process of the vertex-weighted hypergraph is used to predict whether a new testing case belongs to COVID-19 or not. Experiments on a large multi-center pneumonia dataset, consisting of 2148 COVID-19 cases and 1182 CAP cases from five hospitals, are conducted to evaluate the prediction accuracy of the proposed method. Results demonstrate the effectiveness and robustness of our proposed method on the identification of COVID-19 in comparison to state-of-the-art methods.