Lower airway microbiota compositions differ between influenza, COVID-19 and bacteria-related acute respiratory distress syndromes.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is responsible for 400,000 deaths annually worldwide. Few improvements have been made despite five decades of research, partially because ARDS is a highly heterogeneous syndrome including various types of aetiologies. Lower airway microbiota is involved in chronic inflammatory diseases and recent data suggest that it could also play a role in ARDS. Nevertheless, whether the lower airway microbiota composition varies between the aetiologies of ARDS remain unknown. The aim of this study is to compare lower airway microbiota composition between ARDS aetiologies, i.e. pulmonary ARDS due to influenza, SARS-CoV-2 or bacterial infection. METHODS: Consecutive ARDS patients according to Berlin's classification requiring invasive ventilation with PCR-confirmed influenza or SARS-CoV-2 infections and bacterial infections (> 105 CFU/mL on endotracheal aspirate) were included. Endotracheal aspirate was collected at admission, V3-V4 and ITS2 regions amplified by PCR, deep-sequencing performed on MiSeq sequencer (Illumina®) and data analysed using DADA2 pipeline. RESULTS: Fifty-three patients were included, 24 COVID-19, 18 influenza, and 11 bacterial CAP-related ARDS. The lower airway bacteriobiota and mycobiota compositions (ß-diversity) were dissimilar between the three groups (p = 0.05 and p = 0.01, respectively). The bacterial α-diversity was significantly lower in the bacterial CAP-related ARDS group compared to the COVID-19 ARDS group (p = 0.04). In contrast, influenza-related ARDS patients had higher lung mycobiota α-diversity than the COVID-19-related ARDS (p = 0 < 01). CONCLUSION: Composition of lower airway microbiota (both microbiota and mycobiota) differs between influenza, COVID-19 and bacterial CAP-related ARDS. Future studies investigating the role of lung microbiota in ARDS pathophysiology should take aetiology into account.

Impacto de la pandemia en varias enfermedades infecciosas con patrones epidemiológicos distintos de estacionalidad, transmisión y edad / mpact of the pandemic on various infectious diseases with different epidemiological patterns of seasonality, transmission and age

Fundamentos: la pandemia de la covid-19 ha tenido un fuerte impacto sobre otras enfermedades infecciosas. El objetivo de este trabajo fue analizar los cambios epidemiológicos acaecidos durante la pandemia en ocho enfermedades infecciosas con patrones epidemiológicos distintos: la gripe; virus respiratorio sincitial; rotavirus; neumococo; campylobacter; salmonella no tifoidea; gonococia; herpes zóster.métodos: a partir de la red de vigilancia microbiológica, se trazó la serie temporal de casos desde enero de 2017 a marzo de 2023. Se distinguieron tres periodos: prepandemia (referencia), pandemia e inicio de la pospandemia. Se analizó la distribución por edad y sexo en esos periodos. Se calcularon las tasas de incidencia y las razones de tasas (rt). Se estimaron esas rt globales y sus intervalos de confianza al 95% por cada año de edad en menores de cinco años. Resultados: se encontraron diferencias estadísticamente significativas en el impacto que la pandemia tuvo en cada una de esas enfermedades. Algunas, tras un periodo de silencio epidémico, revelaron un repunte intenso pospandémico. Incrementaron la rt global postpandémica la gripe (2,4), vrs (1,9) y gonococia (3,1); recuperó su nivel prepandémico el rotavirus (1,07); y disminuyeron el neumococo (0,84), campylobacter (0,83) y salmonella (0,60). En menores de cinco años, los patrones fueron específicos y hete-rogéneos para cada enfermedad.conclusiones: el impacto de la pandemia es muy diferente en estas enfermedades. Las infecciones víricas estacionales pediá-tricas y de transmisión respiratoria son las que más se ven afectadas, pero con patrones de recuperación de la normalidad distintos. Las infecciones bacterianas gastrointestinales sufren menos variaciones, salvo el rotavirus. La gonococia no interrumpe su tendencia al aumento avistada ya en la prepandemia. El herpes zóster muestra un ligero incremento pospandémico. Se han estudiado varias enfermedades con distinto patrón epidemiológico durante un periodo suficiente para observar cómo se produce la salida de la fase aguda de la pandemia.(AU)

Background: the covid-19 pandemic has had a strong impact on other infectious diseases. The aim of this paper was to analyze the epidemiological changes that occurred during the pandemic in eight infectious diseases with different epidemiological patterns: influenza, respiratory syncytial virus, rotavirus, pneumococcus, campylobacter, non-typhoid salmonella, gonorrhea and herpes zoster.methods: from the microbiological surveillance network, the time series of cases was traced from january 2017 to march 2023. Three periods were distinguished: reference, pandemic and beginning of the post-pandemic. The distribution by age and sex in these periods was analyzed. Incidence rates and rate ratios (rr) were calculated. These rrs and their 95% confidence intervals were estimated overall and by year of age in children under five years of age. Results: statistically significant differences were found in the impact that the pandemic had on each of these diseases. Some, after a period of epidemic silence, have revealed an intense post-pandemic rebound. The post-pandemic global rt increased for influenza (2.4), rsv (1.9) and gonorrhea (3.1); rotavirus recovered its pre-pandemic level (1.07); and pneumococcus (0.84), campylobacter (0.83) and salmonella (0.60) decreased. In children under 5 years of age, the patterns were specific and heterogeneous for each disease.conclusions: the impact of the pandemic is very different in these diseases. Pediatric and respiratory-transmitted seasonal viral infections are the ones that are most affected, but with different patterns of recovery to normality. Gastrointestinal bacterial infections suffer fewer variations, except for rotavirus. Gonorrhea do not interrupt its increasing trend seen in the pre-pandemic. Shingles show a slight post-pandemic increase. Several diseases with different epidemiological patterns have been studied for a sufficient period to observe how the acute phase of the pandemic emerges.(AU)

Impacto y características de la gripe nosocomial a lo largo de 10 temporadas en un hospital universitario de tercer nivel / Impact and characteristics of hospital-acquired influenza over 10 seasons in a third-level university hospital

Objetivos: Analizar las características de los pacientes con gripe nosocomial, compararlas con las de los enfermos con diagnóstico de gripe comunitaria para estudiar posibles diferencias e identificar posibles factores de riesgo asociados a este tipo de gripe. Pacientes y métodos: Estudio observacional, transversal y retrospectivo de los pacientes hospitalizados con diagnóstico microbiológico de gripe en un hospital universitario de tercer nivel durante 10 temporadas, de 2009 a 2019. Se definió como gripe nosocomial aquella infección cuyos síntomas comenzaron 72 h después del ingreso hospitalario y se analizó su incidencia, características y consecuencias. Resultados: Se incluyó a un total de 1.260 pacientes hospitalizados con diagnóstico microbiológico de gripe, de los cuales 110 (8,7%) fueron nosocomiales. Los pacientes con gripe adquirida en el hospital eran más jóvenes (71,74±16,03 años; p=0,044), tuvieron una estancia hospitalaria mayor (24,25±20,25 días; p<0,001), tenían con mayor frecuencia antecedentes de enfermedades pulmonares crónicas (p=0,010), inmunodeficiencias (p<0,001) y se asociaron con mayor desarrollo de sobreinfección bacteriana (p<0,001), distrés respiratorio (p=0,003) e ingreso en la unidad de cuidados intensivos (UCI) (p<0,001). En el análisis por regresión logística multivariante se identificaron como factores de riesgo independientes: inmunodeficiencia (ORa=2,33; IC 95%: 1,47-3,60); ingreso en UCI (ORa=4,29; IC 95%: 2,23-10,91); desarrollo de sobreinfección bacteriana (ORa=1,64; IC 95%: 1,06-2,53) y de distrés respiratorio (ORa=3,88; IC 95%: 1,23-12,23).Conclusiones: La gripe nosocomial es más frecuente en los pacientes con antecedentes de inmunodeficiencia. Además, los enfermos con gripe hospitalaria tienen un riesgo aumentado de sobreinfección bacteriana, ingreso en UCI y desarrollo de distrés respiratorio.(AU)

Objectives: To analyze the characteristics of patients with nosocomial flu, to compare them with patients with community-acquired influenza to study possible differences and to identify possible risk factors associated with this type of flu. Patients and methodsObservational, cross-sectional and retrospective study of hospitalized patients with a microbiological confirmation of influenza in a third-level university hospital over 10seasons, from 2009 to 2019. Nosocomial influenza was defined as that infection whose symptoms began 72h after hospital admission, and its incidence, characteristics and consequences were further analyzed. Results: A total of 1260 hospitalized patients with a microbiological diagnosis of influenza were included, which 110 (8.7%) were nosocomial. Patients with hospital-acquired influenza were younger (71.74±16.03 years, P=0.044), had a longer hospital stay (24.25±20.25 days, P<0.001), had more frequently a history of chronic pulmonary pathologies (P=0.010), immunodeficiency (P<0.001), and were associated with greater development of bacterial superinfection (P<0.001), respiratory distress (P=0.003), and admission to the intensive care unit (ICU) (P<0.001). In the multivariate logistic regression analysis, the following characteristics were identified as independent risk factors: immunodeficiency (ORa=2.33; 95% CI: 1.47-3.60); ICU admission (ORa=4.29; 95% CI: 2.23-10.91); bacterial superinfection (ORa=1.64; 95% CI: 1.06-2.53) and respiratory distress (ORa=3.88; 95% CI: 1.23-12.23). Conclusions: Nosocomial influenza is more common in patients with a history of immunodeficiency. In addition, patients with hospital-acquired influenza had an increased risk of bacterial superinfection, admission to the ICU, and development of respiratory distress.(AU)

Efficacy and effectiveness of influenza vaccination in healthy children. A review of current evidence / Eficacia y efectividad de la vacunación frente a la gripe en niños sanos. Una revisión de la evidencia actual

Influenza is common in healthy children and adolescents and is associated with a high rate of hospitalization in this group, especially for those <5 years. Although the WHO has recommended vaccination in children under 5 years of age since 2012, it is really implemented in few countries today. The aim of this paper was to review the available evidence on the efficacy/effectiveness of influenza vaccination in healthy children <18 years of age through a non-systematic search of studies conducted between 2010 and 2020. Despite the high variability in results due to differences in design, vaccine type and season included in the 41 selected studies, statistically significant studies show efficacy values for the influenza vaccine of between 25.6% and 74.2%, and effectiveness from 26% to 78.8%. Although a systematic review would be necessary to corroborate the evidence, this review suggests that paediatric vaccination is generally an effective measure for preventing influenza in healthy children in line with international organisms’ recommendations.(AU)

La gripe tiene una elevada incidencia en niños y adolescentes sanos, y se asocia a una alta tasa de hospitalización, especialmente en los < 5 años. Desde 2012, la Organización Mundial de la Salud recomienda la vacunación en < 5 años, pero pocos países aplican hoy esta recomendación. El objetivo de este documento es revisar la evidencia disponible sobre la eficacia/efectividad de la vacunación antigripal en niños sanos < 18 años mediante una búsqueda no sistemática de estudios entre 2010-2020. A pesar de la gran variabilidad en los resultados debido a las diferencias de diseño, tipo de vacuna y temporada incluidos en los 41 estudios seleccionados, aquellos con significación estadística muestran valores de eficacia para la vacuna antigripal del 25,6% y al 74,2%, y de efectividad del 26% al 78,8%. Aunque sería necesaria una revisión sistemática para corroborar la evidencia, esta revisión sugiere que la vacunación pediátrica es globalmente una medida eficaz/efectiva para prevenir la gripe en niños sanos, en línea con las recomendaciones de organismos internacionales.(AU)

Microbiota composition in the lower respiratory tract is associated with severity in patients with acute respiratory distress by influenza.

Several factors are associated with the severity of the respiratory disease caused by the influenza virus. Although viral factors are one of the most studied, in recent years the role of the microbiota and co-infections in severe and fatal outcomes has been recognized. However, most of the work has focused on the microbiota of the upper respiratory tract (URT), hindering potential insights from the lower respiratory tract (LRT) that may help to understand the role of the microbiota in Influenza disease. In this work, we characterized the microbiota of the LRT of patients with Influenza A using 16S rRNA sequencing. We tested if patients with different outcomes (deceased/recovered) and use of antibiotics differ in their microbial community composition. We found important differences in the diversity and composition of the microbiota between deceased and recovered patients. In particular, we detected a high abundance of opportunistic pathogens such as Granulicatella, in patients either deceased or with antibiotic treatment. Also, we found antibiotic treatment correlated with lower diversity of microbial communities and with lower probability of survival in Influenza A patients. Altogether, the loss of microbial diversity could generate a disequilibrium in the community, potentially compromising the immune response increasing viral infectivity, promoting the growth of potentially pathogenic bacteria that, together with altered biochemical parameters, can be leading to severe forms of the disease. Overall, the present study gives one of the first characterizations of the diversity and composition of microbial communities in the LRT of Influenza patients and its relationship with clinical variables and disease severity.

Eicosanoid-Activated PPARα Inhibits NFκB-Dependent Bacterial Clearance During Post-Influenza Superinfection.

Secondary bacterial infection (superinfection) post influenza is a serious clinical complication often leading to pneumonia and death. Eicosanoids are bioactive lipid mediators that play critical roles in the induction and resolution of inflammation. CYP450 lipid metabolites are anti-inflammatory lipid mediators that are produced at an excessive level during superinfection potentiating the vulnerability to secondary bacterial infection. Using Nanostring nCounter technology, we have defined the targeted transcriptional response where CYP450 metabolites dampen the Toll-like receptor signaling in macrophages. CYP450 metabolites are endogenous ligands for the nuclear receptor and transcription factor, PPARα. Activation of PPARα hinders NFκB p65 activities by altering its phosphorylation and nuclear translocation during TLR stimulation. Additionally, activation of PPARα inhibited anti-bacterial activities and enhanced macrophage polarization to an anti-inflammatory subtype (M2b). Lastly, Ppara-/- mice, which are partially protected in superinfection compared to C57BL/6 mice, have increased lipidomic responses and decreased M2-like macrophages during superinfection.

Associations and recovery dynamics of the nasopharyngeal microbiota during influenza-like illness in the aging population.

Influenza-like illness (ILI), a disease caused by respiratory pathogens including influenza virus, is a major health concern in older adults. There is little information on changes and recovery dynamics of the nasopharyngeal (NP) microbiota of older adults associated with an ILI. Here, we compared the NP microbiota in older adults reporting (n = 240) or not (n = 157) ILI during the 2014-2015 influenza season at different times of the ILI event. A small but significant effect of the ILI was observed on the microbiota community composition and structure when compared to controls and samples collected at recovery. Corynebacterium was negatively associated with ILI and its abundance increased after recovery. Potential pathobionts such as Haemophilus, Porphyromonas and Gemella had higher abundances during acute-ILI. Stability and changes in the NP microbial community showed individual dynamics. Key core genera, Corynebacterium, Moraxella and Dolosigranulum exhibited higher inter-individual variability in acute-ILI, but showed comparable variability to controls after recovery. Participants in the ILI group with higher core microbiota abundances at the acute phase showed higher microbiota stability after recovery. Our findings demonstrate that acute-ILI is associated with alterations in the phylogenetic structure of the NP microbiota in older adults. The variation in the core microbiota suggests imbalances in the ecosystem, which could potentially play a role in the susceptibility and recovery of the NP microbiota after an ILI event.

Bacterial microbiota in upper respiratory tract of COVID-19 and influenza patients.

The upper respiratory tract is inhabited by diverse range of commensal microbiota which plays a role in protecting the mucosal surface from pathogens. Alterations of the bacterial community from respiratory viral infections could increase the susceptibility to secondary infections and disease severities. We compared the upper respiratory bacterial profiles among Thai patients with influenza or COVID-19 by using 16S rDNA high-throughput sequencing based on MiSeq platform. The Chao1 richness was not significantly different among groups, whereas the Shannon diversity of Flu A and Flu B groups were significantly lower than Non-Flu & COVID-19 group. The beta diversity revealed that the microbial communities of influenza (Flu A and Flu B), COVID-19, and Non-Flu & COVID-19 were significantly different; however, the comparison of the community structure was similar between Flu A and Flu B groups. The bacterial classification revealed that Enterobacteriaceae was predominant in influenza patients, while Staphylococcus and Pseudomonas were significantly enriched in the COVID-19 patients. These implied that respiratory viral infections might be related to alteration of upper respiratory bacterial community and susceptibility to secondary bacterial infections. Moreover, the bacteria that observed in Non-Flu & COVID-19 patients had high abundance of Streptococcus, Prevotella, Veillonella, and Fusobacterium. This study provides the basic knowledge for further investigation of the relationship between upper respiratory microbiota and respiratory disease which might be useful for better understanding the mechanism of viral infectious diseases.

Executive summary. Diagnosis, treatment and prophylaxis of influenza virus infection-Consensus statement of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Pediatric Infectious Diseases (SEIP), the Spanish Association of Vaccinology (AEV), the Spanish Society of Family and Community Medicine (SEMFYC) and the Spanish Society of Preventive Medicine, Public Health and Health Management (SEMPSPGS) / Resumen ejecutivo. Diagnóstico, tratamiento y profilaxis de la infección por el virus de la influenza-Consenso comunicado de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), la Sociedad Española de Enfermedades Infecciosas en Pediatría (SEIP), la Asociación de Vacunología (AEV), la Sociedad Española de Medicina Familiar y Comunitaria (SEMFYC) y la Sociedad Española de Medicina Preventiva, Salud Pública y Gestión en Salud (SEMPSPGS)

The influenza virus has accompanied humans since time immemorial, in the form of annual epidemics and occasionalpandemics. It is a respiratory infection with multiple repercussions on people’s lives at an individual and sociallevel, as well as representing a significant burden on the health system. This Consensus Document arises from thecollaboration of various Spanish scientific societies involved in influenza virus infection. The conclusions drawn arebased on the highest quality evidence available in the scientific literature and, failing that, on the opinion of theexperts convened. The Consensus Document addresses the clinical, microbiological, therapeutic, and preventiveaspects (with respect to the prevention of transmission and in relation to vaccination) of influenza, for both adult andpediatric populations. This Consensus Document aims to help facilitate the clinical, microbiological, and preventiveapproach to influenza virus infection and, consequently, to reduce its important consequences on the morbidity andmortality of the population.(AU)

El virus de la gripe ha acompañado al ser humano desde tiempo inmemorial, en forma de epidemias anuales ypandemias ocasionales. Se trata de una infección respiratoria con múltiples repercusiones sobre la vida de las personasa nivel individual y social, así como una importante sobrecarga para el sistema sanitario. El presente documentode consenso surge de la colaboración de diversas sociedades científicas españolas implicadas en la atención de lainfección por virus de la gripe. Las conclusiones extraídas se han fundamentado en las evidencias de mayor calidaddisponibles en la literatura científica y, en su defecto, en la opinión de los expertos convocados. En el documento deconsenso se abordan los aspectos clínicos, microbiológicos, terapéuticos y preventivos (respecto de la prevención dela transmisión y en relación con la vacunación) de la gripe, tanto para población pediátrica como para adultos. Estedocumento de consenso pretende ayudar a facilitar el abordaje clínico, microbiológico y preventivo de la infecciónpor virus de la gripe y, consecuentemente, a disminuir sus importantes consecuencias sobre la morbimortalidad dela población.(AU)

Potential Association Between Dietary Fibre and Humoral Response to the Seasonal Influenza Vaccine.

Influenza vaccination is an effective public health measure to reduce the risk of influenza illness, particularly when the vaccine is well matched to circulating strains. Notwithstanding, the efficacy of influenza vaccination varies greatly among vaccinees due to largely unknown immunological determinants, thereby dampening population-wide protection. Here, we report that dietary fibre may play a significant role in humoral vaccine responses. We found dietary fibre intake and the abundance of fibre-fermenting intestinal bacteria to be positively correlated with humoral influenza vaccine-specific immune responses in human vaccinees, albeit without reaching statistical significance. Importantly, this correlation was largely driven by first-time vaccinees; prior influenza vaccination negatively correlated with vaccine immunogenicity. In support of these observations, dietary fibre consumption significantly enhanced humoral influenza vaccine responses in mice, where the effect was mechanistically linked to short-chain fatty acids, the bacterial fermentation product of dietary fibre. Overall, these findings may bear significant importance for emerging infectious agents, such as COVID-19, and associated de novo vaccinations.

Disease Tolerance during Viral-Bacterial Co-Infections.

Disease tolerance has emerged as an alternative way, in addition to host resistance, to survive viral-bacterial co-infections. Disease tolerance plays an important role not in reducing pathogen burden, but in maintaining tissue integrity and controlling organ damage. A common co-infection is the synergy observed between influenza virus and Streptococcus pneumoniae that results in superinfection and lethality. Several host cytokines and cells have shown promise in promoting tissue protection and damage control while others induce severe immunopathology leading to high levels of morbidity and mortality. The focus of this review is to describe the host cytokines and innate immune cells that mediate disease tolerance and lead to a return to host homeostasis and ultimately, survival during viral-bacterial co-infection.

Antiviral Gene Expression in Young and Aged Murine Lung during H1N1 and H3N2.

Influenza is a respiratory virus that alone or in combination with secondary bacterial pathogens can contribute to the development of acute pneumonia in persons >65 years of age. Host innate immune antiviral signaling early in response to influenza is essential to inhibit early viral replication and guide the initiation of adaptive immune responses. Using young adult (3 months) and aged adult mice infected with mouse adapted H1N1 or H3N2, the results of our study illustrate dysregulated and/or diminished activation of key signaling pathways in aged lung contribute to increased lung inflammation and morbidity. Specifically, within the first seven days of infection, there were significant changes in genes associated with TLR and RIG-I signaling detected in aged murine lung in response to H1N1 or H3N2. Taken together, the results of our study expand our current understanding of age-associated changes in antiviral signaling in the lung.

Diagnostic value of galactomannan test in non-immunocompromised critically ill patients with influenza-associated aspergillosis: data from three consecutive influenza seasons.

To explore the diagnostic value of a galactomannan (GM) detection for non-immunocompromised critically ill patients with influenza-associated aspergillosis (IAA). In this retrospective case-control study, we explored the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic (ROC) curve (AUC) of serum and bronchoalveolar lavage fluid (BALF) GM tests by four detection strategies at different detection time points and with different compound modes. In total, 90 patients were evaluated. The AUC values of the second serum GM test, the first and second BALF GM tests, were significantly higher (0.839 (95% CI 0.716 to 0.963), P < 0.01; 0.904 (95% CI 0.820 to 0.988), P < 0.01; 0.827 (95% CI 0.694 to 0.961), P = 0.043) than that of the first serum GM test (0.548 (95% CI 0.377 to 0.718)). We found that at least one positive result on two consecutive serum GM tests (0.719 (95% CI 0.588 to 0.849)) was the best compared with the first positive test (0.419 (95% CI 0.342 to 0.641), P < 0.01) and positives on two consecutive tests (0.636 (95% CI 0.483 to 0.790), P = 0.014). However, there were no differences between those three detection strategies of BALF GM. The BALF GM test might have a better diagnostic value for IAA in the ICU than the serum GM test. A possible cutoff value of 1.0 to 1.3 was set for GM from BALF specimens for IAA. A single serum GM test is not routinely recommended, but at least one positive result on two consecutive tests appeared to be useful.

Community-acquired bacteraemia in COVID-19 in comparison to influenza A and influenza B: a retrospective cohort study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic in the Netherlands it was noticed that very few blood cultures from COVID-19 patients turned positive with clinically relevant bacteria. This was particularly evident in comparison to the number of positive blood cultures during previous seasonal epidemics of influenza. This observation raised questions about the occurrence and causative microorganisms of bacteraemia in COVID-19 patients, especially in the perspective of the widely reported overuse of antibiotics and the rising rate of antibiotic resistance. METHODS: We conducted a retrospective cohort study on blood culture results in influenza A, influenza B and COVID-19 patients presenting to two hospitals in the Netherlands. Our main outcome consisted of the percentage of positive blood cultures. The percentage of clinically relevant blood cultures, isolated bacteria and 30-day all-cause mortality served as our secondary outcomes. RESULTS: A total of 1331 viral episodes were analysed in 1324 patients. There was no statistically significant difference (p = 0.47) in overall occurrence of blood culture positivity in COVID-19 patients (9.0, 95% CI 6.8-11.1) in comparison to influenza A (11.4, 95% CI 7.9-14.8) and influenza B patients (10.4, 95% CI 7.1-13.7,). After correcting for the high rate of contamination, the occurrence of clinically relevant bacteraemia in COVID-19 patients amounted to 1.0% (95% CI 0.3-1.8), which was statistically significantly lower (p = 0.04) compared to influenza A patients (4.0, 95% CI 1.9-6.1) and influenza B patients (3.0, 95% CI 1.2-4.9). The most frequently identified bacterial isolates in COVID-19 patients were Escherichia coli (n = 2) and Streptococcus pneumoniae (n = 2). The overall 30-day all-cause mortality for COVID-19 patients was 28.3% (95% CI 24.9-31.7), which was statistically significantly higher (p = <.001) when compared to patients with influenza A (7.1, 95% CI 4.3-9.9) and patients with influenza B (6.4, 95% CI 3.8-9.1). CONCLUSIONS: We report a very low occurrence of community-acquired bacteraemia amongst COVID-19 patients in comparison to influenza patients. These results reinforce current clinical guidelines on antibiotic management in COVID-19, which only advise utilization of antibiotics when a bacterial co-infection is suspected.

Proteins produced by Streptococcus species in the lower respiratory tract can modify antiviral responses against influenza virus in respiratory epithelial cells.

Seasonal influenza spreads during winter in temperate countries. Primary viral pneumoniae resulting from aggravation triggers acute respiratory distress syndrome, which is a serious respiratory disorder. We have identified a unique pattern of lung microbiota in patients with the syndrome. In this study, we hypothesized that the unique microbiota was also associated with primary influenza viral pneumoniae. Bacterial culture supernatants of Streptococcus oralis and Streptococcus mitis detected from the patients significantly increased viral replication (maximum 10-fold increase) in lung epithelial cells. Our results suggest that the lung environment microbiota is significantly involved in viral replication.

Impact of COVID-19 in patients with concurrent co-infections: A systematic review and meta-analyses.

The burden and impact of secondary superadded infections in critically ill coronavirus disease 2019 (COVID-19) patients is widely acknowledged. However, there is a dearth of information regarding the impact of COVID-19 in patients with tuberculosis, HIV, chronic hepatitis, and other concurrent infections. This review was conducted to evaluate the consequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in patients with concurrent co-infections based on the publications reported to date. An extensive comprehensive screening was conducted using electronic databases up to 3rd September 2020 after obtaining registration with PROSPERO (CRD420202064800). The observational studies or interventional studies in English, evaluating the impact of SARS-CoV-2 in patients with concurrent infections are included for the meta-analyses. Our search retrieved 20 studies, with a total of 205,702 patients. Patients with tuberculosis (RR = 2.10; 95% CI, 1.75-2.51; I2 = 0%), influenza (RR = 2.04; 95% CI, 0.15-28.25, I2 = 99%) have an increased risk of mortality during a co-infection with SARS-CoV-2. No significant impact is found in people living with HIV (RR = 0.99; 95% CI, 0.82-1.19; I2 = 30%), Chronic hepatitis (RR = 1.15; 95% CI, 0.73-1.81; I2 = 10%). Several countries (Brazil, Paraguay, Argentina, Peru, Colombia, and Singapore) are on the verge of a dengue co epidemic (cumulative 878,496 and 5,028,380 cases of dengue and COVID-19 respectively). The impact of COVID-19 in patients of concurrent infections with either tuberculosis or influenza is detrimental. The clinical outcomes of COVID-19 in HIV or chronic hepatitis patients are comparable to COVID-19 patients without these concurrent infections.

Capillary leakage provides nutrients and antioxidants for rapid pneumococcal proliferation in influenza-infected lower airways.

Influenza A virus (IAV)-related mortality is often due to secondary bacterial infections, primarily by pneumococci. Here, we study how IAV-modulated changes in the lungs affect bacterial replication in the lower respiratory tract (LRT). Bronchoalveolar lavages (BALs) from coinfected mice showed rapid bacterial proliferation 4 to 6 h after pneumococcal challenge. Metabolomic and quantitative proteomic analyses demonstrated capillary leakage with efflux of nutrients and antioxidants into the alveolar space. Pneumococcal adaptation to IAV-induced inflammation and redox imbalance increased the expression of the pneumococcal chaperone/protease HtrA. Presence of HtrA resulted in bacterial growth advantage in the IAV-infected LRT and protection from complement-mediated opsonophagocytosis due to capsular production. Absence of HtrA led to growth arrest in vitro that was partially restored by antioxidants. Pneumococcal ability to grow in the IAV-infected LRT depends on the nutrient-rich milieu with increased levels of antioxidants such as ascorbic acid and its ability to adapt to and cope with oxidative damage and immune clearance.

Probiotics in Treatment of Viral Respiratory Infections and Neuroinflammatory Disorders.

Inflammation is a biological response to the activation of the immune system by various infectious or non-infectious agents, which may lead to tissue damage and various diseases. Gut commensal bacteria maintain a symbiotic relationship with the host and display a critical function in the homeostasis of the host immune system. Disturbance to the gut microbiota leads to immune dysfunction both locally and at distant sites, which causes inflammatory conditions not only in the intestine but also in the other organs such as lungs and brain, and may induce a disease state. Probiotics are well known to reinforce immunity and counteract inflammation by restoring symbiosis within the gut microbiota. As a result, probiotics protect against various diseases, including respiratory infections and neuroinflammatory disorders. A growing body of research supports the beneficial role of probiotics in lung and mental health through modulating the gut-lung and gut-brain axes. In the current paper, we discuss the potential role of probiotics in the treatment of viral respiratory infections, including the COVID-19 disease, as major public health crisis in 2020, and influenza virus infection, as well as treatment of neurological disorders like multiple sclerosis and other mental illnesses.

Evaluation of the Effectiveness of Metabolites of Bacterial Strains Bacillus thuringiensis against Human Influenza Virus A/Aichi/2/68 (H3N2) In Vitro and In Vivo.

The morphological and physiological characteristics of Bacillus thuringiensis strains were analyzed and conditions for obtaining culture fluid with maximum yield of secreted RNases were determined. Zymographic analysis showed that culture fluid of B. thuringiensis strains along with low-molecular-weight (15-20 kDa) RNases contained enzymes with a molecular weight ~55 kDa and their content depended on the duration and conditions of culturing. Preparations based on B. thuringiensis culture fluid were effective against human influenza virus A/Aichi/2/68 (H3N2). In experiments on mice infected with 10 LD50 influenza virus strain A/Aichi/2/68 (H3N2), we selected effective variants of preparations based on culture fluid of B. thuringiensi strains for preventive administration that provided reliable protection of infected animals (protection coefficient 50%), close to that of the reference drug Tamiflu.