RESUMO
Recent observational studies suggest that gut microorganisms are involved in the onset and development of coronavirus disease 2019 (COVID-19), but the potential causal relationship behind them remains unclear. Exposure data were derived from the MiBioGen consortium, encompassing 211 gut microbiota (n = 18,340). The outcome data were sourced from the COVID-19 host genetics initiative (round 7), including COVID-19 severity (n = 1,086,211), hospitalization (n = 2,095,324), and susceptibility (n = 2,597,856). First, a two-sample Mendelian randomization (TSMR) was performed to investigate the causal effect between gut microbiota and COVID-19 outcomes. Second, a two-step MR was used to explore the potential mediators and underlying mechanisms. Third, several sensitivity analyses were performed to verify the robustness of the results. Five gut microbes were found to have a potential causality with COVID-19 severity, namely Betaproteobacteria (beta = 0.096, p = 0.034), Christensenellaceae (beta = -0.092, p = 0.023), Adlercreutzia (beta = 0.072, p = 0.048), Coprococcus 1 (beta = 0.089, p = 0.032), Eisenbergiella (beta = 0.064, p = 0.024). Seven gut microbes were found to have a potential causality with COVID-19 hospitalization, namely Victivallaceae (beta = 0.037, p = 0.028), Actinomyces (beta = 0.047, p = 0.046), Coprococcus 2 (beta = -0.061, p = 0.031), Dorea (beta = 0.067, p = 0.016), Peptococcus (beta = -0.035, p = 0.049), Rikenellaceae RC9 gut group (beta = 0.034, p = 0.018), and Proteobacteria (beta = -0.069, p = 0.035). Two gut microbes were found to have a potential causality with COVID-19 susceptibility, namely Holdemanella (beta = -0.024, p = 0.023) and Lachnospiraceae FCS020 group (beta = 0.026, p = 0.027). Multi-omics mediation analyses indicate that numerous plasma proteins, metabolites, and immune factors are critical mediators linking gut microbiota with COVID-19 outcomes. Sensitivity analysis suggested no significant heterogeneity or pleiotropy. These findings revealed the causal correlation and potential mechanism between gut microbiota and COVID-19 outcomes, which may improve our understanding of the gut-lung axis in the etiology and pathology of COVID-19 in the future.
Assuntos
COVID-19 , Microbioma Gastrointestinal , SARS-CoV-2 , COVID-19/microbiologia , COVID-19/virologia , Humanos , Microbioma Gastrointestinal/genética , SARS-CoV-2/genética , Análise da Randomização Mendeliana , Hospitalização , Índice de Gravidade de DoençaRESUMO
The clinical course of COVID-19 is variable and often unpredictable. To test the hypothesis that disease progression and inflammatory responses associate with alterations in the microbiome and metabolome, we analyzed metagenome, metabolome, cytokine, and transcriptome profiles of repeated samples from hospitalized COVID-19 patients and uninfected controls, and leveraged clinical information and post-hoc confounder analysis. Severe COVID-19 was associated with a depletion of beneficial intestinal microbes, whereas oropharyngeal microbiota disturbance was mainly linked to antibiotic use. COVID-19 severity was also associated with enhanced plasma concentrations of kynurenine and reduced levels of several other tryptophan metabolites, lysophosphatidylcholines, and secondary bile acids. Moreover, reduced concentrations of various tryptophan metabolites were associated with depletion of Faecalibacterium, and tryptophan decrease and kynurenine increase were linked to enhanced production of inflammatory cytokines. Collectively, our study identifies correlated microbiome and metabolome alterations as a potential contributor to inflammatory dysregulation in severe COVID-19.
Assuntos
COVID-19 , Citocinas , Disbiose , Microbioma Gastrointestinal , SARS-CoV-2 , Triptofano , Humanos , COVID-19/microbiologia , COVID-19/imunologia , Triptofano/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Citocinas/sangue , Citocinas/metabolismo , Metaboloma , Inflamação , Cinurenina/metabolismo , Cinurenina/sangue , Idoso , AdultoRESUMO
SARS-CoV-2, a severe respiratory disease primarily targeting the lungs, was the leading cause of death worldwide during the pandemic. Understanding the interplay between the oral microbiome and inflammatory cytokines during acute infection is crucial for elucidating host immune responses. This study aimed to explore the relationship between the oral microbiome and cytokines in COVID-19 patients, particularly those with and without sputum production. Saliva and blood samples from 50 COVID-19 patients were subjected to 16S ribosomal RNA gene sequencing for oral microbiome analysis, and 65 saliva and serum cytokines were assessed using Luminex multiplex analysis. The Mann-Whitney test was used to compare cytokine levels between individuals with and without sputum production. Logistic regression machine learning models were employed to evaluate the predictive capability of oral microbiome, salivary, and blood biomarkers for sputum production. Significant differences were observed in the membership (Jaccard dissimilarity: p = 0.016) and abundance (PhILR dissimilarity: p = 0.048; metagenomeSeq) of salivary microbial communities between patients with and without sputum production. Seven bacterial genera, including Prevotella, Streptococcus, Actinomyces, Atopobium, Filifactor, Leptotrichia, and Selenomonas, were more prevalent in patients with sputum production (p<0.05, Fisher's exact test). Nine genera, including Prevotella, Megasphaera, Stomatobaculum, Selenomonas, Leptotrichia, Veillonella, Actinomyces, Atopobium, and Corynebacteria, were significantly more abundant in the sputum-producing group, while Lachnoanaerobaculum was more prevalent in the non-sputum-producing group (p<0.05, ANCOM-BC). Positive correlations were found between salivary IFN-gamma and Eotaxin2/CCL24 with sputum production, while negative correlations were noted with serum MCP3/CCL7, MIG/CXCL9, IL1 beta, and SCF (p<0.05, Mann-Whitney test). The machine learning model using only oral bacteria input outperformed the model that included all data: blood and saliva biomarkers, as well as clinical and demographic variables, in predicting sputum production in COVID-19 subjects. The performance metrics were as follows, comparing the model with only bacteria input versus the model with all input variables: precision (95% vs. 75%), recall (100% vs. 50%), F1-score (98% vs. 60%), and accuracy (82% vs. 66%).
Assuntos
COVID-19 , Microbiota , Saliva , Escarro , Humanos , COVID-19/microbiologia , Escarro/microbiologia , Saliva/microbiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Citocinas/sangue , Citocinas/metabolismo , Pulmão/microbiologia , Pulmão/virologia , SARS-CoV-2/isolamento & purificação , RNA Ribossômico 16S/genética , Leptotrichia , Prevotella/isolamento & purificação , Streptococcus/isolamento & purificação , Actinomyces/isolamento & purificação , Boca/microbiologia , Boca/virologia , Aprendizado de Máquina , Biomarcadores/sangueRESUMO
The COVID-19 pandemic has significantly transformed the infection spectrum of various pathogens. This study aimed to evaluate the impact of the COVID-19 pandemic on Staphylococcus aureus (S. aureus) infections among pediatric patients with community acquired pneumonia (CAP). We retrospectively reviewed pediatric CAP admissions before (from 2018 to 2019) and during (from 2020 to 2022) the COVID-19 pandemic. The epidemiology and antimicrobial resistance (AMR) profiles of S. aureus isolates were examined to assess the pandemic's effect. As a result, a total of 399 pediatric CAP patients with S. aureus infections were included. The positivity rate, gender, and age distribution of patients were similar across both periods. There was a marked reduction in respiratory co-infections with Haemophilus influenzae (H. influenzae) during the COVID-19 pandemic, compared to 2019. Additionally, there were significant changes in the resistance profiles of S. aureus isolates to various antibiotics. Resistance to oxacillin and tetracycline increased, whereas resistance to penicillin, gentamicin, and quinolones decreased. Notably, resistance to erythromycin significantly decreased in methicillin-resistant S. aureus (MRSA) strains. The number of S. aureus isolates, the proportion of viral co-infections, and the number of resistant strains typically peaked seasonally, primarily in the first or fourth quarters of 2018, 2019, and 2021. However, shifts in these patterns were noted in the first quarter of 2020 and the fourth quarter of 2022. These findings reveal that the COVID-19 pandemic has significantly altered the infection dynamics of S. aureus among pediatric CAP patients, as evidenced by changes in respiratory co-infections, AMR patterns, and seasonal trends.
Assuntos
Antibacterianos , COVID-19 , Infecções Comunitárias Adquiridas , Infecções Estafilocócicas , Staphylococcus aureus , Humanos , COVID-19/epidemiologia , COVID-19/microbiologia , COVID-19/complicações , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Feminino , Masculino , Criança , Pré-Escolar , Estudos Retrospectivos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Lactente , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Adolescente , Coinfecção/epidemiologia , Coinfecção/microbiologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pandemias , Hospitalização , Farmacorresistência BacterianaRESUMO
Severe COVID-19 has been associated with coinfections with bacterial and fungal pathogens. Notably, patients with COVID-19 who develop Staphylococcus aureus bacteremia exhibit higher rates of mortality than those infected with either pathogen alone. To understand this clinical scenario, we collected and examined S. aureus blood and respiratory isolates from a hospital in New York City during the early phase of the pandemic from both SARS-CoV-2+ and SARS-CoV-2- patients. Whole genome sequencing of these S. aureus isolates revealed broad phylogenetic diversity in both patient groups, suggesting that SARS-CoV-2 coinfection was not associated with a particular S. aureus lineage. Phenotypic characterization of the contemporary collection of S. aureus isolates from SARS-CoV-2+ and SARS-CoV-2- patients revealed no notable differences in several virulence traits examined. However, we noted a trend toward overrepresentation of S. aureus bloodstream strains with low cytotoxicity in the SARS-CoV-2+ group. We observed that patients coinfected with SARS-CoV-2 and S. aureus were more likely to die during the acute phase of infection when the coinfecting S. aureus strain exhibited high or low cytotoxicity. To further investigate the relationship between SARS-CoV-2 and S. aureus infections, we developed a murine coinfection model. These studies revealed that infection with SARS-CoV-2 renders mice susceptible to subsequent superinfection with low cytotoxicity S. aureus. Thus, SARS-CoV-2 infection sensitizes the host to coinfections, including S. aureus isolates with low intrinsic virulence. IMPORTANCE: The COVID-19 pandemic has had an enormous impact on healthcare across the globe. Patients who were severely infected with SARS-CoV-2, the virus causing COVID-19, sometimes became infected with other pathogens, which is termed coinfection. If the coinfecting pathogen is the bacterium Staphylococcus aureus, there is an increased risk of patient death. We collected S. aureus strains that coinfected patients with SARS-CoV-2 to study the disease outcome caused by the interaction of these two important pathogens. We found that both in patients and in mice, coinfection with an S. aureus strain lacking toxicity resulted in more severe disease during the early phase of infection, compared with infection with either pathogen alone. Thus, SARS-CoV-2 infection can directly increase the severity of S. aureus infection.
Assuntos
COVID-19 , Coinfecção , SARS-CoV-2 , Infecções Estafilocócicas , Staphylococcus aureus , COVID-19/complicações , COVID-19/microbiologia , Coinfecção/microbiologia , Coinfecção/virologia , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Infecções Estafilocócicas/microbiologia , Humanos , Animais , Camundongos , SARS-CoV-2/genética , Filogenia , Feminino , Cidade de Nova Iorque/epidemiologia , Masculino , Virulência , Pessoa de Meia-Idade , Sequenciamento Completo do Genoma , Bacteriemia/microbiologia , Modelos Animais de Doenças , IdosoRESUMO
To determine why SARS-CoV-2 appears to thrive specifically well in meat packaging plants, we used SARS-CoV-2 Delta variant and meat packaging plant drain samples to develop mixed-species biofilms on materials commonly found within meat packaging plants (stainless steel (SS), PVC, and ceramic tile). Our data provides evidence that SARS-CoV-2 Delta variant remained viable on all the surfaces tested with and without an environmental biofilm after the virus was inoculated with the biofilm for 5 days at 7°C. We observed that SARS-CoV-2 Delta variant was able to remain infectious with each of the environmental biofilms by conducting plaque assay and qPCR experiments, however, we detected a significant reduction in viability post-exposure to Plant B biofilm on SS, PVC, and on ceramic tile chips, and to Plant C biofilm on SS and PVC chips. The numbers of viable SARS-CoV-2 Delta viral particles was 1.81-4.57-fold high than the viral inoculum incubated with the Plant B and Plant C environmental biofilm on SS, and PVC chips. We did not detect a significant difference in viability when SARS-CoV-2 Delta variant was incubated with the biofilm obtained from Plant A on any of the materials tested and SARS-CoV-2 Delta variant had higher plaque numbers when inoculated with Plant C biofilm on tile chips, with a 2.75-fold difference compared to SARS-CoV-2 Delta variant on tile chips by itself. In addition, we detected an increase in the biofilm biovolume in response to SARS-CoV-2 Delta variant which is also a concern for food safety due to the potential for foodborne pathogens to respond likewise when they come into contact with the virus. These results indicate a complex virus-environmental biofilm interaction which correlates to the different bacteria found in each biofilm. Our results also indicate that there is the potential for biofilms to protect SARS-CoV-2 from disinfecting agents and remaining prevalent in meat packaging plants.
Assuntos
Biofilmes , Embalagem de Alimentos , SARS-CoV-2 , Biofilmes/crescimento & desenvolvimento , SARS-CoV-2/fisiologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , Embalagem de Alimentos/métodos , Humanos , COVID-19/microbiologia , COVID-19/virologia , COVID-19/transmissão , Aço Inoxidável , Carne/microbiologia , Carne/virologiaRESUMO
Critical illness can significantly alter the composition and function of the human microbiome, but few studies have examined these changes over time. Here, we conduct a comprehensive analysis of the oral, lung, and gut microbiota in 479 mechanically ventilated patients (223 females, 256 males) with acute respiratory failure. We use advanced DNA sequencing technologies, including Illumina amplicon sequencing (utilizing 16S and ITS rRNA genes for bacteria and fungi, respectively, in all sample types) and Nanopore metagenomics for lung microbiota. Our results reveal a progressive dysbiosis in all three body compartments, characterized by a reduction in microbial diversity, a decrease in beneficial anaerobes, and an increase in pathogens. We find that clinical factors, such as chronic obstructive pulmonary disease, immunosuppression, and antibiotic exposure, are associated with specific patterns of dysbiosis. Interestingly, unsupervised clustering of lung microbiota diversity and composition by 16S independently predicted survival and performed better than traditional clinical and host-response predictors. These observations are validated in two separate cohorts of COVID-19 patients, highlighting the potential of lung microbiota as valuable prognostic biomarkers in critical care. Understanding these microbiome changes during critical illness points to new opportunities for microbiota-targeted precision medicine interventions.
Assuntos
COVID-19 , Disbiose , Microbioma Gastrointestinal , Pulmão , Microbiota , Humanos , Feminino , Masculino , Disbiose/microbiologia , Pessoa de Meia-Idade , Pulmão/microbiologia , COVID-19/microbiologia , COVID-19/virologia , Idoso , Microbiota/genética , Microbioma Gastrointestinal/genética , Interações entre Hospedeiro e Microrganismos/genética , Estudos Longitudinais , RNA Ribossômico 16S/genética , Insuficiência Respiratória/microbiologia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Adulto , Respiração Artificial , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Estado Terminal , Metagenômica/métodosRESUMO
During the COVID-19 pandemic, facemasks played a pivotal role in preventing person-person droplet transmission of viral particles. However, prolonged facemask wearing causes skin irritations colloquially referred to as 'maskne' (mask + acne), which manifests as acne and contact dermatitis and is mostly caused by pathogenic skin microbes. Previous studies revealed that the putative causal microbes were anaerobic bacteria, but the pathogenesis of facemask-associated skin conditions remains poorly defined. We therefore characterized the role of the facemask-associated skin microbiota in the development of maskne using culture-dependent and -independent methodologies. Metagenomic analysis revealed that the majority of the facemask microbiota were anaerobic bacteria that originated from the skin rather than saliva. Previous work demonstrated direct interaction between pathogenic bacteria and antagonistic strains in the microbiome. We expanded this analysis to include indirect interaction between pathogenic bacteria and other indigenous bacteria classified as either 'pathogen helper (PH)' or 'pathogen inhibitor (PIn)' strains. In vitro screening of bacteria isolated from facemasks identified both strains that antagonized and promoted pathogen growth. These data were validated using a mouse skin infection model, where we observed attenuation of symptoms following pathogen infection. Moreover, the inhibitor of pathogen helper (IPH) strain, which did not directly attenuate pathogen growth in vitro and in vivo, functioned to suppress symptom development and pathogen growth indirectly through PH inhibitory antibacterial products such as phenyl lactic acid. Taken together, our study is the first to define a mechanism by which indirect microbiota interactions under facemasks can control symptoms of maskne by suppressing a skin pathogen.
Assuntos
COVID-19 , Máscaras , Microbiota , Pele , Animais , Camundongos , Humanos , COVID-19/microbiologia , COVID-19/virologia , Pele/microbiologia , Acne Vulgar/microbiologia , SARS-CoV-2 , Feminino , Metagenômica/métodos , Modelos Animais de Doenças , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Interações Microbianas , Dermatite de Contato/etiologiaRESUMO
Background: To date, more than 770 million individuals have become coronavirus disease 2019 (COVID-19) convalescents worldwide. Emerging evidence highlights the influence of COVID-19 on the oral microbiome during both acute and convalescent disease phases. Front-line healthcare workers are at an elevated risk of exposure to viral infections, and the effects of COVID-19 on their oral microbiome remain relatively unexplored. Methods: Oropharyngeal swab specimens, collected one month after a negative COVID-19 test from a cohort comprising 55 healthcare workers, underwent 16S rRNA sequencing. We conducted a comparative analysis between this post-COVID-19 cohort and the pre-infection dataset from the same participants. Community composition analysis, indicator species analysis, alpha diversity assessment, beta diversity exploration, and functional prediction were evaluated. Results: The Shannon and Simpson indexes of the oral microbial community declined significantly in the post-COVID-19 group when compared with the pre-infection cohort. Moreover, there was clear intergroup clustering between the two groups. In the post-COVID-19 group, the phylum Firmicutes showed a significant increase. Further, there were clear differences in relative abundance of several bacterial genera in contrast with the pre-infection group, including Streptococcus, Gemella, Granulicatella, Capnocytophaga, Leptotrichia, Fusobacterium, and Prevotella. We identified Gemella enrichment in the post-COVID-19 group, potentially serving as a recovery period performance indicator. Functional prediction revealed lipopolysaccharide biosynthesis downregulation in the post-COVID-19 group, an outcome with host inflammatory response modulation and innate defence mechanism implications. Conclusion: During the recovery phase of COVID-19, the oral microbiome diversity of front-line healthcare workers failed to fully return to its pre-infection state. Despite the negative COVID-19 test result one month later, notable disparities persisted in the composition and functional attributes of the oral microbiota.
Assuntos
Bactérias , COVID-19 , Pessoal de Saúde , Microbiota , Orofaringe , RNA Ribossômico 16S , SARS-CoV-2 , Humanos , COVID-19/microbiologia , Orofaringe/microbiologia , Orofaringe/virologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , Adulto , RNA Ribossômico 16S/genética , Masculino , Feminino , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Pessoa de Meia-Idade , Estudos de CoortesRESUMO
Acute ischemic stroke (AIS) patients with active COVID-19 infection often have more severe symptoms and worse recovery. COVID-19 infection can cause gut microbiota dysbiosis, which is also a risk factor for poor outcomes in AIS patients. However, the association between gut microbiota and functional outcomes among AIS patients with COVID-19 infection has not been fully clarified yet. In this study, we performed 16S rRNA gene sequencing to characterize the gut microbial community among AIS patients with acute COVID-19 infection, AIS patients with post-acute COVID-19 infection, and AIS patients without COVID-19 infection. We found that AIS patients with acute COVID-19 experienced poorer recovery and significant gut dysbiosis, characterized by higher levels of Enterobacteriaceae and lower levels of Ruminococcaceae and Lachnospiraceae. Furthermore, a shorter time window (less than 28 days) between COVID-19 infection and stroke was identified as a risk factor for poor functional outcomes in AIS patients with COVID-19, and the enrichment of Enterobacteriaceae was indicated as a mediator in the relationship between infection time window and poor stroke outcomes. Our findings highlight the importance of early intervention after COVID-19 infection, especially by regulating the gut microbiota, which plays a role in the prognosis of AIS patients with COVID-19 infection.IMPORTANCEThe gut microbiota plays an important role in the association between respiratory system and cerebrovascular system through the gut-lung axis and gut-brain axis. However, the specific connection between gut bacteria and the functional outcomes of acute ischemic stroke (AIS) patients with COVID-19 is not fully understood yet. In our study, we observed a significant decrease in bacterial diversity and shifts in the abundance of key bacterial families in AIS patients with acute COVID-19 infection. Furthermore, we identified that the time window was a critical influence factor for stroke outcomes, and the enrichment of Enterobacteriaceae acted as a mediator in the relationship between the infection time window and poor stroke outcomes. Our research provides a new perspective on the complex interplay among AIS, COVID-19 infection, and gut microbiota dysbiosis. Moreover, recognizing Enterobacteriaceae as a potential mediator of poor stroke prognosis offers a novel avenue for future exploration and therapeutic interventions.
Assuntos
COVID-19 , Disbiose , Microbioma Gastrointestinal , AVC Isquêmico , Humanos , COVID-19/complicações , COVID-19/microbiologia , COVID-19/epidemiologia , Microbioma Gastrointestinal/fisiologia , Masculino , Feminino , AVC Isquêmico/microbiologia , Pessoa de Meia-Idade , Idoso , SARS-CoV-2 , RNA Ribossômico 16S/genética , Fatores de RiscoRESUMO
The COVID-19 pandemic has caused many fatalities worldwide and continues to affect the health of the recovered patients in the form of long-COVID. In this study, we compared the gut microbiome of uninfected infants and children before the pandemic began (BEFORE cohort, n=906) to that of after the pandemic (AFTER cohort, n=220) to examine the potential impact of social distancing and life habit changes on infant/children gut microbiome. Based on 16S rRNA sequencing, we found a significant change in microbiome composition after the pandemic, with Bacteroides enterotype increasing to 35.45% from 30.46% before the pandemic. qPCR quantification indicated that the bacterial loads of seven keystone taxa decreased by 91.69%-19.58%. Quantitative microbiome profiling, used to enhance the resolution in detecting microbiome differences, revealed a greater explained variance of pandemic on microbiome compared to gender, as well as a significant decrease in bacterial loads in 15 of the 20 major genera. The random forest age-predictor indicated the gut microbiomes were less mature in the after-pandemic cohort than in the before-pandemic cohort in the children group (3-12 years old) and had features of a significantly younger age (average of 1.86 years). Lastly, body weight and height were significantly lower in the after-pandemic cohort than in the before-pandemic cohort in infants (<1 year of age), which was associated with a decrease in bacterial loads in the fecal microbiome.
Assuntos
COVID-19 , Fezes , Microbioma Gastrointestinal , RNA Ribossômico 16S , Humanos , COVID-19/epidemiologia , COVID-19/microbiologia , COVID-19/virologia , Lactente , Pré-Escolar , Feminino , Masculino , RNA Ribossômico 16S/genética , Criança , Fezes/microbiologia , Fezes/virologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , Pequim/epidemiologia , Pandemias , Carga Bacteriana , Estudos de Coortes , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificaçãoRESUMO
Recent studies highlight the crucial role of the gut microbiome in post-infectious complications, especially in patients recovering from severe COVID-19. Our research aimed to explore the connection between gut microbiome changes and the cytokine profile of patients with post-COVID syndrome. Using 16S rRNA amplicon sequencing, we analyzed the composition of the gut microbiome in 60 COVID-19 patients over the course of one year. We also measured the levels of serum cytokines and chemokines using the Milliplex system. Our results showed that severe SARS-CoV-2 infection cases, especially those complicated by pneumonia, induce a pro-inflammatory microbial milieu with heightened presence of Bacteroides, Faecalibacterium, and Prevotella_9. Furthermore, we found that post-COVID syndrome is characterized by a cross-correlation of various cytokines and chemokines MDC, IL-1b, Fractalkine, TNFa, FGF-2, EGF, IL-1RA, IFN-a2, IL-10, sCD40L, IL-8, Eotaxin, IL-12p40, and MIP-1b as well as a shift in the gut microbiome towards a pro-inflammatory profile. At the functional level, our analysis revealed associations with post-COVID-19 in homolactic fermentation, pentose phosphate, NAD salvage, and flavin biosynthesis. These findings highlight the intricate interplay between the gut microbiota, their metabolites, and systemic cytokines in shaping post-COVID symptoms. Unraveling the gut microbiome's role in post-infectious complications opens avenues for new treatments for those patients with prolonged symptoms.
Assuntos
COVID-19 , Citocinas , Microbioma Gastrointestinal , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/microbiologia , COVID-19/complicações , COVID-19/sangue , Citocinas/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , RNA Ribossômico 16S/genética , Síndrome de COVID-19 Pós-Aguda , Fezes/microbiologia , Fezes/virologiaRESUMO
Introduction: Although the existence of Candida species in the respiratory tract is often considered commensal, it is crucial to recognize the significance of Candida colonization in immunocompromised or COVID-19 patients. The emergence of Candida auris as an emerging pathogen further emphasizes the importance of monitoring yeast infection/colonization, particularly in COVID-19 patients. Methods: In this study, respiratory samples mainly from COVID-19 patients, primarily those suspected of having a fungal infection, were cultured on Sabouraud dextrose agar plates and the yeast colonies were identified using a two-step multiplex PCR method. The samples suspected of C. auris underwent specific nested PCR followed by sequence analysis. Results: A total of 199 respiratory samples were collected from 73 women and 126 men, ranging in age from 1.6 to 88 years. Among the patients, 141 had COVID-19, 32 had cancer, 5 were hospitalized in ICU, 2 had chronic obstructive pulmonary disease)COPD(, and others were patients with combination diseases. From these samples, a total of 334 yeast strains were identified. C. albicans (n=132, 39.52%) was the most common species, followed by C. tropicalis (n=67, 20%), C. glabrata (n=56, 16.76%), C. krusei (n=18, 5.4%), C. parapsilosis (n=17, 5.08%), Saccharomyces cerevisiae (n=10, 3%), C. kefyr (n=9, 2.6%), C. dubliniensis (n=7, 2.1%), C. lusitaniae (n=5, 1.5%), C. auris (n=3, 0.9%), C. guilliermondii (n=2, 0.6%), C. rugosa (n=1, 0.3%), C. intermedia (n=1, 0.3%), and Trichosporon spp. (n=1, 0.3%). C. auris was detected in a patient in ICU and two COVID-19 patients. While its presence was confirmed through sequence analysis, our extensive efforts to isolate C. auris were unsuccessful. Conclusion: While C. albicans colonization remains prevalent, our study found no evidence of Candida lung infection. Since the role of Candida colonization in airway secretions remains ambiguous due to limited research, further studies are imperative to shed light on this matter.
Assuntos
COVID-19 , Candida auris , Candidíase , SARS-CoV-2 , Humanos , COVID-19/microbiologia , Idoso , Pessoa de Meia-Idade , Feminino , Masculino , Idoso de 80 Anos ou mais , Adulto , Pré-Escolar , Candidíase/microbiologia , Criança , Adolescente , Adulto Jovem , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Lactente , Candida auris/genética , Candida auris/isolamento & purificação , Candida/isolamento & purificação , Candida/classificação , Candida/genética , Sistema Respiratório/microbiologia , Sistema Respiratório/virologia , Reação em Cadeia da Polimerase MultiplexRESUMO
BACKGROUND: Staphylococcus aureus (S. aureus) associated with COVID-19 has not been well documented. This cross-sectional study evaluated the association between nasal S. aureus carriage and COVID-19. METHODS AND RESULTS: Nasopharyngeal samples were collected from 391 participants presenting for COVID-19 test in Lagos, Nigeria, and S. aureus was isolated from the samples. Antimicrobial susceptibility test was done by disc diffusion method. All S. aureus isolates were screened for the presence of mecA, panton-valentine leucocidin (PVL) and toxic shock syndrome toxin (TSST) virulence genes by polymerase chain reaction. Staphylococcal protein A (spa) typing was conducted for all the isolates. Participants with COVID-19 had double the prevalence of S. aureus (42.86%) compared to those who tested negative (20.54%). A significant association was seen between S. aureus nasal carriage and COVID-19 (p = 0.004). Antimicrobial sensitivity results showed resistance to oxacillin (100%), cefoxitin (53%), and vancomycin (98.7%). However, only 41% of the isolates harbored the mecA gene, with SCCmecV being the most common SCCmec type. There was no association between the carriage of virulence genes and COVID-19. A total of 23 Spa types were detected, with t13249 and t095 being the two most common spa types. CONCLUSION: This study examined the association between nasal S. aureus carriage and SARS-COV-2 infection. Further research is required to fully explore the implications of S. aureus co-infection with COVID-19.
Assuntos
COVID-19 , SARS-CoV-2 , Infecções Estafilocócicas , Staphylococcus aureus , Humanos , COVID-19/microbiologia , COVID-19/epidemiologia , COVID-19/virologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Estudos Transversais , Masculino , Feminino , Staphylococcus aureus/genética , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Staphylococcus aureus/isolamento & purificação , Adulto , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Pessoa de Meia-Idade , Toxinas Bacterianas/genética , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Comorbidade , Proteínas de Bactérias/genética , Virulência/genética , Nigéria/epidemiologia , Farmacorresistência Bacteriana Múltipla/genética , Antibacterianos/farmacologia , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Testes de Sensibilidade Microbiana , Proteínas de Ligação às Penicilinas/genética , Leucocidinas/genética , Exotoxinas/genética , Fatores de Virulência/genética , Adulto JovemRESUMO
Background: During the coronavirus disease 2019 (COVID-19) pandemic, in patients treated for SARS-CoV-2 infection, infections with the Klebsiella pneumoniae bacteria producing New Delhi metallo-B-lactamase (NDM) carbapenemase in the USA, Brazil, Mexico, and Italy were observed, especially in intensive care units (ICUs). This study aimed to assess the impact of Klebsiella pneumoniae NDM infection and other bacterial infections on mortality in patients treated in ICUs due to COVID-19. Methods: The 160 patients who qualified for the study were hospitalized in ICUs due to COVID-19. Three groups were distinguished: patients with COVID-19 infection only (N = 72), patients with COVID-19 infection and infection caused by Klebsiella pneumoniae NDM (N = 30), and patients with COVID-19 infection and infection of bacterial etiology other than Klebsiella pneumoniae NDM (N = 58). Mortality in the groups and chosen demographic data; biochemical parameters analyzed on days 1, 3, 5, and 7; comorbidities; and ICU scores were analyzed. Results: Bacterial infection, including with Klebsiella pneumoniae NDM type, did not elevate mortality rates. In the group of patients who survived the acute phase of COVID-19 the prolonged survival time was demonstrated: the median overall survival time was 13 days in the NDM bacterial infection group, 14 days in the other bacterial infection group, and 7 days in the COVID-19 only group. Comparing the COVID-19 with NDM infection and COVID-19 only groups, the adjusted model estimated a statistically significant hazard ratio of 0.28 (p = 0.002). Multivariate analysis revealed that age, APACHE II score, and CRP were predictors of mortality in all the patient groups. Conclusion: In patients treated for SARS-CoV-2 infection acquiring a bacterial infection due to prolonged hospitalization associated with the treatment of COVID-19 did not elevate mortality rates. The data suggests that in severe COVID-19 patients who survived beyond the first week of hospitalization, bacterial infections, particularly Klebsiella pneumoniae NDM, do not significantly impact mortality. Multivariate analysis revealed that age, APACHE II score, and CRP were predictors of mortality in all the patient groups.
Assuntos
COVID-19 , Farmacorresistência Bacteriana Múltipla , Unidades de Terapia Intensiva , Infecções por Klebsiella , Klebsiella pneumoniae , SARS-CoV-2 , beta-Lactamases , Humanos , COVID-19/mortalidade , COVID-19/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Masculino , Feminino , Infecções por Klebsiella/mortalidade , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/epidemiologia , beta-Lactamases/metabolismo , beta-Lactamases/genética , Pessoa de Meia-Idade , Idoso , Adulto , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Idoso de 80 Anos ou maisRESUMO
Invasive pulmonary aspergillosis is a severe fungal infection primarily affecting immunocompromised patients. Individuals with severe viral infections have recently been identified as vulnerable to developing invasive fungal infections. Both influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) are linked to high mortality rates, emphasizing the urgent need for an improved understanding of disease pathogenesis to unveil new molecular targets with diagnostic and therapeutic potential. The recent establishment of animal models replicating the co-infection context has offered crucial insights into the mechanisms that underlie susceptibility to disease. However, the development and progression of human viral-fungal co-infections exhibit a significant degree of interindividual variability, even among patients with similar clinical conditions. This observation implies a significant role for host genetics, but information regarding the genetic basis for viral-fungal co-infections is currently limited. In this review, we discuss how genetic factors known to affect either antiviral or antifungal immunity could potentially reveal pathogenetic mechanisms that predispose to IAPA or CAPA and influence the overall disease course. These insights are anticipated to foster further research in both pre-clinical models and human patients, aiming to elucidate the complex pathophysiology of viral-associated pulmonary aspergillosis and contributing to the identification of new diagnostic and therapeutic targets to improve the management of these co-infections.
Assuntos
COVID-19 , Coinfecção , Humanos , Coinfecção/microbiologia , Coinfecção/imunologia , Coinfecção/virologia , COVID-19/imunologia , COVID-19/complicações , COVID-19/microbiologia , COVID-19/virologia , Animais , Aspergilose Pulmonar/imunologia , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Aspergilose Pulmonar Invasiva/imunologia , Aspergilose Pulmonar Invasiva/microbiologiaRESUMO
Throughout the COVID-19 pandemic, extensive research has been conducted on SARS-COV-2 to elucidate its genome, prognosis, and possible treatments. However, few looked at the microbial markers that could be explored in infected patients and that could predict possible disease severity. The aim of this study is to compare the nasopharyngeal microbiota of healthy subjects, moderate, under medication, and recovered SARS-COV-2 patients. In 2020, 38 nasopharyngeal swabs were collected from 6 healthy subjects, 14 moderates, 10 under medication and 8 recovered SARS-COV-2 patients at the Prince Mohammed Bin Abdulaziz Hospital Riyadh. Metatranscriptomic sequencing was performed using Minion Oxford nanopore sequencing. No significant difference in alpha as well as beta diversity was observed among all four categories. Nevertheless, we have found that Streptococcus spp including Streptococcus pneumoniae and Streptococcus thermophilus were among the top 15 most abundant species detected in COVID-19 patients but not in healthy subjects. The genus Staphylococcus was found to be associated with COVID-19 patients compared to healthy subjects. Furthermore, the abundance of Leptotrichia was significantly higher in healthy subjects compared to recovered patients. Corynebacterium on the other hand, was associated with under-medication patients. Taken together, our study revealed no differences in the overall microbial composition between healthy subjects and COVID-19 patients. Significant differences were seen only at specific taxonomic level. Future studies should explore the nasopharyngeal microbiota between controls and COVID-19 patients while controlling for confounders including age, gender, and comorbidities; since these latter could affect the results and accordingly the interpretation.IMPORTANCEIn this work, no significant difference in the microbial diversity was seen between healthy subjects and COVID-19 patients. Changes in specific taxa including Leptotrichia, Staphylococcus, and Corynebacterium were only observed. Leptotrichia was significantly higher in healthy subjects, whereas Staphylococcus and Corynebacterium were mostly associated with COVID-19, and specifically with under-medication SARS-COV-2 patients, respectively. Although the COVID-19 pandemic has ended, the SARS-COV-2 virus is continuously evolving and the emergence of new variants causing more severe disease should be always kept in mind. Microbial markers in SARS-COV-2 infected patients can be useful in the early suspicion of the disease, predicting clinical outcomes, framing hospital and intensive care unit admission as well as, risk stratification. Data on which microbial marker to tackle is still controversial and more work is needed, hence the importance of this study.
Assuntos
COVID-19 , Sequenciamento de Nucleotídeos em Larga Escala , Microbiota , Nasofaringe , SARS-CoV-2 , Humanos , COVID-19/microbiologia , COVID-19/virologia , COVID-19/epidemiologia , COVID-19/diagnóstico , Nasofaringe/microbiologia , Nasofaringe/virologia , Microbiota/genética , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Metagenômica/métodos , Metagenoma , Idoso , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Índice de Gravidade de Doença , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/classificaçãoRESUMO
Candida species are the primary cause of fungal infections in intensive care units (ICUs). Despite the increasing prevalence of Candida-related infections, monitoring the progression of these infections from colonization in COVID-19 ICU patients lacks sufficient information. This study aims prospectively to compare 62 COVID-19 and 60 non-COVID-19 ICU patients from admission to discharge in terms of colonization development, rates, isolated Candida species, risk factors, and Candida infections during hospitalization. A total of 1464 samples were collected at specific time intervals from various body sites [mouth, skin (axilla), rectal, and urine]. All samples were inoculated onto CHROMagar Candida and CHROMagar Candida Plus media, and isolates identified using MALDI-TOF MS. COVID-19 patients exhibited significantly higher colonization rates in oral, rectal, and urine samples compared to non-COVID-19 patients, (p < 0.05). Among the Candida species, non-albicans Candida was more frequently detected in COVID-19 patients, particularly in oral (75.8%-25%; p < 0.001) and rectal regions (74.19% - 46.66%; p < 0.05). Colonization with mixed Candida species was also more prevalent in the oropharyngeal region (p < 0.05). Mechanical ventilation and corticosteroid use emerged as elevated risk factors among COVID-19 patients (p < 0.05). Despite the colonization prevalence, both COVID-19-positive and negative patients exhibited low incidences of Candida infections, with rates of 9.67% (n = 6/62) and 6.67% (n = 3/60), respectively. Consequently, although Candida colonization rates were higher in COVID-19 ICU patients, there was no significant difference in Candida infection development compared to the non-COVID-19 group. However, the elevated rate of non-albicans Candida isolates highlights potential future infections, particularly given their intrinsic resistance in prophylactic or empirical treatments if needed. Additionally, the high rate of mixed colonization emphasizes the importance of using chromogenic media for routine evaluation.
This is the first prospective cohort study comparing Candida colonization features including species and body sites from the time of admission to the externalization in intensive care unit patients with and without COVID-19. It provides key points that can be referenced for fungal approaches in future disasters.
Assuntos
COVID-19 , Candida , Candidíase , Unidades de Terapia Intensiva , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , COVID-19/microbiologia , COVID-19/epidemiologia , Masculino , Estudos Prospectivos , Feminino , Pessoa de Meia-Idade , Candida/isolamento & purificação , Candida/classificação , Idoso , Candidíase/epidemiologia , Candidíase/microbiologia , Turquia/epidemiologia , Adulto , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Prevalência , Boca/microbiologia , Boca/virologiaRESUMO
INTRODUCTION: Aim of the study was the molecular characterization of 21 ceftazidime/avibactam resistant (CZA-R) Klebsiella pneumoniae strains, collected in the period October 2021-March 2022 from an Intensive Care COVID Unit in a Northern Italian Hospital. METHODS: After growth on selective/chromogenic culture media and susceptibility tests assessment, resistance genes content was ascertained for all the isolates by the HybriSpot 12 multiplexing, PCR and Whole-Genome Sequencing (WGS). Clonality was assessed by PFGE and MLST according to the Pasteur scheme. A SNPs-based phylogenetic tree was obtained comparing representative isolates and global genomes. The blaKPC gene horizontal transmission was evaluated by conjugation experiments. blaKPC-166 was cloned in a pCR2.1 vector and transformed in chemically competent TOP10 cells. RESULTS: Sixteen inpatients resulted positive for colonization and/or infection by KPC-producing K. pneumoniae (KPC-Kp) strains. The 21 CZA-R KPC-Kp isolates obtained showed MDR phenotype; susceptibility to meropenem was always retained. All the CZA-R KPC-Kp presented a novel blaKPC variant, named blaKPC-166, showing a single nucleotide substitution (T811C) compared to the blaKPC-94; but related to blaKPC-2. TWO DIFFERENT PULSOTYPES WERE DETECTED: A in 18/21 and B in 1/21 cases, two strains from the same patient being untypable by PFGE. Interestingly, the outbreak was sustained by the high-risk clone ST307, although the ST22, ST6342, ST6418 and ST6811 have also been identified and associated to KPC-166. Worryingly, blaKPC-166 could be transferred horizontally and, after cloning, it conferred resistance to CZA. DISCUSSION: This novel variant confers CZA-resistance and carbapenems susceptibility restoration. As KPC-166 was found expressed by multiple Kp clones, greater efforts should be made to prevent the further dissemination of such strains in Italian clinical settings.
Assuntos
Antibacterianos , Compostos Azabicíclicos , Ceftazidima , Surtos de Doenças , Combinação de Medicamentos , Unidades de Terapia Intensiva , Infecções por Klebsiella , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , beta-Lactamases , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Humanos , Ceftazidima/farmacologia , Ceftazidima/uso terapêutico , Itália/epidemiologia , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/tratamento farmacológico , Compostos Azabicíclicos/farmacologia , beta-Lactamases/genética , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , COVID-19/epidemiologia , COVID-19/virologia , COVID-19/microbiologia , Filogenia , Proteínas de Bactérias/genética , Sequenciamento Completo do Genoma , Masculino , Tipagem de Sequências Multilocus , FemininoRESUMO
BACKGROUND: Co-infection with other pathogens in coronavirus disease 2019 (COVID-19) patients exacerbates disease severity and impacts patient prognosis. Clarifying the exact pathogens co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is premise of the precise treatment for COVID-19 patients. METHODS: Sputum samples were collected from 17 patients in the COVID-19 positive group and 18 patients in the COVID-19 negative group. DNA extraction was performed to obtain the total DNA. Sequencing analysis using 16S and ITS rRNA gene was carried out to analyze the composition of bacterial and fungal communities. Meanwhile, all the samples were inoculated for culture. RESULTS: We did not observe significant differences in bacterial composition between the COVID-19 positive and negative groups. However, a significantly higher abundance of Candida albicans was observed in the upper respiratory tract samples from the COVID-19 positive group compared to the COVID-19 negative group. Moreover, the Candida albicans strains isolated from COVID-19 positive group exhibited impaired secretion of aspartyl proteinases. CONCLUSION: COVID-19 positive patients demonstrate a notable increase in the abundance of Candida albicans, along with a decrease in the levels of aspartyl proteinases, indicating the alteration of microbiota composition of upper respiratory tract.