The Intratumor Bacterial and Fungal Microbiome Is Characterized by HPV, Smoking, and Alcohol Consumption in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) tumor phenotypes and clinical outcomes are significantly influenced by etiological agents, such as HPV infection, smoking, and alcohol consumption. Accordingly, the intratumor microbiome has been increasingly implicated in cancer progression and metastasis. However, few studies characterize the intratumor microbial landscape of HNSCC with respect to these etiological agents. In this study, we aimed to investigate the bacterial and fungal landscape of HNSCC in association with HPV infection, smoking, and alcohol consumption. RNA-sequencing data were extracted from The Cancer Genome Atlas (TCGA) regarding 449 tissue samples and 44 normal samples. Pathoscope 2.0 was used to extract the microbial reads. Microbe abundance was compared to clinical variables, oncogenic signatures, and immune-associated pathways. Our results demonstrated that a similar number of dysregulated microbes was overabundant in smokers and nonsmokers, while heavy drinkers were characterized by an underabundance of dysregulated microbes. Conversely, the majority of dysregulated microbes were overabundant in HPV+ tumor samples when compared to HPV- tumor samples. Moreover, we observed that many dysregulated microbes were associated with oncogenic and metastatic pathways, suggesting their roles in influencing carcinogenesis. These microbes provide insights regarding potential mechanisms for tumor pathogenesis and progression with respect to the three etiological agents.

Cardiovascular, cerebrovascular, and renal co-morbidities in COVID-19 patients: A systematic-review and meta-analysis.

BACKGROUND: COVID-19 has infected over 35 million people worldwide and led to over 1 million deaths. Several risk factors that increase COVID-19 severity have emerged, including age and a history of cardiovascular disease, hypertension, or kidney disease. However, a number of outstanding questions persist, including whether the above comorbidities correlate with increased mortality from COVID-19 or whether age is a significant confounding variable that accounts for the observed relationship between COVID-19 severity and other comorbidities. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of studies documenting COVID-19 patients with hypertension, cardiovascular disease, cerebrovascular disease, or chronic kidney disease. We classified COVID-19 cases into severe/non-severe or deceased/surviving and calculated the odds ratio (OR) for each of the four comorbidities in these cohorts. 36 studies, comprising 22,573 patients, are included in our meta-analysis. We found that hypertension is the most prevalent comorbidity in deceased COVID-19 patients (55.4%; CI: 49.4-61.3%), followed by cardiovascular disease (30.7%; CI: 22.6-38.8%), cerebrovascular disease (13.4%; CI: 9.12-19.2%), then chronic kidney disease (9.05%; CI: 5.57-15.0%). The risk of death is also significantly higher for patients with these comorbidities, with the greatest risk factor being chronic kidney disease (OR: 8.86; CI: 5.27-14.89), followed by cardiovascular disease (OR: 6.87; CI: 5.56-8.50), hypertension (OR: 4.87; CI: 4.19-5.66), and cerebrovascular disease (OR: 4.28; CI: 2.86-6.41). These risks are significantly higher than previously reported, while correlations between comorbidities and COVID-19 severity are similar to previously reported figures. Using meta-regression analysis with age as a moderating variable, we observed that age contributes to the observed risks but does not explain them fully. CONCLUSIONS: In this meta-analysis, we observed that cardiovascular, cerebrovascular, and kidney-related comorbidities in COVID-19 significantly contributes to greater risk of mortality and increased disease severity. We also demonstrated that age may not be a confounder to these associations.

Identification of Lung and Blood Microbiota Implicated in COVID-19 Prognosis.

The implications of the microbiome on Coronavirus disease 2019 (COVID-19) prognosis has not been thoroughly studied. In this study we aimed to characterize the lung and blood microbiome and their implication on COVID-19 prognosis through analysis of peripheral blood mononuclear cell (PBMC) samples, lung biopsy samples, and bronchoalveolar lavage fluid (BALF) samples. In all three tissue types, we found panels of microbes differentially abundant between COVID-19 and normal samples correlated to immune dysregulation and upregulation of inflammatory pathways, including key cytokine pathways such as interleukin (IL)-2, 3, 5-10 and 23 signaling pathways and downregulation of anti-inflammatory pathways including IL-4 signaling. In the PBMC samples, six microbes were correlated with worse COVID-19 severity, and one microbe was correlated with improved COVID-19 severity. Collectively, our findings contribute to the understanding of the human microbiome and suggest interplay between our identified microbes and key inflammatory pathways which may be leveraged in the development of immune therapies for treating COVID-19 patients.

Using machine learning of clinical data to diagnose COVID-19: a systematic review and meta-analysis.

BACKGROUND: The recent Coronavirus Disease 2019 (COVID-19) pandemic has placed severe stress on healthcare systems worldwide, which is amplified by the critical shortage of COVID-19 tests. METHODS: In this study, we propose to generate a more accurate diagnosis model of COVID-19 based on patient symptoms and routine test results by applying machine learning to reanalyzing COVID-19 data from 151 published studies. We aim to investigate correlations between clinical variables, cluster COVID-19 patients into subtypes, and generate a computational classification model for discriminating between COVID-19 patients and influenza patients based on clinical variables alone. RESULTS: We discovered several novel associations between clinical variables, including correlations between being male and having higher levels of serum lymphocytes and neutrophils. We found that COVID-19 patients could be clustered into subtypes based on serum levels of immune cells, gender, and reported symptoms. Finally, we trained an XGBoost model to achieve a sensitivity of 92.5% and a specificity of 97.9% in discriminating COVID-19 patients from influenza patients. CONCLUSIONS: We demonstrated that computational methods trained on large clinical datasets could yield ever more accurate COVID-19 diagnostic models to mitigate the impact of lack of testing. We also presented previously unknown COVID-19 clinical variable correlations and clinical subgroups.

Comparative Analysis of Age- and Gender-Associated Microbiome in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma.

The intra-tumor microbiota has been increasingly implicated in cancer pathogenesis. In this study, we aimed to examine the microbiome in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and determine its compositional differences with relation to age and gender. After grouping 497 LUAD and 433 LUSC patients by age and gender and removing potential contaminants, we identified differentially abundant microbes in each patient cohort vs. adjacent normal samples. We then correlated dysregulated microbes with patient survival rates, immune infiltration, immune and cancer pathways, and genomic alterations. We found that most age and gender cohorts in both LUAD and LUSC contained unique, significantly dysregulated microbes. For example, LUAD-associated Escherichia coli str. K-12 substr. W3110 was dysregulated in older female and male patients and correlated with both patient survival and genomic alterations. For LUSC, the most prominent bacterial species that we identified was Pseudomonas putida str. KT2440, which was uniquely associated with young LUSC male patients and immune infiltration. In conclusion, we found differentially abundant microbes implicated with age and gender that are also associated with genomic alterations and immune dysregulations. Further investigation should be conducted to determine the relationship between gender and age-associated microbes and the pathogenesis of lung cancer.