The risk factors for coronavirus disease 2019 (COVID-19) severity are still poorly understood. Considering the pivotal role of the gut microbiota on host immune and inflammatory functions, we investigated the association between changes in the gut microbiota composition and the clinical severity of COVID-19. We conducted a multicenter cross-sectional study prospectively enrolling 115 COVID-19 patients categorized according to: (1) the WHO Clinical Progression Scale—mild, 19 (16.5%); moderate, 37 (32.2%); or severe, 59 (51.3%), and (2) the location of recovery from COVID-19—ambulatory, 14 (household isolation, 12.2%); hospitalized in ward, 40 (34.8%); or hospitalized in the intensive care unit, 61 (53.0%). Gut microbiota analysis was performed through 16S rRNA gene sequencing, and the data obtained were further related to the clinical parameters of COVID-19 patients. The risk factors for COVID-19 severity were identified by univariate and multivariable logistic regression models. In comparison to mild COVID-19 patients, the gut microbiota of moderate and severe patients have: (a) lower Firmicutes/Bacteroidetes ratio; (b) higher abundance of Proteobacteria; and (c) lower abundance of beneficial butyrate-producing bacteria such as the genera Roseburia and Lachnospira. Multivariable regression analysis showed that the Shannon diversity index [odds ratio (OR) = 2.85, 95% CI = 1.09–7.41, p = 0.032) and C-reactive protein (OR = 3.45, 95% CI = 1.33–8.91, p = 0.011) are risk factors for severe COVID-19 (a score of 6 or higher in the WHO Clinical Progression Scale). In conclusion, our results demonstrated that hospitalized patients with moderate and severe COVID-19 have microbial signatures of gut dysbiosis; for the first time, the gut microbiota diversity is pointed out as a prognostic biomarker of COVID-19 severity.
Risk assessment of central nervous system (CNS) infection patients is of key importance in predicting likely pathogens. However, data are lacking on the epidemiology globally. We performed a multicenter study to understand the burden of community-acquired CNS (CA-CNS) infections between 2012 and 2014. A total of 2583 patients with CA-CNS infections were included from 37 referral centers in 20 countries. Of these, 477 (18.5%) patients survived with sequelae and 227 (8.8%) died, and 1879 (72.7%) patients were discharged with complete cure. The most frequent infecting pathogens in this study were Streptococcus pneumoniae (n = 206, 8%) and Mycobacterium tuberculosis (n = 152, 5.9%). Varicella zoster virus and Listeria were other common pathogens in the elderly. Although staphylococci and Listeria resulted in frequent infections in immunocompromised patients, cryptococci were leading pathogens in human immunodeficiency virus (HIV)-positive individuals. Among the patients with any proven etiology, 96 (8.9%) patients presented with clinical features of a chronic CNS disease. Neurosyphilis, neurobrucellosis, neuroborreliosis, and CNS tuberculosis had a predilection to present chronic courses. Listeria monocytogenes, Staphylococcus aureus, M. tuberculosis, and S. pneumoniae were the most fatal forms, while sequelae were significantly higher for herpes simplex virus type 1 (p < 0.05 for all). Tackling the high burden of CNS infections globally can only be achieved with effective pneumococcal immunization and strategies to eliminate tuberculosis, and more must be done to improve diagnostic capacity.
Background. This study aims to describe the characteristics of tuberculosis (TB) patients requiring intensive care and to determine the in-hospital mortality and the associated predictive factors. Methods. Retrospective cohort study of all TB patients admitted to the ICU of the Infectious Diseases Department of Centro Hospitalar de São João (Porto, Portugal) between January 2007 and July 2014. Comorbid diagnoses, clinical features, radiological and laboratory investigations, and outcomes were reviewed. Univariate analysis was performed to identify risk factors for death. Results. We included 39 patients: median age was 52.0 years and 74.4% were male. Twenty-one patients (53.8%) died during hospital stay (15 in the ICU). The diagnosis of isolated pulmonary TB, a positive smear for acid-fast-bacilli and a positive PCR for Mycobacterium tuberculosis in patients of pulmonary disease, severe sepsis/septic shock, acute renal failure and Multiple Organ Dysfunction Syndrome on admission, the need for mechanical ventilation or vasopressor support, hospital acquired infection, use of adjunctive corticotherapy, smoking, and alcohol abuse were significantly associated with mortality (p < 0.05). Conclusion. This cohort of TB patients requiring intensive care presented a high mortality rate. Most risk factors for mortality were related to organ failure, but others could be attributed to delay in the diagnostic and therapeutic approach, important targets for intervention.
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