General dynamics of the URT microbiome and microbial signs of recovery in COVID-19 patients.

COVID-19 is caused by an airborne virus, SARS-CoV-2. The upper respiratory tract (URT) is, therefore, the first system to endure the attack. Inhabited by an assemblage of microbial communities, a healthy URT wards off the invasion. However, once invaded, it becomes destabilised, which could be crucial to the establishment and progression of the infection. We examined 696 URT samples collected from 285 COVID-19 patients at three time-points throughout their hospital stay and 100 URT samples from 100 healthy controls. We used 16S ribosomal RNA sequencing to evaluate the abundance of various bacterial taxa, α-diversity, and ß-diversity of the URT microbiome. Ordinary least squares regression was used to establish associations between the variables, with age, sex, and antibiotics as covariates. The URT microbiome in the COVID-19 patients was distinctively different from that of healthy controls. In COVID-19 patients, the abundance of 16 genera was significantly reduced. A total of 47 genera were specific to patients, whereas only 2 were unique to controls. The URT samples collected at admission differed more from the control than from the samples collected at later stages of treatment. The following four genera originally depleted in the patients grew significantly by the end of treatment: Fusobacterium, Haemophilus, Neisseria, and Stenotrophomonas. Our findings strongly suggest that SARS-CoV-2 caused significant changes in the URT microbiome, including the emergence of numerous atypical taxa. These findings may indicate increased instability of the URT microbiome in COVID-19 patients. In the course of the treatment, the microbial composition of the URT of COVID-19 patients tended toward that of controls. These microbial changes may be interpreted as markers of recovery.

Cognitive impairment in long-living adults: a genome-wide association study, polygenic risk score model and molecular modeling of the APOE protein.

Background: Cognitive impairment is an irreversible, aging-associated condition that robs people of their independence. The purpose of this study was to investigate possible causes of this condition and propose preventive options. Methods: We assessed cognitive status in long-living adults aged 90+ (n = 2,559) and performed a genome wide association study using two sets of variables: Mini-Mental State Examination scores as a continuous variable (linear regression) and cognitive status as a binary variable (> 24, no cognitive impairment; <10, impairment) (logistic regression). Results: Both variations yielded the same polymorphisms, including a well-known marker of dementia, rs429358in the APOE gene. Molecular dynamics simulations showed that this polymorphism leads to changes in the structure of alpha helices and the mobility of the lipid-binding domain in the APOE protein. Conclusion: These changes, along with higher LDL and total cholesterol levels, could be the mechanism underlying the development of cognitive impairment in older adults. However, this polymorphism is not the only determining factor in cognitive impairment. The polygenic risk score model included 45 polymorphisms (ROC AUC 69%), further confirming the multifactorial nature of this condition. Our findings, particularly the results of PRS modeling, could contribute to the development of early detection strategies for predisposition to cognitive impairment in older adults.