Dementia, infections and vaccines: 30 years of controversy.

This paper reports the proceedings of a virtual meeting convened by the European Interdisciplinary Council on Ageing (EICA), to discuss the involvement of infectious disorders in the pathogenesis of dementia and neurological disorders leading to dementia. We recap how our view of the infectious etiology of dementia has changed over the last 30 years in light of emerging evidence, and we present evidence in support of the implication of infection in dementia, notably Alzheimer's disease (AD). The bacteria and viruses thought to be responsible for neuroinflammation and neurological damage are reviewed. We then review the genetic basis for neuroinflammation and dementia, highlighting the genes that are currently the focus of investigation as potential targets for therapy. Next, we describe the antimicrobial hypothesis of dementia, notably the intriguing possibility that amyloid beta may itself possess antimicrobial properties. We further describe the clinical relevance of the gut-brain axis in dementia, the mechanisms by which infection can move from the intestine to the brain, and recent findings regarding dysbiosis patterns in patients with AD. We review the involvement of specific pathogens in neurological disorders, i.e. SARS-CoV-2, human immunodeficiency virus (HIV), herpes simplex virus type 1 (HSV1), and influenza. Finally, we look at the role of vaccination to prevent dementia. In conclusion, there is a large body of evidence supporting the involvement of various infectious pathogens in the pathogenesis of dementia, but large-scale studies with long-term follow-up are needed to elucidate the role that infection may play, especially before subclinical or clinical disease is present.

COVID-19 clinical phenotypes and short-term outcomes: differences between the first and the second wave of pandemic in Italy.

Objectives: There are no comparative studies between patients belonging to the first and second waves of the SARS-CoV-2 pandemic, the virus triggering coronavirus disease 2019 (COVID-19). In this retrospective observational study, we analyzed the clinical characteristics and the short-term outcomes of two groups of laboratory-confirmed COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS) belonging to two different waves of the pandemic. Methods: We analyzed 97 consecutive patients from 11 March 2020 to 31 May 2020 and 52 consecutive patients from 28 August 2020 to 15 October 2020. Results: Patients belonging to the second wave were younger, had a lower number of concomitant chronic conditions (multimorbidity), and had a milder clinical phenotype. Medical treatments and respiratory support use have changed during the COVID-19 pandemic, based on different laboratory results and disease clinical features. Patients in the second wave had better short-term clinical outcomes, with lower death rates and more step-down transfers to a general ward. Conclusion: The present findings show a clear phenotypic difference in patients hospitalized at different stages of the COVID-19 pandemic in Italy. These results can help to stratify clinical risk and to better tailor medical treatments and respiratory support for patients with ARDS and COVID-19 pneumonia.

Bilevel and continuous positive airway pressure and factors linked to all-cause mortality in COVID-19 patients in an intermediate respiratory intensive care unit in Italy.

Objectives: In the present single-centered, retrospective, observational study, we reported findings from 78 consecutive laboratory-confirmed COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS) hospitalized in an intermediate Respiratory Intensive Care Unit, subdividing the patients into two groups according to their clinical outcome, dead patients and discharged patients.Methods: We further subdivided patients depending on the noninvasive respiratory support used during hospitalization.Results: In those patients who died, we found significant older age and higher multimorbidity and higher values of serum lactate dehydrogenase, C-reactive protein, and D-dimer. Among patients who were submitted to bilevel positive airway pressure (BPAP), those who died had a significant shorter number of days in overall length of stay and lower values of arterial oxygen partial pressure to fractional inspired oxygen ratio (PaO2/FiO2 ratio) compared to those who survived. No difference in all-cause mortality was observed between the two different noninvasive respiratory support groups [48% for continuous positive airway pressure (CPAP) and 52% for BPAP].Conclusion: In COVID-19 patients with moderate-to-severe ARDS using BPAP in an intermediate level of hospital care had more factors associated to all-cause mortality (shorter length of stay and lower baseline PaO2/FiO2 ratio) compared to those who underwent CPAP.