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.

Social Frailty in the COVID-19 Pandemic Era.

Special attention and efforts to protect from or reduce health-related outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus triggering coronavirus disease 2019 (COVID-19), should be applied in susceptible populations, including frail older people. In particular, the early death cases occurred primarily in older people with a frailty status, possibly due to a weaker immune system fostering faster progression of the viral infection. Frailty is an age-related multidimensional clinical condition defined as a non-specific state of vulnerability, identifying older people at increased risk of falls, institutionalization, hospitalization, disability, dementia, and death. Among frailty phenotypes, social frailty has been least studied. It considers the role of socioeconomic context as a vulnerability status later in life. COVID-19 does not affect all populations equally, and social inequalities contribute to drive the spread of infections. It was known that the perception of social isolation, e.g., loneliness, affects mental and physical health, but the implicated molecular mechanisms, also related to the immune system, and its associated cognitive and health-related sequelae, are poorly understood. The increasing psychological distress derived by prolonged exposure to stress due to the lockdown scenario, and the reduced sources of support, contributed to making heavy demands on personal resources, i.e., self-efficacy and interpersonal variables. So, perceived loneliness may be a factor associated with psychological distress and an outcome in itself. In the COVID-19 pandemic era, a correct assessment of social frailty may be essential in terms of the prevention of late-life neuropsychiatric disorders.

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.

More skilled clinical management of COVID-19 patients modified mortality in an intermediate respiratory intensive care unit in Italy.

BACKGROUND: Some studies investigated epidemiological and clinical features of laboratory-confirmed patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the virus causing coronavirus disease 2019 (COVID-19), but limited attention has been paid to the follow-up of hospitalized patients on the basis of clinical setting and the expertise of clinical management. METHODS: In the present single-centered, retrospective, observational study, we reported findings from 87 consecutive laboratory-confirmed COVID-19 patients with moderate-to-severe acute respiratory syndrome hospitalized in an intermediate Respiratory Intensive Care Unit (RICU), subdividing the patients in two groups according to the admission date (before and after March 29, 2020). RESULTS: With improved skills in the clinical management of COVID-19, we observed a significant lower mortality in the T2 group compared with the T1 group and a significantly difference in terms of mortality among the patients transferred in Intensive Care Unit (ICU) from our intermediate RICU (100% in T1 group vs. 33.3% in T2 group). The average length of stay in intermediate RICU of ICU-transferred patients who survived in T1 and T2 was significantly longer than those who died (who died 3.3 ± 2.8 days vs. who survived 6.4 ± 3.3 days). T CONCLUSIONS: The present findings suggested that an intermediate level of hospital care may have the potential to modify survival in COVID-19 patients, particularly in the present phase of a more skilled clinical management of the pandemic.

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.