Older people have paid a huge toll in terms of mortality during the coronavirus disease-19 (COVID-19) pandemic. Frailty may have contributed to the vulnerability of older people to more severe clinical presentation. We aimed at reviewing available evidence about frailty and COVID-19. We searched PUBMED, Web of Science, and EMBASE from 1 December 2019 to 29 May 2020. Study selection and data extraction were performed by three independent reviewers. Qualitative synthesis was conducted and quantitative data extracted when available. Forty papers were included: 13 editorials, 15 recommendations/guidelines, 3 reviews, 1 clinical trial, 6 observational studies, 2 case reports. Editorials and reviews underlined the potential clinical relevance of assessing frailty among older patients with COVID-19. However, frailty was only investigated in regards to its association with overall mortality, hospital contagion, intensive care unit admission rates, and disease phenotypes in the few observational studies retrieved. Specific interventions in relation to frailty or its impact on COVID-19 treatments have not been evaluated yet. Even with such limited evidence, clinical recommendations on the use of frailty tools have been proposed to support decision making about escalation plan. Ongoing initiatives are expected to improve knowledge of COVID-19 interaction with frailty and to promote patient-centered approaches.

Alzheimer's disease (AD) is a neurodegenerative disorder mainly characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles, loss of synapses and neurons and chronic neuroinflammation. Emerging data highlight the involvement of innate immunity, that has been shown to play opposing roles during the AD progression. Activated microglia and reactive astrocytes exert neuroprotection mediated through Aβ phagocytosis in the early stage, whereas, as the disease progresses, they fail in Aβ clearance and exert detrimental effects, including neuroinflammation and neurodegeneration. Specific toll-like receptors (TLRs) and coreceptors can directly or indirectly be activated to induce Aβ uptake or inflammatory responses, depending on the disease stage. Fibrillar Aβ can directly interact with TLR2, TLR4, and CD14 to induce microglial Aβ phagocytosis in the beginning stages, and neuroinflammatory responses in the late stages. Early TLR3-mediated signal enhances neuronal Aβ autophagy, although it increases neuronal apoptosis in the late AD stage. Similarly, TLR7, TLR8 and TLR9 can enhance microglial Aβ uptake in the early stage, but over time they contribute to neuroinflammation. Therefore, TLRs, and in particular TLR2 and TLR4, represent a suitable target for therapeutic intervention within the disease progression and targeting them carefully could increase Aβ autophagy and phagocytosis or reduce inflammatory responses. Several modulators with selective TLR agonist or antagonist activity have been developed, and many of them could have a therapeutic benefit in AD patients. This paper outlines the role of specific TLRs in AD, also focusing on TLR-targeted compounds yet indicated for the treatment of other inflammatory diseases, that could be used to treat the different stages of the disease.

The aim of our study was to assess respiratory function at the time of clinical recovery and 6 weeks after discharge in patients surviving to COVID-19 pneumonia. Methods Our case series consisted of 13 patients with COVID-19 pneumonia. Results At the time of clinical recovery, FEV1 (2.07 ± 0.72 L) and FVC (2.25 ± 0.86 L) were lower compared to lower limit of normality (LLN) values (2.56 ± 0.53 L, p = 0.004, and 3.31 ± 0.65 L, p < 0.001, respectively), while FEV1/FVC (0.94 ± 0.07) was higher compared to upper limit of normality (ULN) values (0.89 ± 0.01, p = 0.029). After 6 weeks pulmonary function improved but FVC was still lower than ULN (2.87 ± 0.81, p = 0.014). Conclusion These findings suggest that COVID-19 pneumonia may result in clinically relevant alterations in pulmonary function tests, with a mainly restrictive pattern.