COVID-19 presents with a wide range of clinical neurological manifestations. It has been recognized that SARS-CoV-2 infection affects both the central and peripheral nervous system, leading to smell and taste disturbances; acute ischemic and hemorrhagic cerebrovascular disease; encephalopathies and seizures; and causes most surviving patients to have long lasting neurological symptoms. Despite this, typical neuropathological features associated with the infection have still not been identified. Studies of post-mortem examinations of the cerebral cortex are obtained with difficulty due to laboratory safety concerns. In addition, they represent cases with different neurological symptoms, age or comorbidities, thus a larger number of brain autoptic data from multiple institutions would be crucial. Histopathological findings described here are aimed to increase the current knowledge on neuropathology of COVID-19 patients. We report post-mortem neuropathological findings of ten COVID-19 patients. A wide range of neuropathological lesions were seen. The cerebral cortex of all patients showed vascular changes, hyperemia of the meninges and perivascular inflammation in the cerebral parenchyma with hypoxic neuronal injury. Perivascular lymphocytic inflammation of predominantly CD8-positive T cells mixed with CD68-positive macrophages, targeting the disrupted vascular wall in the cerebral cortex, cerebellum and pons were seen. Our findings support recent reports highlighting a role of microvascular injury in COVID-19 neurological manifestations.

Introduction: Chronic obstructive pulmonary disease (COPD) is the third cause of mortality and it is smoking-related. It is characterized by a non-reversible airflow limitation and a progressive worsening of the respiratory function. Objective: The aim of this study is to point out the benefit of smoking cessation combined with a single inhaler triple therapy in terms of clinical and functional outcome in this setting. Methods: A retrospective analysis was performed in patients affected by severe COPD and at least one exacerbation a year, who underwent a smoking cessation program. All patients underwent a 6 min walking test, body plethysmography, and an exhaled test for carbon monoxide. The modified medical research council test (mMRC) test, the Fagestrom nicotine dependency test (FTND) and the COPD assessment test (CAT) questionnaire were also administered. All patients were checked at the baseline and in the six-month follow-up after the start of the treatment. Results: Smoking cessation was achieved by 51% of patients within a month and it was confirmed by eCO measure (<7 ppm). Patients who quit smoking reported better results after six months compared with patients who did not. The increase in FEV1 within the group of quitters was 90 mL (p < 0.05) and the walking test improved by 90 m (p < 0.01); eCO decreased by 15 ppm (p < 0.01) while FVC increased by 70 mL (p < 0.05). No significant changes were recorded within the group of sustainers. The difference in functional changes between groups was significant with regard to FEV1, cCO, and WT. Conclusions: Smoking cessation enhances the efficacy of single inhaler triple therapy, improving clinical and functional variables after six months from the start.

Imiquimod is a TLR7/8 agonist that has anticancer therapeutic efficacy in the treatment of precancerous skin lesions and certain nonmelanoma skin cancers. To test our hypothesis that imiquimod enhances DNA repair as a mechanism for its anticancer activity, the nucleotide excision repair genes were studied in bone marrow-derived cells. Imiquimod enhanced the expression of xeroderma pigmentosum (XP) A and other DNA repair genes (quantitative real-time PCR analysis) and resulted in an increased nuclear localization of the DNA repair enzyme XPA. This was dependent on MyD88, as bone marrow-derived cells from MyD88^−/− mice did not increase XPA gene expression and did not enhance the survival of MyD88^−/−-derived bone marrow-derived cells after UV B exposure as was observed in bone marrow-derived cells from MyD88^+/+ mice. Imiquimod also enhanced DNA repair of UV light (UVL)-irradiated gene expression constructs and accelerated the resolution of cyclobutane pyrimidine dimers after UVL exposures in P388 and XS52. Lastly, topical treatment of mouse skin with 5% imiquimod cream prior to UVL irradiation resulted in a decrease in the number of cyclobutane pyridimine dimer-positive APC that were found in local lymph nodes 24 h after UVL irradiation in both wild-type and IL-12 gene-targeted mice. In total, these data support the idea that TLR7 agonists such as imiquimod enhance DNA repair in bone marrow-derived cells. This property is likely to be an important mechanism for its anticancer effects because it protects cutaneous APC from the deleterious effects of UVL.