Multiple sclerosis as a model to investigate SARS-CoV-2 effect on brain atrophy.

INTRODUCTION: Data on structural brain changes after infection with SARS-CoV-2 is sparse. We postulate multiple sclerosis as a model to study the effects of SARS-CoV-2 on brain atrophy due to the unique availability of longitudinal imaging data in this patient group, enabling assessment of intraindividual brain atrophy rates. METHODS: Global and regional cortical gray matter volumes were derived from structural MRIs using FreeSurfer. A linear model was fitted to the measures of the matching pre-SARS-CoV-2 images with age as an explanatory variable. The residuals were used to determine whether the post-SARS-CoV-2 volumes differed significantly from the baseline. RESULTS: Fourteen RRMS patients with a total of 113 longitudinal magnetic resonance images were retrospectively analyzed. We found no acceleration of brain atrophy after infection with SARS-CoV-2 for global gray matter volume (p = 0.17). However, on the regional level, parahippocampal gyri showed a tendency toward volume reduction (p = 0.0076), suggesting accelerated atrophy during or after infection. CONCLUSIONS: Our results illustrate the opportunity of using longitudinal MRIs from existing MS registries to study brain changes associated with SARS-CoV-2 infections. We would like to address the global MS community with a call for action to use the available cohorts, reproduce the proposed analysis, and pool the results.

IDIOPATHIC MULTIFOCAL CHOROIDITIS WITH SERPIGINOUS-LIKE PERIPAPILLARY CHORIORETINAL ATROPHY.

PURPOSE: To report nine cases of multifocal choroiditis with serpiginous-like peripapillary chorioretinal atrophy. METHODS: A retrospective observational case series of eyes with multifocal choroiditis with serpiginous-like peripapillary chorioretinal atrophy. Multimodal imaging findings were reviewed and presented. RESULTS: Fifteen eyes of 9 patients (6 women and 3 men), with a mean age of 48.1 years (median, 46 years; range, 23-74 years), presented with multifocal choroiditis serpiginous-like peripapillary chorioretinal atrophy. All 15 eyes presented with serpiginoid peripapillary changes and had discrete patches of atrophy or punched-out scars in the posterior pole or periphery. Eleven eyes (73.3%) had cone-shaped retinal pigment epithelium elevations on optical coherence tomography, 10 eyes (66.7%) had mild vitritis, and 4 eyes (26.7%) had peripheral curvilinear streak lesions. Three eyes (20%) had choroidal neovascularization. All patients responded well to treatment with systemic immunosuppression, local corticosteroid injections, and/or intravitreal anti-vascular endothelial growth factor injections. CONCLUSION: Multifocal choroiditis may present with peripapillary chorioretinal changes resembling a serpiginous-like choroiditis in addition to the classic findings of patches of atrophy or punched-out scars in the posterior pole or periphery, cone-shaped retinal pigment epithelium elevated on optical coherence tomography and peripheral curvilinear streak lesions.

Development of transgenic models susceptible and resistant to SARS-CoV-2 infection in FVB background mice.

Coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is currently spreading globally. To overcome the COVID-19 pandemic, preclinical evaluations of vaccines and therapeutics using K18-hACE2 and CAG-hACE2 transgenic mice are ongoing. However, a comparative study on SARS-CoV-2 infection between K18-hACE2 and CAG-hACE2 mice has not been published. In this study, we compared the susceptibility and resistance to SARS-CoV-2 infection between two strains of transgenic mice, which were generated in FVB background mice. K18-hACE2 mice exhibited severe weight loss with definitive lethality, but CAG-hACE2 mice survived; and differences were observed in the lung, spleen, cerebrum, cerebellum, and small intestine. A higher viral titer was detected in the lungs, cerebrums, and cerebellums of K18-hACE2 mice than in the lungs of CAG-hACE2 mice. Severe pneumonia was observed in histopathological findings in K18-hACE2, and mild pneumonia was observed in CAG-hACE2. Atrophy of the splenic white pulp and reduction of spleen weight was observed, and hyperplasia of goblet cells with villi atrophy of the small intestine was observed in K18-hACE2 mice compared to CAG-hACE2 mice. These results indicate that K18-hACE2 mice are relatively susceptible to SARS-CoV-2 and that CAG-hACE2 mice are resistant to SARS-CoV-2. Based on these lineage-specific sensitivities, we suggest that K18-hACE2 mouse is suitable for highly susceptible model of SARS-CoV-2, and CAG-hACE2 mouse is suitable for mild susceptible model of SARS-CoV-2 infection.

Ospemifene: A Novel Oral Therapy for Vulvovaginal Atrophy of Menopause.

Vulvovaginal atrophy (VVA) resulting from estrogen deprivation at menopause often results in distressing vaginal dryness and dyspareunia. Fewer than 25% of affected women seek help for this condition citing embarrassment, cultural values, an aging or unavailable partner and concerns about use of estrogens following the Women's Health Initiative. Available non-hormonal treatments, such as moisturizers, while affording some relief can be messy to apply and do not prevent disease progression. A new oral selective estrogen receptor modulator, ospemifene, has been found to have strong estrogenic activity in vaginal tissues without adverse estrogenic effects at other sites.