Similar to its predecessors, coronavirus disease 2019 (COVID-19) exhibits neurotrophic properties, which lead to progression of neurologic sequelae. Besides direct viral invasion to the central nervous system (CNS), indirect CNS involvement through viral-mediated immune response is plausible. Aberrant immune pathways such as extreme release of cytokines (cytokine storm), autoimmunity mediated by cross-reactivity between CNS components and viral particles, and microglial activation propagate CNS damage in these patients. Here, we review the currently available evidence to discuss the plausible immunologic pathways that may contribute to the development of COVID-19 neurological complications, namely Alzheimer's disease, Parkinson's disease, stroke, multiple sclerosis, Guillain-Barre syndrome, seizure, and brainstem involvement.

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BACKGROUNDAngiotensin II activation by angiotensin-converting enzyme (ACE) is a significant mediator in wound healing and collagen production. In this study, the effect of topical application of ACE on hypertrophic scar formation has been studied in a clinical trial.METHODSThirty patients with hypertrophic scar and itching after treatment of 2nd or 3rd degree burns participated in this double-blinded clinical trial. Subjects had two same-degree scars on symmetrical sites of body which were randomly allocated into two groups. One side was treated with 1% enalapril ointment and the other side with placebo twice daily. During a 6-months follow-up, a scoring table for itching was completed on a daily basis by patients. Furthermore, a single surgeon measured size of scars once a month. The mean size, thickness and itching score were calculated for each scar and compared between medication and placebo-treated scars. RESULTSThe mean size of scars in enalapril treated side was significantly less than scars in the placebo side. Additionally, enalapril treated scars had significantly lower itching scores compared to the placebo group.CONCLUSIONTopical enalapril significantly decreases the clinical parameters of hypertrophic scar and also itching as an indirect indicative of scar improvement. Furthermore, enalapril proved to be clinically safe for patients with low incidence of adverse drug reactions and acceptable cost effectiveness.

Purpose The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction in COVID-19. We aimed to aggregate the results of the studies which reported imaging of the olfactory system of patients with COVID-19 versus controls. Methods PubMed and EMBASE were searched to identify relevant literature reporting the structural imaging characteristics of the olfactory bulb (OB), olfactory cleft, olfactory sulcus (OS), or olfactory tract in COVID-19 patients. Hedge’s g and weighted mean difference were used as a measure of effect size. Quality assessment, subgroup analyses, meta-regression, and sensitivity analysis were also conducted. Results Ten studies were included in the qualitative synthesis, out of which seven studies with 183 cases with COVID-19 and 308 controls without COVID-19 were enrolled in the quantitative synthesis. No significant differences were detected in analyses of right OB volume and left OB volume. Likewise, right OS depth and left OS depth were also not significantly different in COVID-19 cases compared to non-COVID-19 controls. Also, we performed subgroup analysis, meta-regression, and sensitivity analysis to investigate the potential effect of confounding moderators. Conclusion The findings of this review did not confirm alterations in structural imaging of the olfactory system, including OB volume and OS depth by Covid-19 which is consistent with the results of recent histopathological evaluations. Supplementary Information The online version contains supplementary material available at 10.1007/s00234-022-03014-8.

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