We read with great interest the commentary by Helmich and Bloem [1] in which the authors suggested that patients with Parkinson's disease (PD) may not only face a greater risk of developing worse coronavirus disease 2019 (COVID-19)-related respiratory outcomes, but also a variety of "hidden sorrows" of the pandemic. The authors argue that PD patients may suffer from chronic stress and lack of physical activity associated with social isolation. As the COVID-19 continues snaking its way around the world (as of April 29, 2020, global cases topped 3 million), we would like to further highlight several impacts that the ongoing COVID-19 pandemic may induce on the global burden of PD. Preliminary studies suggested that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the etiologic agent of the COVID-19, may have a potential neurotropism in humans though such feature has not been conclusively demonstrated yet [2, 3]. Similar to other respiratory viruses, the SARS-CoV-2 may gain access to the Central Nervous System (CNS) by the hematogenous route or axonal transport along with the olfactory neuroepithelium [4, 5]. The olfactory pathway hypothesis for SARS-CoV-2 neuroinvasion is supported by the fact

Because a number of data studies include some controversial results about Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and Down syndrome (DS), we performed a meta-analysis to determine a more precise estimation of this association. Studies were searched on PubMed, EMBASE and Lilacs-Scielo, up to April 2013, and they were eligible if they included case mothers (DSM) that have gave birth to children with DS, and controls mothers (CM) that have gave birth to healthy children without chromosomal abnormality, syndrome or malformation. The combined odds ratio with 95% confidence intervals was calculated by fixed or random effects models to assess the strength of associations. Potential sources of heterogeneity between studies were evaluated using Q test and the I(2). Publication bias was estimated using Begg's test and Egger's linear regression test. Sensitivity analyses were performed by using allelic, dominant, recessive and codominant genetic models, Hardy-Weinberg equilibrium (HWE) and ethnicity. Twenty-two studies with 2,223 DSM and 2,807 CM were included for MTHFR C677T and 15 studies with 1,601 DSM and 1,849 CM were included for MTHFR A1298C. Overall analysis suggests an association of the MTHFR C677T polymorphism with maternal risk for DS. Moreover, no association between the MTHFR A1298C polymorphism and maternal risk for DS was found. There is also evidence of higher heterogeneity, with I(2) test values ranging from 8 to 89%. No evidence of publication bias was found. Taken together, our meta-analysis implied that the T allele carriers might carry an increased maternal risk for DS.

Inconclusive results of the association between genetic polymorphisms involved in folate metabolism and maternal risk for Down syndrome (DS) have been reported. Therefore, this meta-analysis was conducted. We searched electronic databases through May, 2014, for eligible studies. Pooled odds ratios with 95% confidence intervals were used to assess the strength of the association, which was estimated by fixed or random effects models. Heterogeneity among studies was evaluated using Q-test and I 2 statistic. Subgroup and sensitivity analyses were also conducted. Publication bias was estimated using Begg's and Egger's tests. A total of 17 case-controls studies were included. There was evidence for an association between the MTRR c.66A>G (rs1801394) polymorphism and maternal risk for DS. In the subgroup analysis, increased maternal risk for DS was found in Caucasians. Additionally, the polymorphic heterozygote MTHFD1 1958GA genotype was associated significantly with maternal risk for DS, when we limit the analysis by studies conformed to Hardy-Weinberg equilibrium. Finally, considering MTR c.2756A>G (rs1805087), TC2 c.776C>G (rs1801198), and CBS c.844ins68, no significant associations have been found, neither in the overall analyses nor in the stratified analyses by ethnicity. In conclusion, our meta-analysis suggested that the MTRR c.66A>G (rs1801394) polymorphism and MTHFD1 c.1958G>A (rs2236225) were associated with increased maternal risk for DS.

We thank the ICM technical facilities PHENO-ICMICE, iGENSEQ and ICM.Quant.