Delineating the SARS-CoV-2 Induced Interplay between the Host Immune System and the DNA Damage Response Network.

COVID-19 is an infectious disease caused by the SARS-CoV-2 coronavirus and characterized by an extremely variable disease course, ranging from asymptomatic cases to severe illness. Although all individuals may be infected by SARS-CoV-2, some people, including those of older age and/or with certain health conditions, including cardiovascular disease, diabetes, cancer, and chronic respiratory disease, are at higher risk of getting seriously ill. For cancer patients, there are both direct consequences of the COVID-19 pandemic, including that they are more likely to be infected by SARS-CoV-2 and more prone to develop severe complications, as well as indirect effects, such as delayed cancer diagnosis or treatment and deferred tests. Accumulating data suggest that aberrant SARS-CoV-2 immune response can be attributed to impaired interferon signaling, hyper-inflammation, and delayed adaptive immune responses. Interestingly, the SARS-CoV-2-induced immunological abnormalities, DNA damage induction, generation of micronuclei, and the virus-induced telomere shortening can abnormally activate the DNA damage response (DDR) network that plays a critical role in genome diversity and stability. We present a review of the current literature regarding the molecular mechanisms that are implicated in the abnormal interplay of the immune system and the DDR network, possibly contributing to some of the COVID-19 complications.

The gut microbiome molecular mimicry piece in the multiple sclerosis puzzle.

The etiological complexity of multiple sclerosis, an immune-mediated, neurodegenerative disease with multifactorial etiology is still elusive because of an incomplete understanding of the complex synergy between contributing factors such as genetic susceptibility and aberrant immune response. Recently, the disease phenotypes have also been shown to be associated with dysbiosis of the gut microbiome, a dynamic reservoir of billions of microbes, their proteins and metabolites capable of mimicring the autoantigens. Microbial factors could potentially trigger the neuroinflammation and symptoms of MS. In this perspective article, we discussed how microbial molecules resulting from a leaky gut might mimic a host's autoantigen, potentially contributing to the disease disequilibrium. It further highlights the importance of targeting the gut microbiome for alternate therapeutic options for the treatment of MS.

Gut dysbiosis and lack of short chain fatty acids in a Chinese cohort of patients with multiple sclerosis.

BACKGROUND: Recent studies, mostly conducted in Western countries, showed that gut microbes are involved in the pathogenesis of multiple sclerosis (MS). OBJECTIVE: The aim of this study was to investigate whether gut dysbiosis is relevant to the initiation and progression of MS in a Chinese population. METHODS: Next-generation sequencing (NGS) and gas chromatography (GC) were integrated and used to compare the fecal bacterial communities and the short-chain fatty acid (SCFA) levels among relapsing-remitting MS (RRMS) patients (n = 34), neuromyelitis optica spectrum disorder (NMOSD) patients (n = 34), and healthy controls (HCs) (n = 34). T-cell profile analyses were performed by flow cytometry for MS patients and matched controls (n = 12). RESULTS: (1) The gut microbiome of MS patients was characterized by an increase of Streptococcus and a decrease of Prevotella_9; additionally, compared to NMOSD patients, Prevotella_9 was found to be much more abundant in MS patients. (2) A striking depletion of fecal acetate, propionate, and butyrate was observed in MS patients compared to HCs. (3) The abundance of Streptococcus was negatively correlated with the proportion of pTregs (P < 0.05) and positively correlated with Th17 cells (P < 0.05) in the peripheral blood, while the abundance of Prevotella_9 was negatively correlated with the Th17 cell frequency (P < 0.01), and the fecal SCFA level was positively correlated with pTreg frequency (P < 0.05). CONCLUSIONS: Gut dysbiosis and a lack of SCFAs exist in Chinese MS patients, which might be related to an aberrant immune response of MS; this relationship may have a diagnostic and therapeutic value for patients with MS.