Gut Microbiota Might Act as a Potential Therapeutic Pathway in COVID-19.

It has been very recently suggested that individuals with chronic gut inflammation are highly susceptible to COVID-19. They constitute the serious cases of COVID-19, in which inflammatory cytokine storm is observed. On the contrary, the healthy gut microbiota is linked with low chronic gut and systemic inflammation. This raises the idea that maintenance of the healthy gut microbiota and prevention of gut microbial dysbiosis in COVID-19 patients might avoid the increased cytokine storm, which in turn might reduce the mortality rate. It has been shown that the modulation of the gut microbiota is an effective strategy to strengthen immunity and might be a possible treatment for individuals with viral infections. Currently, there is no clinical data considering the impact of the modulation of the gut microbiota on the treatment of COVID-19. We hypothesize that targeting the gut microbiota might be a novel therapeutic approach or at least a supportive therapy. In the present review article, we described the interaction between SARS-CoV-2 and gut microbiota dysbiosis through two possible mechanisms, including aberrant immune activation and aberrant mammalian target of rapamycin (mTOR) activation. Further, the disruption of the gastrointestinal reninangiotensin system (GI RAS), dysregulation of the coagulation and fibrinolytic systems, and the activity of human serine proteases in COVID-19 pathogenesis were addressed. We also provided possible strategies to restore all the discussed aspects via gut microbiota modulation.

A comprehensive overview of identified mutations in SARS CoV-2 spike glycoprotein among Iranian patients.

Since late 2019, when SARS-CoV-2 was reported at Wuhan, several sequence analyses have been performed and SARS-CoV-2 genome sequences have been submitted in various databases. Moreover, the impact of these variants on infectivity and response to neutralizing antibodies has been assessed. In the present study, we retrieved a total number of 176 complete and high-quality S glycoprotein sequences of Iranian SARS-COV-2 in public database of the GISAID and GenBank from April 2020 up to May 2021. Then, we identified the number of variables, singleton and parsimony informative sites at both gene and protein levels and discussed the possible functional consequences of important mutations on the infectivity and response to neutralizing antibodies. Phylogenetic tree was constructed to represent the relationship between Iranian SARS-COV2 and variants of concern (VOC), variants of interest (VOI) and reference sequence. We found that the four current VOCs - Alpha, Beta, Gamma and Delta - are circulated in different regions in Iran. The Delta variant is notably more transmissible than other variants, and is expected to become a dominant variant. However, some of the Delta variants in Iran carry an additional mutation, namely E1202Q in the HR2 subdomain that might confer an advantage to viral/cell membrane fusion process. We also observed some more common mutations such as an N-terminal domain (NTD) deletion at position I210 and P863H in fusion peptide-heptad repeat 1 span region in Iranian SARS-COV-2. The reported mutations in the current project have practical significance in prediction of disease spread as well as design of vaccines and drugs.

Assessment of ACE1 variants and ACE1/ACE2 expression in COVID-19 patients.

Contribution of the renin-angiotensinogen system in the risk of COVID-19 and related complications have been assessed by several groups. However, the results are not consistent. We examined levels of ACE1 and ACE2 in the circulation of two groups of COVID-19 patients (ICU-admitted and general ward-admitted patients) compared with healthy controls. We also genotyped two polymorphisms in ACE1 gene (the ACE1-I/D polymorphism rs1799752 and rs4359) to appraise their association with expression levels of ACE1 and ACE2. Expression level of ACE1 was significantly higher in ICU patients compared with non-ICU patients (P value = 0.02). However, its expression was not significantly different between total COVID-19 patients and total controls (P value = 0.34). ACE2 expression was not different ether between two groups of COVID-19 patients (P value = 0.12) or between total COVID-19 patients and total controls (P value = 0.79). While distribution of rs1799752 and rs4359 alleles was similar between study groups, genotype frequencies of rs1799752 were differently distributed among total COVID-19 patients and controls (P value = 0.00001). Moreover, genotypes of the other polymorphism tended to be distinctively distributed among these two groups (P value = 0.06). In the total population of patients and controls, different ACE1 mRNA levels were observed among carriers of different rs1799752 genotypes; of note, ID genotype carriers showed a higher expression of ACE1 compared with II genotype carriers (P = 0.01). ACE1 polymorphisms might affect risk of COVID-19 and expression of ACE transcripts.