Background The COVID-19 pandemic remains an emerging public health crisis with serious adverse effects. The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV--2) infection, targeting angiotensin-converting enzyme-2 (ACE2) receptor for cell entry. However, changes in the renin-angiotensin system (RAS) balance alter an individual’s susceptibility to COVID-19 infection. We aimed to evaluate the association between AGT rs699 C > T, ACE rs4646994 I/D, and AGTR1 rs5186 C > A variants and the risk of COVID-19 infection and the severity in a sample of the southeast Iranian population. Methods A total of 504 subjects, including 258 COVID-19 positives, and 246 healthy controls, were recruited. Genotyping of the ACE gene rs4646994, and AGT rs699, and AGTR1 rs5186 polymorphisms was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP), respectively. Results Our results showed that the II genotype of ACE rs4646994 and the I allele decreased the risk of COVID-19 infection. Moreover, we found that the TC genotype and C allele of AGT rs699 increased the risk of COVID-19 infection. The AGTR1 rs5186 was not associated with COVID-19 infection. Also, we did not find any association between these polymorphisms and the severity of the disease. However, we found a significantly higher age and prevalence of diabetes and hypertension in patients with severe disease than a non-severe disease. Conclusions These findings suggest that ACE rs4646994 and AGT rs699 polymorphisms increase the risk of COVID-19 infection in a southeast Iranian population.

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Cognitive functions such as working memory require integrated activity among different brain regions. Notably, entorhinal cortex (EC) activity is associated with the successful working memory task. Olfactory bulb (OB) oscillations are known as rhythms that modulate rhythmic activity in widespread brain regions during cognitive tasks. Since the OB is structurally connected to the EC, we hypothesized that OB could modulate EC activity during working memory performance. Herein, we explored OB–EC functional connectivity during spatial working memory performance by simultaneous recording local field potentials when rats performed a Y-maze task. Our results showed that the coherence of delta, theta, and gamma-band oscillations between OB and EC was increased during correct trials compared to wrong trials. Cross-frequency coupling analyses revealed that the modulatory effect of OBs low-frequency phase on EC gamma power and phase was enhanced when animals correctly performed working memory task. The influx of information from OB to EC was also increased at delta and gamma bands within correct trials. These findings indicated that the modulatory influence of OB rhythms on EC oscillations might be necessary for successful working memory performance.

Neural oscillations synchronize the activity of brain regions during cognitive functions, such as spatial working memory. Olfactory bulb (OB) oscillations are ubiquitous rhythms that can modulate neocortical and limbic regions. However, the functional connectivity between the OB and areas contributing to spatial working memory, such as the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC), is less understood. Hence, we investigated functional interaction between OB and the vHPC–mPFC circuit during the spatial working memory performance in rats. To this end, we analyzed the simultaneously recorded local field potentials from OB, vHPC, and mPFC when rats explored the Y-maze and compared the brain activities of correct trials vs. wrong trials. We found that coupling between the vHPC and mPFC was augmented during correct trials. The enhanced coherence of OB activity with the vHPC–mPFC circuit at delta (< 4 Hz) and gamma (50–80 Hz) ranges were observed during correct trials. The cross-frequency analysis revealed that the OB delta phase increased the mPFC gamma power within corrected trials, indicating a modulatory role of OB oscillations on mPFC activity during correct trials. Moreover, the correlation between OB oscillations and the vHPC–mPFC circuit was increased at the delta range during correct trials, exhibiting enhanced synchronized activity of these regions during the cognitive task. We demonstrated a functional engagement of OB connectivity with the vHPC–mPFC circuit during spatial working memory task performance.