Comparative study of CNR1 and CNR2 cannabinoid receptors expression levels in COVID-19 patients with and without diabetes mellitus: Recommendations for future research targets.

BACKGROUND AND AIMS: The COVID-19 pandemic has prompted researchers to look for effective therapeutic targets. The effect of endocannabinoid system against infectious diseases is investigated for several years. In this study, we evaluated the expression level of CNR1 and CNR2 genes in patients with COVID-19 with and without diabetes to provide new insights regarding these receptors and their potential effect in COVID-19 disease. METHODS: In this study, peripheral blood monocytes cells (PBMCs) were isolated from eight different groups including COVID-19 patients, diabetic patients, and healthy individuals. RNA were extracted to evaluate the expression level of CNR1 and CNR2 genes using real-time PCR. The correlation between the expression levels of these genes in different groups were assessed. RESULTS: A total of 80 samples were divided into 8 groups, with each group consisting of ten samples. When comparing severe and moderate COVID-19 groups to healthy control group, the expression levels of the CNR1 and CNR2 genes were significantly higher in the severe and moderate COVID-19 groups. There were no significant differences between the mild COVID-19 group and the healthy control group. It was found that the expression levels of these genes in patients with diabetes who were infected with SARS-COV-2 did not differ across COVID-19 groups with varying severity, but they were significantly higher when compared to healthy controls. CONCLUSION: Our study suggests the possible role of endocannabinoid system during SARS-COV-2 pathogenicity as the expression of CNR1 and CNR2 were elevated during the disease.

Epidemic size, trend and spatiotemporal mapping of SARS-CoV-2 using geographical information system in Alborz Province, Iran.

BACKGROUND: The first confirmed cases of COVID-19 in Iran were reported in Qom city. Subsequently, the neighboring provinces and gradually all 31 provinces of Iran were involved. This study aimed to investigate the case fatility rate, basic reproductive number in different period of epidemic, projection of daily and cumulative incidence cases and also spatiotemporal mapping of SARS-CoV-2 in Alborz province, Iran. METHODS: A confirmed case of COVID-19 infection was defined as a case with a positive result of viral nucleic acid testing in respiratory specimens. Serial interval (SI) was fitted by gamma distribution and considered the likelihood-based R0 using a branching process with Poisson likelihood. Seven days average of cases, deaths, doubling times and CFRs used to draw smooth charts. kernel density tool in Arc GIS (Esri) software has been employed to compute hot spot area of the study site. RESULTS: The maximum-likelihood value of R0 was 2.88 (95%, CI: 2.57-3.23) in the early 14 days of epidemic. The case fatility rate for Alborz province (Iran) on March 10, was 8.33% (95%, CI:6.3-11), and by April 20, it had an increasing trend and reached 12.9% (95%,CI:11.5-14.4). The doubling time has been increasing from about two days and then reached about 97 days on April 20, 2020, which shows the slowdown in the spread rate of the disease. Also, from March 26 to April 2, 2020 the whole Geographical area of Karj city was almost affected by SARS-CoV-2. CONCLUSIONS: The R0 of COVID-19 in Alborz province was substantially high at the beginning of the epidemic, but with preventive measures and public education and GIS based monitoring of the cases,it has been reduced to 1.19 within two months. This reduction highpoints the attainment of preventive measures in place, however we must be ready for any second epidemic waves during the next months.

Effect of Ammonium Chloride in addition to standard of care in outpatients and hospitalized COVID-19 patients: A randomized clinical trial.

OBJECTIVE: The COVID-19 pandemic has called an urgent need for drug repurposing to improve the outcome of the disease. Quaternary ammonium compounds have been demonstrated to have antiviral effects and may be of use against SARS-CoV-2 infections. DESIGN: In this double-blind, single-center study, we enrolled patients with positive PCR test and/or CT findings for COVID-19. The participants of each group were randomly assigned to Diphenhydramine Compound (Diphenhydramine + Ammonium Chloride) plus standard of care or to Diphenhydramine alone and standard of care groups. The primary outcome was all-cause mortality within 30 days of randomization. Secondary outcomes include viral burden, clinical status, assessed by a 5-point ordinal scale, and length of stay in hospitalized patients. RESULTS: A total of 120 patients were included in the trial, 60 of which were assigned to the Ammonium Chloride group. The primary endpoint was not statistically different between the two groups (HR: 3.02 (95% CI, 0.57-16.06; p = 0.195)). Recovery time and viral burden were significantly lower in the Ammonium Chloride group, corresponding to an odds ratios of 1.8 (95% CI, 1.15-2.83; p = 0.01) and 7.90 (95% CI, 1.62-14.17; p = 0.014), respectively. CONCLUSION: The findings of this study advocate the careful addition of Ammonium Chloride to standard of care for COVID-19 patients.