ABSTRACT
Objective: Post-COVID 19 depression has gained much attention due to the increasing percentage of depressive symptoms reported by COVID-19 survivors. Among many factors postulated to be responsible for this depression, neuroinflammation gained the most attention. Therefore, in current work, we selected an anandamide reuptake inhibitor, VDM11, as a possible candidate for managing post-COVID depression. Methods: The role of VDM11 in attenuating neuroinflammation was established by using network pharmacology, molecular docking, and an in vivo LPS-induced depression model. Results: The results of network pharmacology revealed that among all the genes that can be targeted by VDM11, 47 genes were directly linked to the pathophysiology of depression. Additionally, on the basis of protein-protein interaction (PPI) analysis, the top 10 hub genes probably responsible for VDM11 antidepressant attribute were screened. These genes include MAPK3, TNF-alpha, IL-1beta, IL-6, PPARG, MAPK1, CNR1, MTOR, NR3C1, and IGF1R. These genes were also enriched in GO and KEGG analysis. Molecular docking was carried out with top five hub genes screened by PPI network and KEGG analysis which showed that VDM11 interacts well with these targets. The antidepressant potential of VDM11 was also assessed by employing a LPS-induced depression model. Animals provided with VDM11 demonstrated increased exploration time and spontaneous alterations in elevated plus and Y maze models. Additionally, the level of astrocyte marker GFAP, microglia marker CD11b, and proinflammatory cytokines, including TNFalpha, IL-1beta, and IL-6, in the hippocampus were significantly reduced by VDM11, further strengthening its role in neuroinflammation. Conclusion: VDM11, an anandamide reuptake inhibitor, might serve as a possible candidate for post-COVID depression, probably by modulating neuroinflammation. However, detailed pharmacological studies are required to validate these outcomes.
ABSTRACT
Background: Ascorbic acid represents an appealing option for clinicians to utilize in the context of a global health pandemic of COVID-19 patients due to its proposed clinical efficacy, relative safety, and low cost. Objectives: The aim of this study was to evaluate the efficacy and safety of using ascorbic acid in supplemental dose as adjunctive therapy in critically ill patients with COVID-19. Methods: : This was a multi-center, non-interventional, retrospective cohort study. All critically ill adult patients admitted to ICU with a confirmed COVID-19 between March 1st to December 31 st , 2020 were included in the final analysis. The study was conducted at two large governmental tertiary hospitals in Saudi Arabia. The purpose was to investigate the association between clinical outcomes with ascorbic acid use as an adjunctive therapy in COVID-19 after propensity score matching using baseline severity scores, systemic use of corticosteroids and study centers. Results: : A 739 patients were included in this study; 296 patients were included after propensity score matching. There was no association between the administration of ascorbic acid and in-hospital mortality nor 30-day ICU mortality (OR (95%CI): 0.77 (0.476, 1.234), p-value=0.2738 and OR (95%CI): 0.73 (0.438 ,1.204), p-value=0.215 respectively). Using ascorbic acid was associated with lower incidence of thrombosis compared with the non-ascorbic acid group (6.1% vs. 13% respectively); OR (95%CI): 0.42 (0.184, 0.937), p-value=0.0342). Conclusion: Supplemental dose of ascorbic acid as an adjunctive therapy in COVID19 critically ill patients was not associated with mortality benefits; but associated with lower incidence of thrombosis. Further studies are required to confirm these findings.
Subject(s)
COVID-19 , ThrombosisABSTRACT
Background: Due to its supposed clinical efficacy, relative safety, and low cost, ascorbic acid represents an appealing option for clinicians to utilize in the context of a global health pandemic of COVID-19 patients.Objectives: The aim of this study was to evaluate the efficacy and safety of using ascorbic acid as adjunctive therapy in critically ill patients with COVID-19. Methods: This was a multi-center, non-interventional, retrospective cohort study. All critically ill adult patients admitted to ICU with a confirmed COVID-19 between March 1st to December 31st, 2020 were included in the final analysis. The study was conducted at two large governmental tertiary hospitals in Saudi Arabia. The purpose was to investigate the association between clinical outcomes with ascorbic acid use as an adjunctive therapy in COVID-19 after propensity score matching using baseline severity scores, systemic use of corticosteroids and study centers. Results: A 739 patients were included in this study; 296 patients were included after propensity score matching. There was no association between the administration of ascorbic acid and in-hospital mortality nor 30-day ICU mortality (OR (95%CI): 0.77 (0.476, 1.234), p-value=0.2738 and OR (95%CI): 0.73 (0.438 ,1.204), p-value=0.215 respectively). Using ascorbic acid was associated with lower incidence of thrombosis compared with the non-ascorbic acid group (6.1% vs. 13% respectively); OR (95%CI): 0.42 (0.184, 0.937), p-value=0.0342).Conclusion: Ascorbic acid use as an adjunctive therapy in COVID19 critically ill patients was not associated with mortality benefits; but associated with lower incidence of thrombosis. Further studies are required to confirm these findings.
Subject(s)
COVID-19 , Critical Illness , ThrombosisABSTRACT
Background: Estimated seroprevalence of Coronavirus Infectious Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is a critical evidence for a better evaluation of the virus spread and monitoring the progress of the COVID-19 pandemic in a population. In the Kingdom of Saudi Arabia (KSA), SARS-CoV-2 seroprevalence has been reported in specific regions, but an extensive nationwide study has not been reported. Here, we report a nationwide study to determine the prevalence of SARS-CoV-2 in the population of KSA during the pandemic, using serum samples from healthy blood donors, non-COVID patients and healthcare workers (HCWs) in six different regions of the kingdom, with addition samples from COVID-19 patients.Methods: A total of 11703 serum samples were collected from different regions of the KSA including; 5395 samples from residual healthy blood donors (D); 5877 samples from non-COVID patients collected through residual sera at clinical biochemistry labs from non-COVID patients (P); and 400 samples from consented HCWs. To determine the seroprevalence of SARS-CoV-2, all serum samples, in addition to positive control sera from RT-PCR confirmed COVID-19 patients, were subjected to in-house ELISA with a sample pooling strategy, which was further validated by testing individual samples that make up some of the pools, with a statistical estimation method to report seroprevalence estimates.Results: Overall (combining D and P groups) seroprevalence estimate was around 11% in Saudi Arabia; and was 5.1% (Riyadh), 1.5% (Jazan), 18.4% (Qassim), 20.8% (Hail), 14.7% (ER; Alahsa), and 18.8% in Makkah. Makkah samples were only D group and had a rate of 24.4% and 12.8% in the cities of Makkah and Jeddah, respectively. The seroprevalence in Saudi Arabia across the sampled areas would be 12 times the COVID-19 infection rate. Among HCWs, 7.5% (4.95-10.16 CI 95%) had reactive antibodies to SARS-CoV-2 without reporting any previously confirmed infection. This was higher in HCWs with hypertension. The study also presents the demographics and prevalence of co-morbidities in HCWs and subset of non-COVID-19 population.Conclusion: Our study estimates the overall national serological prevalence of COVID-19 in Saudi Arabia to be 11%, with an apparent disparity between regions.Funding Statement: This study was funded by KAIMRC, Grant: RC20/180; PI: Naif K. Alharbi.Declaration of Interests: The authors declare no conflict of interest.Ethics Approval Statement: The study was approved by the IRB in KAIMRC (Ministry of National Guard Health Affairs) for project number RC20-180. Residual samples from blood banks and clinical laboratories were obtained after an IRB approval. COVID-19 patients and HCWs signed informed consents to give blood samples.