Background: Mesenchymal stem cells (MSCs) are known to have immunomodulatory, anti-inflammatory, anti-apoptotic, and angiogenesis effects that are useful for relieving inflammation, recovery, and protection of lung tissues in COVID-19 patients. Secretome, a secretory product of MSCs, has several advantages over MSCs. We conducted a study to investigate secretomes’ effectiveness and safety profile as a treatment for severe COVID-19. Methods: A double-blind, multicenter, randomized, placebo-controlled trial was conducted between February 2021 and July 2021 in three top COVID-19 referral hospitals in the Greater Jakarta area, Indonesia. Eligible subjects (n=40) were randomized in a 1:1 ratio to an intervention group (n=20) and a control group (n=20). The primary outcome of this study was the changes in inflammatory markers and the ratio of inflammatory to anti-inflammatory markers. The secondary outcomes of this study included clinical outcome, laboratory outcome, radiological outcome, RT-PCR result conversion, and safety profile of MSC secretome. Results: Our analysis showed that on the 14th day after placebo administration, IL-6 level in the control group was significantly increased [4.110 (2.403–12.820) at baseline to 13.320 (2.958–33.285) on the 14th day after intervention, p=0.017]. The IL-6/IL-10 ratio in the control group was significantly increased (p=0.036) on the 14th day after placebo administration. We also found that most of the subjects who received placebo had high levels of IL-6 and ferritin (p=0.043) on the seventh day after the intervention. However, we found no significant differences in inflammatory marker levels on the seventh day and 14th day after intervention between both groups. There was no adverse event reported. There were no significant differences in the laboratory outcome, radiology outcome, RT-PCR result conversion, and safety profiles between both groups. Conclusions: MSC secretome can control inflammation in patients with severe COVID-19 and has a good safety profile. MSC secretome is a promising treatment modality for severe COVID-19.
Background Status of the latest developments from the spread of COVID-19 in Indonesia has reached 15438 cases with 1028 cases of patients died, updated on May 13, 2020. Unfortunately, the number of infected continues to overgrow, and no drugs have been approved for effective treatment. This research aims to find potential candidate compounds in Indonesian herbal as COVID-19 supportive therapy using machine learning and pharmacophore modeling approach. Methods For a machine learning approach, we used three classification methods that have different principles in decision making, such as SVM, MLP, and Random Forest. By using these different methods, it is expected that more optimal screening results can be obtained than using only one method. Moreover, for a pharmacophore modeling approach, we did the structure-based method on the 3D structure of SARS-CoV-2 main protease (3CLPro) and using known SARS, MERS, and SARS-CoV-2 repurposing drugs from literature as data sets on the ligand-based method. Lastly, we used molecular docking to analyse the interaction between 3CLpro (main protease) protein with 14 hit compounds from the Indonesian Herbal Database (HerbalDB) and Lopinavir as a positive control. Results The models yielded by SVM, RF, and MLP were used for screening in herbal compounds obtained from HerbalDB and got 125 potential compounds. Whereas the structure-based pharmacophore modeling gave eight hit compounds and the ligand-based methods produced more than a hundred hit compounds. Based on the screening on HerbalDB using these two prediction approaches, we got 14 hit compounds candidates. Further analysis was done using molecular docking to know the interaction between each compound and main protease of SARS-CoV-2 as inhibitory agents. From molecular docking analysis, we got six potential compounds as the main protease of SARS-CoV-2 inhibitor, i.e Hesperidin, Kaempferol-3,4'-di-O-methyl ether (Ermanin); Myricetin-3-glucoside, Peonidine 3-(4’-arabinosylglucoside); Quercetin 3-(2G-rhamnosylrutinoside); and Rhamnetin 3-mannosyl-(1–2)-alloside. Conclusions Herbal compounds from various plants were potential as candidates of SARS-CoV-2 antivirals. Based on our research and literature study, one of the potential commodity crops in Indonesia is Psidium guajava (guava) and can be directly used by the community.
Objective Chronic periodontitis has been proposed to be linked to coronavirus disease (COVID-19) on the basis of itsinflammation mechanism. We aimed to evaluate this association by investigating the expression of Angiotensin Converting Enzyme-2 (ACE2) in periodontal compartments, which contain dysbiosis-associated pathogenic bacteria, and how it can be directly or indirectly involved in exacerbating inflammation in periodontal tissue. Material and Methods This observational clinical study included 23 adult hospitalized patients admitted to Universitas Indonesia Hospital with PCR-confirmed COVID-19, while 6 non-COVID-19 participants come to periodontal clinic were included as control. Using real time-PCR (qPCR) and gingival crevicular fluids (GCF) samples from COVID-19 patients with and without diabetes and periodontitis, we assessed the mRNA expression of angiotensin-converting enzyme 2 (ACE2), IL-6, IL8, complement C3, and LL37 as well as the relative proportion of Porphyromonas gingivalis , Fusobacterium nucleatum , and Veillonella parvula to represent the dysbiosis condition in periodontal microenvironment. All analyses were performed to determine their relationship. Results ACE2 mRNA expression was detected in the GCF of periodontitis-COVID-19 patients with and without diabetes. However, only periodontitis-COVID-19 patients with diabetes showed a positive relationship between ACE2 expression and inflammatory conditions in the periodontal microenvironment. In addition, the interplay between pro-inflammatory cytokine (Il-6) and complement C3 could be used as a predictor of the severity of periodontal inflammation in COVID-19 patients with diabetes. Conclusion The study data show that the SARS-CoV-2 entry gene is expressed in the GCF of patients with COVID-19, and its expression correlates with inflammatory markers.
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