The immunomodulatory properties of MSCs are proposed to originate from their secretion of pro- and anti-inflammatory cytokines, interaction with immune cells, and ability to potentially replace damaged cells by differentiation (157, 158, 162C164). available medical treatment options for COVID-19. Remdesivir, tocilizumab, and dexamethasone are some of the treatment options that have shown the most promise, but further randomized trials are required to particularly address timing and dosages to confidently create standardized protocols. For the SA population, two healthcare sectors exist. In the private sector, patients with medical insurance may have greater access to a wider range of treatment options than those in the public sector. The latter serves >80% of the population, and resource constraints require the identification of drugs with the most cost-effective use for the greatest number of affected patients. activity of CQ against SARS-CoV-2 was reported by Wang et al. (13) The anti-viral effects are mediated through viral entry blockade (prevention of glycosylation of host receptors) (14), increasing the pH (alkalinization) of intracellular endosomes (which usually have an acidic environment) (13, 15) as well as immunomodulatory effects (14). A large observational study from New York city in the United States KIAA0288 of America (USA) reported that the use of HCQ in 1,372 hospitalized patients did not increase or decrease the risk of intubation or death (16). The routine use of HCQ at this center was thus discontinued. Although one randomized trial from China has shown clinical benefit in a cohort of 62 patients, with a shorter period to resolution of pneumonia compared to the control group (80.6 vs. 54.8%) (17), another report of 30 patients again showed no difference between the treatment and control groups (18). A randomized trial of 150 patients attempted to determine whether initiation of HCQ for moderate to moderate disease could decrease the unfavorable conversion rate in patients (time from positive to unfavorable test result) (19). Not only was no difference found in the HCQ group compared to controls, but a higher adverse event rate was shown with HCQ leading investigators to conclude that its use in mild-moderate disease should not be advocated. Borba et al. also showed that high doses of CQ, especially if used concomitantly with azithromycin and/or oseltamivir, resulted in a prolonged QTc interval on electrocardiogram (ECG) which may lead to fatal cardiac arrhythmias (9). A large multi-center retrospective observational study of 2,541 patients from Michigan in the USA showed improved survival in patients receiving HCQ, either alone or in combination with azithromycin (20). The authors claim that the early, standardized, safe dosing of HCQ as well as the use of an electrocardiogram (ECG) Dibutyl sebacate based algorithm to identify cardiac risk factors to guide the administration of HCQ, may have led to their Dibutyl sebacate positive results. A systematic review and meta-analysis of the use of HCQ with or without azithromycin (21) concluded that HCQ alone did not reduce mortality in hospitalized patients and that the addition of azithromycin greatly increased the mortality risk. The RECOVERY collaborative group then published their findings of HCO vs. standard of care in hospitalized COVID-19 patients and found no positive impact on mortality outcome with use of this drug (22). The World Health Organization (WHO) Solidarity trial (23) also found no benefit, and to date no data exists advocating for use of this drug in COVID-19 patients. Artesunate Artesunate is an artemisinin, a class of compounds originally derived from extracts of (sweet wormwood) for the treatment of malaria (24), and has since been adopted by the World Health Organization (WHO). The use of artesunate has surpassed the use of chloroquines for the treatment of malaria and more recently for COVID-19 (25C27). Evidence for the use of spp. extracts in traditional medicine dates back to 340 common era (CE) in Chinese culture (28) and is well-known across African cultures (29). Artesunate has been shown to have anti-viral properties against double- and single-stranded deoxyribose nucleic acid (DNA) and ribonucleic acid (RNA) viruses including human cytomegalovirus (HCMV), herpes viruses, hepatitis B and C, and related viruses (including Epstein-Barr virus) Dibutyl sebacate (30), providing the premise for deployment against SARS-CoV-2. The anti-viral mechanism of artesunate is usually thought to hinge on suppression of nuclear factor kappa.
The immunomodulatory properties of MSCs are proposed to originate from their secretion of pro- and anti-inflammatory cytokines, interaction with immune cells, and ability to potentially replace damaged cells by differentiation (157, 158, 162C164)
- by globalhealth