COVID-19 vaccination clinical trials should consider multiple doses of BCG

Abstract

Vaccine repositioning is a hot research topic as an alternative to the traditional vaccine approach, which is a costly and time-consuming process due to the availability of previous safety and toxicology data. Multiple-dose BCG vaccine repurposing for COVID-19 will be an uprising breakthrough of vaccine discovery with safer outcomes. BCG induces cross-protection that might not be related to the target disease as innate immune cells, including monocytes and natural killer cells, contribute to this immune protection as known as “trained immunity” [1]. BCG had multifaceted protection against TB, Leprosy & heterogeneous pathogens [2]. Moreover, it was repositioned as a treatment for type-1 diabetes, many types of cancer & multiple sclerosis [2]. BCG vaccine accelerates the “resetting” of the immune system [3] or “turn on” immunity mechanism that agrees with its pleiotropic repurposing for many diseases. Multiple-dose BCG vaccine was used for reversing type-1 diabetes & for treating bladder cancer [4-5]. While intravesical multiple doses of BCG for bladder cancer showed many complications [6-7], intradermal multiple doses of BCG for diabetes showed high safety profile [4]. As recent studies have shown that upon certain vaccinations, human innate immune cells can undergo extensive metabolic and epigenetic reprogramming, which results in enhanced immune responses upon heterologous re-infection, a process termed trained immunity [8]; The author recommends that COVID-19 vaccination clinical trials should consider multiple doses of BCG. After reviewing the recent COVID-19 literature, although some preliminary studies suggested BCG to fight COVID-19 [9-12], they did not consider the use of multiple intradermal BCG vaccination (at least 2 doses, 4 weeks apart [4]) for the prophylaxis of COVID-19 outbreak. I do recommend that diabetic patients should participate in clinical trials to benefit from the reported BCG anti-hyperglycemic effect [4]. What if safe multiple doses of BCG turned on the immunity and protected people from COVID-19 more efficiently than a single dose?

A Systems Biology Workflow for Drug and Vaccine Repurposing: Identifying Small-molecule BCG Mimics to Prevent COVID-19 Mortality

“…Another 60-year follow-up study, showed that BCG vaccine e cacy persisted for 50 to 60 years after a single dose of BCG. [33] These studies serve as additional evidence from the literature supporting our claim that a single dose of an 'effective' BCG vaccination to infants can have a very long duration of protection against pathogens including SARS-CoV-2.…”

“…A recent publication [33] in Lancet has questioned whether BCG's effects can last for a long time. Our top enriched pathway map ( Figure 4B) indicates that BCG's effects can be long-lasting if the effects were exerted on thymus-generated Th 0 cells, which can occur to a greater extent very early in life before reaching thymic involution by puberty.…”

Avoiding COVID-19 Complications with Diabetic Patients Could Be Achieved by Multi-Dose Bacillus Calmette–Guérin Vaccine: A Case Study of Beta Cells Regeneration by Serendipity

“…As reported by the first author in a preprint submitted as a letter to the editor, BCG Vaccine repositioning to COVID-19 is a cost-effective alternative to the traditional vaccine approach as BCG induces non-specific protection as innate immune cells, including monocytes and natural killer cells. It protects from TB and Leprosy while it is suggested to treat bladder cancer and diabetes by turning on immunity and it resets the epigenetic programming of some genes and immunity related markers [46]. The author recommends that COVID-19 vaccination clinical trials should consider multiple doses of BCG as some preliminary studies suggested BCG to fight COVID-19 but they did not consider the use of multiple intradermal BCG vaccination (at least 2 doses, 4 weeks apart) for the prophylaxis (&/or treatment) of COVID-19 [46].…”

“…It protects from TB and Leprosy while it is suggested to treat bladder cancer and diabetes by turning on immunity and it resets the epigenetic programming of some genes and immunity related markers [46]. The author recommends that COVID-19 vaccination clinical trials should consider multiple doses of BCG as some preliminary studies suggested BCG to fight COVID-19 but they did not consider the use of multiple intradermal BCG vaccination (at least 2 doses, 4 weeks apart) for the prophylaxis (&/or treatment) of COVID-19 [46]. Recently, COVID-19 epidemiological study confirmed that universal BCG vaccination reduced morbidity and mortality in certain geographical areas [47].…”

“…The combination of reduced morbidity and mortality makes BCG vaccination a potential new tool in the fight against COVID-19. Some countries started a clinical trial that included single dose BCG vaccine as a prophylaxis from COVID-19 or at least they predict the vaccinated health care professional may develop less severe symptoms if got infected [46].…”