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

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?