Could BCG be used to protect against COVID-19?

Redelman-Sidi, Gil

doi:10.1038/s41585-020-0325-9

Cited by 113 publications

(111 citation statements)

References 9 publications

Supporting

Mentioning

103

Contrasting

Unclassified

Order By: Relevance

“…No reuse allowed without permission. mortality related to COVID-19 (36)(37). Interestingly, BCG is closely related to Mtb which enhanced ASC based defense mechanism of CD271+MSCs to fight against MHV-1 infection.…”

Section: Discussionmentioning

confidence: 99%

Coronavirus activates a stem cell-mediated defense mechanism that reactivates dormant tuberculosis: implications in COVID-19 pandemic

Pathak

Gayan

Pal

et al. 2020

Preprint

View full text Add to dashboard Cite

We postulate that similar to bacteria, adult stem cells may also exhibit altruistic defense mechanism to protect their niche. Here, we provide preliminary data on the altruistic stem cell (ASC) based defense against a mouse corona virus; MHV-1 infection. In a mouse model of mesenchymal stem cell (MSC) mediated M. tuberculosis (Mtb) dormancy, MHV-1 infection in the lung exhibited 20 fold lower viral loads than the healthy control mice, suggesting the potential enhancement of an anti-MHV-1 defense by Mtb. This defense involved the in vivo expansion and reprogramming of CD271+ MSCs in the lung to ASC phenotype characterized by activation of genes involved in the HIF-2alpha stemness pathway. The conditioned media of the ASCs exhibited direct anti-viral activity in an in vitro model of MHV-1 induced toxicity to type II alveolar epithelial cells. MHV-1 infected Mtb harboring group versus MHV-1 alone groupexhibited an 8-fold (p<0.02; n=4) higher ASC reprogramming and 5-fold (p<0.001; n=3, student t test) higher anti-viral activity. However, ASCs facilitated intracellular replication and extracellular release of Mtb. Thus, our data suggest that MSCs exert an innate defense against MHV-1 by activating the ASC defense mechanism, which might be exploited by dormant Mtb to undergo reactivation. Hence, our findings may provide a novel anti-viral defense mechanism against novel corona virus SARS-Cov2, which could be further utilized to develop vaccine

show abstract

Section: Discussionmentioning

confidence: 99%

Coronavirus activates a stem cell-mediated defense mechanism that reactivates dormant tuberculosis: implications in COVID-19 pandemic

Pathak

Gayan

Pal

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Since we rst described the association between BCG vaccination policies and CFR, several additional studies have corroborated this nding [13,23]. Sala et al demonstrated that TB infection and BCG vaccination strategies were associated with decreased incidence and mortality related to COVID-19 [15].…”

Section: Discussionmentioning

confidence: 56%

The association of Coronavirus Disease-19 mortality and prior bacille Calmette-Guerin vaccination: a robust ecological evaluation using unsupervised machine learning

Brooks

Puri

Garg

et al. 2020

Preprint

View full text Add to dashboard Cite

Population-level data have suggested that bacille Calmette-Guerin (BCG) vaccination may lessen the severity of Coronavirus Disease-19 (COVID-19) prompting clinical trials in this area. Some reports have demonstrated conflicting results. We performed a robust, ecologic analysis comparing COVID-19 related mortality (CSM) between strictly selected countries based on BCG vaccination program status utilizing publicly available databases and machine learning to define the association between active BCG vaccination programs and CSM. Validation was performed using linear regression and country-specific modeling. CSM was lower for 80% of similarly clustered countries with a BCG vaccination policy for at least the preceding 15 years (BCG15). CSM increased significantly for each increase in the percent population over age 65. The total population of a country and BCG15 were significantly associated with improved CSM. There was a consistent association between countries with a BCG vaccination for the preceding 15 years, but not other vaccination programs, and CSM.

show abstract

“…There are studies discussing the possible therapeutic effect of the BCG vaccine on COVID-19. [2][3][4] However, thus far, previous studies have not been discussed the immunity acquired from natural infection by M. tuberculosis, which we assumed to be a real factor against the impact of COVID-19. The results from the statistical analysis supported our hypothesis, which proposes that latent tuberculosis infection may be the real contributor for natural trained immunity, and BCG vaccination could be spuriously associated with the low impact of COVID-19 ( Figure 1).…”

Section: Discussionmentioning

confidence: 99%

“…Currently, the Bacillus Calmette-Guérin (BCG) vaccine has gained increasing attention for its speculated e cacy against COVID-19, [2][3][4] which is based on the concept of trained natural immunity. 5 Studies have focused on the different effects of COVID-19 between countries wherein BCG vaccination programmes are currently in place and countries wherein they are not.…”

Section: Introductionmentioning

confidence: 99%

Association between past tuberculosis epidemic and COVID-19-related mortality through latent infection by natural immunity

Inoue

Kashima

2020

Preprint

View full text Add to dashboard Cite

The coronavirus disease (COVID-19) pandemic has created a remarkable and varying impact in each region, which calls for broad attention. Recently, the Bacillus Calmette-Guérin (BCG) vaccination has been regarded as a potential candidate to explain this difference. Herein, we hypothesised that past tuberculosis epidemic may act as a latent explanatory factor for the worldwide difference in COVID-19 impact. We compared two indicators of past tuberculosis epidemic, namely, incidence (90 countries for the incidence rate in 1990) and mortality (28 countries for the mortality rate in 1950) with COVID-19 mortality rate. An inverse relationship exists between both past epidemic indicators and COVID-19 mortality. The rate ratio of the cumulative COVID-19 mortality per 1 million was 1.08 (95% confidence interval [CI]: 0.98–1.18) per 1 unit decrease in the incidence rate of tuberculosis per 100,000 people. This association existed even after adjusting for potential confounders (elderly rate, diabetes prevalence, mortality rate from cardiovascular disease, and gross domestic product per capita) [adjusted rate ratio: 1.05, 95% CI: (1.03–1.08)]. After latent infection, Mycobacterium tuberculosis survives in the human body and may continue to stimulate trained immunity for lifetime. Our study has revealed one possible mechanism underlying the region-based variation in the COVID-19 impact.

show abstract

Could BCG be used to protect against COVID-19?

Cited by 113 publications

References 9 publications

Coronavirus activates a stem cell-mediated defense mechanism that reactivates dormant tuberculosis: implications in COVID-19 pandemic

Coronavirus activates a stem cell-mediated defense mechanism that reactivates dormant tuberculosis: implications in COVID-19 pandemic

The association of Coronavirus Disease-19 mortality and prior bacille Calmette-Guerin vaccination: a robust ecological evaluation using unsupervised machine learning

Association between past tuberculosis epidemic and COVID-19-related mortality through latent infection by natural immunity

Contact Info

Product

Resources

About