The retrospective study of the metabolic patterns of BCG-vaccination in type-2 diabetic individuals in COVID-19 infection

Abstract

BackgroundThe cross-protective nature of Bacillus Calmette-Guerin (BCG) vaccine against SARS-CoV-2 virus was previously suggested, however its effect in COVID-19 patients with type 2 diabetes (T2D) and the underlying metabolic pathways has not been addressed. This study aims to investigate the difference in the metabolomic patterns of type 2 diabetic patients with BCG vaccination showing different severity levels of COVID-19 infection.MethodsSixty-seven COVID-19 patients were categorized into diabetic and non-diabetic individuals who had been previously vaccinated or not with BCG vaccination. Targeted metabolomics were performed from serum samples from all patients using tandem mass spectrometry. Statistical analysis included multivariate and univariate models.ResultsData suggested that while BCG vaccination may provide protection for individuals who do not have diabetes, it appears to be linked to more severe COVID-19 symptoms in T2D patients (p = 0.02). Comparing the metabolic signature of BCG vaccinated T2D individuals to non-vaccinated counterparts revealed that amino acid (sarcosine), cholesterol esters (CE 20:0, 20:1, 22:2), carboxylic acid (Aconitic acid) were enriched in BCG vaccinated T2D patients, whereas spermidine, glycosylceramides (Hex3Cer(d18:1_22:0), Hex2Cer(d18:1/22:0), HexCer(d18:1/26:1), Hex2Cer(d18:1/24:0), HexCer(d18:1/22:0) were higher in BCG vaccinated non- T2D patients. Furthermore, data indicated a decrease in sarcosine synthesis from glycine and choline and increase in spermidine synthesis in the BCG vaccinated cohort in T2D and non-T2D groups, respectively.ConclusionThis pilot study suggests increased severity of COVID-19 in BCG vaccinated T2D patients, which was marked by decreased sarcosine synthesis, perhaps via lower sarcosine-mediated removal of viral antigens.

COVID-19 and Comorbidities: What Has Been Unveiled by Metabolomics?

“…Moreover, the data suggested a reduction in sarcosine synthesis from glycine and choline, alongside an elevation in spermidine synthesis in the BCG-vaccinated cohort, observed in T2D and non-T2D groups, respectively. Additionally, the research highlights the potential negative effect of BCG in diabetic patients with COVID-19 [53]. Despite the relevance of the study, it has gaps that need to be addressed by future research, including a larger number of participants, sex matching, and consideration of the interval between BCG revaccination and SARS-CoV-2 infection.…”

“…In the initial phases of COVID-19 vaccine development, countries implementing neonatal Bacillus Calmette-Guérin (BCG) vaccination had fewer cases and lower mortality rates of COVID-19 compared with countries without such vaccination, sparking researchers' exploration of the potential cross-protective effects of the BCG vaccine against COVID-19 [51,52]. To assess the efficacy of BCG against COVID-19 in diabetic patients, a retrospective study was conducted by Anwardeen et al using serum samples from 77 COVID-19 patients stratified into diabetic and non-diabetic groups, based on their previous BCG vaccination status [53]. These samples were subjected to targeted metabolomic analysis.…”