Trained Immunity, BCG and SARS-CoV-2 General Outline and Possible Management in COVID-19
Abstract
:1. Introduction–Bacillus Calmette–Guérin
2. Trained Immunity in General
2.1. Early Observations of BCG’s Effect on Innate Immunity
2.2. Innate Immunity, Immune Responses to BCG and Trained Immunity
2.3. The Molecular Basis of Trained Immunity
3. SARS-CoV-2 and Trained Immunity
4. Challenges and Perspective
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ADP | Adenosine diphosphate |
AMP | Adenosine monophosphate |
AMPK | AMP-activated protein kinase |
APCs | Antigen presenting cells |
BCG | Bacillus Calmette–Guérin |
BPTES | Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide |
CCL3 | Chemokine (C-C motif) ligand 3 |
CCL4 | Chemokine (C-C motif) ligand 4 |
CD4+ | Cluster of differentiation 4 |
CD8+ | Cluster of differentiation 8 |
CD11b | Cluster of differentiation 11b |
CD14 | Cluster of differentiation 14 |
CLRs | C-type lectin receptors |
COVID-19 | Coronavirus disease 2019 |
CXCL10 | C-X-C motif chemokine ligand 10 |
DAMPs | Danger-associated molecular patterns |
DC | Dendritic cell |
DNA | Deoxyribonucleic acid |
DTP | Diphtheria, tetanus, pertussis |
GMP | Guanosine monophosphate |
H3K4 | Histone 3 lysine 4 |
H3K9 | Histone 3 lysine 9 |
HIF1α | Hypoxia-inducible factor 1 α |
HIV | Human immunodeficiency virus |
HNF-1α | Hepatocyte nuclear factor-1α |
HNF-1β | Hepatocyte nuclear factor-1β |
HMG-CoA | 3-hydroxy-3-methyl-glutaryl-coenzyme A |
IFN-γ | Interferon γ |
IGF-1R | Insulin-like growth factor-1 receptor |
IgG | Immunoglobulin G |
IL-1β | Interleukin 1-β |
IL-1ra | Interleukin 1 receptor antagonist |
IL-6 | Interleukin 6 |
LPS | Lipopolysaccharide |
MHC | Major histocompatibility complex |
mRNA | Messenger ribonucleic acid |
mTOR | Mammalian target of rapamycin |
mTORC1 | mTOR complex 1 |
mTORC2 | mTOR complex 2 |
NAD+ | Nicotinamide adenine dinucleotide oxidised form |
NADH | Nicotinamide adenine dinucleotide reduced form |
NLRs | Nucleotide-binding oligomerisation domain-like receptors |
PAMPs | Pathogen associated molecular patterns |
PCR | Polymerase chain reaction |
PI3K/Akt | Phosphoinositide 3-kinase/protein kinase B |
PRRs | Pattern recognition receptors |
RLRs | Retinoic acid-inducible gene-I-like receptors |
S6K1 | Ribosomal protein S6 kinase 1 |
SARS-CoV-2 | Severe acute respiratory syndrome coronavirus 2 |
SCID | Severe combined immunodeficiency |
TB | Tuberculosis |
Th1 | T helper type 1 |
Th17 | T helper type 17 |
TLR4 | Toll like receptor 4 |
TLRs | Toll-like receptors |
TNF-α | Tumour necrosis factor α |
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Type of Study | Organism | Stimulating Factor | Results | Reference |
---|---|---|---|---|
Cytokine and epigenetic analysis | Human monocytes, mouse model | BCG, Candida albicans, Staphylococcus aureus | Increased levels of proinflammatory cytokines; epigenetic changes in promoters of proinflammatory genes and TLR4 | [26] |
Identification of metabolic pathways | Human monocytes, mouse model | β-glucan | Activation of glycolysis and mTOR pathway | [30] |
Identification of metabolic pathways | Human monocytes, mouse model | BCG | Activation of glycolysis, mTOR pathway, and glutamine metabolism | [33] |
Identification of metabolic pathways | Human monocytes, mouse model | BCG, β-glucan | Activation of mevalonate pathway | [34] |
Identification of signalling pathways | Human monocytes and bone marrow cells | BCG, Candida albicans | Activation of HNF-1α/HNF-1β | [39] |
Evaluation of the impact of diet | Human monocytes, mouse model | oxLDL, LPS | Western-type diet increased inflammatory response | [40] |
Type of Study | Study Population | Country | Results | Statistical Significance | Reference |
---|---|---|---|---|---|
Observational study | 120 adult COVID-19 patients of a federal health care centre | United States of America | The BCG-vaccinated group had a lower risk of hospitalisation compared with the unvaccinated group. | Significant | [47] |
Observational study | 103 SARS-CoV-2 PCR positive adult patients | Pakistan | No significant differences in the course of COVID-19. Lower mortality in the BCG-vaccinated group. | Depending on the parameter | [48] |
Observational study | 465 healthcare workers with SARS-CoV-2 infection | Turkey | Hospitalised patients had a history of direct contact with tuberculosis. Lower mortality in this group. | Significant | [50] |
Observational study | 6201 healthcare workers | United States of America | COVID-19 disease symptoms was significantly lower in the BCG-vaccinated group. | Significant | [51] |
Cohort study with revaccination | 280 healthcare workers previously vaccinated with BCG | United Arab Emirates | SARS-CoV-2 infection occurred only in the non-revaccinated group. | Significant | [49] |
Clinical trial | 516 elderly patients | Greece | Reduced risk of SARS-CoV-2 infection. | Significant | [52] |
Clinical trial | 138 healthcare workers | Brazil | Reduction in the incidence of COVID-19 in the vaccinated group. | Insignificant | [53] |
Clinical trial | 378 adult patients recovering from COVID-19 | Brazil | BCG-vaccinated participants had increased return of smell and taste at six weeks of follow-up. No adverse effects of BCG revaccination in adult patients. | Significant | [54,55] |
Clinical trial | 2014 elderly patients | The Netherlands | No differences in incidence of infections, including COVID-19. Reduced number of days of dyspnoea in the BCG-vaccinated group. | Depending on the parameter | [56] |
Clinical trial | 1511 healthcare workers | The Netherlands | No difference in the number of days of absenteeism from work. | Insignificant | [57] |
Clinical trial | 144 adult patients with type I diabetes | United States of America | Lower incidence of COVID-19 in the BCG-vaccinated group. | Significant | [58] |
Clinical trial | 717 healthcare workers | Poland | No difference in incidence of COVID-19 between the vaccinated and unvaccinated group. | Insignificant | [41,59] |
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Zapolnik, P.; Kmiecik, W.; Mazur, A.; Czajka, H. Trained Immunity, BCG and SARS-CoV-2 General Outline and Possible Management in COVID-19. Int. J. Mol. Sci. 2023, 24, 3218. https://doi.org/10.3390/ijms24043218
Zapolnik P, Kmiecik W, Mazur A, Czajka H. Trained Immunity, BCG and SARS-CoV-2 General Outline and Possible Management in COVID-19. International Journal of Molecular Sciences. 2023; 24(4):3218. https://doi.org/10.3390/ijms24043218
Chicago/Turabian StyleZapolnik, Paweł, Wojciech Kmiecik, Artur Mazur, and Hanna Czajka. 2023. "Trained Immunity, BCG and SARS-CoV-2 General Outline and Possible Management in COVID-19" International Journal of Molecular Sciences 24, no. 4: 3218. https://doi.org/10.3390/ijms24043218