Tuberculosis vaccine BCG: the magical effect of the old vaccine in the fight against the COVID-19 pandemic

References

• Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5(4):536–544.
   PubMed Web of Science ®Google Scholar
• Worldometers. Reported Cases and Deaths by Country and Territory, https://www.worldometers.info/coronavirus/#countries. Accessed November 28, 2020.
   Google Scholar
• Global tuberculosis programme and global programme on vaccines. Statement on BCG revaccination for the prevention of tuberculosis. Wkly Epidemiol Rec. 1995;70(32):229–231.
   PubMedGoogle Scholar
• Randomised controlled trial of single BCG, repeated BCG, or combined BCG and killed Mycobacterium leprae vaccine for prevention of leprosy and tuberculosis in Malawi. Karonga Prevention Trial Group. Lancet. 1996;348(9019):17–24.
   PubMed Web of Science ®Google Scholar
• Whelan KT, Pathan AA, Sander CR, et al. Safety and immunogenicity of boosting BCG vaccinated subjects with BCG: comparison with boosting with a new TB vaccine, MVA85A. PLoS One. 2009;4(6):e5934. doi:https://doi.org/10.1371/journal.pone.0005934.
   PubMedGoogle Scholar
• Hatherill M, Geldenhuys H, Pienaar B, et al. Safety and reactogenicity of BCG revaccination with isoniazid pretreatment in TST positive adults. Vaccine. 2014;32(31):3982–3988. doi:https://doi.org/10.1016/j.vaccine.2014.04.084.
   PubMed Web of Science ®Google Scholar
• Nemes E, Geldenhuys H, Rozot V, et al. Prevention of M. tuberculosis Infection with H4:IC31 Vaccine or BCG Revaccination. N Engl J Med. 2018;379(2):138–149., doi:https://doi.org/10.1056/NEJMoa1714021.
   PubMed Web of Science ®Google Scholar
• Kumar J, Meena J. Demystifying BCG vaccine and COVID-19 relationship. Indian Pediatr. 2020;57(6):588–589. doi:https://doi.org/10.1007/s13312-020-1872-0.
   PubMed Web of Science ®Google Scholar
• ClinicalTrials.gov. Bacillus Calmette Guerin, COVID, and SARS-CoV-2. https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=BCG&cntry=&state=&city=&dist. 2020.
   Google Scholar
• Luca S, Mihaescu T. History of BCG vaccine. Maedica (Bucur). 2013;8(1):53–58.
   PubMedGoogle Scholar
• Brewer TF, Colditz GA. Relationship between bacille Calmette-Guérin (BCG) strains and the efficacy of BCG vaccine in the prevention of tuberculosis. Clin Infect Dis. 1995;20(1):126–135. doi:https://doi.org/10.1093/clinids/20.1.126.
   PubMedGoogle Scholar
• Cernuschi T, Malvolti S, Nickels E, et al. Bacillus Calmette-Guérin (BCG) vaccine: a global assessment of demand and supply balance. Vaccine. 2018;36(4):498–506. doi:https://doi.org/10.1016/j.vaccine.2017.12.010.
   PubMed Web of Science ®Google Scholar
• Behr MA, Small PM. A historical and molecular phylogeny of BCG strains. Vaccine. 1999;17(7-8):915–922. doi:https://doi.org/10.1016/S0264-410X(98)00277-1.
   PubMed Web of Science ®Google Scholar
• Chen JM, Islam ST, Ren H, et al. Differential productions of lipid virulence factors among BCG vaccine strains and implications on BCG safety. Vaccine. 2007;25(48):8114–8122. doi:https://doi.org/10.1016/j.vaccine.2007.09.041.
   PubMedGoogle Scholar
• Liu J, Tran V, Leung AS, et al. BCG vaccines: their mechanisms of attenuation and impact on safety and protective efficacy. Hum Vaccin. 2009;5(2):70–78. doi:https://doi.org/10.4161/hv.5.2.7210.
   PubMed Web of Science ®Google Scholar
• Miyasaka M. Is BCG vaccination causally related to reduced COVID-19 mortality?EMBO Mol Med. 2020;12(6):e12661. doi:https://doi.org/10.15252/emmm.202012661.
   PubMed Web of Science ®Google Scholar
• Davids V, Hanekom WA, Mansoor N, et al. The effect of bacille Calmette-Guérin vaccine strain and route of administration on induced immune responses in vaccinated infants. J Infect Dis. 2006;193(4):531–536. doi:https://doi.org/10.1086/499825.
   PubMed Web of Science ®Google Scholar
• Wu B, Huang C, Garcia L, et al. Unique gene expression profiles in infants vaccinated with different strains of Mycobacterium bovis bacille Calmette-Guerin. Infect Immun. 2007;75(7):3658–3664. doi:https://doi.org/10.1128/IAI.00244-07.
   PubMed Web of Science ®Google Scholar
• Arts RJW, Moorlag SJCFM, Novakovic B, et al. BCG vaccination protects against experimental viral infection in humans through the induction of cytokines associated with trained immunity. Cell Host Microbe. 2018;23(1):89–100.e5. doi:https://doi.org/10.1016/j.chom.2017.12.010.
   PubMed Web of Science ®Google Scholar
• Salem A, Nofal A, Hosny D. Treatment of common and plane warts in children with topical viable Bacillus Calmette-Guerin. Pediatr Dermatol. 2013;30(1):60–63. doi:https://doi.org/10.1111/j.1525-1470.2012.01848.x.
   PubMed Web of Science ®Google Scholar
• Podder I, Bhattacharya S, Mishra V, et al. Immunotherapy in viral warts with intradermal Bacillus Calmette-Guerin vaccine versus intradermal tuberculin purified protein derivative: a double-blind, randomized controlled trial comparing effectiveness and safety in a tertiary care center in Eastern India. Indian J Dermatol Venereol Leprol. 2017;83(3):411. doi:https://doi.org/10.4103/0378-6323.193623.
   PubMed Web of Science ®Google Scholar
• Daulatabad D, Pandhi D, Singal A. BCG vaccine for immunotherapy in warts: is it really safe in a tuberculosis endemic area?Dermatol Ther. 2016;29(3):168–172. doi:https://doi.org/10.1111/dth.12336.
   PubMedGoogle Scholar
• Stensballe LG, Nante E, Jensen IP, et al. Acute lower respiratory tract infections and respiratory syncytial virus in infants in Guinea-Bissau: a beneficial effect of BCG vaccination for girls community based case-control study. Vaccine. 2005;23(10):1251–1257. doi:https://doi.org/10.1016/j.vaccine.2004.09.006.
   PubMed Web of Science ®Google Scholar
• Hollm-Delgado MG, Stuart EA, Black RE. Acute lower respiratory infection among Bacille Calmette-Guérin (BCG)-vaccinated children. Pediatrics. 2014;133(1):e73-81–e81. doi:https://doi.org/10.1542/peds.2013-2218.
   PubMedGoogle Scholar
• Leentjens J, Kox M, Stokman R, et al. BCG vaccination enhances the immunogenicity of subsequent influenza vaccination in healthy volunteers: a randomized, placebo-controlled pilot study. J Infect Dis. 2015;212(12):1930–1938. doi:https://doi.org/10.1093/infdis/jiv332.
   PubMed Web of Science ®Google Scholar
• Anderson FD, Ushijima RN, Larson CL. Recurrent herpes genitalis. Treatment with Mycobacterium bovis (BCG). Obstet Gynecol. 1974;43(6):797–805.
   PubMed Web of Science ®Google Scholar
• Hippmann G, Wekkeli M, Rosenkranz AR, et al. Nonspecific immune stimulation with BCG in Herpes simplex recidivans. Follow-up 5 to 10 years after BCG vaccination. Wien Klin Wochenschr. 1992;104(7):200–204., [].
   PubMedGoogle Scholar
• Scheid A, Borriello F, Pietrasanta C, et al. Adjuvant effect of Bacille Calmette-Guérin on Hepatitis B vaccine immunogenicity in the preterm and term newborn. Front Immunol. 2018;9:29. doi:https://doi.org/10.3389/fimmu.2018.00029.
   PubMedGoogle Scholar
• Benitez MLR, Bender CB, Oliveira TL, et al. Mycobacterium bovis BCG in metastatic melanoma therapy. Appl Microbiol Biotechnol. 2019;103(19):7903–7916. doi:https://doi.org/10.1007/s00253-019-10057-0.
   PubMedGoogle Scholar
• Pettenati C, Ingersoll MA. Mechanisms of BCG immunotherapy and its outlook for bladder cancer. Nat Rev Urol. 2018;15(10):615–625. doi:https://doi.org/10.1038/s41585-018-0055-4.
   PubMed Web of Science ®Google Scholar
• Sharquie KE, Hayani RK. BCG as a new therapeutic and prophylactic agent in patients with severe oral aphthosis. Clin Exp Rheumatol. 2005;23(6):914.
   PubMed Web of Science ®Google Scholar
• Abbas AM, AbouBakr A, Bahaa N, et al. The effect of BCG vaccine in the era of COVID-19 pandemic. Scand J Immunol. 2020;92(6):e12947. doi:https://doi.org/10.1111/sji.12947.
   PubMedGoogle Scholar
• Ohrui T, Nakayama K, Fukushima T, et al. Prevention of elderly pneumonia by pneumococcal, influenza and BCG vaccinations. Nihon Ronen Igakkai Zasshi. 2005;42(1):34–36. doi:https://doi.org/10.3143/geriatrics.42.34.
   PubMedGoogle Scholar
• Belizário JE. Trained innate immunity, COVID-19 therapeutic dilemma, and fake science. Clinics (Sao Paulo). 2020;75:e2124. doi:https://doi.org/10.6061/clinics/2020/e2124.
   PubMed Web of Science ®Google Scholar
• Aaby P, Roth A, Ravn H, et al. Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period?J Infect Dis. 2011;204(2):245–252. doi:https://doi.org/10.1093/infdis/jir240.
   PubMed Web of Science ®Google Scholar
• Biering-Sørensen S, Aaby P, Lund N, et al. Early BCG-Denmark and neonatal mortality among infants weighing <2500 g: a randomized controlled trial. Clin Infect Dis. 2017;65(7):1183–1190.
   PubMed Web of Science ®Google Scholar
• Wardhana DE, Sultana A, Mandang VV, et al. The efficacy of Bacillus Calmette-Guerin vaccinations for the prevention of acute upper respiratory tract infection in the elderly. Acta Med Indones. 2011;43(3):185–190.
   PubMedGoogle Scholar
• Murin CD, Wilson IA, Ward AB. Antibody responses to viral infections: a structural perspective across three different enveloped viruses. Nat Microbiol. 2019;4(5):734–747. doi:https://doi.org/10.1038/s41564-019-0392-y.
   PubMedGoogle Scholar
• Triozzi PL, Tuthill RJ, Borden E. Re-inventing intratumoral immunotherapy for melanoma. Immunotherapy. 2011;3(5):653–671. doi:https://doi.org/10.2217/imt.11.46.
   PubMed Web of Science ®Google Scholar
• Floc’h F, Werner GH. Increased resistance to virus infections of mice inoculated with BCG (Bacillus calmette-guérin).Ann Immunol (Paris). 1976;127(2):173–186.
   PubMedGoogle Scholar
• Starr SE, Visintine AM, Tomeh MO, et al. Effects of immunostimulants on resistance of newborn mice to herpes simplex type 2 infection. Proc Soc Exp Biol Med. 1976;152(1):57–60. doi:https://doi.org/10.3181/00379727-152-39327.
   PubMedGoogle Scholar
• Spencer JC, Ganguly R, Waldman RH. Nonspecific protection of mice against influenza virus infection by local or systemic immunization with Bacille Calmette-Guérin. J Infect Dis. 1977;136(2):171–175. doi:https://doi.org/10.1093/infdis/136.2.171.
   PubMedGoogle Scholar
• Mukherjee S, Subramaniam R, Chen H, et al. Boosting efferocytosis in alveolar space using BCG vaccine to protect host against influenza pneumonia. PLoS One. 2017;12(7):e0180143. doi:https://doi.org/10.1371/journal.pone.0180143.
   PubMedGoogle Scholar
• Kulkarni S, Mukherjee S, Pandey A, et al. Bacillus calmette-guérin confers neuroprotection in a murine model of Japanese encephalitis. Neuroimmunomodulation. 2016;23(5–6):278–286. doi:https://doi.org/10.1159/000452171.
   PubMed Web of Science ®Google Scholar
• Lodmell DL, an, Ewalt d. LC. Enhanced resistance against encephalomyocarditis virus infection in mice, induced by a nonviable Mycobacterium tuberculosis oil-droplet vaccine. Infect Immun. 1978;19(1):225–230. doi:https://doi.org/10.1128/IAI.19.1.225-230.1978.
   PubMedGoogle Scholar
• Lodmell DL, an, Ewalt d. LC. Induction of enhanced resistance against encephalomyocarditis virus infection of mice by nonviable Mycobacterium tuberculosis: mechanisms of protection. Infect Immun. 1978;22(3):740–745. doi:https://doi.org/10.1128/IAI.22.3.740-745.1978.
   PubMedGoogle Scholar
• Suenaga T, Okuyama T, Yoshida I, et al. Effect of Mycobacterium tuberculosis BCG infection on the resistance of mice to ectromelia virus infection: participation of interferon in enhanced resistance. Infect Immun. 1978;20(1):312–314. doi:https://doi.org/10.1128/IAI.20.1.312-314.1978.
   PubMedGoogle Scholar
• Sakuma T, Suenaga T, Yoshida I, et al. Mechanisms of enhanced resistance of Mycobacterium bovis BCG-treated mice to ectromelia virus infection. Infect Immun. 1983;42(2):567–573. doi:https://doi.org/10.1128/IAI.42.2.567-573.1983.
   PubMedGoogle Scholar
• Ikeda S, Negishi T, Nishimura C. Enhancement of non-specific resistance to viral infection by muramyldipeptide and its analogs. Antiviral Res. 1985;5(4):207–215. doi:https://doi.org/10.1016/0166-3542(85)90025-7.
   PubMedGoogle Scholar
• Mathurin KS, Martens GW, Kornfeld H, et al. CD4 T-cell-mediated heterologous immunity between mycobacteria and poxviruses. J Virol. 2009;83(8):3528–3539. doi:https://doi.org/10.1128/JVI.02393-08.
   PubMed Web of Science ®Google Scholar
• Ishihara C, Mizukoshi N, Iida J, et al. Suppression of Sendai virus growth by treatment with N alpha-acetylmuramyl-L-alanyl-D-isoglutaminyl-N epsilon-stearoyl-L-lysine in mice. Vaccine. 1987;5(4):295–301. doi:https://doi.org/10.1016/0264-410X(87)90155-1.
   PubMedGoogle Scholar
• Kleinnijenhuis J, Quintin J, Preijers F, et al. BCG-induced trained immunity in NK cells: role for non-specific protection to infection. Clin Immunol. 2014;155(2):213–219. doi:https://doi.org/10.1016/j.clim.2014.10.005.
   PubMed Web of Science ®Google Scholar
• Kleinnijenhuis J, Quintin J, Preijers F, et al. Bacille calmette-guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci USA. 2012;109(43):17537–17542. doi:https://doi.org/10.1073/pnas.1202870109.
   PubMed Web of Science ®Google Scholar
• Martinon F, Agostini L, Meylan E, et al. Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome. Curr Biol. 2004;14(21):1929–1934. doi:https://doi.org/10.1016/j.cub.2004.10.027.
   PubMed Web of Science ®Google Scholar
• Gallagher J, Watson C, Ledwidge M. Association of Bacille Calmette-Guérin (BCG), adult pneumococcal and adult seasonal influenza vaccines with Covid-19 adjusted mortality rates in level 4 European countries. medRxiv. 2020:2020.06.03.20121624.
   Google Scholar
• Ozdemir C, Kucuksezer UC, Tamay ZU. Is BCG vaccination affecting the spread and severity of COVID-19?Allergy. 2020;75(7):1824–1827. doi:https://doi.org/10.1111/all.14344.
   PubMed Web of Science ®Google Scholar
• Ogimi C, Qu P, Boeckh M, et al. Association between live childhood vaccines and COVID-19 outcomes: a national-level analysis. medRxiv, 2020.
   PubMedGoogle Scholar
• Weng C-H, Saal A, Butt WW-W, et al. Bacillus Calmette-Guérin vaccination and clinical characteristics and outcomes of COVID-19 in Rhode Island, United States: a cohort study. Epidemiol Infect. 2020;148:e140. doi:https://doi.org/10.1017/S0950268820001569.
   PubMed Web of Science ®Google Scholar
• Berg MK, Yu Q, Salvador CE, et al. Mandated Bacillus Calmette-Guérin (BCG) vaccination predicts flattened curves for the spread of COVID-19. Sci Adv. 2020;6(32):eabc1463. doi:https://doi.org/10.1126/sciadv.abc1463.
   PubMed Web of Science ®Google Scholar
• Escobar LE, Molina-Cruz A, Barillas-Mury C. BCG vaccine protection from severe coronavirus disease 2019 (COVID-19). Proc Natl Acad Sci U S A. 2020;117(30):17720–17726. doi:https://doi.org/10.1073/pnas.2008410117.
   PubMed Web of Science ®Google Scholar
• Madan M, Pahuja S, Mohan A, et al. TB infection and BCG vaccination: are we protected from COVID-19?Public Health. 2020;185:91–92. doi:https://doi.org/10.1016/j.puhe.2020.05.042.
   PubMed Web of Science ®Google Scholar
• Urashima M, Otani, K, Hasegawa Y, et al. BCG vaccination and mortality of COVID-19 across 173 countries: an ecological study. Int J Environ Res Public Health. 2020;17(15).
   Web of Science ®Google Scholar
• Noval Rivas M, Ebinger, JE, Wu, M, et al. BCG vaccination history associates with decreased SARS-CoV-2 seroprevalence across a diverse cohort of healthcare workers. J Clin Invest. 2020.
   Web of Science ®Google Scholar
• Li WX. Worldwide inverse correlation between Bacille Calmette-Guérin immunization and COVID-19 morbidity and mortality. 2020.
   Google Scholar
• Klinger D, Blass I, Rappoport N, et al. Significantly improved COVID-19 outcomes in countries with higher BCG vaccination coverage: a multivariable analysis. Vaccines (Basel), 2020;8(3):378. doi:https://doi.org/10.3390/vaccines8030378.
   Google Scholar
• Wickramasinghe D, Wickramasinghe N, Kamburugamuwa SA, et al. Correlation between immunity from BCG and the morbidity and mortality of COVID-19. Trop Dis Travel Med Vaccines. 2020;6(1):17., doi:https://doi.org/10.1186/s40794-020-00117-z.
   PubMedGoogle Scholar
• Joy M, Malavika B, Asirvatham ES, et al. Is BCG associated with reduced incidence of COVID-19? A meta-regression of global data from 160 countries. Clin Epidemiol Glob Health. 2021;9:202–203. doi:https://doi.org/10.1016/j.cegh.2020.08.015.
   PubMedGoogle Scholar
• Moorlag SJCFM, van Deuren RC, van Werkhoven CH, et al. Safety and COVID-19 symptoms in individuals recently vaccinated with BCG: a retrospective cohort study. Cell Rep Med. 2020;1(5):100073. doi:https://doi.org/10.1016/j.xcrm.2020.100073.
   PubMedGoogle Scholar
• Miller A, Reandelar MJ, Fasciglione K, et al. Correlation between universal BCG vaccination policy and reduced mortality for COVID-19. medRxiv. 2020:2020.03.24.20042937.
   Google Scholar
• Kinoshita M, Tanaka M. Impact of Routine Infant BCG Vaccination on COVID-19. J Infect. 2020;81(4):625–633. doi:https://doi.org/10.1016/j.jinf.2020.08.013.
   PubMed Web of Science ®Google Scholar
• Kumar A, Misra S, Verma V, et al. Global impact of environmental temperature and BCG vaccination coverage on the transmissibility and fatality rate of COVID-19. PLoS One. 2020;15(10):e0240710. doi:https://doi.org/10.1371/journal.pone.0240710.
   PubMedGoogle Scholar
• Ebina-Shibuya R, Horita N, Namkoong H, et al. Current national policies for infant universal bacille Calmette-Guérin vaccination were associated with lower mortality from coronavirus disease 2019. Clin Exp Vaccine Res. 2020;9(2):179–182. doi:https://doi.org/10.7774/cevr.2020.9.2.179.
   PubMedGoogle Scholar
• Khade SM, Yabaji SM, Srivastava J. An update on COVID-19: SARS-CoV-2 life cycle, immunopathology, and BCG vaccination. Prep Biochem Biotechnol. 2020:1–9.
   PubMed Web of Science ®Google Scholar
• Lindestam Arlehamn CS, Sette A, Peters B. Lack of evidence for BCG vaccine protection from severe COVID-19. Proc Natl Acad Sci U S A. 2020;117(41):25203–25204. doi:https://doi.org/10.1073/pnas.2016733117.
   PubMedGoogle Scholar
• Hidvégi M, Nichelatti M. Bacillus Calmette-Guerin vaccination policy and consumption of ammonium chloride-enriched confectioneries may be factors reducing COVID-19 death rates in Europe. Isr Med Assoc J. 2020;8(22):435–438.
   Google Scholar
• Sharma A, Kumar Sharma S, Shi Y, et al. BCG vaccination policy and preventive chloroquine usage: do they have an impact on COVID-19 pandemic?Cell Death Dis. 2020;11(7):516. doi:https://doi.org/10.1038/s41419-020-2720-9.
   PubMed Web of Science ®Google Scholar
• Islam MZ, Zahan MK‐E, Al‐Bari MAA. Convergence between global BCG vaccination and COVID-19 pandemic. J Med Virol. 2021;93(3):1496–1505. doi:https://doi.org/10.1002/jmv.26450.
   PubMedGoogle Scholar
• Ebina-Shibuya R, Horita N, Namkoong H, Kaneko T. National policies for paediatric universal BCG vaccination were associated with decreased mortality due to COVID-19. Respirology. 2020;25(8):898–899. doi:https://doi.org/10.1111/resp.13885.
   PubMedGoogle Scholar
• Sayed A, Challa KT, Arja S. Epidemiological differences of COVID-19 over the world. Cureus. 2020;12(9):e10316. doi:https://doi.org/10.7759/cureus.10316.
   PubMedGoogle Scholar
• Iwasaki A, Grubaugh ND. Why does Japan have so few cases of COVID-19?EMBO Mol Med. 2020;12(5):e12481. doi:https://doi.org/10.15252/emmm.202012481.
   PubMed Web of Science ®Google Scholar
• Hensel J, McAndrews KM, McGrail DJ, Dowlatshahi DP, LeBleu VS, Kalluri R. Protection against SARS-CoV-2 by BCG vaccination is not supported by epidemiological analyses. Sci Rep. 2020;10(1):18377. doi:https://doi.org/10.1038/s41598-020-75491-x.
   PubMed Web of Science ®Google Scholar
• Ręka G, Korzeniowska A, Piecewicz-Szczęsna H. The influence of vaccination against tuberculosis with the Bacillus-Calmette-Guérin(BCG) vaccine on COVID-19 incidence and mortality - review of the literature. Przegl Epidemiol. 2020;74(2):290–302. doi:https://doi.org/10.32394/pe.74.22.
   PubMedGoogle Scholar
• Wassenaar TM, Buzard GS, Newman DJ. BCG vaccination early in life does not improve COVID-19 outcome of elderly populations, based on nationally reported data. Lett Appl Microbiol. 2020;71(5):498–505. doi:https://doi.org/10.1111/lam.13365.
   PubMed Web of Science ®Google Scholar
• Riccò M, Gualerzi G, Ranzieri S, et al. Stop playing with data: there is no sound evidence that Bacille Calmette-Guérin may avoid SARS-CoV-2 infection (for now). Acta Biomed. 2020;91(2):207–213. doi:https://doi.org/10.23750/abm.v91i2.9700.
   PubMedGoogle Scholar
• Hamiel U, Kozer E, Youngster I. SARS-CoV-2 rates in BCG-vaccinated and unvaccinated young adults. Jama. 2020;323(22):2340–2341. doi:https://doi.org/10.1001/jama.2020.8189.
   PubMed Web of Science ®Google Scholar
• de Chaisemartin C, de Chaisemartin L. BCG vaccination in infancy does not protect against COVID-19. Evidence from a natural experiment in Sweden. Clin Infect Dis. 2020. doi:https://doi.org/10.1093/cid/ciaa1223.
   Web of Science ®Google Scholar
• Karabay O. Investigation of the frequency of COVID-19 in patients treated with intravesical BCG. Rev Assoc Med Bras. 2020;2(2):91–95.
   Google Scholar
• Szigeti R, Kellermayer D, Trakimas G, et al. BCG epidemiology supports its protection against COVID-19? A word of caution. PLoS One. 2020;15(10):e0240203. doi:https://doi.org/10.1371/journal.pone.0240203.
   PubMed Web of Science ®Google Scholar
• Aksu K, Naziroğlu T, Özkan P. Factors determining COVID-19 pneumonia severity in a country with routine BCG vaccination. Clin Exp Immunol. 2020;202(2):220–225. doi:https://doi.org/10.1111/cei.13507.
   PubMed Web of Science ®Google Scholar
• Dara M, Sotgiu G, Reichler MR, et al. New diseases and old threats: lessons from tuberculosis for the COVID-19 response. Int J Tuberc Lung Dis. 2020;24(5):544–545. doi:https://doi.org/10.5588/ijtld.20.0151.
   PubMedGoogle Scholar
• Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol. 2020;38(1):1–9. doi:https://doi.org/10.12932/AP-200220-0772.
   PubMed Web of Science ®Google Scholar
• Lyadova IV, Panteleev AV. Th1 and Th17 Cells in tuberculosis: protection, pathology, and biomarkers. Mediators Inflamm. 2015;2015:854507. doi:https://doi.org/10.1155/2015/854507.
   PubMed Web of Science ®Google Scholar
• Gordon DE, Jang GM, Bouhaddou M, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020;583(7816):459–468. doi:https://doi.org/10.1038/s41586-020-2286-9.
   PubMed Web of Science ®Google Scholar
• Glisic S, Perovic VR, Sencanski M, et al. Biological rationale for the repurposing of BCG vaccine against SARS-CoV-2. J Proteome Res. 2020;19(11):4649–4654. doi:https://doi.org/10.1021/acs.jproteome.0c00410.
   PubMedGoogle Scholar
• Tomita Y, Sato R, Ikeda T, et al. BCG vaccine may generate cross-reactive T cells against SARS-CoV-2: in silico analyses and a hypothesis. Vaccine. 2020;38(41):6352–6356. doi:https://doi.org/10.1016/j.vaccine.2020.08.045.
   PubMed Web of Science ®Google Scholar
• Nuovo G, Tili E, Suster D, et al. Strong homology between SARS-CoV-2 envelope protein and a Mycobacterium sp. antigen allows rapid diagnosis of Mycobacterial infections and may provide specific anti-SARS-CoV-2 immunity via the BCG vaccine. Ann Diagn Pathol. 2020;48:151600. doi:https://doi.org/10.1016/j.anndiagpath.2020.151600.
   PubMed Web of Science ®Google Scholar
• Nicola M, Alsafi Z, Sohrabi C, et al. The socio-economic implications of the coronavirus pandemic (COVID-19): a review. Int J Surg. 2020;78:185–193. doi:https://doi.org/10.1016/j.ijsu.2020.04.018.
   PubMed Web of Science ®Google Scholar
• Zabetakis I, Lordan R, Norton C, et al. COVID-19: the inflammation link and the role of nutrition in potential mitigation. Nutrients. 2020;12(5):1466. doi:https://doi.org/10.3390/nu12051466.
   PubMed Web of Science ®Google Scholar
• Begum J, Mir NA, Dev K, et al. Challenges and prospects of COVID-19 vaccine development based on the progress made in SARS and MERS vaccine development. Transbound Emerg Dis. 2020; 1–4. doi:https://doi.org/10.1111/tbed.13804.
   Google Scholar
• Karlsen APH, Wiberg S, Laigaard J, et al. A systematic review of trial registry entries for randomized clinical trials investigating COVID-19 medical prevention and treatment. PLoS One. 2020;15(8):e0237903. doi:https://doi.org/10.1371/journal.pone.0237903.
   PubMed Web of Science ®Google Scholar
• El Taguri A, Nasef A. The world is waiting, use sequential analysis and get us the evidence-based treatment we need for COVID-19. Libyan J Med. 2020;15(1):1770518. doi:https://doi.org/10.1080/19932820.2020.1770518.
   PubMed Web of Science ®Google Scholar
• Rey-Jurado E, Soto J, Gálvez N, et al. A safe and efficient BCG vectored vaccine to prevent the disease caused by the human respiratory syncytial virus. Hum Vaccin Immunother. 2017;13(9):2092–2097. doi:https://doi.org/10.1080/21645515.2017.1334026.
   PubMed Web of Science ®Google Scholar
• Yitbarek K, Abraham G, Girma T, et al. The effect of Bacillus Calmette-Guérin (BCG) vaccination in preventing severe infectious respiratory diseases other than TB: Implications for the COVID-19 pandemic. Vaccine. 2020;38(41):6374–6380., doi:https://doi.org/10.1016/j.vaccine.2020.08.018.
   PubMed Web of Science ®Google Scholar
• Moorlag SJCFM, Arts RJW, van Crevel R, et al. Non-specific effects of BCG vaccine on viral infections. Clin Microbiol Infect. 2019;25(12):1473–1478. doi:https://doi.org/10.1016/j.cmi.2019.04.020.
   PubMed Web of Science ®Google Scholar
• Kochhar S. Communicating vaccine safety during the development and introduction of vaccines. Curr Drug Saf. 2015;10(1):55–59. doi:https://doi.org/10.2174/157488631001150407110435.
   PubMedGoogle Scholar
• Redelman-Sidi G. Could BCG be used to protect against COVID-19?Nat Rev Urol. 2020;17(6):316–317. doi:https://doi.org/10.1038/s41585-020-0325-9.
   PubMed Web of Science ®Google Scholar