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1.
Vaccines (Basel) ; 10(10)2022 Sep 30.
Article in English | MEDLINE | ID: covidwho-2066606

ABSTRACT

Despite controversy over the protective effect of the BCG (Bacille Calmette-Guérin) vaccine in preventing pulmonary tuberculosis (TB) in adults, it has been used worldwide since 1921. Although the first reports in the 1930s had noted a remarkable decrease in child mortality after BCG immunization, this could not be explained solely by a decrease in mortality from TB. These observations gave rise to the suggestion of nonspecific beneficial effects of BCG vaccination, beyond the desired protection against M. tuberculosis. The existence of an innate immunity-training mechanism based on epigenetic changes was demonstrated several years ago. The emergence of the pandemic caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in 2019 revived the debate about whether the BCG vaccine can affect the immune response against the virus or other unrelated pathogens. Due to the mortality of the coronavirus disease (COVID-19), it is important to verify each factor that may have a potential protective value against the severe course of COVID-19, complications, and death. This paper reviews the results of numerous retrospective studies and prospective trials which shed light on the potential of a century-old vaccine to mitigate the pandemic impact of the new virus. It should be noted, however, that although there are numerous studies intending to verify the hypothesis that the BCG vaccine may have a beneficial effect on COVID-19, there is no definitive evidence on the efficacy of the BCG vaccine against SARS-CoV-2.

2.
Vaccines (Basel) ; 10(10)2022 Sep 27.
Article in English | MEDLINE | ID: covidwho-2066593

ABSTRACT

There is evidence that vaccination against seasonal influenza can improve innate immune responses to COVID-19 and decrease disease severity. However, less is known about whether it could also impact the humoral immunity in SARS-CoV-2 infected patients. The present study aimed to compare the SARS-CoV-2 specific humoral responses (IgG antibodies against nucleocapsid; anti-N, receptor binding domain; anti-RBD, subunit S2; anti-S2, and envelope protein; anti-E) between non-hospitalized, COVID-19 unvaccinated, and mild COVID-19 convalescent patients who were and were not vaccinated against influenza during the 2019/2020 epidemic season (n = 489 and n = 292, respectively). The influenza-vaccinated group had significantly higher frequency and titers of anti-N antibodies (75 vs. 66%; mean 559 vs. 520 U/mL) and anti-RBD antibodies (85 vs. 76%; mean 580 vs. 540 U/mL). The prevalence and concentrations of anti-S2 and anti-E antibodies did not differ between groups (40-43%; mean 370-375 U/mL and 1.4-1.7%; mean 261-294 U/mL) and were significantly lower compared to those of anti-RBD and anti-N. In both groups, age, comorbidities, and gender did not affect the prevalence and concentrations of studied antibodies. The results indicate that influenza vaccination can improve serum antibody levels produced in response to SARS-CoV-2 infection.

4.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-343329

ABSTRACT

COVID-19 continues to exact a toll on human health despite the availability of several vaccines. Bacillus Calmette Guérin (BCG) has been shown to confer heterologous immune protection against viral infections including COVID-19 and has been proposed as vaccine against SARS-CoV-2 (SCV2). Here we tested intravenous BCG vaccination against COVID-19 using the golden Syrian hamster model together with immune profiling and single cell RNA sequencing (scRNAseq). We observed that BCG reduced both lung SCV2 viral load and bronchopneumonia. This was accompanied by an increase in lung alveolar macrophages, a reversal of SCV2-mediated T cell lymphopenia, and reduced lung granulocytes. Single cell transcriptome profiling showed that BCG uniquely recruits immunoglobulin-producing plasma cells to the lung suggesting accelerated local antibody production. BCG vaccination also recruited elevated levels of Th1, Th17, Treg, CTLs, and Tmem cells, and differentially expressed gene (DEG) analysis showed a transcriptional shift away from exhaustion markers and towards antigen presentation and repair. Similarly, BCG enhanced lung recruitment of alveolar macrophages and reduced key interstitial macrophage subsets, with both cell-types also showing reduced IFN-associated gene expression. Our observations indicate that BCG vaccination protects against SCV2 immunopathology by promoting early lung immunoglobulin production and immunotolerizing transcriptional patterns among key myeloid and lymphoid populations.

5.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-343311

ABSTRACT

Background: Both malaria and latent tuberculosis (TB) are possible factors related to decreased COVID-19 mortality. Therefore, malaria endemicity is a possible confounder when conducting a study on the correlation of latent TB prevalence to COVID-19 mortality. Previous studies regarding the effect of latent TB prevalence on COVID-19 mortality did not adjust malaria endemicity as a possible confounder as many malaria-endemic countries are highly TB prevalent countries. The main aim of this study is to look for the influence of TB prevalence on COVID-19 mortality. TB prevalence reflects latent TB prevalence since TB prevalence represents the ice burg of total TB prevalence. Material and methods: The total chosen countries were 69 non-malaria endemic countries. Countries were classified according to TB prevalence groups into low, moderate, and high prevalent groups. COVID-19 deaths/Million(M) inhabitant were taken as reported on September 2, 2020. "Kendall's-τ Correlation Coefficient", "Kruskal-Wallis test, and Mann-Whitney test were used in statistical analyses. Results: We found inverse relationships between TB prevalence and COVID-19 deaths/ (M) inhabitant and a highly significant correlation coefficient was reported (0.008) in Kendall's-τ correlation coefficient test. Kruskal-Wallis test showed a significant relationship within studied groups. Furthermore, the low TB prevalent group had significant reverse associations with both high and moderate TB prevalent groups in the Mann-Whitney test. Conclusion: In the absence of possible malaria confounding, TB prevalence in malaria free countries is inversely related to COVID-19 mortality in a highly significant association.

6.
Front Immunol ; 13: 959656, 2022.
Article in English | MEDLINE | ID: covidwho-2022746

ABSTRACT

Bacillus Calmette-Guerin (BCG) has been used as a vaccine against tuberculosis since 1921 and remains the only currently approved vaccine for this infection. The recent discovery that BCG protects against initial infection, and not just against progression from latent to active disease, has significant implications for ongoing research into the immune mechanisms that are relevant to generate a solid host defense against Mycobacterium tuberculosis (Mtb). In this review, we first explore the different components of immunity that are augmented after BCG vaccination. Next, we summarize current efforts to improve the efficacy of BCG through the development of recombinant strains, heterologous prime-boost approaches and the deployment of non-traditional routes. These efforts have included the development of new recombinant BCG strains, and various strategies for expression of important antigens such as those deleted during the M. bovis attenuation process or antigens that are present only in Mtb. BCG is typically administered via the intradermal route, raising questions about whether this could account for its apparent failure to generate long-lasting immunological memory in the lungs and the inconsistent level of protection against pulmonary tuberculosis in adults. Recent years have seen a resurgence of interest in the mucosal and intravenous delivery routes as they have been shown to induce a better immune response both in the systemic and mucosal compartments. Finally, we discuss the potential benefits of the ability of BCG to confer trained immunity in a non-specific manner by broadly stimulating a host immunity resulting in a generalized survival benefit in neonates and the elderly, while potentially offering benefits for the control of new and emerging infectious diseases such as COVID-19. Given that BCG will likely continue to be widely used well into the future, it remains of critical importance to better understand the immune responses driven by it and how to leverage these for the design of improved vaccination strategies against tuberculosis.


Subject(s)
COVID-19 , Mycobacterium bovis , Tuberculosis , Animals , BCG Vaccine , COVID-19/prevention & control , Disease Models, Animal , Vaccination
7.
Clin Infect Dis ; 75(1): e938-e946, 2022 Aug 24.
Article in English | MEDLINE | ID: covidwho-2017845

ABSTRACT

BACKGROUND: Older age is associated with increased severity and death from respiratory infections, including coronavirus disease 2019 (COVID-19). The tuberculosis BCG vaccine may provide heterologous protection against nontuberculous infections and has been proposed as a potential preventive strategy against COVID-19. METHODS: In this multicenter, placebo-controlled trial, we randomly assigned older adults (aged ≥60 years; n = 2014) to intracutaneous vaccination with BCG vaccine (n = 1008) or placebo (n = 1006). The primary end point was the cumulative incidence of respiratory tract infections (RTIs) that required medical intervention, during 12 months of follow-up. Secondary end points included the incidence of COVID-19, and the effect of BCG vaccination on the cellular and humoral immune responses. RESULTS: The cumulative incidence of RTIs requiring medical intervention was 0.029 in the BCG-vaccinated group and 0.024 in the control group (subdistribution hazard ratio, 1.26 [98.2% confidence interval, .65-2.44]). In the BCG vaccine and placebo groups, 51 and 48 individuals, respectively tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with polymerase chain reaction (subdistribution hazard ratio, 1.053 [95% confidence interval, .71-1.56]). No difference was observed in the frequency of adverse events. BCG vaccination was associated with enhanced cytokine responses after influenza, and also partially associated after SARS-CoV-2 stimulation. In patients diagnosed with COVID-19, antibody responses after infection were significantly stronger if the volunteers had previously received BCG vaccine. CONCLUSIONS: BCG vaccination had no effect on the incidence of RTIs, including SARS-CoV-2 infection, in older adult volunteers. However, it improved cytokine responses stimulated by influenza and SARS-CoV-2 and induced stronger antibody titers after COVID-19 infection. CLINICAL TRIALS REGISTRATION: EU Clinical Trials Register 2020-001591-15 ClinicalTrials.gov NCT04417335.


Subject(s)
COVID-19 , Influenza, Human , Aged , BCG Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , Cytokines , Humans , Pandemics/prevention & control , SARS-CoV-2 , Vaccination
8.
Front Immunol ; 13: 873067, 2022.
Article in English | MEDLINE | ID: covidwho-2005866

ABSTRACT

In a recent study of our group with the acronym ACTIVATE, Bacillus Calmete-Guérin (BCG) vaccination reduced the occurrence of new infections compared to placebo vaccination in the elderly. Most benefit was found for respiratory infections. The ACTIVATE-2 study was launched to assess the efficacy of BCG vaccination against coronavirus disease 2019 (COVID-19). In this multicenter, double-blind trial, 301 volunteers aged 50 years or older were randomized (1:1) to be vaccinated with BCG or placebo. The trial end points were the incidence of COVID-19 and the presence of anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies, which were both evaluated through 6 months after study intervention. Results revealed 68% relative reduction of the risk to develop COVID-19, using clinical criteria or/and laboratory diagnosis, in the group of BCG vaccine recipients compared with placebo-vaccinated controls, during a 6-month follow-up (OR 0.32, 95% CI 0.13-0.79). In total, eight patients were in need of hospitalization for COVID-19: six in the placebo group and two in the BCG group. Three months after study intervention, positive anti-SARS-CoV-2 antibodies were noted in 1.3% of volunteers in the placebo group and in 4.7% of participants in BCG-vaccinated group. These data indicate that BCG vaccination confers some protection against possible COVID-19 among patients older than 50 years with comorbidities. BCG vaccination may be a promising approach against the COVID-19 pandemic.


Subject(s)
Bacillus , COVID-19 , Aged , Antibodies, Viral , BCG Vaccine , COVID-19/prevention & control , Humans , Pandemics/prevention & control , Vaccination
9.
Sudan J Paediatr ; 22(1): 10-18, 2022.
Article in English | MEDLINE | ID: covidwho-1994863

ABSTRACT

Heterologous immunity is a well-known concept in immunology wherein prior exposure to an antigen confers cross-protection against an unrelated antigen. With the surge in global COVID-19 cases, there has been significant research into the application of vaccine-induced heterologous immunity associated with measles, mumps and rubella (MMR) vaccine, Bacillus Calmette-Guérin vaccine, oral polio vaccine, and hepatitis A vaccine in curbing the worst outcomes of COVID-19 infection. Despite having specific vaccines against COVID-19, it is worthwhile exploring the application of available vaccines in the prevention of severe disease until the vaccines reach all sections of the population across the globe. In this article, we aim to outline the concept of heterologous immunity and its relevance in context to MMR vaccine and COVID-19.

10.
Front Immunol ; 13: 921728, 2022.
Article in English | MEDLINE | ID: covidwho-1987494

ABSTRACT

Fibroblasts of different origins are known to possess stromal memory after inflammatory episodes. However, there are no studies exploring human lung fibroblast memory which may predict a subsequent inflammatory response in chronic respiratory diseases and COVID-19. MRC-5 and HF19 human lung fibroblast cell lines were treated using different primary and secondary stimulus combinations: TNFα-WD-TNFα, Poly (I:C)-WD-TNFα, TNFα-WD-Poly (I:C), or LPS-WD-TNFα with a 24-h rest period (withdrawal period; WD) between the two 24-h stimulations. TLR3 and NF-κB inhibitors were used to determine pathways involved. The effect of SARS-Cov-2 spike protein to inflammatory response of lung fibroblasts was also investigated. mRNA expressions of genes and IL6 release were measured using qRT-PCR and ELISA, respectively. Statistical significance was determined by using one- or two-way ANOVA, followed by Bonferroni's post hoc analysis for comparison of multiple groups. Preexposure with Poly (I:C) significantly increased TNFα-induced IL6 gene expression and IL6 release in both cell lines, while it affected neither gene expressions of IL1B, IL2, IL8, and MMP8 nor fibrosis-related genes: ACTA2, COL1A1, POSTN, and TGFB1. Inhibition of TLR3 or NF-κB during primary stimulation significantly downregulated IL6 release. Simultaneous treatment of MRC-5 cells with SARS-CoV-2 spike protein further increased TNFα-induced IL6 release; however, preexposure to Poly (I:C) did not affect it. Human lung fibroblasts are capable of retaining inflammatory memory and showed an augmented response upon secondary exposure. These results may contribute to the possibility of training human lung fibroblasts to respond suitably on inflammatory episodes after viral infection.


Subject(s)
COVID-19 , Interleukin-6/genetics , Tumor Necrosis Factor-alpha , Fibroblasts/metabolism , Gene Expression , Humans , Inflammation/chemically induced , Inflammation/genetics , Inflammation/metabolism , Interleukin-6/metabolism , Lung/metabolism , NF-kappa B/metabolism , Poly I-C/metabolism , Poly I-C/pharmacology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Toll-Like Receptor 3/genetics , Toll-Like Receptor 3/metabolism , Tumor Necrosis Factor-alpha/metabolism
11.
Front Immunol ; 13: 872695, 2022.
Article in English | MEDLINE | ID: covidwho-1952330

ABSTRACT

The frequent severe COVID-19 course in patients with periodontitis suggests a link of the aetiopathogenesis of both diseases. The formation of intravascular neutrophil extracellular traps (NETs) is crucial to the pathogenesis of severe COVID-19. Periodontitis is characterised by an increased level of circulating NETs, a propensity for increased NET formation, delayed NET clearance and low-grade endotoxemia (LGE). The latter has an enormous impact on innate immunity and susceptibility to infection with SARS-CoV-2. LPS binds the SARS-CoV-2 spike protein and this complex, which is more active than unbound LPS, precipitates massive NET formation. Thus, circulating NET formation is the common denominator in both COVID-19 and periodontitis and other diseases with low-grade endotoxemia like diabetes, obesity and cardiovascular diseases (CVD) also increase the risk to develop severe COVID-19. Here we discuss the role of propensity for increased NET formation, DNase I deficiency and low-grade endotoxaemia in periodontitis as aggravating factors for the severe course of COVID-19 and possible strategies for the diminution of increased levels of circulating periodontitis-derived NETs in COVID-19 with periodontitis comorbidity.


Subject(s)
COVID-19 , Endotoxemia , Extracellular Traps , Periodontitis , Endotoxemia/metabolism , Humans , Lipopolysaccharides/metabolism , Neutrophils , Periodontitis/pathology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
12.
Journal of Army Medical University ; 44(11):1079-1086, 2022.
Article in Chinese | Scopus | ID: covidwho-1955155

ABSTRACT

Acute severe hepatitis in children of unknown cause is a childhood liver disease of unknown etiology that emerged suddenly during the global pandemic of coronavirus disease 2019, Since it was reported in early April 2022, it has involved more than 20 countries around the world with about 450 cases, mainly in Europe and North America, and no similar ease has been reported in China.The disease occurs mostly in children under 5 years of age and is characterized mainly by liver disease manifestations such as jaundice and elevated transaminases, with rare respiratory symptoms;a few cases develop into liver failure and need liver transplantation, and most eases have a good prognosis.The disease is currently considered to be caused by infection, but the exact pathogen remains unclear.Adenovirus is detected in blood in many cases, so the possibility of infection caused by adenovirus should be considered;and factors such as laek of trained immunity and persistent inflammatory in children with COVID-19 should also be considered.The disease is no evidence of interpersonal transmission, infectivity is low, but the possibility of a pandemic outbreak in countries with a high prevalence of COVID-2019 needs to be guarded against;hand hygiene and respiratory protection may reduce the risk of morbidity.This article provides an overview of the epidemiological and clinical features of the disease and analyzes its nature, etiology and transmission risk in order to provide updated awareness of its clinical diagnosis and treatment. © 2022 by the authors.

13.
Front Immunol ; 13: 895020, 2022.
Article in English | MEDLINE | ID: covidwho-1933685

ABSTRACT

Tuberculosis (TB), caused by respiratory infection with Mycobacterium tuberculosis, remains a major global health threat. The only licensed TB vaccine, the one-hundred-year-old Bacille Calmette-Guérin has variable efficacy and often provides poor protection against adult pulmonary TB, the transmissible form of the disease. Thus, the lack of an optimal TB vaccine is one of the key barriers to TB control. Recently, the development of highly efficacious COVID-19 vaccines within one year accelerated the vaccine development process in human use, with the notable example of mRNA vaccines and adenovirus-vectored vaccines, and increased the public acceptance of the concept of the controlled human challenge model. In the TB vaccine field, recent progress also facilitated the deployment of an effective TB vaccine. In this review, we provide an update on the current virus-vectored TB vaccine pipeline and summarize the latest findings that might facilitate TB vaccine development. In detail, on the one hand, we provide a systematic literature review of the virus-vectored TB vaccines are in clinical trials, and other promising candidate vaccines at an earlier stage of development are being evaluated in preclinical animal models. These research sharply increase the likelihood of finding a more effective TB vaccine in the near future. On the other hand, we provide an update on the latest tools and concept that facilitating TB vaccine research development. We propose that a pre-requisite for successful development may be a better understanding of both the lung-resident memory T cell-mediated mucosal immunity and the trained immunity of phagocytic cells. Such knowledge could reveal novel targets and result in the innovative vaccine designs that may be needed for a quantum leap forward in vaccine efficacy. We also summarized the research on controlled human infection and ultra-low-dose aerosol infection murine models, which may provide more realistic assessments of vaccine utility at earlier stages. In addition, we believe that the success in the ongoing efforts to identify correlates of protection would be a game-changer for streamlining the triage of multiple next-generation TB vaccine candidates. Thus, with more advanced knowledge of TB vaccine research, we remain hopeful that a more effective TB vaccine will eventually be developed in the near future.


Subject(s)
COVID-19 , Tuberculosis Vaccines , Tuberculosis , Animals , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Mice , Tuberculosis/prevention & control , Vaccine Development
14.
EClinicalMedicine ; 48: 101414, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1926368

ABSTRACT

Background: BCG vaccination prevents severe childhood tuberculosis (TB) and was introduced in South Africa in the 1950s. It is hypothesised that BCG trains the innate immune system by inducing epigenetic and functional reprogramming, thus providing non-specific protection from respiratory tract infections. We evaluated BCG for reduction of morbidity and mortality due to COVID-19 in healthcare workers in South Africa. Methods: This randomised, double-blind, placebo-controlled trial recruited healthcare workers at three facilities in the Western Cape, South Africa, unless unwell, pregnant, breastfeeding, immunocompromised, hypersensitivity to BCG, or undergoing experimental COVID-19 treatment. Participants received BCG or saline intradermally (1:1) and were contacted once every 4 weeks for 1 year. COVID-19 testing was guided by symptoms. Hospitalisation, COVID-19, and respiratory tract infections were assessed with Cox proportional hazard modelling and time-to-event analyses, and event severity with post hoc Markovian analysis. This study is registered with ClinicalTrials.gov, NCT04379336. Findings: Between May 4 and Oct 23, 2020, we enrolled 1000 healthcare workers with a median age of 39 years (IQR 30-49), 70·4% were female, 16·5% nurses, 14·4% medical doctors, 48·5% had latent TB, and 15·3% had evidence of prior SARS-CoV-2 exposure. Hospitalisation due to COVID-19 occurred in 15 participants (1·5%); ten (66·7%) in the BCG group and five (33·3%) in the placebo group, hazard ratio (HR) 2·0 (95% CI 0·69-5·9, p = 0·20), indicating no statistically significant protection. Similarly, BCG had no statistically significant effect on COVID-19 (p = 0·63, HR = 1·08, 95% CI 0·82-1·42). Two participants (0·2%) died from COVID-19 and two (0·2%) from other reasons, all in the placebo group. Interpretation: BCG did not protect healthcare workers from SARS-CoV-2 infection or related severe COVID-19 disease and hospitalisation. Funding: Funding provided by EDCTP, grant number RIA2020EF-2968. Additional funding provided by private donors including: Mediclinic, Calavera Capital (Pty) Ltd, Thys Du Toit, Louis Stassen, The Ryan Foundation, and Dream World Investments 401 (Pty) Ltd. The computations were enabled by resources in project SNIC 2020-5-524 provided by the Swedish National Infrastructure for Computing (SNIC) at UPPMAX, partially funded by the Swedish Research Council through grant agreement No. 2018-05,973.

15.
Médecine et Maladies Infectieuses Formation ; 2022.
Article in English | ScienceDirect | ID: covidwho-1882374

ABSTRACT

Résumé Le BCG a fêté ses 100 ans en juillet 2021, en pleine pandémie de COVID-19, alors qu'une baisse des prises en charge de cas de tuberculose avait lieu suite à la diminution des activités de dépistage à travers le monde. Si le développement vaccinal permet d'envisager un vaccin plus efficace et mieux toléré que le BCG, on peut retenir que celui-ci réduit, lorsqu'il est administré dans l'enfance, le risque de tuberculose maladie mais aussi de mortalité toute cause, notamment dans les pays à faibles revenus. Son impact chez l'adulte reste moins évident. Cependant, l'effet protecteur observé vis-à-vis d'autres pathogènes (pressenti par Calmette lui-même) a conduit à évaluer l'efficacité de la revaccination par le BCG à l’âge adulte. BCG celebrated its 100th birthday in July 2021 in the midst of the COVID-19 pandemic, while a decrease in tuberculosis case management was observed as a direct result of a decrease in screening activities throughout the world. If the vaccine development makes it possible to envisage a more effective and better tolerated vaccine than BCG, we can remember that BCG reduces, in childhood, the risk of tuberculosis disease but also of all-cause mortality, particularly in low-income countries. Its impact in adults remains less clear. However, its ability to protect against other pathogens (anticipated by Calmette himself) has led to an evaluation of the efficacy of revaccination with BCG in adulthood.

16.
Clin Transl Discov ; 2(2): e60, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1881399

ABSTRACT

Endeavors to identify potentially protective variables for COVID-19 impact on certain populations have remained a priority. Multiple attempts have been made to attribute the reduced COVID-19 impact on populations to their Bacillus-Calmette-Guérin (BCG) vaccination coverage ignoring the fact that the effect of childhood BCG vaccination wanes within 5 years while most of the COVID-19 cases and deaths have occurred in aged with comorbidities. Since the supposed protection being investigated could come from heterologous 'trained immunity' (TI) conferred by exposure to Mycobacterium spp. (i.e., environmental and BCG), it is argued that the estimates of the prevalence of TI in populations currently available as latent tuberculosis infection (LTBI) prevalence would be a better variable to evaluate such assertions. Indeed, when we analyze the European populations (24), and erstwhile East and West Germany populations completely disregarding their BCG vaccination coverage, the populations with higher TI prevalence consistently display reduced COVID-19 impact as compared to their lower TI prevalence neighbors. The TI estimates of the populations not the BCG coverage per se, negatively correlated with pandemic phase-matched COVID-19 incidences (r(24): -0.79 to -0.57; p-value < .004), mortality (r(24): -0.63 to -0.45; p-value < .03), and interim case fatality rates (i-CFR) data. To decisively arrive at dependable conclusions about the potential protective benefit gained from BCG vaccination in COVID-19, the ongoing or planned randomized controlled trials should consciously consider including measures of TI as: (a) all individuals immunized do not respond equally, (b) small study groups from higher background TI could fail to indicate any protective effect.

17.
Front Biosci (Landmark Ed) ; 27(5): 157, 2022 05 13.
Article in English | MEDLINE | ID: covidwho-1876486

ABSTRACT

Coronavirus disease 2019 (COVID-19), which broke out at the end of 2019, is a global pandemic and seriously threatens human health. Vaccination is the most effective way to prevent and control COVID-19. At present, more than 13 COVID-19 vaccines have been urgently authorized for use, but the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has brought unprecedented challenges to the protective efficiency of these COVID-19 vaccines. In particular, the recent emergence of Delta and Omicron variants, which are rapidly spreading worldwide, may bring many challenges to the medical systems. Interestingly, previous studies have shown that the Bacillus Calmette-Guerin (BCG) vaccine used to prevent tuberculosis can induce non-specific trained immunity, protecting against infectious diseases caused by respiratory viruses. Therefore, there is a hypothesis that BCG plays an essential role in reducing the incidence, severity, hospitalization, and mortality of COVID-19 and enhancing the protection efficiency of the COVID-19 vaccine. To confirm this hypothesis, 56 clinical trials have been conducted globally to assess BCG's protective effectiveness against COVID-19 infection. Herein, this review discussed the trained immunity induced by BCG and its underlying mechanisms and summarised BCG's latest research progress in preventing COVID-19, especially the ongoing clinical trials. We hope this review will provide new strategies for fighting against COVID-19.


Subject(s)
BCG Vaccine , COVID-19 , BCG Vaccine/therapeutic use , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Humans , SARS-CoV-2
18.
Clin Microbiol Infect ; 28(9): 1278-1285, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1872991

ABSTRACT

OBJECTIVES: The COVID-19 pandemic increases healthcare worker (HCW) absenteeism. The bacillus Calmette-Guérin (BCG) vaccine may provide non-specific protection against respiratory infections through enhancement of trained immunity. We investigated the impact of BCG vaccination on HCW absenteeism during the COVID-19 pandemic. METHODS: HCWs exposed to COVID-19 patients in nine Dutch hospitals were randomized to BCG vaccine or placebo in a 1:1 ratio, and followed for one year using a mobile phone application. The primary endpoint was the self-reported number of days of unplanned absenteeism for any reason. Secondary endpoints included documented COVID-19, acute respiratory symptoms or fever. This was an investigator-funded study, registered at ClinicalTrials.gov (NCT03987919). RESULTS: In March/April 2020, 1511 HCWs were enrolled. The median duration of follow-up was 357 person-days (interquartile range [IQR], 351 to 361). Unplanned absenteeism for any reason was observed in 2.8% of planned working days in the BCG group and 2.7% in the placebo group (adjusted relative risk 0.94; 95% credible interval, 0.78-1.15). Cumulative incidences of documented COVID-19 were 14.2% in the BCG and 15.2% in the placebo group (adjusted hazard ratio (aHR) 0.94; 95% confidence interval (CI), 0.72-1.24). First episodes of self-reported acute respiratory symptoms or fever occurred in 490 (66.2%) and 443 (60.2%) participants, respectively (aHR: 1.13; 95% CI, 0.99-1.28). Thirty-one serious adverse events were reported (13 after BCG, 18 after placebo), none considered related to study medication. CONCLUSIONS: During the COVID-19 pandemic, BCG-vaccination of HCW exposed to COVID-19 patients did not reduce unplanned absenteeism nor documented COVID-19.


Subject(s)
COVID-19 , Mycobacterium bovis , Absenteeism , BCG Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , Health Personnel , Humans , Pandemics/prevention & control , SARS-CoV-2
19.
Vaccines (Basel) ; 10(5)2022 May 04.
Article in English | MEDLINE | ID: covidwho-1820454

ABSTRACT

Background:Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is a live attenuated vaccine mainly administered to newborns and used for over 100 years to prevent the disease caused by Mycobacterium tuberculosis (M. tb). This vaccine can induce immune response polarization towards a Th1 profile, which is desired for counteracting M. tb, other mycobacteria, and unrelated intracellular pathogens. The vaccine BCG has been used as a vector to express recombinant proteins and has been shown to protect against several diseases, particularly respiratory viruses. Methods: BCG was used to develop recombinant vaccines expressing either the Nucleoprotein from SARS-CoV-2 or Andes orthohantavirus. Mice were immunized with these vaccines with the aim of evaluating the safety and immunogenicity parameters. Results: Immunization with two doses of 1 × 108 CFU or one dose of 1 × 105 CFU of these BCGs was safe in mice. A statistically significant cellular immune response was induced by both formulations, characterized as the activation of CD4+ and CD8+ T cells. Stimulation with unrelated antigens resulted in increased expression of activation markers by T cells and secretion of IL-2 and IFN-γ, while increased secretion of IL-6 was found for both recombinant vaccines; all of these parameters related to a trained immunity profile. The humoral immune response elicited by both vaccines was modest, but further exposure to antigens could increase this response. Conclusions: The BCG vaccine is a promising platform for developing vaccines against different pathogens, inducing a marked antigen-specific immune response.

20.
Turkish Journal of Immunology ; 10(1):12-21, 2022.
Article in Turkish | Academic Search Complete | ID: covidwho-1818496

ABSTRACT

Tuberculosis (TB) is an infectious disease that has deeply affected societies throughout human history due to the serious effects of Mycobacterium tuberculosis complex. The Bacille Calmette-Guérin (BCG) vaccine, which has a historical importance in the prevention of TB, has been administered to more than 4 billion people with its 100-year history. While the studies to develop a more effective vaccine than BCG in the prevention of TB continue, BCG has surprisingly came to the fore again on its 100th birthday with the studies on the protection of BCG against the coronavirus disease pandemic. In addition to the non-specific/non-TB effect of BCG on infectious diseases, it has been used as a ‘‘Food and Drug Administration’’ approved immunomodulator in the treatment of bladder cancer in humans since 1976. In addition, studies on its use as an immunotherapy agent in topical treatment for common genital warts are ongoing. Although the fact that the BCG vaccine reduces the risk of TB infection by approximately 50% is actually a limited efficacy, the non-specific effects of heterologous and trained immunity in protection against other infections keep the interest in the vaccine alive. This study was planned to compile the discovery and development history of BCG vaccine, its history and its effect on immunological mechanisms in non-TB infectious diseases. (English) [ FROM AUTHOR] Tüberküloz (TB) Mycobacterium tuberculosis kompleksi’nin etken olduğu ciddi etkileri nedeniyle insanlık tarihi boyunca toplumları derinden etkileyen bulaşıcı bir hastalıktır. TB’den korunmada tarihi bir öneme sahip olan Bacille Calmette-Guérin (BCG) aşısı 100 yıllık geçmişi ile bugüne kadar 4 milyardan fazla kişiye uygulanmıştır. TB’den korunmada BCG’den daha etkili aşı geliştirme çalışmaları sürerken, BCG’nin koronavirüs hastalığı pandemisine karşı koruyuculuğu ile ilgili çalışmalarla BCG, 100. yaş gününde yeniden şaşırtıcı bir şekilde gündeme gelmiştir. BCG’nin, bulaşıcı hastalıklar üzerindeki non-spesifik/TB dışı etkisine ek olarak, insanlarda mesane kanseri tedavisinde 1976 tarihinden itibaren “Gıda ve Ílaç Dairesi” onaylı immünomodülatör olarak kullanılmaktadır. Ayrıca, yaygın genital siğiller için topikal tedavide immünoterapi ajanı olarak kullanımına yönelik çalışmalar da sürmektedir. BCG aşısının TB enfeksiyonu riskini yaklaşık %50 oranında azaltması aslında sınırlı bir etkinlik olsa da diğer enfeksiyonlara karşı korunmada heterolog ve eğitimli bağışıklık aracılığı ile non-spesifik etkilerinin ortaya konması aşıya olan ilgiyi canlı tutmaktadır. Bu çalışma BCG aşısının keşfedilme ve gelişim öyküsünü, tarihçesini ve TB dışı enfeksiyon hastalıklarındaki immünolojik mekanizmalara etkisini derlemek için planlanmıştır. (Turkish) [ FROM AUTHOR] Copyright of Turkish Journal of Immunology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

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