Reactivation of BCG vaccination scars after mRNA -SARS- CoV2 -vaccine and SARS-CoV2 infection: Two case reports

Case report Purpose: To report two cases of reactivation of BCG vaccination scars, the first after mRNA -SARS- CoV2 -vaccine and the second after SARS-CoV2 infection. Case 1: A 33 year-old woman, a nursing assistant, was referred with erythema and swelling of her BCG vaccination scar 24 hours after receiving her second dose of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) and, 10 months later, after receiving her third dose with the mRNA-1273 (Moderna) vaccine. Case 2: A 60 year-old woman, a medical doctor, was referred with erythema and swelling of her two BCG vaccination scars (one administered at birth and the second one at the age of 10), 12 days after testing positive for SARS-CoV2 associated with homolateral supraclavicular and axillary adenopathy's . In both cases, total IgE values and D-dimer were normal and symptoms resolved spontaneously within 7 days, without further treatment. Discussion(s): Bacillus Calmette-Guerin (BCG) local scar inflammatory reactions have been described with Kawasaki disease in children, with other viral infections such as measles and human herpesvirus type 6 (HHV6) infection and following influenza vaccination. The relationship between the BCG vaccine and SARS-CoV2 remains unclear. Even in mid-2020 and during the first years of the pandemic, it was proposed that the BCG vaccine could be protective against SARS-CoV2 infection. Several studies were launched to evaluate this hypothesis, with no conclusive results in this regard. Along the last two years, some cases of reactivation of BCG vaccination scars have been reported after vaccination with mRNA -SARS- CoV2 -vaccines. To our knowledge, this is the first reported case of reactivation of BCG vaccination scars after SARS-CoV2 infection. Conclusion(s): We report the first case of BCG vaccine scar inflammation as a local reaction following SARS-CoV2 infection. The reactivation of BCG vaccine scar after receiving mRNA vaccines and after SARS-CoV2 infection might have been caused by an immunological reaction due to a cross reactivity phenomenon between BCG and SARS-CoV2. The immunological and clinical implication of this reaction needs to be further studied. Clinicians need to be aware of this local reaction to SARS-CoV2 vaccines and infection. (Figure Presented).

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

Background: The 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. Methods: Sixty-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. Results: Data 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. Conclusion: This 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.

An Observational Study on the Early Stages of the Covid-19 Pandemic in Pakistan

Bachground: The coronavirus disease 2019 (COVID-19) pandemic, which started on February 26, 2020 in city of karachi, spread quickly throughout Pakistan. Material(s) and Method(s): The design of this study was a observational study design and this study was conducted at king Edward medical University Lahore. More than 6,200 persons were afflicted by the illness in the first seven weeks, and there were more than 111 documented fatalities. Many problems arise if we contrast the COVID-19 tragedies in Pakistan with those in nations like China, Iran, and the European Union. The geography of the nation, poverty, poor literacy rates, environmental circumstances, sanitary conditions, and dietary habits are only a few of the difficulties we face in containing this epidemic. Although there are terrible circumstances in each of these areas, Pakistan's COVID-19 epidemic was slower than that of other developing nations. Result(s): The impact of COVID-19 appears to be lessened by Pakistan's humid hot temperature, early reaction to COVID-19, population immune system, BCG vaccination, and the proportion of young individuals. In this essay, we explore the COVID-19 pandemic outbreak in China, Iran, and Pakistan and present its day-to-day changes. We outline the COVID-19 structure and how it compares to SARS-COV and SARS-COV2. The use of Remdesivir (an adenosine analogue used against RNA viruses), Chloroquine (a widely used anti-malarial drug), convalescent plasma, neutralising antibodies targeting the ACE-2 receptor, and an ACE-2-like molecule that might bind to the S protein of the coronavirus are also covered in terms of treatment options and their drawbacks. Also covered are the effects of COVID-19 on Pakistan's economy and government relief measures. Conclusion(s): In conclusion, it may be said that the support systems in place may not be sufficient to stop the spread of the virus. Even with the meagre assistance offered, it is weaker for rural places where the virus's effects may be severe than in the nation's cities. Further research is required as the epidemic develops to better understand governmental efforts to contain the virus and its effects across the nation.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Impact of BCG Vaccine Against the Pandemic of Corona (COVID-19): A Review

The explanations behind the wide spreadability of coronavirus sickness (COVID-19) are not known properly in this world. Several clinical investigations have indicated that the BCG antibody impacts on the immune system and human sicknesses which take part in the host system to such an extent that numerous types of viral diseases are extensively diminished or reduced. Subsequently, it was also observed in different studies that the recurrence and seriousness of numerous microbial or viral diseases, including COVID-19, will be lower in few countries where BCG Immunization programs are carried out. Few clinical investigations proposed by the epidemiological data have shown that the BCG antibody has a valuable impact in the treatment of COVID-19. So the BCG immunization may be found valuable in the coming months, particularly in the countries, where mass BCG immunization is done. Further thorough BCG immunization clinical trial is required to establish the above findings and its clinical significance. In future, this investigation will concentrate on the BCG vaccine and it may forestall the event of SARS-CoV-2 contamination and its succession in the large population.Copyright © 2021 Bentham Science Publishers.

A Note on the Potential BCG Vaccination - COVID-19 Molecular Link

Objective: Our goal was to elucidate a potential molecular link between the past and current tuberculosis vaccine Bacillus Calmette-Guerin (BCG;a live attenuated strain of Mycobacterium bovis) immunization policies and COVID-19. Method(s): Our sequence homology analyses have demonstrated that there is an intriguing level of sequence homology between a few of the BCG and Sars-CoV-2 proteins. Result(s): The data suggest that the BCG-specific memory B-cells that are preserved in BCG-vaccinated patients cross-recognize SARS-CoV-2 and that this cross-recognition may affect the virus proliferation and COVID-19 severity. Conclusion(s): Our results can stimulate the sharply focused follow-up experimental studies.Copyright © 2020 Bentham Science Publishers.

Influence of COVID19 pandemic on change of attitude about tuberculosis among patients with respiratory diseases in Serbia

Introduction: The COVID19 pandemic has changed the way of life all over the world, many diseases have started to reactivate and reappear. Tuberculosis (TB) can be among them despite the existence of effective measures and programs to control it. The aim of study was to establish patients' knowledge of TB at the time of the COVID19 pandemic. Method(s): The prospective study included patients with respiratory diseases who were interviewed (questionnaire with 27 questions) at the Institute of Pulmonary Diseases of Vojvodina (Serbia) in the period September-December 2021. Result(s): A total of 600 patients in two groups were surveyed (300 outpatient-AMB;300 in-hospital-HOS). Almost all patients in both groups knew that TB was a contagious disease (562, 93.6%, p=0.735);a curable disease (521, AMB-240, 80.0%, HOS-281, 93.7%, p=0.052). Less than 50% said bacteria was the causative agent (273 patients, AMB-149 patients, 49%, HOS-124, 41.3%, p=0.041). The 3/4 patients in both groups (521 patients, p=0.590) responded that cough was a way of transmission. Nearly 30% of all patients are unaware of the existence of TB vaccine (BCG), while 1/3 of patients believe that the vaccine cannot helps (204 patients, AMB-141, 47%, HOS-63, 21%, p=0.014). Conclusion(s): Patients showed mediocre knowledge of TB, especially with reference to TB immunization measures. The probable reason lies in the various informations in the media about immunization against COVID19 and the consequent rejection of the success of immunization against TB. It is necessary to intensify the education of the population about the positive effects of all types of immunization in order to prevent the disease.

Can BCG Vaccine Be a Potential Tool for COVID-19?

SARS-CoV-2 has affected essentially all countries worldwide and caused millions of people to become infected and die. Therefore, it is extremely valuable to investigate new approaches to stop the most scarring ongoing pandemic. BCG vaccine has been proposed that it could reduce the rate of new COVID cases and limit the severity of infection since TB and COVID-19 have similar dominant effects, such as cytokine storm and improper immune response. This review aimed to focus on the latest literature data on trained immunity as well as the possible cross protection effect of BCG vaccine against COVID-19. The first immune response to BCG vaccines has started with the stimulation of adaptive immune response and establishment of the immunological memory of antigen-specific T and B cells to target infectious agents. In the past years, innate immune response was thought to be not having the talent to adapt and "learn” from previous exposure to a pathogen. Trained immunity is conceivable as 'de facto' innate immune system memory. Some researches argue that there is a strong relationship between BCG immunization and COVID-19 although some are against this argument. Based on the data obtained from different research studies and ongoing clinical trials, there is still no evidence that BCG vaccine is effective against COVID-19. Besides assumptions, knowns and unknowns, the clinical efficiency of BCG vaccine against SARS-CoV-2 should be validated by accurate scientific clinical reports in different age groups to understand the potential benefits of BCG vaccine to limit COVID-19 incidence and mortality.

Differences in Immune Responses in Individuals of Indian and European Origin: Relevance for the COVID-19 Pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, large differences in susceptibility and mortality due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported between populations in Europe and South Asia. While both host and environmental factors (including Mycobacterium bovis BCG vaccination) have been proposed to explain this, the potential biological substrate of these differences is unknown. We purified peripheral blood mononuclear cells from individuals living in India and the Netherlands at baseline and 10 to 12 weeks after BCG vaccination. We compared chromatin accessibility between the two populations at baseline, as well as gene transcription profiles and cytokine production capacities upon stimulation. The chromatin accessibility of genes important for adaptive immunity was higher in the Indians than in the Europeans, while the latter had more accessible chromatin regions in genes of the innate immune system. At the transcriptional level, we observed that the Indian volunteers displayed a more tolerant immune response to stimulation, in contrast to a more exaggerated response in the Europeans. BCG vaccination strengthened the tolerance program in the Indians but not in the Europeans. These differences may partly explain the different impact of COVID-19 on the two populations. IMPORTANCE In this study, we assessed the differences in immune responses in individuals from India and Europe. This aspect is of great relevance, because of the described differences in morbidity and mortality between India and Europe during the pandemic. We found a significant difference in chromatin accessibility in immune cells from the two populations, followed by a more balanced and effective response in individuals from India. These exciting findings represent a very important piece of the puzzle for understanding the COVID-19 pandemic at a global level.

The effect of Bacillus Calmette-Guerin vaccine sonicates on coronavirus 229E infection of human pulmonary endothelium and development of the inflammatory response

It is postulated that vaccination against tuberculosis with Bacillus Cal-mette-Gue'rin (BCG) vaccine may translate into lower incidence of respiratory tract infections by modulating the release of pro-inflammatory cytokines by innate immune cells. This modulation may be due to epigenetic changes in these cells resulting in an increase in the production of pro-inflammatory cytokines such as IL-1 beta, IL-6 or TNF-alpha. It is not known whether the pulmonary vascular endothelium equip-ped with molecular pattern recognition receptors (PRRs) and with en-try receptors for human coronaviruses can be infected by them, or whether BCG vaccination may modulate its susceptibility to infection with these viruses. This study analyzes the effect of the HCoV 229E human coronavirus on human pulmonary vascular endothelium. Mo-reover, the influence of BCG sonicates on susceptibility to HCoV 229E endothelial infection and the generation of antiviral and inflammatory responses was assessed.

Pathogenesis of SARS-CoV-2 and Mycobacterium tuberculosis Coinfection.

Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, is an infectious disease that poses severe threats to global public health and significant economic losses. The COVID-19 global burden is rapidly increasing, with over 246.53 million COVID-19 cases and 49.97 million deaths reported in the WHO 2021 report. People with compromised immunity, such as tuberculosis (TB) patients, are highly exposed to severe COVID-19. Both COVID-19 and TB diseases spread primarily through respiratory droplets from an infected person to a healthy person, which may cause pneumonia and cytokine storms, leading to severe respiratory disorders. The COVID-19-TB coinfection could be fatal, exacerbating the current COVID-19 pandemic apart from cellular immune deficiency, coagulation activation, myocardial infarction, and other organ dysfunction. This study aimed to assess the pathogenesis of SARS-CoV-2-Mycobacterium tuberculosis coinfections. We provide a brief overview of COVID19-TB coinfection and discuss SARS-CoV-2 host cellular receptors and pathogenesis. In addition, we discuss M. tuberculosis host cellular receptors and pathogenesis. Moreover, we highlight the impact of SARS-CoV-2 on TB patients and the pathological pathways that connect SARS-CoV-2 and M. tuberculosis infection. Further, we discuss the impact of BCG vaccination on SARS-CoV-2 cases coinfected with M. tuberculosis, as well as the diagnostic challenges associated with the coinfection.

Clinical impact of COVID-19 on tuberculosis.

During COVID-19 pandemic, a lot of diseases suffered from a limited access to health care services, owing to the use of resources, both technical and financial, mainly directed towards such a dramatic outbreak. Among these, tuberculosis (TB) has been one of the most penalized, with a huge delay both in diagnosis and in start of treatment, with a consequential dramatic increase in morbidity and mortality. COVID-19 and tuberculosis share similar common pathogenetic pathways, and both diseases affect primarily the lungs. About the impact of TB on COVID-19 severity and mortality, data are unclear and literature reports are often conflicting. Certainly, considering the management of coinfected patients, there are pharmacokinetic interactions between several drugs used for the therapy of SARS-CoV-2 infection and the treatment of TB.

BCG vaccine: Its relevance in the prevention of tuberculosis and beyond

BCG, a live attenuated vaccine was developed against tuberculosis at the beginning of the 20th century. It has been the most used vaccine in the world, with around 130 million children vaccinated every year. Although, there are varying estimates of its efficacy in preventing pulmonary tuberculosis, protection was higher in trials further from the equator, where environmental mycobacteria are less and with lower risk of diagnostic detection bias. Protection against meningeal and miliary tuberculosis also appeared greater than for pulmonary tuberculosis. BCG Vaccine has been shown to decrease neonatal mortality due to the prevention of neonatal sepsis and various upper respiratory tract infections (URTI). BCG vaccine also has nonspecific protective effects against protozoan infections. This nonspecific effects of BCG vaccine in humans and animal models have been attributed to Heterologous immunity and Trained Immunity. BCG as adjuvant immune therapy is shown promising results for patients of malignant melanoma. Intravesical BCG Vaccine is now being used as standard therapy for nonmuscle invasive bladder cancer (NMIBC). . BCC vaccine administered at birth enhances many vaccine responses. Ecological studies suggested that countries and regions that mandate BCG vaccination for their population have a lower number of infections and a reduced mortality from COVID-19. It has been hypothesized that BCG vaccination might be a potent preventive measure against SARS- CoV-2 infection and/or may reduce COVID-19 disease severity. Countries with a low TB incidence and a low BCG coverage had the highest incidence of COVID-19 per 100,000 population. Countries with high TB incidence and BCG coverage had much lower rates of COVID-19 infection. In addition, the case rate fatality rate appeared to be lower in these countries. A study to evaluate the effectiveness of the BCG vaccine in reducing morbidity and mortality in elderly individuals in COVID-19 hotspots in India highlights, the effect of BCG vaccination in modulating the frequencies of both innate and adaptive immune cell subsets and in inducing heightened total antibody levels. Whether this translates to improved protective immunity to non - specific infections like SARS-CoV2 remains to be determined.

Efficacy of Bacillus Calmette-Guérin (BCG) Vaccination in Reducing the Incidence and Severity of COVID-19 in High-Risk Population (BRIC): a Phase III, Multi-centre, Quadruple-Blind Randomised Control Trial.

INTRODUCTION: Universal coverage of vaccines alone cannot be relied upon to protect at-risk populations in lower- and middle-income countries against the impact of the coronavirus disease 2019 (COVID-19) pandemic and newer variants. Live vaccines, including Bacillus Calmette-Guérin (BCG), are being studied for their effectiveness in reducing the incidence and severity of COVID-19 infection. METHODS: In this multi-centre quadruple-blind, parallel assignment randomised control trial, 495 high-risk group adults (aged 18-60 years) were randomised into BCG and placebo arms and followed up for 9 months from the date of vaccination. The primary outcome was the difference in the incidence of COVID-19 infection at the end of 9 months. Secondary outcomes included the difference in the incidence of severe COVID-19 infections, hospitalisation rates, intensive care unit stay, oxygen requirement and mortality at the end of 9 months. The primary analysis was done on an intention-to-treat basis, while safety analysis was done per protocol. RESULTS: There was no significant difference in the incidence rates of cartridge-based nucleic acid amplification test (CB-NAAT) positive COVID-19 infection [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.54-2.14] in the two groups, but the BCG arm showed a statistically significant decrease in clinically diagnosed (symptomatic) probable COVID-19 infections (OR 0.38, 95% CI 0.20-0.72). Compared with the BCG arm, significantly more patients developed severe COVID-19 pneumonia (CB-NAAT positive) and required hospitalisation and oxygen in the placebo arm (six versus none; p = 0.03). One patient belonging to the placebo arm required intensive care unit (ICU) stay and died. BCG had a protective efficacy of 62% (95% CI 28-80%) for likely symptomatic COVID-19 infection. CONCLUSIONS: BCG is protective in reducing the incidence of acute respiratory illness (probable symptomatic COVID-19 infection) and severity of the disease, including hospitalisation, in patients belonging to the high-risk group of COVID-19 infection, and the antibody response persists for quite a long time. A multi-centre study with a larger sample size will help to confirm the findings in this study. CLINICAL TRIALS REGISTRY: Clinical Trials Registry India (CTRI/2020/07/026668).

The Bacillus Calmette­Guérin (BCG) vaccine has been studied previously in several settings, including reducing childhood mortalities due to viral infections and induction of trained immunity and reducing upper respiratory tract infections and pneumonia in older adults. This multi-centre trial has tried to evaluate the efficacy of BCG revaccination in reducing the incidence and severity of COVID-19 infections in adults between 18 and 60 years of age belonging to the high-risk group owing to the presence of comorbidities including diabetes, chronic kidney disease, chronic liver disease and chronic lung diseases. A single dose of BCG vaccine produced significantly high titres of BCG antibodies lasting for six months. While there was no significant reduction in the incidence of COVID-19 infection, there was an 8.4% reduction in the incidence of symptomatic COVID-19 disease at the end of 9 months of follow-up. In addition, there were significantly fewer severe COVID-19 infections requiring hospital stay and oxygen support. However, the overall numbers of severe COVID-19 infections were low. Thus, the study shows that BCG can protect against symptomatic and severe COVID-19 disease. However, it might not reduce the incidence of new infections. The study results are significant for low- and middle-income countries without adequate coverage of primary doses of COVID-19 vaccination, let alone the booster doses. Future studies should evaluate the BCG vaccine's efficacy as a booster compared with routine COVID-19 vaccine boosters.

Covid-19 Pandemic Impact on Unaccompanied Asylum Seeking Children (Uasc) Tuberculosis Screening Service

Aims Unaccompanied asylum-seeking children (UASC) are a vulnerable group who experience lot of physical and mental health difficulties during their journey. In the UK, it is statutory for all UASC to have Initial Health Assessment (IHA). NICE recommends screening for specific high-risk groups in the UK. These groups include: close contacts of patients with TB (Tuberculosis), healthcare workers, immunosuppressed patients (for example those with HIV) and migrants from countries where TB is common. Some of UASC come from countries with high incidence of TB infection. It is important to ensure that children at high risk of TB are identified and screened to avoid potential public health consequences. The effect of the pandemic on USAC is not fully understood. It is important to ensure that children at high risk of TB are identified and screened to avoid potential public health consequences. The effect of the pandemic on USAC is not fully understood. An audit was completed in a big paediatric setting at a children's hospital in the United Kingdom exploring the local TB screening uptake pre-pandemic (prior to 2020) and midpandemic (2020-2021). The audit compared practice of the local USAC clinic with the national guidelines on migrant health guidance. The pattern of USAC pre-pandemic and midpandemic were compared. Methods Details of the USAC children were retrieved from the 'Looked after Children' database in the hospital. Following the initial health assessment, the USAC who were deemed to be at increased risk of TB were referred to the asylum-seeking service for the screening and subsequent referrals to the chest clinic. The risk factors were guided by the country of origin, their symptoms and the BCG immunisation status. Results 33 USAC were seen for initial health assessment over 2 years period. The demographic characteristics and country of origin were similar prior to and after March 2020. 18 UASC were seen in 12-month period prior to March 2020. 77.7% of these qualified for TB screening. 15 USAC were seen in the 12-month period after March 2020. 73.3% of these qualified for TB screening. Of the 33 USAC, 25 met the criteria for TB screening and were therefore referred to the asylum-seeking team for the screen. 15/25 (60%) received the screening. None of these 15 children were diagnosed with active TB but 3 (16.6%) were diagnosed and treated for latent TB. Each of 10 young people who missed the screening were identified and advised to be followed through. The missed screening was mainly due to non-clinic attendance or young person's move out of the area. Conclusion In this audit, the number of UASC and the proportion of them that required TB screening did not change during the pandemic. TB screening identified a significant number of cases of latent TB but no active TB. A few of young people missed their TB screening which has potentially serious consequences if they were infected. Joint working groups with the local authority established and UASC pathway streamlined to avoid similar situations in future.

Efficacy of BCG Vaccination Against Respiratory Tract Infections in Older Adults During the Coronavirus Disease 2019 Pandemic.

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.

Recombinant BCG-LTAK63 Vaccine Candidate for Tuberculosis Induces an Inflammatory Profile in Human Macrophages.

Tuberculosis (TB) is one of the top 10 leading causes of death worldwide. The recombinant BCG strain expressing the genetically detoxified A subunit of the thermolabile toxin from Escherichia coli (LTAK63) adjuvant (rBCG-LTAK63) has previously been shown to confer superior protection and immunogenicity compared to BCG in a murine TB infection model. To further investigate the immunological mechanisms induced by rBCG-LTAK63, we evaluated the immune responses induced by rBCG-LTAK63, BCG, and Mycobacterium tuberculosis (Mtb) H37Rv strains in experimental infections of primary human M1 and M2 macrophages at the transcriptomic and cytokine secretion levels. The rBCG-LTAK63-infected M1 macrophages more profoundly upregulated interferon-inducible genes such as IFIT3, OAS3, and antimicrobial gene CXCL9 compared to BCG, and induced higher levels of inflammatory cytokines such as IL-12(p70), TNF-ß, and IL-15. The rBCG-LTAK63-infected M2 macrophages more extensively upregulated transcripts of inflammation-related genes, TAP1, GBP1, SLAMF7, TNIP1, and IL6, and induced higher levels of cytokines related to inflammation and tissue repair, MCP-3 and EGF, as compared to BCG. Thus, our data revealed an important signature of immune responses induced in human macrophages by rBCG-LTAK63 associated with increased inflammation, activation, and tissue repair, which may be correlated with a protective immune response against TB.

Effect of BCG Vaccination against SARS-CoV-2 Infection.

Based on previous studies, we found that Bacillus Calmette-Guérin (BCG) vaccination may play a role in preventing SARS-CoV-2 infection. Therefore, we conducted a meta-analysis to investigate this protective effect. We searched the Embase, PubMed, Web of Science, Cochrane Library, BioRxiv, and MedRxiv databases for studies that evaluated the relationship between BCG vaccination and SARS-CoV-2 infection or COVID-19 disease. The quality of all included studies was assessed using the Risk of Bias in Non-randomized Studies of Interventions and the Agency for Healthcare Research and Quality data tools. Review Manager (Version 5.3) was used to conduct all the data analyses. A total of eight studies were ultimately included in our meta-analysis. Our primary analysis found a significantly lower SARS-CoV-2 infection rate in the BCG vaccination group compared to the control group, with an odds ratio of 0.61, (95% confidence interval 0.39 to 0.95, P = 0.03; I2 = 31%, and P = 0.21, respectively). Our study indicates that BCG vaccination can protect against SARS-CoV-2 infection. However, there is insufficient evidence that BCG vaccination can reduce the severity of COVID-19.

Research progress on the BCG-induced trained immunity:mechanism and role

The purpose of Bacillus Calmette-Guérin (BCG) vaccination is to prevent Mycobacterium tuberculosis infection, but studies have shown that BCG activates innate immunity, causes epigenetic reprogramming and metabolic changes of myeloid cells, and forms innate immune memory or trained immunity. When bone marrow-like cells are stimulated by pathogens again, they show enhanced immune response and promote the host's nonspecific defense ability. Innate immune memory is also called training immunity. In recent years, BCG-induced innate immune memory has attracted much attention, and it will guide the design of novel vaccine. This article reviews the application of BCG in prevention and treatment of corone virus disease 2019, the non-specific protection and mechanism of BCG-mediated trained immunity.