scholarly journals Does Latent Tuberculosis Lead to a Spurious Correlation between BCG and COVID-19 Mortality?

Author(s):  
Tareef Fadhil Raham

Abstract Background: Many factors have been suggested to confound coronavirus disease 2019 (COVID-19) studies, and BCG studies have been criticized for not adjusting for many confounders. We conducted this study to analyze the presumed effectiveness of the Bacillus Calmette–Guérin (BCG) vaccine in decreasing the COVID-19 mortality rate, and to answer the question of whether this is confounded by latent tuberculosis (LTB) prevalence.Materials and methods: We chose sixty-nine malaria-free countries with different BCG vaccination policies. TB prevalence was considered as a proxy for LTB. The BCG, TB prevalence, and COVID-19 mortality data are publically available. Contingency coefficients (C.C.) and a ROC analysis were used to assess the relationship between TB prevalence and BCG status, and identify cutoff points in each BCG group category. A stem–leaf plot was also used to explore the data’s apparent behavior concerning COVID-19 in relation to the BCG groups.Results: TB prevalence was significantly associated with BCG status. The BCG vaccination status apparently had a relationship with BCG status.Conclusions: TB is suggested to have a confounding effect on BCG results, leading to a spurious correlation between BCG and COVID-19 mortality.

2017 ◽  
Vol 21 (39) ◽  
pp. 1-54 ◽  
Author(s):  
Punam Mangtani ◽  
Patrick Nguipdop-Djomo ◽  
Ruth H Keogh ◽  
Lucy Trinder ◽  
Peter G Smith ◽  
...  

Background Until recently, evidence that protection from the bacillus Calmette–Guérin (BCG) vaccination lasted beyond 10 years was limited. In the past few years, studies in Brazil and the USA (in Native Americans) have suggested that protection from BCG vaccination against tuberculosis (TB) in childhood can last for several decades. The UK’s universal school-age BCG vaccination programme was stopped in 2005 and the programme of selective vaccination of high-risk (usually ethnic minority) infants was enhanced. Objectives To assess the duration of protection of infant and school-age BCG vaccination against TB in the UK. Methods Two case–control studies of the duration of protection of BCG vaccination were conducted, the first on minority ethnic groups who were eligible for infant BCG vaccination 0–19 years earlier and the second on white subjects eligible for school-age BCG vaccination 10–29 years earlier. TB cases were selected from notifications to the UK national Enhanced Tuberculosis Surveillance system from 2003 to 2012. Population-based control subjects, frequency matched for age, were recruited. BCG vaccination status was established from BCG records, scar reading and BCG history. Information on potential confounders was collected using computer-assisted interviews. Vaccine effectiveness was estimated as a function of time since vaccination, using a case–cohort analysis based on Cox regression. Results In the infant BCG study, vaccination status was determined using vaccination records as recall was poor and concordance between records and scar reading was limited. A protective effect was seen up to 10 years following infant vaccination [< 5 years since vaccination: vaccine effectiveness (VE) 66%, 95% confidence interval (CI) 17% to 86%; 5–10 years since vaccination: VE 75%, 95% CI 43% to 89%], but there was weak evidence of an effect 10–15 years after vaccination (VE 36%, 95% CI negative to 77%; p = 0.396). The analyses of the protective effect of infant BCG vaccination were adjusted for confounders, including birth cohort and ethnicity. For school-aged BCG vaccination, VE was 51% (95% CI 21% to 69%) 10–15 years after vaccination and 57% (95% CI 33% to 72%) 15–20 years after vaccination, beyond which time protection appeared to wane. Ascertainment of vaccination status was based on self-reported history and scar reading. Limitations The difficulty in examining vaccination sites in older women in the high-risk minority ethnic study population and the sparsity of vaccine record data in the later time periods precluded robust assessment of protection from infant BCG vaccination > 10 years after vaccination. Conclusions Infant BCG vaccination in a population at high risk for TB was shown to provide protection for at least 10 years, whereas in the white population school-age vaccination was shown to provide protection for at least 20 years. This evidence may inform TB vaccination programmes (e.g. the timing of administration of improved TB vaccines, if they become available) and cost-effectiveness studies. Methods to deal with missing record data in the infant study could be explored, including the use of scar reading. Funding The National Institute for Health Research Health Technology Assessment programme. During the conduct of the study, Jonathan Sterne, Ibrahim Abubakar and Laura C Rodrigues received other funding from NIHR; Ibrahim Abubakar and Laura C Rodrigues have also received funding from the Medical Research Council. Punam Mangtani received funding from the Biotechnology and Biological Sciences Research Council.


2020 ◽  
Vol 12 (3) ◽  
pp. 97-104
Author(s):  
Luana Nepomuceno Gondim Costa Lima ◽  
Jasna Letícia Pinto Paz ◽  
Maria do Perpétuo Socorro Corrêa Amador Silvestre ◽  
Letícia Siqueira Moura ◽  
Ismari Perini Furlaneto ◽  
...  

In 2018, 208,619 new cases of leprosy were reported to the World Health Organization (WHO). Of these, 30,957 occurred in the Americas region and 28,660 (92.6% of the total in the Americas) were reported in Brazil. This study aimed to show the reality of the profile of a population in an endemic leprosy area in northern Brazil in relation to age, gender, and bacillus Calmette–Guérin (BCG) vaccination status through the collection of data in the field with the evaluation of the study individuals, who were recruited by spontaneous demand. A total of 405 individuals participated in the study, with 100 multibacillary, 57 paucibacillary, and 248 healthy contacts. A relationship was observed between the occurrence of the disease, as well as the multibacillary form with the largest age group. The male gender was associated with leprosy per se, with the multibacillary form and was the largest representative of the group that was not vaccinated once. BCG vaccination was effective both in protecting against leprosy per se and in the multibacillary form. These results are limited by sample size, may not be conclusive, and will need further confirmation in a larger cohort.


Author(s):  
Masao Fukui ◽  
Kohei Kawaguchi ◽  
Hiroaki Matsuura

In the middle of the global COVID-19 pandemic, the BCG hypothesis, the prevalence and severity of the COVID-19 outbreak seems to be correlated with whether a country has a universal coverage of Bacillus-Calmette-Guérin (BCG), a vaccine for tuberculosis disease (TB), has emerged and attracted the attention of scientific community and media outlets. However, all existing claims are based on cross-country correlations that do not exclude the possibility of spurious correlation. We merged country-age-level case statistics with the start/termination years of BCG vaccination policy and conducted a regression discontinuity and difference-indifference analysis. The results do not support the BCG hypothesis.


Author(s):  
Yutaka Akiyama ◽  
Takashi Ishida

AbstractIn this manuscript, we showed a statistically significant difference of the doubling times of the death toll between the group of countries with national universal Bacillus Calmette-Guerin (BCG) vaccination and the group without it for recent years. Based on a statistical test, the distributions of the doubling time of these two groups were significantly different (p=0.007). Miller et al. reported the relationship between BCG vaccination and mortality for COVID-19 based on deaths per million inhabitants. However, they did not take into account the differences in COVID-19 detection rates among the countries and the epidemic stages of the countries. Therefore we used a doubling time of the death toll as a more stable indicator instead. We also investigated the dependency of the BCG strains. Among the 42 BCG-vaccinated countries, the median doubling time of the eight countries using “Tokyo 172-1” strain at least partially (Japan, Iraq, Malaysia, South Korea, Philippines, Saudi Arabia, Pakistan, and Bangladesh) was 7.2 days, and that of the other 34 vaccinated countries was 5.5 days. Their distributions were also significantly different (p=0.026).


2000 ◽  
Vol 39 (01) ◽  
pp. 10-15 ◽  
Author(s):  
S. P. Müller ◽  
Ch. Reiners ◽  
A. Bockisch ◽  
Katja Brandt-Mainz

Summary Aim: Tumor scintigraphy with 201-TICI is an established diagnostic method in the follow-up of differentiated thyroid cancer. We investigated the relationship between thyroglobulin (Tg) level and tumor detectability. Subject and methods: We analyzed the scans of 122 patients (66 patients with proven tumor). The patient population was divided into groups with Tg above (N = 33) and below (N = 33) 5 ng/ml under TSH suppression or above (N = 33) and below (N = 33) 50 ng/ml under TSH stimulation. Tumor detectability was compared by ROC-analysis (True-Positive-Fraction test, specificity 90%). Results: There was no significant difference (sensitivity 75% versus 64%; p = 0.55) for patients above and below 5 ng/ml under TSH suppression and a just significant difference (sensitivity 80% versus 58%; p = 0.04) for patients above and below 50 ng/ml under TSH stimulation. In 18 patients from our sample with tumor, Tg under TSH suppression was negative, but 201-TICI-scan was able to detect tumor in 12 patients. Conclusion: Our results demonstrate only a moderate dependence of tumor detectability on Tg level, probably without significant clinical relevance. Even in patients with slight Tg elevation 201-TICI scintigraphy is justified.


2020 ◽  
Author(s):  
Yue-Cune Chang

BACKGROUND The Coronavirus Disease-19 (COVID-19) is the new form of an acute infectious respiratory disease and has quickly spread over most continents in the world. Recently, it has been shown that Bacille Calmette-Guerin (BCG) might protect against COVID-19. This study aims to investigate the possible correlation between BCG vaccination and morbidity/mortality/recovery rate associated with COVID-19 infection. OBJECTIVE Our findings confirm that the BCG vaccination might protect against COVID-19 virus infection. METHODS Data of COVID-19 confirmed cases, deaths, recoveries, and population were obtained from https://www.worldometers.info/coronavirus/ (Accessed on 12 June, 2020). To have meaningful comparisons among countries’ mortality and recovery rates, we only choose those countries with COVID-19 infected cases at least 200. The Poisson regression and logistic regression were used to explore the relationship between BCG vaccination and morbidity, mortality and recovery rates. RESULTS Among those 158 countries with at least 200 COVID-19 infected cases, there were 141 countries with BCG vaccination information available. The adjusted rates ratio of COVID-19 confirmed cases for Current BCG vaccination vs. non-Current BCG vaccination was 0.339 (with 95% CI= (0.338,0.340)). Moreover, the adjusted odds ratio (OR) of death and recovery after coronavirus infected for Current BCG vaccination vs. non-Current BCG vaccination were 0.258 (with 95% CI= (0.254,0.261)) and 2.151 (with 95% CI= (2.140,2.163)), respectively. CONCLUSIONS That data in this study show the BCG might provide the protection against COVID-19, with consequent less COVID-19 infection and deaths and more rapid recovery. BCG vaccine might bridge the gap before the disease-specific vaccine is developed, but this hypothesis needs to be further tested in rigorous randomized clinical trials. INTERNATIONAL REGISTERED REPORT RR2-https://doi.org/10.1101/2020.06.14.20131268


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1012.2-1012
Author(s):  
Y. Matsumoto ◽  
Y. Sugioka ◽  
M. Tada ◽  
T. Okano ◽  
K. Mamoto ◽  
...  

Background:The Global Leadership Initiative on Malnutrition (GLIM) criteria, the first international criteria for diagnosis of malnutrition, was released in 2018 [1]. Patients with rheumatoid arthritis (RA) are thought to be prone to malnutrition due to decreased food intake and increased muscle catabolism caused by chronic inflammation or pain. However, there has been no report to assess the nutritional status of RA patients in accordance with the GLIM criteria. In addition, commonly used blood nutrient indicators such as albumin might not be appropriate as nutritional indicators for RA because these values are affected by inflammation.Objectives:This study aims to examine the rates of malnutrition in RA patients according to GLIM criteria, and the relationship between blood nutrient indicators and the severity of malnutrition.Methods:In this study, we conducted a cross-sectional survey of 135 female RA patients in 2020. According to the GLIM criteria, patients were considered to be malnourished if patients had one of the following phenotypic: (1) low body mass index, (2) non-volitional weight loss, (3) reduced muscle mass, and one of the following etiologic: (1) reduced food intake or assimilation, (2) disease burden/inflammatory condition. Reduced muscle mass was evaluated by measuring calf circumference, and inflammatory condition was evaluated by Disease Activity Score (DAS) 28. In accordance with the GLIM criteria, the severity of malnutrition was judged as three levels: no problem, moderate, and severe malnutrition. Albumin, transthyretin, transferrin, retinol binding protein, zinc, iron, ceruloplasmin, and total cholesterol were assessed as blood nutrition indicators. Also grip strength was assessed. We compared each nutritional indicator among the three groups according to the severity of malnutrition using age-adjusted analysis of covariance, and examined the relationship between each nutritional indicator and the severity of malnutrition using receiver operating characteristic (ROC) analysis.Results:In RA patients, 20% were classified as severe malnutrition, and 40% were moderate or more. Serum iron levels were significantly lower in the severe malnutrition group compared to the no problem group (p = 0.001). In ROC analysis, serum iron, zinc, albumin, and grip strength (area under curve; AUC; 0.680, 0.696, 0.636, 0.790, respectively) were significant parameters for classification of moderate and severe malnutrition. Serum iron and grip strength (AUC for respective parameters were 0.741, 0.747) were significant parameters for classification of severe malnutrition.Conclusion:Evaluation based on the GLIM criteria showed that about 40% of RA patients were under moderate or severe malnutrition. It was suggested that serum iron and grip strength might be useful to predict the severity of malnutrition.References:[1]Cederholm T, Jensen GL, Correia MITD, Gonzalez MC, Fukushima R, Higashiguchi T, et al. GLIM criteria for the diagnosis of malnutrition – A consensus report from the global clinical nutrition community. Clinical Nutrition 2019; 38: 1-9.Acknowledgements:We thank to Tomoko Nakatsuka, and the Center for Drug & Food Clinical Evaluation, Osaka City University Hospital, for management and collection of the study data. We also thank to study participants.Disclosure of Interests:Yoshinari Matsumoto Grant/research support from: Yamada Research Grant, Yuko Sugioka: None declared, Masahiro Tada: None declared, Tadasi Okano Speakers bureau: AbbVie, Asahikasei, Astellas Pharma Inc, Ayumi Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiich Sankyo, Eisai, Janssen, Lilly, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Ono Pharmaceutical, Pfizer, Sanofi, Takeda Pharmaceutical, Teijin Pharma and UCB, Grant/research support from: AbbVie, Eisai, Mitsubishi Tanabe Pharma Corporation and Nipponkayaku, Kenji Mamoto: None declared, Kentaro Inui Speakers bureau: Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma, Janssen Pharmaceutical K.K., Astellas Pharma Inc., Takeda Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Abbvie GK, Pfizer Inc., Eisai Co., Ltd., Chugai Pharmaceutical Co., Ltd, Grant/research support from: anssen Pharmaceutical K.K., Astellas Pharma Inc., Sanofi K.K., Abbvie GK, Takeda Pharmaceutical Co. Ltd., QOL RD Co. Ltd., Mitsubishi Tanabe Pharma, Ono Pharmaceutical Co. Ltd., Eisai Co., Ltd., Daiki Habu: None declared, Tatsuya Koike Speakers bureau: AbbVie, Astellas Pharma Inc, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Janssen, Lilly, Mitsubishi Tanabe Pharma Corporation, MSD, Ono Pharmaceutical, Pfizer, Roche, Takeda Pharmaceutical, Teijin Pharma, and UCB, Grant/research support from: AbbVie, Astellas Pharma Inc, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Janssen, Lilly, Mitsubishi Tanabe Pharma Corporation, MSD, Ono Pharmaceutical, Pfizer, Roche, Takeda Pharmaceutical, Teijin Pharma, and UCB


2021 ◽  
pp. 1-14
Author(s):  
Conor Fearon ◽  
Alfonso Fasano

Studies focusing on the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19), and Parkinson’s disease (PD) have provided conflicting results. We review the literature to investigate: 1) Are PD patients at higher risk for contracting COVID-19 and are there specific contributing factors to that risk? 2) How does COVID-19 affect PD symptoms? 3) How does COVID-19 present in PD patients? 4) What are the outcomes in PD patients who contract COVID-19? 5) What is the impact of COVID-19 on PD care? 6) Does COVID-19 increase the risk of developing PD? A literature search was performed from 1979 to 2020 using the terms: ‘Parkinson’s disease’ and ‘parkinsonism’ combined with: ‘COVID-19’; ‘SARS-CoV-2’ and ‘coronavirus’. It does not appear that PD is a specific risk factor for COVID-19. There is evidence for direct/indirect effects of SARS-CoV-2 on motor/non-motor symptoms of PD. Although many PD patients present with typical COVID-19 symptoms, some present atypically with isolated worsening of parkinsonian symptoms, requiring increased anti-PD therapy and having worse outcomes. Mortality data on PD patients with COVID-19 is inconclusive (ranging from 5.2%to 100%). Patients with advanced PD appear to be particularly vulnerable. Single cases of acute hypokinetic-rigid syndrome have been described but no other convincing data has been reported. The rapidity with which COVID-19 has swept across the globe has favored the proliferation of studies which lack scientific rigor and the PD literature has not been immune. A coordinated effort is required to assimilate data and answer these questions in larger PD cohorts.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sayori Kobayashi ◽  
Takashi Yoshiyama ◽  
Kazuhiro Uchimura ◽  
Yuko Hamaguchi ◽  
Seiya Kato

AbstractUniversal Bacillus Calmette–Guérin (BCG) vaccination is recommended in countries with high tuberculosis (TB) burden. Nevertheless, several countries have ceased universal BCG vaccination over the past 40 years, with scarce comparative epidemiological analyses regarding childhood TB after the policy change. We analysed data on childhood TB in countries that ceased universal BCG vaccination. Data sources included national/international databases, published papers, annual TB reports, and public health authority websites. Childhood TB notification rate increased in one of seven countries with available data. Pulmonary TB and TB lymphadenitis were the main causes of increasing childhood cases, while changes in severe forms of TB cases were minor. Maintaining high vaccine coverage for the target group was a common challenge after shifting selective vaccination. In some countries showing no increase in childhood TB after a BCG policy change, the majority of childhood TB cases were patients from abroad or those with overseas parents; these countries had changed immigration policies during the same period. Heterogeneity in childhood TB epidemiology was observed after ceasing universal BCG vaccination; several factors might obscure the influence of vaccination policy change. Lessons learned from these countries may aid in the development of better BCG vaccination strategies.


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