Role of latent tuberculosis infections in reduced COVID-19 mortality: Evidence from an instrumental variable method analysis

Takahashi, Harutaka

doi:10.1016/j.mehy.2020.110214

Cited by 16 publications

(23 citation statements)

References 6 publications

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“…In this study the prevalence of mycobacterium spp. (standardized to BCG vaccine coverae) exposure of the populations is negatively associated with COVID-19 deaths per million populations, this supports the previous mentioned studies 25,26, 27,28…”

Section: Discussionsupporting

confidence: 89%

“…However, the scenario in high prevalence countries like many countries in Asia and Africa is quite the opposite, where reinfection due to contact with active cases rather than reactivation contributes to a high disease burden 24 . Latent TB infections was suggested to create heterogeneous immune response to COX-COV2 viral infection in different patterns and severity according to different BCG status 25 further studies consolidate such latent TB role thereafter 26,27,28 .…”

Section: Introductionmentioning

confidence: 89%

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Influence of Malaria Edemicity and Standardized TB Prevalence to BCG Coverage on Covid-19 Mortality

2020

Preprint

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Background: Regarding SARS-CoV-2 it is well known that a substantial percentage of adult population cannot get infected if exposed to this novel coronavirus. Several studies give primary indication of the possible role of preexisting immunity whether cross immunity or not. Possible role of latent TB and BCG and malaria have been already suggested to create innate cross heterogeneous immunity. We look for influence of these factors on Covid-19 mortality in malarious countries. Material and methods:80 malarious countries are enrolled in this study. Hierarchical multiple regression type of analyses is used for data analyses. TB prevalence/ 100,000 population standardized to BCG coverage rates is taken as direct factor in the test. Malaria incidence /1000 population is considered as intermediate factor and the outcome is COVID-19 mortality/ 1 million (M) population. Results: TB prevalence is associated with reduced COVID-19 mortality and malaria have an additional effect in reducing COVID-19 mortality. The results show with robust statistical support that TB prevalence was also associated with reduced COVID-19 mortality with additional effect that is also observed in TB and BCG coverage rate. Conclusions: Malaria and standardized TB prevalence are statistical significant factors predicting COVID-19 mortality in negative associations.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 89%

Influence of Malaria Edemicity and Standardized TB Prevalence to BCG Coverage on Covid-19 Mortality

2020

Preprint

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“…Few studies are investigating the relationship between LTBI and COVID-19 with this hypothesis. In the study of Takahashi [ 1 ], it was shown that LTBI was associated with a decrease in the COVID-19 mortality rate. In our study, no difference was found between the TBF test-positive group and the TBF test-negative group regarding the frequency of COVID-19.…”

Section: Discussionmentioning

confidence: 99%

“…Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, affected the whole world after the first case was reported in Wuhan, China, in December 2019 [ 1 ]. While the COVID-19 pandemic continues its impact with high mortality and morbidity, the search to reduce these effects continues.…”

Section: Introductionmentioning

confidence: 99%

The Relationship between Pre-Pandemic Interferon Gamma Release Assay Test Results and COVID-19 Infection: Potential Prognostic Value of Indeterminate IFN-γ Release Assay Results

Börekçi

Karakas

Sirekbasan

et al. 2021

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Objective. To reveal the relationship between interferon-gamma release assay (IGRA) test (Standard ETB-Feron ELISA (TBF)) results performed within 12 months before the COVID-19 pandemic and the frequency of COVID-19 infections and the severity of COVID-19. Methods. The retrospective TBF test results and contact information of 684 patients aged over 18 years who underwent TBF testing between March 11th, 2019, and March 10th, 2020, were obtained. Of the 684 patients contacted by phone, 365 agreed to participate in the study and were enrolled. The patients were divided into three groups (TBF test positive, negative, and indeterminate). The data obtained from the questionnaire were compared statistically. Results. According to the TBF test results, positive (n = 51, 14%), negative (n = 286, 78.3%), and indeterminate (n = 28, 7.7%) groups were compared. The frequency of COVID-19 infections in the indeterminate group was found significantly higher than that in the positive and negative groups ( p = 0.005 ). When the group with COVID-19 (n = 46, 12.6%) was compared with the group without (n = 319, 87.4%), no difference was found in terms of age, sex, body mass index, smoking history and number of cigarettes smoked, TB history, diabetes mellitus, hypertension, coronary artery disease, and biologic and corticosteroid therapy use. Only the frequency of obstructive pulmonary disease was significantly higher in the group without COVID-19 ( p = 0.033 ). Conclusion. The frequency of COVID-19 infection was increased in patients with indeterminate TBF test results. Indeterminate TBF test results may be a guide in terms of risk stratification in groups at risk for COVID-19.

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“…Furthermore, cross immune heterogenecity was suggested between BCG and certain viral diseases since BCG induces trained immunity through expressing heterologous antigens of different pathogens which have been developed and tested since 1991 30 . Different studies have already show statistical associations of BCG vaccinations and TB prevalence status with reduced severity of COVID-19 disease 31,32,33,34, 35 . These studies suggest that BCG and natural latent TB infection induce heterogeneous immunity against SARS-CoV2.…”

Section: Introductionmentioning

confidence: 98%

Do low TB prevalence and lack of BCG Vaccinations Contribute to Emergence of Multisystem Inflammatory Syndrome in Children?

Tf¹

2020

Preprint

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Background: Emergence of new multisystem inflammatory syndrome in children (MIS-C) is thought to be associated with COVID-19 pandemic. Covid-19 morbidity and mortality variances among countries have been suggested by previous works to be influenced by BCG and previous latent TB infection (which is reflected by TB prevalence) possibly through inducing heterogeneous immunity against SARS-CoV-2. Aim: To examine influence of BCG status and TB prevalence on variances among countries which report new multisystem inflammatory syndrome in children (MIS-C). Methods: We choose all countries which report MIS-C till 23/6/2020, number of cases for each 10 million inhabitants was examined among 3 categories of countries classified according to BCG program status. TB prevalence, MIS-C no. / 10 million (M) population and Covid- 19 deaths/M are taken as markers. Receiver operation characteristic - (ROC) curve, with some relative indicators such as (sensitivity and specificity rates), estimation area of trade - off between sensitivity and specificity, and cutoff points are used with different studied markers for discriminating different three pairs of countries (which have different BCG practices). Results: MIS-C No/10 M inhabitants in countries never gave BCG vaccination versus (vs) countries currently give vaccine shows area under ROC- curve equal to 0.000 with a symbiotic significant of 0.034 and (95% CI interval of 0.000-0.000) also MIS-C No/10 M inhabitants in countries not currently give BCG vaccination ( with previous mass vaccination programs) vs countries currently give mass vaccination shows area under ROC- curve equal to 0.094 with a symbiotic significant of 0.027and ( 95% CI interval of 0.000 -0.280). Important not significant finding MIS-C No/10 M inhabitants in countries never gave BCG vaccination vs countries not currently give vaccine shows area under ROC- curve equal to 0.583 with a symbiotic significant of 0.683 and (95% CI interval of 0.074-0.759). COVID-19 deaths / M inhabitants in countries never gave BCG vaccination vs countries currently give vaccine show area under ROC- curve equal to 0.083 with a symbiotic informative and reportable value of 0.077 and (95% CI interval of 0.000-0.309 also COVID-19 deaths/ M inhabitants in countries not currently give BCG vaccination vs countries currently giving vaccine show area under ROC- curve equal to 0.188 with a symbiotic informative reportable value of 0.089 and ( 95% CI interval of 0.000-0.452). Important finding is the not significant association of COVID-19 deaths /M inhabitants with countries never gave BCG vaccination vs countries not currently giving vaccine area under ROC- curve equal to 0.417 with a symbiotic significant of 0.683 and (95% CI interval of 0.078 - 0.755). Regarding TB prevalence marker or discriminator the areas under curve were informative and reportable and too generating with the leftover markers in all 3 pairs of countries signifying inverse relations with covide-19 mortality and MIS-C no. Conclusions: BCG vaccinations and high TB prevalence are found to be related to decrease MIS-C no. and COVID-19 deaths this might explain variances among countries worldwide. Further studies to confirm this relation and to confirm possible similar relations in Kawasaki disease(KD) or KD like illnesses in previous epidemics is recommended. Review of TB programs and consolidation of BCG programs might be considered urgently.

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Role of latent tuberculosis infections in reduced COVID-19 mortality: Evidence from an instrumental variable method analysis

Cited by 16 publications

References 6 publications

Influence of Malaria Edemicity and Standardized TB Prevalence to BCG Coverage on Covid-19 Mortality

Influence of Malaria Edemicity and Standardized TB Prevalence to BCG Coverage on Covid-19 Mortality

The Relationship between Pre-Pandemic Interferon Gamma Release Assay Test Results and COVID-19 Infection: Potential Prognostic Value of Indeterminate IFN-γ Release Assay Results

Do low TB prevalence and lack of BCG Vaccinations Contribute to Emergence of Multisystem Inflammatory Syndrome in Children?

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