Abstract
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.
Strengths and limitations of this study
To our knowledge, this study will be the first addressing TB prevalence status influence on MIS-C incidence in countries with different BCG vaccination status practices.
This study also will address disparities raised regarding variances in incidence of MIS-C and COVID-19 deaths rates among countries.
This study discusses possible relation of KD or KD like illnesses with previous pandemics according to various TB prevalence of some countries.
Potential confounding factors still exist.
Another limitation is that this study is done in mid of COVID-19 pandemic.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
no funding
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Footnotes
tareeffadhil{at}yahoo.com +9647901584338
Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv
The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, University of Washington, and Vrije Universiteit Amsterdam.
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