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

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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

BCG vaccinations and high TB prevalence are found to be associated with decrease MIS-C no. and COVID-19 deaths

Conclusions

Findings might explain variances in MIS-C incidence and in COVID-19 mortality among countries worldwide. Further studies to confirm this relation and to confirm possible similar relations in Kawasaki disease(KD) in previous epidemics is recommended.

What is Known

  • -

    Although the etiology for KD remains unknown, available evidence supports the hypothesis that the pathogenesis is closely associated with dysregulation of immune responses to an infectious agent.

  • -

    BCG and / or Latent TB have heterogeneous beneficial effects.

  • What is New

    Our study shows that TB prevalence and implementing BCG vaccination have negative statistical association with MIS-C cases and COVID-19 mortality.

    Article activity feed

    1. SciScore for 10.1101/2020.07.18.20156893: (What is this?)

      Please note, not all rigor criteria are appropriate for all manuscripts.

      Table 1: Rigor

      Institutional Review Board Statementnot detected.
      Randomizationnot detected.
      Blindingnot detected.
      Power Analysisnot detected.
      Sex as a biological variablenot detected.

      Table 2: Resources

      Software and Algorithms
      SentencesResources
      We check also: Wikipedia.
      Wikipedia
      suggested: (Wikipedia, RRID:SCR_004897)
      All statistical operations were performed through using the ready-made statistical package SPSS, ver. 22
      SPSS
      suggested: (SPSS, RRID:SCR_002865)

      Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


      Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
      Limitations of this study includes but not limited to the following: overlap case definition with Kawasaki disease25, retrograde classification of cases, underreporting, under registration, limited no. of countries reported the disease up to 13/6/2020 and limited number of reported cases. Furthermore, this study is done at early time of emergence of this new disease with existence of continuous reporting new cases from different countries in the view of increased awareness of the disease 39,40,41,42,43, 44. Also, there was no agreed international nor EU case definition for MIS-C neither specific diagnostic code during study period making the impact of the new syndrome more difficult to be fully assessed. The statistical negative association between MIS-C and BCG is highly significant between countries which give BCG vaccination versus those not given BCG vaccine. This is statistical association and not necessary means causation although direct beneficial effect to BCG vaccination is suggested. Another mode of protection which might explain this relation in countries already ceased BCG vaccinations which also shows significant negative association is through herd immunity. On the other hand, those with no BCG vaccination are the worst among 3 groups. This negative association also found between BCG practicing and COVID-19 deaths. Similar to BCG, TB prevalence(which reflects latent TB status) shows less significant but informative and reportable association and too generating w...

      Results from TrialIdentifier: No clinical trial numbers were referenced.


      Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


      Results from JetFighter: We did not find any issues relating to colormaps.


      Results from rtransparent:
      • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
      • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
      • No protocol registration statement was detected.

      About SciScore

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