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On tuberculosis and COVID-19 co-infection

Marina Tadolini, José-María García-García, François-Xavier Blanc, Sergey Borisov, Delia Goletti, Ilaria Motta, Luigi Ruffo Codecasa, Simon Tiberi, Giovanni Sotgiu, Giovanni Battista Migliori on behalf of the GTN TB/COVID group
European Respiratory Journal 2020 56: 2002328; DOI: 10.1183/13993003.02328-2020
Marina Tadolini
1Unit of Infectious Diseases, Dept of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
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José-María García-García
2Tuberculosis Research Programme (PII-TB), SEPAR, Barcelona, Spain
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François-Xavier Blanc
3Centre Hospitalier Universitaire, Nantes, France
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Sergey Borisov
4Moscow Research and Clinical Center for TB Control, Moscow, Russian Federation
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Delia Goletti
5Translational Research Unit, National Institute for Infectious Diseases “L. Spallanzani”, IRCCS, Rome, Italy
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Ilaria Motta
6Dipartimento di Scienze Mediche, Clinica Universitaria Malattie Infettive, Ospedale Amedeo di Savoia, Torino, Italia
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Luigi Ruffo Codecasa
7TB Reference Centre, Villa Marelli Institute, Niguarda Hospital, Milan, Italy
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Simon Tiberi
8Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
9Division of Infection, Royal London Hospital, Barts Health NHS Trust, London, UK
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Giovanni Sotgiu
10Clinical Epidemiology and Medical Statistics Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
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Giovanni Battista Migliori
11Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri IRCCS, Tradate, Italy
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  • For correspondence: giovannibattista.migliori@icsmaugeri.it
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Abstract

COVID-19 may boost tuberculosis given infection and mortality, further studies are needed https://bit.ly/2Z2r5XO

From the authors:

We wish to thank A.K. Khurana and D. Aggarwal for their interest in our research letter and comments.

In their correspondence, the authors raised two important issues, namely the possible association between tuberculosis (TB) and coronavirus disease 2019 (COVID-19) (can infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) re-activate TB?), and the effects of TB on early mortality in co-infected patients.

Our research letter reported the first cohort of patients with diagnosis of TB (including post-treatment sequelae) and COVID-19. The article was aimed at reporting what was observed at the beginning of the epidemic among some of the most affected countries. This explains the small numbers described and the countries involved. At the time the article was submitted, several countries in Africa, Europe and Latin America represented in the Global Tuberculosis Network (GTN) had no TB/COVID-19 patients to report.

In the absence of previous cohorts and scientific information on TB/COVID-19 co-infection, we have described the timing of diagnosis of the two diseases, observing that one third had COVID-19 diagnosed prior to TB and 18% were diagnosed simultaneously.

We agree, it is possible that the diagnosis of COVID-19 was made before TB because of acute onset of symptoms caused by SARS-CoV-2 in addition to the alarm generated by the COVID-19 pandemic, which determined rapid access to radiological examinations and subsequent discovery of underlying TB. In fact we commented on this in point 3 of our article [1], and we abstained from making any clear statement about causal association. However, we could not exclude that the infection by SARS-CoV-2 or the drugs utilised might have accelerated the progression of a pre-existing TB infection to disease.

However, apart from the speculation on what disease comes first, it is evident that the co-existence of TB and COVID-19 poses a challenge in differential diagnosis [1].

The study was observational, and based on a relatively small cohort, and therefore we fully agree that larger prospective studies are necessary to shed further light on this to establish whether there is an association or not.

A.K. Khurana and D. Aggarwal also raised the important question of whether TB has a real effect or “weight” in increasing the probability of death in COVID-19 patients.

The issue has been described in a second article [2] which reports the findings of 69 patients from our original cohort plus a second cohort [3] which was managed in a reference hospital in Northern Italy.

The patients more likely to die were those of older age with pre-existing comorbidities [2].

It is important to emphasise that the cohort of young migrants without comorbidities reported elsewhere [2, 3] experienced a milder form of COVID-19 with no deaths.

However, in countries where risk factors for mortality are highly prevalent among young individuals (smoking, alcohol and substance abuse, HIV co-infection, among others), particularly in the presence of drug resistance and difficult access to diagnosis (delayed diagnosis), the impact of mortality may be higher. We agree that, in resource-limited settings, poverty and malnutrition might play an important role in increasing morbidity and mortality.

Furthermore, we do agree that the population of individuals with post-TB treatment sequelae deserves further evaluation, given the potential effect of both TB and COVID-19 on quality of life and subsequent need for rehabilitation [4–6].

In order to better understand the implication of TB and COVID-19 co-infection the study is continuing: more countries and a larger sample size will help answering some of the questions left open by our original study [1]. We will be happy to collaborate with all interested colleagues.

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Acknowledgements

The article is part of the scientific activities of the Global Tuberculosis Network (GTN); GREPI (Groupe de Recherche et d'Enseignement en Pneumo-Infectiologie), a working group from SPLF (Société de Pneumologie de Langue Française); SEPAR (Sociedad Española de Neumología and Cirugía Torácica); Moscow Society of Phtisiology and of the WHO Collaborating Centre for Tuberculosis and Lung Diseases, Tradate, ITA-80, 2017-2020- GBM/RC/LDA).

Footnotes

  • The members of the GTN TB/COVID group are: Jan-Willem Alffenaar (Australia); Pierre Bachez (Belgium); Denise Rossato Silva (Brazil); Claire Andréjak, François-Xavier Blanc, Samir Dourmane, Mathilde Fréchet Jachym, Antoine Froissart, Soazic Grard, Armine Izadifar, Damien Le Du, Frédéric Rivière and Frédéric Schlemmer (France); Rosella Centis, Luigi Ruffo Codecasa, Lia D'Ambrosio, Vania Giacomet, Delia Goletti, Gina Gualano, Filippo Lipani, Giovanni Battista Migliori, Ilaria Motta, Maria Musso, Fabrizio Palmieri, Emanuele Pontali, Matteo Saporiti, Paolo Scarpellini, Giovanni Sotgiu, Antonio Spanevello, Claudia Stochino, Marina Tadolini, Alessandro Torre, Simone Villa and Dina Visca (Italy); Evgeny Belilovski, Sergey Borisov and Elena Sumarokova (Russian Federation); Paul Anantharajah Tambyah and Catherine Wei Min Ong (Singapore); José Cardoso-Landivar, María-Luiza De Souza-Galvão, Angel Dominguez-Castellano, José-María García-García, Margarita Marín Royo, Teresa Rodrigo, Adrián Sánchez-Montalvá, Eva Tabernero and Miguel Zabaleta Murguiondo (Spain); Pierre-Alexandre Bart and Jesica Mazza-Stalder (Switzerland); Simon Tiberi (UK).

  • Conflict of interest: M. Tadolini has nothing to disclose.

  • Conflict of interest: J-M. García-García has nothing to disclose.

  • Conflict of interest: F-X. Blanc has nothing to disclose.

  • Conflict of interest: S. Borisov has nothing to disclose.

  • Conflict of interest: D. Goletti has nothing to disclose.

  • Conflict of interest: I. Motta has nothing to disclose.

  • Conflict of interest: L.R. Codecasa has nothing to disclose.

  • Conflict of interest: S. Tiberi has nothing to disclose.

  • Conflict of interest: G. Sotgiu has nothing to disclose.

  • Conflict of interest: G.B. Migliori has nothing to disclose.

  • Received June 15, 2020.
  • Accepted June 15, 2020.
  • Copyright ©ERS 2020
http://creativecommons.org/licenses/by-nc/4.0/

This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

References

  1. ↵
    1. Tadolini M,
    2. Codecasa LR,
    3. García-García JM, et al.
    Active tuberculosis, sequelae and COVID-19 co-infection: first cohort of 49 cases. Eur Respir J 2020; 56: 2001398. doi:10.1183/13993003.01398-2020
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Motta I,
    2. Centis R,
    3. D'Ambrosio L, et al.
    Tuberculosis, COVID-19 and migrants: preliminary analysis of deaths occurring in 69 patients from two cohorts. Pulmonology 2020; 26: 233–240.
    OpenUrl
  3. ↵
    1. Stochino C,
    2. Villa S,
    3. Zucchi P, et al.
    Clinical characteristics of COVID-19 and active tuberculosis co-infection in an Italian reference hospital. Eur Respir J 2020; in press [https://doi.org/10.1183/13993003.01708-2020]. doi:10.1183/13993003.01708-2020
  4. ↵
    1. Visca D,
    2. Zampogna E,
    3. Sotgiu G, et al.
    Pulmonary rehabilitation is effective in patients with tuberculosis pulmonary sequelae. Eur Respir J 2019; 53: 1802184. doi:10.1183/13993003.02184-2018
    OpenUrlAbstract/FREE Full Text
    1. Zumla A,
    2. Marais BJ,
    3. McHugh TD, et al.
    The increasing threat of respiratory tract infections to global health security – COVID-19 and tuberculosis. Int J Tuberc Lung Dis 2020 [https://doi.org/10.5588/ijtld.20.0387]. doi:10.5588/ijtld.20.0387.
  5. ↵
    1. Visca D,
    2. Tiberi S,
    3. Pontali E, et al.
    Tuberculosis in the time of COVID-19: quality of life and digital innovation. Eur Respir J 2020; 56: 2001998. doi:10.1183/13993003.01998-2020
    OpenUrlAbstract/FREE Full Text
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On tuberculosis and COVID-19 co-infection
Marina Tadolini, José-María García-García, François-Xavier Blanc, Sergey Borisov, Delia Goletti, Ilaria Motta, Luigi Ruffo Codecasa, Simon Tiberi, Giovanni Sotgiu, Giovanni Battista Migliori
European Respiratory Journal Aug 2020, 56 (2) 2002328; DOI: 10.1183/13993003.02328-2020

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On tuberculosis and COVID-19 co-infection
Marina Tadolini, José-María García-García, François-Xavier Blanc, Sergey Borisov, Delia Goletti, Ilaria Motta, Luigi Ruffo Codecasa, Simon Tiberi, Giovanni Sotgiu, Giovanni Battista Migliori
European Respiratory Journal Aug 2020, 56 (2) 2002328; DOI: 10.1183/13993003.02328-2020
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