Developing health policies in patients presenting with SARS-CoV-2: consider tuberculosis

The global pandemic of COVID-19 has led to a prominent public health response, with many countries introducing highly proactive measures for screening and identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has gained the dubious honour as the single greatest infectious cause of global mortality in 2020. Active COVID-19 disease encompasses cough, fever, fatigue, and shortness of breath among other signs and symptoms.1Min Ong CW Migliori GB Raviglione M et al.Epidemic and pandemic viral infections: impact on tuberculosis and the lung. A consensus by the World Association for Infectious Diseases and Immunological Disorders (WAidid), Global Tuberculosis Network (GTN) and members# of ESCMID Study Group for Mycobacterial Infections (ESGMYC).Eur Respir J. 2020; (published online July 2.)https://doi.org/10.1183/13993003.01727-2020Google Scholar, 2Guan WJ Ni ZY Hu Y et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; 382: 1708-1720Crossref PubMed Scopus (19693) Google Scholar Risk factors for severe COVID-19 disease include diabetes, chronic obstructive pulmonary disease, immune suppression, and age. Some select population demographics (people who are Black, Hispanic, or a member of another ethnic minority group), in association with overcrowded housing and homelessness, are also at risk of severe disease and mortality.3Wolff D Nee S Hickey NS Marschollek M Risk factors for Covid-19 severity and fatality: a structured literature review.Infection. 2020; (published online Aug 28.)https://doi.org/10.1007/s15010-020-01509-1Crossref Scopus (281) Google Scholar These features occur equally in patients presenting with tuberculosis,4WHOGlobal Tuberculosis Report 2019.https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1Date: 2019Date accessed: March 30, 2020Google Scholar and patients with tuberculosis can also present with acute community-acquired pneumonia.5Wei M Yongjie Zhao Zhuoyu Qian et al.Pneumonia caused by Mycobacterium tuberculosis.Microbes Infect. 2020; 22: 278-284Crossref Scopus (30) Google Scholar Before COVID-19, tuberculosis was associated with the highest burden of global mortality caused by an infectious disease;4WHOGlobal Tuberculosis Report 2019.https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1Date: 2019Date accessed: March 30, 2020Google Scholar however, the redirection of resources towards curtailing the pandemic have resulted in legitimate fears of tuberculosis control programmes being neglected.6Migliori GB Thong PM Akkerman OW et al.Worldwide effects of coronavirus disease pandemic on 19 tuberculosis services, January–April 2020.Emerg Infect Dis. 2020; (published online Sept 11.)https://doi.org/10.3201/eid2611.203163Crossref Scopus (135) Google Scholar An early analysis of 49 patients presenting with the two diseases showed that 53·0% of the patients were diagnosed with tuberculosis before a COVID-19 diagnosis, 28·5% of patients were initially diagnosed with COVID-19, and 18·3% had both diseases diagnosed within the same week.7Tadolini M Codecasa LR García-García JM et al.Active tuberculosis, sequelae and COVID-19 co-infection: first cohort of 49 cases.Eur Respir J. 2020; 562001398Crossref Scopus (281) Google Scholar COVID-19 might have precipitated the diagnosis of pre-existing and undiagnosed tuberculosis; given its typically chronic course, tuberculosis was most likely to have been acquired before the patients were infected with SARS-CoV-2. Preliminary findings from a global study that is ongoing appear to confirm this assumption (Migliori GB, personal communication). SARS-CoV-2 might additionally negatively affect T-cell-mediated immunity, causing lymphopenia, particularly in those with a severe form of the disease,8Chen Z John Wherry E T cell responses in patients with COVID-19.Nat Rev Immunol. 2020; 20: 529-536Crossref PubMed Scopus (534) Google Scholar which could reactivate latent tuberculosis or render patients with COVID-19 more susceptible to acquiring a tuberculosis infection. Any symptomatic patient presenting with presumptive COVID-19 from a population at a high risk for tuberculosis, or from a country in which tuberculosis is highly endemic,4WHOGlobal Tuberculosis Report 2019.https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1Date: 2019Date accessed: March 30, 2020Google Scholar should have both diseases considered when it comes to submitting specimens for diagnosis, because of the potential reactivation of latent tuberculosis caused by the presence of SARS-CoV-2, or the greater frequency of tuberculosis presenting as community-acquired pneumonia in those populations. It should be a sine qua non that both tests be requested at the time of consultation, particularly if there are concomitant symptoms and signs pointing to tuberculosis (appendix). Similarly, any patient presenting with a cough, fever, and presumptive COVID-19 in a country that is highly endemic for HIV should be screened for both tuberculosis and HIV, if the patient's current status for tuberculosis and HIV is unknown, as well as following appropriate pre-test and post-test counselling for HIV. In countries where tuberculosis is not highly endemic, if the history and presentation of the patient are suggestive of tuberculosis, appropriate diagnostic tests should be done. This procedure is particularly true of patients at a high risk of tuberculosis, who might be at risk of severe disease, including patients with previous lung damage due to tuberculosis, such as chronic obstructive pulmonary disease.4WHOGlobal Tuberculosis Report 2019.https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1Date: 2019Date accessed: March 30, 2020Google Scholar Specifically, WHO states: "There is thus a stronger case for concurrent testing for both conditions in [these individuals] even if the clinical picture is atypical."9WHOWorld Health Organization (WHO) information note tuberculosis and COVID-19.https://www.who.int/docs/default-source/documents/tuberculosis/infonote-tb-covid-19.pdf?sfvrsn=b5985459_18Date: May 12, 2020Date accessed: May 12, 2020Google Scholar A confirmatory diagnosis of COVID-19 is dependent on the isolation and amplification of viral RNA.10Loeffelholz MJ Tang YW Laboratory diagnosis of emerging human coronavirus infections - the state of the art.Emerg Microbes Infect. 2020; 9: 747-756Crossref PubMed Scopus (536) Google Scholar Various automated systems have been developed, targeting specific areas of the viral genome, some of which are pre-existing platforms for tuberculosis or HIV.10Loeffelholz MJ Tang YW Laboratory diagnosis of emerging human coronavirus infections - the state of the art.Emerg Microbes Infect. 2020; 9: 747-756Crossref PubMed Scopus (536) Google Scholar Current WHO recommendations for tuberculosis diagnostics have standardised the Cepheid Xpert platform using MTB/RIF Ultra tests.4WHOGlobal Tuberculosis Report 2019.https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1Date: 2019Date accessed: March 30, 2020Google Scholar Given the overlap in the diagnostic platforms available and that sputum specimens might be used for COVID-19 diagnosis in severe disease,10Loeffelholz MJ Tang YW Laboratory diagnosis of emerging human coronavirus infections - the state of the art.Emerg Microbes Infect. 2020; 9: 747-756Crossref PubMed Scopus (536) Google Scholar and although it is highly advantageous that these platforms are multipurpose, there is real concern that testing for either tuberculosis or for COVID-19 might be done at the cost of the other. Resources should be mobilised to ensure that there is adequate testing capacity for both diseases.9WHOWorld Health Organization (WHO) information note tuberculosis and COVID-19.https://www.who.int/docs/default-source/documents/tuberculosis/infonote-tb-covid-19.pdf?sfvrsn=b5985459_18Date: May 12, 2020Date accessed: May 12, 2020Google Scholar Irrespective of the final diagnosis, the appropriate steps for contact tracing will need to be undertaken following national and WHO guidelines, ensuring that those responsible for contact tracing have full and appropriate personal protective equipment provided.9WHOWorld Health Organization (WHO) information note tuberculosis and COVID-19.https://www.who.int/docs/default-source/documents/tuberculosis/infonote-tb-covid-19.pdf?sfvrsn=b5985459_18Date: May 12, 2020Date accessed: May 12, 2020Google Scholar Infectious disease management strategies, including diagnosis, treatment, follow-up, and containment, have been enabled by the COVID-19 pandemic. This newly acquired ability to synthesise and simultaneously implement scientific knowledge should continue in the future. Governments should retain processes permitting the inclusion of new evidence rapidly into policy and practice as they emerge. A clear policy integrating diagnostics and care for both diseases will ensure that tuberculosis programmes are not disrupted in COVID-19 control efforts, but rather enhance tuberculosis diagnosis and control. For updates on COVID-19 deaths see https://covid19.who.int/ For updates on COVID-19 deaths see https://covid19.who.int/ We declare no competing interests. Download .pdf (.13 MB) Help with pdf files Supplementary appendix