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Volume 26, Number 11—November 2020
Research Letter

Four Patients with COVID-19 and Tuberculosis, Singapore, April–May 2020

Sai Meng Tham, Wei Yang Lim, Chun Kiat Lee, Jerold Loh, Arthi Premkumar, Benedict Yan, Adrian Kee, Louis Chai, Paul Anantharajah Tambyah, and Gabriel YanComments to Author 
Author affiliation: National University Health System, Singapore

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Abstract

Coronavirus disease (COVID-19) and tuberculosis (TB) developed in 4 foreign workers living in dormitories in Singapore during April–May 2020. Clinical manifestations and atypical radiographic features of COVID-19 led to the diagnosis of TB through positive interferon-gamma release assay and culture results. During the COVID-19 pandemic, TB should not be overlooked.

As the world focuses on the coronavirus disease (COVID-19) pandemic, caution must be taken to not overlook tuberculosis (TB). COVID-19 was first diagnosed in Singapore in January 2020, after cases were imported from Wuhan, China. Subsequent sustained community transmission of the virus followed a wave of imported cases from local residents returning from abroad (1). The outbreak in Singapore is being driven by spread within migrant worker dormitories. As of June 28, 2020, Singapore reported 43,459 confirmed cases of COVID-19, of which 41,010 were in dormitory residents (1). TB is endemic to Singapore; annual incidence rate is ≈40 cases/100,000 population (2), and a large proportion of cases are in nonpermanent residents.

We describe migrant workers in Singapore dormitories who were co-infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2) and Mycobacterium tuberculosis. For all 4 patients, TB was diagnosed by positive interferon-gamma release assay (IGRA) (QIAGEN, https://www.qiagen.com); M. tuberculosis was isolated from pleural fluid culture from patient 4 only (Table).

Patient 1 was a 32-year-old man from India with a 2-day history of fever and cough. He was positive for SARS-CoV-2 by reverse transcription PCR (RT-PCR) of a nasopharyngeal swab sample. Radiographs showed bilateral cavitary lung lesions (Figure 1, panel A). Sputum samples were smear negative and culture negative for acid-fast bacilli (AFB) and negative by molecular testing for M. tuberculosis nucleic acids (Cepheid Xpert MTB/RIF, https://www.cepheid.com). The IGRA for TB result was positive. In consideration of the clinical manifestations and risk factors, anti-TB therapy (ATT) was started, and interval radiographic imaging showed resolution.

Patient 2 was a 33-year-old man from India with an 8-day history of fever and cough and a 1-month history of weight loss (3 kg). He was positive for SARS-CoV-2 by RT-PCR of a nasopharyngeal swab sample. Radiographs showed a right-sided pleural effusion (Figure 1, panel B). Pleural fluid analysis revealed a lymphocytic exudative effusion with an adenosine deaminase (ADA) level of 130 U/L (reference range <40 U/L), but the fluid was negative for SARS-CoV-2 by RT-PCR. Sputum and pleural fluid were smear negative for AFB and M. tuberculosis nucleic acid negative by molecular testing; culture results are pending. IGRA was positive for TB, and ATT was started with subsequent clinical improvement.

Patient 3 was a 22-year old man from India with a 10-day history of fever and cough (associated with exertional dyspnea) and pleuritic chest pain. He was positive for SARS-CoV-2 by RT-PCR of a nasopharyngeal swab sample. Radiographs showed a right-sided pleural effusion (Figure 1, panel C). Pleural fluid analysis revealed a lymphocytic exudative effusion with an ADA level of 112 U/L and interleukin-6 (IL-6) level of >1,000 pg/mL, but the fluid was negative for SARS-CoV-2 by RT-PCR. Sputum and pleural fluid were smear negative for AFB and negative for M. tuberculosis nucleic acids by molecular testing; culture results are pending. IGRA was positive for TB and ATT was started; symptoms subsequently resolved.

Patient 4 was a 40-year old man from Bangladesh with a 3-day history of fever and cough. He was positive for SARS-CoV-2 by RT-PCR from a nasopharyngeal swab sample. Radiographs showed a left-sided pleural effusion with bilateral consolidation (Figure 1, panel D). Pleural fluid analysis revealed a lymphocytic exudative effusion with an ADA level of 62 U/L and an IL-6 level of >1,000 pg/mL, but the fluid was negative for SARS-CoV-2 by RT-PCR. Sputum and pleural fluid were smear negative for AFB and negative for M. tuberculosis nucleic acids by molecular testing, but the IGRA for TB was positive. ATT was started, and pleural fluid cultures were subsequently positive for M. tuberculosis.

All 4 patients were workers who resided in dormitories and had COVID-19 but atypical radiographic features; typical radiographic features for COVID-19 patients include ground-glass opacities, multifocal patchy consolidation, and peripheral interstitial changes (3). Despite confirmed diagnoses of COVID-19, the 4 patients’ pulmonary radiologic findings were more consistent with those for TB, highlighting the value of considering other pulmonary pathologic conditions for patients with COVID-19.

Risk factors for TB include low socioeconomic status and overcrowded living conditions (4). Of note, patients 1 and 3 resided in the same dormitory. Migrant worker dormitories are often inadequately ventilated and crowded, resulting in residents being more susceptible to infectious diseases, including dengue, Zika, and varicella (5,6). The same working and living conditions have served as a catalyst for the rapid transmission of SARS-CoV-2, and potentially TB, in this population. Improving screening processes and living conditions and implementing routine vaccination strategies for this population may prevent future infectious disease outbreaks.

As the COVID-19 pandemic continues, care for patients with TB may be compromised as additional strains are placed on essential services. The 4 cases we report highlight a serious public health issue. Precautionary measures must be undertaken to be vigilant of an epidemic within the ongoing pandemic—TB. To ensure that care is not compromised, clinicians treating these at-risk populations should be aware of possible co-infection with M. tuberculosis and SARS-CoV-2 in patients with atypical radiographic features of COVID-19.

Dr. Tham is an infectious diseases senior resident in the Department of Medicine at the National University Hospital of Singapore. His research interests include virology and public health.

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References

  1. Ministry of Health Singapore. COVID-19 situation report [cited 2020 Jun 29]. https://covidsitrep.moh.gov.sg
  2. Shi  H, Han  X, Jiang  N, Cao  Y, Alwalid  O, Gu  J, et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. 2020;20:42534. DOIPubMed
  3. Narasimhan  P, Wood  J, Macintyre  CR, Mathai  D. Risk factors for tuberculosis. Pulm Med. 2013;2013:828939. DOIPubMed
  4. Sadarangani  SP, Lim  PL, Vasoo  S. Infectious diseases and migrant worker health in Singapore: a receiving country’s perspective. J Travel Med. 2017;24:19. DOIPubMed
  5. Ho  ZJM, Hapuarachchi  HC, Barkham  T, Chow  A, Ng  LC, Lee  JMV, et al.; Singapore Zika Study Group. Outbreak of Zika virus infection in Singapore: an epidemiological, entomological, virological, and clinical analysis. Lancet Infect Dis. 2017;17:81321. DOIPubMed

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Cite This Article

DOI: 10.3201/eid2611.202752

Original Publication Date: July 15, 2020

Table of Contents – Volume 26, Number 11—November 2020

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Gabriel Yan, Division of Infectious Diseases, Department of Medicine, National University Health System, NUHS Tower Block, 1E Kent Ridge Rd, 119228, Singapore

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Page created: July 15, 2020
Page updated: October 19, 2020 1:40 PM EDT
Page reviewed: October 19, 2020 1:40 PM EDT
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
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