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Table of Contents
CASE REPORT
Year : 2020  |  Volume : 11  |  Issue : 3  |  Page : 164-168

Severe acute respiratory syndrome coronavirus-2 and tuberculosis coinfection: Double trouble


1 Department of Pulmonary and Critical Care Medicine, Medeor JCS Institute of Pulmonary, Critical Care and Sleep Medicine, New Delhi, India
2 Department of Pulmonary and Critical Care Medicine, Ayushman Hospital and Health Service, Delhi, India

Date of Submission27-Jun-2020
Date of Decision19-Jul-2020
Date of Acceptance20-Jul-2020
Date of Web Publication18-Aug-2020

Correspondence Address:
Dr. Abhijeet Singh
Department of Pulmonary and Critical Care Medicine, Medeor JCS Institute of Pulmonary, Critical Care and Sleep Medicine, B-33, 34 Qutab Institutional Area, New Delhi - 110 016
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/INJMS.INJMS_72_20

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  Abstract 


The ongoing pandemic of novel coronavirus disease 2019 (COVID-19) has received worldwide attention by becoming a major global health threat. We encountered one case with COVID-19 and tuberculosis (TB) coinfection, which has not been frequently reported. A 76-year-old female presented with acute respiratory symptoms superimposed on chronic symptoms, suggestive to have pneumonia. Oropharyngeal throat swab sample for COVID-19 was positive as detected by real-time reverse transcriptase–polymerase chain reaction assay. GeneXpert Ultra detected Mycobacterium tuberculosis complex with rifampicin resistance indeterminate. The patient was treated with appropriate management. Clinicians should suspect coinfection with TB during the ongoing pandemic of COVID-19 as therapeutic strategies need to be determined timely to improve outcomes and prevent transmission in the community.

Keywords: Coinfection, coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, tuberculosis


How to cite this article:
Singh A, Gupta A, Das K. Severe acute respiratory syndrome coronavirus-2 and tuberculosis coinfection: Double trouble. Indian J Med Spec 2020;11:164-8

How to cite this URL:
Singh A, Gupta A, Das K. Severe acute respiratory syndrome coronavirus-2 and tuberculosis coinfection: Double trouble. Indian J Med Spec [serial online] 2020 [cited 2020 Oct 28];11:164-8. Available from: http://www.ijms.in/text.asp?2020/11/3/164/292391




  Introduction Top


The 2019 novel coronavirus (2019-nCoV) or recently renamed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by World Health Organization (WHO), has been rapidly spreading with emergence from Wuhan City of Hubei Province of China in December 2019 to the rest of the world involving 203 other countries.[1],[2] Disease-associated with SARS-CoV-2, also termed as coronavirus disease 2019 (COVID-19), has now become a major threat to global health. The WHO has declared this disease as a pandemic on March 11, 2020. Since then (as on June 20, 2020), almost 8.5 million confirmed cases with 0.45 million deaths had been reported worldwide.[2] The clinical features of COVID-19 are variable, ranging from asymptomatic state to pneumonia, acute respiratory distress syndrome, and multi-organ dysfunction. Tuberculosis (TB) is already existing as unprecedented pandemic worldwide with an estimated 10 million with mortality of 1.2 million among human immunodeficiency virus (HIV)-negative, and an additional 0.25 million among HIV-positive people with mortality of 1.2 million in 2018.[3] Around one-fourth of the world population is estimated to have latent TB infection.[3] Convergence of TB and COVID-19 pandemics will be more deadly with the propensity to cause sustained community transmission across all countries. To our knowledge, the coinfection of SARS-CoV-2 and TB has been reported with limited evidence. Here, we present one case of coinfection of SARS-CoV-2 and TB.


  Case Report Top


A 76-year-old female presented to our emergency on March 20, 2020, with a 1.5-month history of low-grade intermittent fever, nonproductive cough, and decreased appetite with an eventual weight loss of 4 kg. She had worsening of symptoms 5 days before presentation with high-grade fever followed by breathlessness 3 days before her presentation. There was no prior history of pulmonary TB, any recent hospital admission, and no known contact with patients or family members having active TB. Her background history revealed that she was hypertensive, taking tablet amlodipine 10 mg once daily. On physical examination at the time of admission, the patient was febrile (102°F) and had an arterial blood pressure of 140/80 mmHg, a heart rate of 110 beats/min, respiratory rate of 32 breaths/min, and oxygen saturation of 86% on room air. Chest auscultation revealed bilateral crepitation with bronchial breathing on the left side. The findings of the remainder of the systemic examination were unremarkable. The arterial blood gas on room air showed a PaO2 of 52 mmHg (normal range: 80–100), PaCO2 of 30 mmHg (normal range: 35–45), HCO3 of 18 mmol (normal range: 22–26), pH of 7.46 (normal range: 7.35–7.45), and wide alveolar-arterial gradient of 36 mm Hg (expected normal value - 23) suggestive of acute hypoxemic respiratory failure. Routine blood tests revealed the following: Hemoglobin level of 11.5 g/dL (normal range: 12–15 g/dl), leukocyte count of 7600 cells/mm3 (normal range: 4000–11000 cells/mm3) with 90% neutrophils (normal range: 40%–80%), 7.0% lymphocytes (normal range: 20%–40%), and 3.0% monocytes (normal range: 2%–10%), platelet count 220,000/mm3 (normal range: 150,000/mm3–410,000/mm3), serum sodium level 133 mmol/L (normal range: 135–145 mmol/l), urea 62.7 mg/dL (normal range: 16–48 mg/dl) and creatinine 2.72 mg/dL (normal range: 0.7–1.2 mg/dl). The erythrocyte sedimentation rate was elevated with 65 mm (normal range: 0–30 in 1st h). Other remarkable blood test findings included serum lactate dehydrogenase 550 U/L (normal range: 135–225 U/L), High sensitive C-reactive protein-55 mg/l (Normal value: <5 mg/l), procalcitonin 0.5 ng/ml (normal range: 0.0–0.5 ng/ml), NT-pro Brain Natriuretic Peptide level 600 pg/ml (normal range: 0–249 pg/ml), ferritin level 426.2 ng/ml (normal range: 13–150 ng/ml), troponin-I negative, creatine phosphokinase (CPK) 430 U/L (normal range: 0–200 U/L) and CPK-MB 30.7 U/L (normal range: 0–25 U/L). Chest radiograph revealed left lower zone alveolar opacity likely lobar consolidation, as shown in [Figure 1]a. Computed tomography (CT) thorax revealed left lower lobe dense consolidation having air bronchogram with underlying effusion and bilateral ground glassing, as shown in [Figure 1]b, [Figure 1]c, [Figure 1]d, [Figure 1]e, [Figure 1]f. Provisional diagnosis of community-acquired pneumonia was established initially. A therapeutic trial of intravenous antibiotics (Ceftriaxone 1 g twice daily and Azithromycin 500 mg once daily) was initiated after the collection of cultures along with other supportive measures. Ziehl–Neelsen staining of two consecutive sputum smear samples was negative for acid-fast bacilli (AFB). Her oxygenation was maintained with SpO2 around 95% with a simple face mask with flow rate 8 L/min on admission. A short trial of intermittent noninvasive ventilation was also provided to reduce work of breathing even after achieving oxygenation. Aerobic culture of sputum, blood, and urine collected at admission, were sterile. A 2D echocardiogram revealed mild concentric left ventricular hypertrophy with preserved ejection fraction, grade 1 diastolic dysfunction, and no vegetations. Throat swab was negative for respiratory viruses, including influenza. Serology was negative for HIV, hepatitis B and C. In view of the height of novel SARS CoV-2 pandemic worldwide, throat swab for SARS CoV-2 was also sent and found to be positive as detected by validated real-time reverse transcriptase–polymerase chain reaction assay for both E-Sarbeco and RdRP genes. GeneXpert Ultra of sputum revealed rifampicin indeterminate Mycobacterium tuberculosis complex (MTBC). It was advised in view of high clinical suspicion for TB with chronicity of symptoms and radiological findings. Based on these reports, the history of the patient was again reviewed after inquiring all family members staying along with her. She was confirmed to have had direct contact with her grandson who traveled from France 12 days before the onset of acute symptoms and returned back after 5 days. Thereafter, her grandson also turned out to be COVID-19 positive. The treatment was modified on lines of COVID-19 that included injectable azithromycin 500 mg IV once daily, injectable methylprednisolone 40 mg IV twice daily, tablet hydroxychloroquine 400 mg twice daily for the first day followed by 400 mg once daily for 4 days, tablet vitamin C 500 mg twice daily and tablet N-acetyl cysteine 600 mg twice daily. Anti-tuberculous regimen (Rifampicin-R, Isoniazid-Z, Ethambutol-E, and Pyrazinamide-Z) was also started for the TB component. No adverse events were reported. The patient was shifted to COVID-19 designated hospital on March 24, 2020 for further management as per national policy guidelines. Written informed consent was obtained from the patient for using clinical records in this study.
Figure 1: (a) Chest X-ray showing left lower zone alveolar opacity likely consolidation; (b-f) Computed tomography thorax (mediastinal and lung window) showing bilateral diffuse ground glassing and left lower lobe dense consolidation having air bronchogram with underlying effusion

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  Discussion Top


We have reported this case with particular interest due to coinfection of SARS-CoV-2 and pulmonary TB, which is less frequently reported. There are studies that have reported coinfection of SARS-CoV-2 with other respiratory pathogens, particularly influenza virus.[4],[5],[6],[7] Few studies have previously reported coinfection of TB with other coronaviruses SARS-CoV-1 and MERS-COV during outbreaks in 2003 and 2012, respectively.[8],[9],[10],[11] Most of the cases had pulmonary TB initially followed by viral superinfection[8],[9],[11] while few contracted TB after recovery from viral infection.[10] Co-infection of TB and COVID-19 can also exist as there is the possibility that both could augment each other with a transient decrease in cellular immunity leading to new infection or exaggerated reactivation of latent infection, based on previous experience with other coronaviruses. This relationship could not be underestimated as few studies have recently reported coinfection of SARS-CoV-2 with TB as summarized in [Table 1].[12],[13],[14],[15],[16],[17] An observational study recently reported that persons with latent TB have increased susceptibility for SARS-CoV-2 infection associated with rapid progression and severe involvement.[16] TB infection was more common among patients with SARS-CoV-2 infection than in those with bacterial or other viral infections. A retrospective multicentric study belonging to Global Tuberculosis Network (GTN), reported that COVID-19 can occur before, simultaneously, or after the diagnosis of TB.[17] Although this coinfection might be a mere coincidence there could be a temporal relationship.[12],[13] This could be due to insufficient infection control practices compounded by a higher susceptibility of TB cases.[13] SARS-CoV-2 can induce type 1 interferons that inhibit immune responses mediated by interferon-gamma, leading to flare-up of TB infection, as observed for infections with other viruses like influenza and SARS-CoV-1.[18] However, a recent study observed that SARS-CoV-2 did not significantly induce any types of interferons and only upregulated few pro-inflammatory cytokines or chemokines, unlike SARS-CoV-1.[19] More evidence is required regarding this coinfection. Differentiation between TB and SARS-CoV-2 is quite difficult as both can manifest with similar respiratory symptoms like fever, cough, breathlessness, and weakness, but there is the gradual or chronic progression of symptoms in TB as compared to acute or rapid progression in case of COVID-19. Both also share common risk factors like advanced age, diabetes, malnutrition, immunosuppression, and other chronic illnesses. The radiological picture of unilateral noncavitating consolidation with effusion and bilateral ground-glassing on CT thorax is atypical for both pulmonary TB as well COVID-19.[20],[21] To be able to assign it to either of the two pathologies definitely is seemingly challenging, as reported in other studies.[12],[13],[17] Radiologists are still trying to explore definite radiological patterns for the novel COVID-19. A study from Italy reported no characteristic radiological features for COVID-19 in most of the cases with coinfection.[13] Our patient tested positive for both RT-PCR and GeneXpert Ultra for COVID-19 and MTBC, respectively. We advised GeneXpert despite smear-negative for AFB as per policy framed by the National TB Elimination Programme of India.[22] There is a possibility that these results could be false positive. It is recommended that genotypic tests should be repeated or confirmed with gold standard culture and phenotypic drug susceptibility test for M. tuberculosis to reconfirm findings. Both these tests are highly specific for diagnosing respective diseases and unlikely to be false positive. The results of conventional culture are usually delayed by three to six weeks, whereas liquid culture are prone to contamination. A study reported that the diagnosis of TB was confirmed by culture in 14 out of 18 COVID-19 patients as detected by GeneXpert MTB/RIF.[13] It becomes quite uncertain whether to continue treatment or not for the remaining 4 patients as the diagnosis of TB becomes questionable. Appropriate clinical judgment is warranted in order to avoid unfavorable outcomes in such patients. Timely initiation of treatment should be our priority in these subsets of patients, especially in high TB burden settings. Genotypic tests should be advised for the rapid diagnosis of these patients to achieve early initiation of treatment and curbing nosocomial as well as community transmission in this ongoing pandemic. Since our patient had a history of contact, advanced age, hypertension, and acute kidney injury, the presence of this co-infection was suspected, and management for both infections was initiated. Treatment was initiated early due to the severity of illness that was predicted on the basis of strong clinical suspicion and laboratory findings. Neutrophil-lymphocyte ratio was also high (12.85) in our case that suggests a poor prognosis. This is in accordance with an observational study from China that proposed neutrophil-lymphocyte ratio as one of the parameters for severe disease.[23] It also further highlights the point that no single radiological pattern can safely rule in or rule out either COVID-19 in a pandemic situation or TB in a high burden country like India. TB with HIV coinfection is also prevailing in many countries. The situation will be more difficult to tackle if there is associated drug resistance. Patients of COVID-19 either having active TB infection or previous history of TB with or without sequelae will be more at risk of worse outcomes. However, larger studies are required to unveil this association for further validation. It can be anticipated that as more number of cases are evolving, we might encounter the most deadly combination of drug-resistant TB, HIV, and COVID-19. The limitation of our study is the lack of data regarding treatment response and outcome. Unfortunately, the culture sample of our case got contaminated and could not be repeated as the patient was referred to COVID-19 designated hospital according to prevailing national policy. Few studies have supported the fact that these patients require serial monitoring with clinical, radiological, and microbiological assessment not only to confirm the diagnosis but also to track treatment response, any adverse events or drug interactions and outcome.[13],[14],[15] Our purpose of reporting this case was just to highlight the possibility of coexisting infections in high burden countries for TB like India, which are also facing COVID-19 pandemic. Therapeutic strategies like intense monitoring, timely decision for implementing appropriate ventilatory strategies, aggressive contact tracing, appropriate infection control and use of steroids or other immunosuppressive drugs like IL-6 inhibitor (Tocilizumab) for COVID-19, need to be prioritized with these subset of patients to avoid severity or complications.[24],[25]
Table 1: Characteristic of studies reporting tuberculosis and Coronavirus Disease 2019 coinfection

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  Conclusions Top


Clinicians should remain cautious while dealing with cases of COVID-19 and TB coinfection, particularly in countries where TB is endemic. Suspicion of TB (a chronic disease) in cases of COVID-19 (acute illness) should be made if there is a long antecedent history, as in this case, or if the patient fails to improve in at least 2 weeks' time. Diagnosis of TB must not be missed or delayed in view of ongoing COVID-19 pandemic as it may lead to poor outcomes and enhanced transmission of infection in the community if left untreated.

Consent for publication

The authors certify that they have obtained all appropriate patient consent forms.

Declaration of patient consent

The patient has given consent for images and other clinical information to be reported in the journal. The patient understands that their names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

None.

Conflicts of interest

There are no conflicts of interest.



 
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