The impact of COVID-19 on TB in Iran: An illustrative study

Abstract

The COVID-19 pandemic has caused significant disruptions in TB services across the globe. Like many other countries, TB case notifications decreased during the pandemic in Iran. In this paper, we describe two cases of concomitant COVID-19 and TB infection whose diagnosis of pulmonary TB was delayed amid the pandemic. We depict how atypical imaging findings may guide physicians to pulmonary TB diagnosis and discuss strategies to maximize TB case detection.

1. Introduction

Since the beginning of the COVID-19 pandemic, there have been disruptions in the global number of people diagnosed with tuberculosis (TB), TB disease incidence, and mortality. Decreases in TB case notifications in this period have been impacted by the reduced capacity of health systems to provide care and the lower demand for individuals to seek medical care [1].In 2019, before the COVID-19 pandemic, TB was reported as the primary culprit for infection-related death worldwide, signifying the importance of controlling this disease [1].

In Iran, similar to many other countries across the world, the number of TB case notifications substantially decreased in 2020, reflecting the impact of the COVID-19 pandemic on TB services. In 2020, the total number of new and relapse TB cases notified was 5993, while this number was 8524 and 8906 in 2019 and 2018, respectively. In other words, the number of new and relapse TB case notifications fell by about 30% from 2019 to 2020. Also, the ratio of sputum smear-positive TB cases to sputum smear-negative TB cases increased in 2020 compared with 2019 and 2018. This is important from the public health perspective as patients with sputum smear-positive TB are more infectious than patients with sputum smear-negative TB [2]. Therefore, contact tracing will play an essential role in limiting the transmission of TB in Iran in the coming years.

Patients with pulmonary TB and COVID-19 share similar symptoms, such as cough, fever, and fatigue. In addition, they might have overlapping radiographic findings on chest imaging[3]. Therefore, identifying COVID-19 and TB coinfection is challenging and may lead to diagnostic delays and worse clinical outcomes. In this study, we present two illustrative cases of concurrent TB and COVID-19 in which the diagnosis of pulmonary TB was delayed amid the pandemic. In both cases, COVID-19 diagnosis was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR), and pulmonary TB suspicion was made due to atypical imaging findings. The presence of acid-fast bacilli (AFB) on sputum smear microscopy confirmed the diagnosis of concomitant TB in both patients.

2. Patient 1

A 78-year-old man was admitted to the hospital for a positive SARS-CoV-2 PCR test. He complained of a non-productive cough, pleuritic chest pain, and worsening dyspnea for the past four days. The patient also had noted a loss of appetite and weight loss (3–4 kg) over the past 2–3 months but had no history of myalgia, rhinorrhea, night sweats, or hemoptysis. He had a negative history of tobacco smoking and alcohol consumption. On initial examination, oxygen saturation was 97% (at room air), heart rate was 90 beats/min, the temperature was 36.5 °C, blood pressure was 130/78 mmHg, and respiratory rate was 20 breaths/min. Lab tests were unremarkable except for elevated C-reactive protein (CRP) and ferritin levels. The patient was hospitalized for further evaluation and treatment. He received Remdesevir, dexamethasone, and prophylactic anticoagulant for therapy. On chest x-ray, bilateral multifocal mixed interstitial and alveolar infiltration were seen. Chest computed tomography (CT) revealed partial loss of volume of the right middle lobe and small-sized mediastinal, but not hilar lymphadenopathies without pleural effusion (Fig. 1). These findings prompted the evaluation of Mycobacterium tuberculosis. AFB smear was positive, and Xpert MTB/RIF assay detected Mycobacterium tuberculosis susceptible to rifampin. The patient denied close contact with infected patients and had no prior history of TB or COVID-19 infection. However, the patient recalled that he had tested negative for COVID-19 twice since the pandemic's beginning due to cough and dyspnea. Standard quadruple therapy was started for the patient, and he was finally discharged after 35 days.

Fig. 1.

Chest imaging findings of patient 1. (A) Chest x-ray (PA) shows bilateral multifocal mixed interstitial and alveolar infiltration more dominant in the right upper and left lower lobes. Scattered parenchymal nodular densities are also seen elsewhere. (B) A spiral chest CT scan shows diffuse bilateral mixed alveolar and interstitial infiltration throughout both lung fields, particularly in the right upper lobe, right paratracheal lymphadenopathy, and (C) right middle lobe consolidation and partial collapse and left lower lobe alveolar infiltration with air bronchogram. Parenchymal nodules are also seen in the right lower lobe. No evidence of pleural effusion. (D) and (E) lung windows that show alveolar and interstitial infiltration. (F) Shows few small prevascular mediastinal lymph nodes.

3. Patient 2

A 76-year-old woman was admitted to the hospital with a possible diagnosis of COVID-19. The patient had a productive cough and dyspnea over the last month with no history of fever, chills, rhinorrhea, and hemoptysis. Her past medical history was significant for diabetes, hypertension, and coronary artery disease. She had sought medical care three times for cough during the COVID-19 pandemic but had not undergone further evaluation due to negative COVID-19 test results. On initial examination, the patient had an oxygen saturation of 97% (with an O2 mask) and a heart rate of 90 beats/min. Her temperature and blood pressure were 36.7 °C and 110/90 mm/Hg, respectively. Lab tests showed leukocytosis with an elevated erythrocyte sedimentation rate (ESR), CRP, lactate dehydrogenase (LDH), D-dimer, and ferritin levels. During hospitalization, the COVID-19 diagnosis was confirmed with a positive PCR test, and we began therapy with Remdesevir and prophylactic anticoagulant. A Chest CT scan showed bronchial narrowing and cavity formation in the left lower lobe. In addition, few calcified hilar lymph nodes were seen. (Fig. 2), and the patient was tested for TB. AFB were seen on sputum smear microscopy, and Xpert MTB/RIF assay detected Mycobacterium tuberculosis susceptible to rifampin. Quadruple therapy was administered to the patient, and she was discharged after three weeks.

Fig. 2.

Chest imaging findings of patient 2. (G)A spiral chest computed tomography (CT) scan shows bronchial narrowing of the right mainstem bronchus and left lower lobe bronchus with partial loss of volume of both lower lobes and mediastinal shift towards the right. Increased pulmonary artery diameter (33.5 mm) due to chronic pulmonary disease is observed. (H) Subsequent atelectatic segments in both lower lobes are noted with an irregular and thick-walled cavitary lesion in the left lower lobe and (I) multifocal tree-in-bud pattern of infiltration in the lower lobes of both lungs, suggestive of TB. (J) Calcified hilar lymph node.

4. Discussion

Recently, there has been a primary focus on COVID-19, and patients with respiratory symptoms have been triaged mainly for severe acute respiratory infections. Subsequently, those with a coinfection between SARS-CoV-2 and other respiratory pathogens, such as TB, might have been overlooked.

Iran has an estimated TB incidence of 10–49 cases per 100,000 population per year [1]. In countries with a high incidence of TB, the diagnosis of SARS-CoV-2 and Mycobacterium tuberculosis coinfection should be considered in the setting of atypical imaging findings and/or clinical manifestations. When TB remains undetected, the risk of disease transmission significantly increases due to the non-self-limiting nature of the disease.

COVID-19 pneumonia typically manifests with bilateral subpleural and peripheral ground glass opacities on chest CT. On the other hand, TB radiologic characteristics include unilateral infiltrates, cavities, consolidations, and mediastinal and hilar lymphadenopathy [4], [5]. “Tree-in-bud” appearance and fine nodularity are also commonly associated with TB. Bronchiectasis, pleural thickening and/or effusion, lung nodules, fibrosis, and lymphadenopathy have been described in both COVID-19 and TB patients. Although rare, pulmonary cavitation has been reported in patients with severe COVID-19 pneumonia as well [6], [7]. Given the overlapping imaging features of COVID-19 with TB at chest CT, laboratory tests can be used to aid the diagnosis of presumptive cases.

Comorbidities such as diabetes and chronic renal failure, and older age – particularly >65 years – are associated with disease severity in COVID-19 and TB [5], [8]. Therefore, it is imperative to consider concomitant infection with SARS-CoV-2 and M. tuberculosis in suspected patients with these conditions to prevent significant morbidity and mortality.

Taken together, we emphasize that clinicians should provide simultaneous testing for TB and COVID-19 for individuals when indicated, as advised by the World Health Organization (WHO) [1]. In the Philippines, TB screening was offered to individuals after COVID-19 vaccination or during COVID-19 screening to enhance TB case-finding[9]. In response to the detrimental impact of the COVID-19 pandemic on global TB services, other innovative and feasible strategies should be applied to maximize TB case detection, prevention, and care.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.