Tuberculosis during the COVID-19 Pandemic: Retrospective Analysis in a Tertiary Hospital in Portugal ()
1. Introduction
Tuberculosis (TB) is a preventable and mainly curable infectious disease, caused by the bacillus Mycobacterium tuberculosis [1]. Despite coexisting for at least 15000 years, the disease reached widespread proportions during the 18th and 19th centuries in rapidly urbanizing and industrializing Europe and North America [2] [3], and since then, it has persisted as a global epidemic with disproportionate effects on low-income populations [4]. Today, it is responsible for around 1,5 million deaths each year, more than any other infectious disease [5], and about a quarter of the global population is estimated to have been infected with the bacteria [6].
Following infection, the estimated lifetime risk for reactivation and progression to active disease is 5% - 10% [7], notably during the first two years and in immunocompromised patients, such as those co-infected with the human immunodeficiency virus (HIV), in which the risk is estimated to be 18 times higher [8]. Besides immune status, other determinants for infection acquisition and disease development include poverty, undernourishment, smoking and diabetes. About 90% of the patients are adults with more cases among men [9].
Tuberculosis typically affects the lungs (pulmonary TB) but can also involve other sites (extrapulmonary TB) [10]. Despite substantial improvement in testing, culture remains the reference standard for tuberculosis diagnosis, detection of drug resistance and monitoring the response to therapy [11]. Without treatment, the mortality of the disease is high, ranging from 70% in individuals with sputum smear-positive and 20% in people with sputum smear-negative pulmonary TB. Effective antibacterial drugs were first developed in the 1940s, and currently recommended regimens can achieve a cure in about 85% of the patients [12].
The World Health Organization’s End TB Strategy was launched in 2015 as a joint commitment to ending the tuberculosis pandemic, targeting large reductions in its incidence rate, mortality and associated expenditures up to year 2035 [13]. Despite falling short of the milestones outlined, an encouraging decline in the global burden of the disease has since then been observed [14]. The COVID-19 pandemic inflicted profound health and social upheaval, significantly disrupting early TB diagnosis, screening, and access to treatment. As a result, the most immediate consequence was a sharp decline in new TB cases: global notifications dropped from 7.1 million in 2019 to 5.8 million in 2020, with only partial recovery in 2021 [15] [16]. This trend was mirrored in most high-income countries in Europe, North America, and Australia, where notifications declined while mortality increased [17]. Moreover, country-specific data, such as Armenia’s 37.6% reduction in active TB case detection, primarily due to decreased testing and contact tracing, highlight the widespread operational breakdown in TB surveillance, diagnosis, and control [18].
The present work aimed to characterize the experience of a Portuguese tertiary care center concerning the management of hospitalized patients with tuberculosis during COVID-19.
2. Methods
For the purpose of this study, a retrospective observational cohort analysis was conducted at the Department of Infectious Diseases of a tertiary care center in Porto, Portugal. The electronic hospital database (SClínico®) was systematically reviewed to identify all adult patients admitted for inpatient care between January 2020 and December 2022 who were subsequently diagnosed with tuberculosis during the course of hospitalization. All identified patients meeting these criteria were included in the study. Relevant clinical and demographic variables were extracted from medical records, and no missing information was identified.
Diagnostic criteria followed World Health Organization’s consolidated guidelines on Tuberculosis [19]. Confirmed TB was defined by the identification of Mycobacterium tuberculosis complex (MTC) from clinical specimens through culture or molecular testing. Suspected TB included patients lacking microbiological confirmation but presenting compatible clinical, histological, or radiological features. Pulmonary TB involves infection of lung parenchyma, with smear-positive and smear-negative cases classified according to initial acid-fast sputum results. Extrapulmonary TB refers to disease affecting organs other than the lungs.
The descriptive analysis was conducted using SPSS® version 29.0.1.1. This study was conducted in accordance with the Declaration of Helsinki and approved by the institution’s Ethics Committee, which waived the informed consent of the patients.
3. Results
A total of 72 patients were diagnosed with tuberculosis during the study period. Of these, 62 (86.1%) had pulmonary TB and 10 (13.9%) had extrapulmonary TB; disseminated TB was identified in 19 cases (26.4%). The cohort was predominantly male (72.2%) with a median age of 54 years (range 18 - 92). Eighteen patients (25.0%) reported current or past employment in high-risk occupations (e.g., construction, healthcare, industrial work, commercial sex work); three individuals (4.2%) were incarcerated at the time of diagnosis, and two (2.8%) were in precarious socioeconomic situations. Regarding lifestyle factors, 22 patients (30.6%) were active smokers, 12 (16.7%) had alcohol dependence, and 11 (15.3%) had a history of substance abuse. Identifiable immunosuppressive conditions were present in 28 patients (38.9%), including 15 (20.8%) with HIV infection. The median interval from symptom onset to diagnosis was 60 days (range 1 - 730), with immunocompetent patients experiencing a shorter diagnostic delay (median 45 vs 75 days). Detailed demographic and clinical characteristics are summarized in Table 1 and Table 2.
Table 1. Sociodemographic and behavioral characteristics of the study population.
Characteristics of the population |
Sociodemographic Characteristics |
N = 72 (%) |
Gender |
Female |
20 (27.8%) |
Male |
52 (72.2%) |
Age |
Median |
54 years |
Minimum Value |
18 years |
Maximum Value |
92 years |
18 - 30 years |
9 (12.5%) |
31 - 50 years |
19 (26.38%) |
51 - 65 years |
22 (30.56%) |
>65 years |
22 (30.56%) |
Occupation |
Non-Risky Occupation |
18 (25.0%) |
Retired from Non-Risky Occupation |
14 (19.4%) |
Risky Occupation |
10 (13.9%) |
Unknown |
9 (12.5%) |
Retired from Risky Occupation |
8 (11.1%) |
Unemployed |
8 (11.1%) |
Inmate |
2 (2.8%) |
Homeless |
2 (2.8%) |
Former Inmate |
1 (1.4%) |
Habits of the Population |
n (%) |
Smoking |
Yes |
22 (30.6%) |
No |
40 (55.6%) |
Ex-smoker |
10 (13.8%) |
Alcoholism |
Yes |
12 (16.7%) |
No |
57 (79.1%) |
Ex-alcoholic |
3 (4.2%) |
Drug Consumption |
No |
58 (80.6%) |
Cocaine |
1 (1.4%) |
Cocaine and Heroin |
7 (9.7%) |
Narcotics |
1 (1.4%) |
Cannabinoids |
1 (1.4%) |
Ex-drug user |
4 (5.5%) |
Pulmonary TB predominated in both immunocompetent (35 cases, 79.5%) and immunosuppressed patients (27 cases, 96.4%). Common presenting symptoms included weight loss (77.4%), fatigue (74.2%), cough (71.0%), fever (46.8%), night sweats (30.6%), dyspnea (24.2%), hemoptysis (12.9%), and pleuritic chest pain (9.7%). Among the 62 pulmonary TB cases, 35 (56.4%) had isolated pulmonary involvement, while 27 (43.6%) also exhibited extrapulmonary disease. As depicted in Table 3, diagnostic confirmation was achieved in 56 patients (90.3%): 52 by culture alone, 4 by molecular testing alone, and 38 by both methods. Sputum-smear microscopy was positive in 37 patients (59.7%), necessitating airborne isolation precautions. Radiological cavitation was observed in 33 cases (53.2%). Among MTC strains isolated by culture, 50 (96.2%) were drug-susceptible, one (1.9%) was polyresistant, and one (1.9%) was multidrug-resistant. Extrapulmonary sites among the 27 patients with concurrent involvement included: lymph nodes (9 cases, 33.3%); genitourinary tract (8 cases, 29.6%), osteoarticular system (7 cases, 25.9%); pleura or pericardium (7 cases, 25.9%), including 6 pleural cases and 1 pericardial effusion causing tamponade; gastrointestinal tract (4 cases, 14.8%); and central nervous system (3 cases, 11.1%).
Among the 10 patients with exclusively extrapulmonary TB, the affected sites were lymph nodes (4 cases), osteoarticular system (3 cases), pleura (3 cases), central nervous system (2 cases), gastrointestinal tract (1 case), and genitourinary system (1 case) (Table 4). Although disseminated TB was more common in the immunosuppressed cohort (35.7% vs. 20.5%), isolated extrapulmonary TB predominated among immunocompetent patients (20.5% vs. 3.6%).
Table 2. Comorbidities of the study population.
Comorbidities in the individuals of the sample |
Hypertension |
19 (26.4%) |
Diabetes |
14 (19.4%) |
Pulmonary and respiratory disease |
Obstructive disease |
11 (15.3%) |
Sequelae of TB |
3 (4.2%) |
Pneumoconiosis |
2 (2.8%) |
Obstructive Sleep Apnea Syndrome |
1 (1.4%) |
Structural disease |
1 (1.4%) |
Hepatic disease |
Non-Cirrhotic |
9 (12.5%) |
Cirrhotic |
4 (5.6%) |
Chronic renal disease |
6 (8.3%) |
Infection with HIV |
15 (20.8%) |
|
- CD4 count < 200 |
11 (73.3%) |
|
- CD4 count > 200 |
4 (26.7%) |
Immunosuppression |
27 (37.5%) |
|
- By HIV |
15 (55.6%) |
|
- By drugs |
9 (33.3%) |
|
- By neoplasm |
3 (11.1%) |
Previous infection with Tuberculosis |
11 (15.3%) |
During hospitalization, 14 patients (19.4%) were transferred to Intensive Care Unit (ICU), of whom 6 (8.3%) required mechanical ventilation. ICU admission and invasive ventilation were more frequent among patients without known immunosuppressive conditions than those with (27.3% vs. 7.1% and 11.4% vs. 3.6%, respectively). Antitubercular therapy was initiated in all but one patient, who died of respiratory failure before the diagnosis was confirmed. Following treatment initiation, 22 patients (30.6%) experienced adverse drug reactions, most commonly hepatic toxicity (18 cases), followed by cutaneous manifestations (4 cases) and neurological symptoms (3 cases).
Table 3. Clinical description of cases with pulmonary tuberculosis.
Pulmonary Tuberculosis |
Pulmonary disease only |
35 (56.4%) |
Pulmonary and extrapulmonary disease |
27 (43.6%) |
Type of diagnosis |
|
Confirmed |
56 (90.3%) |
Suspected |
6 (9.7%) |
Method of diagnosis |
|
Microbiological evidence |
56 (90.3%) |
Isolation in cultures |
52 (92.8%) |
STB |
41 (73.2%) |
BAL |
5 (8.9%) |
Both |
4 (7.1%) |
Identification using Polymerase Chain Reaction |
4 (7.1%) |
Both |
38 (67.8%) |
Clinical evidence or imaging results |
6 (9.7%) |
Disease characteristics |
|
Direct microscopy |
37 (59.7%) |
Lung cavitation |
33 (53.2%) |
Cultural TSA |
|
Sensitive |
50 (96.2%) |
Polyresistant |
1 (1.9%) |
Multi-drug resistant (MDR-TB) |
1 (1.9%) |
Extrapulmonary sites in Pulmonary Tuberculosis |
|
Lymph node disease |
9 (33.3%) |
Genitourinary disease |
8 (29.6%) |
Osteoarticular disease |
7 (25.9%) |
Pleuro-pericardial disease |
7 (25.9%) |
Gastrointestinal disease |
4 (14.8%) |
Central Nervous System disease |
3 (11.1%) |
Regarding outcomes, 64 patients (88.9%) were discharged with clinical improvement and referred for continued follow-up, 3 (4.2%) left against medical advice, and 5 (6.9%) died during hospitalization. Within six months, 13 patients (18.1%) were readmitted due to symptom exacerbation or treatment failure. In-hospital mortality was similar in patients with and without immunosuppressive conditions (7.4% vs. 6.8%), while readmission rates were slightly higher among the immunosuppressed cohort (21.4% vs. 15.9%).
Table 4. Clinical description of cases with extrapulmonary tuberculosis.
Extrapulmonary Tuberculosis Only |
No. Cases |
10 patients |
Type of Extrapulmonary Tuberculosis |
|
Lymph Node tuberculosis |
4 (40%) |
|
- with specific symptoms of lymph node involvement |
0 |
Osteoarticular tuberculosis |
3 (30%) |
|
- with specific symptoms of osteoarticular involvement |
2 (66.7%) |
Pleuro-pericardial tuberculosis |
3 (30%) |
|
- with specific symptoms of cardiopulmonary involvement |
2 (66.7%) |
CNS tuberculosis |
2 (20%) |
|
- with specific symptoms of CNS involvement |
2 (100%) |
Genitourinary tuberculosis |
1 (10%) |
|
- with specific symptoms of genitourinary involvement |
0 |
Gastrointestinal tuberculosis |
1 (10%) |
|
- with specific symptoms of gastrointestinal involvement |
1 (100%) |
Symptoms |
|
Fever |
4 (40%) |
Fatigue |
7 (70%) |
Loss of weight |
5 (50%) |
Excessive sweating |
2 (20%) |
4. Discussion
This retrospective analysis characterizes the demographic and clinical profile of 72 patients with tuberculosis admitted during the COVID-19 pandemic to an infectious diseases ward at a tertiary hospital in Porto, Portugal. Consistent with established epidemiological trends, the majority of patients were male and over 50 years of age—recognized risk factors for active TB. Notably, while over one-third of patients exhibited immunosuppressive conditions, most did not display the socioeconomic or clinical vulnerabilities commonly linked to increased risk, such as substance abuse, unstable housing, incarceration, or chronic comorbidities, despite these factors being significant predictors of TB incidence in Portugal. [20]-[22].
Immunosuppression is a well-recognized risk factor for more severe and atypical manifestations of TB, including a higher likelihood of disseminated disease and poorer clinical outcomes [23]-[25]. In this cohort, disseminated TB was more frequent among immunosuppressed patients, consistent with existing evidence. Conversely, isolated extrapulmonary TB was more commonly observed in immunocompetent individuals, contrasting with patterns typically seen in HIV-associated TB, where extrapulmonary involvement is often multifocal. Mortality rates were similar across both groups, diverging from most published data, which may be explained by consistent inpatient care, timely diagnosis, or sample size limitations. Notably, six-month readmission rates were higher in immunosuppressed patients, suggesting greater vulnerability to treatment failure or complications. Overall, these findings align with the broader literature—highlighting increased rates of disseminated TB and adverse outcomes in immunosuppressed individuals, despite comparable short-term mortality.
A key finding of the study was a significant diagnostic delay, with a median time of 60 days—and in some cases, extending up to 730 days—from symptom onset to TB diagnosis, far exceeding typical pre-pandemic timelines [26]. Although not the central focus of this study, such latency has been well-documented in the literature and is likely attributable to a combination of patient- and system-level barriers exacerbated by the COVID-19 pandemic. For example, healthcare-seeking behaviors were often delayed due to fear of SARS-CoV-2 exposure, contributing to more advanced disease at the time of presentation. In addition, the symptomatic overlap between TB and COVID-19 frequently led to misdiagnosis or deferral of appropriate investigations [27]. Notably, many patients in this cohort did not present with traditional risk factors, which likely reduced clinical suspicion. In such cases, individuals with respiratory symptoms were often funneled into COVID-19 screening pathways, where mycobacterial testing was seldom pursued due to a low perceived likelihood of disease [28]. On a broad health system level, widespread service disruption—including lockdowns, reallocation of resources, and reduced access to services—contributed to sharp declines in TB case detection and treatment initiation, as reported globally [29]. These factors are consistent with the clinical severity observed in this cohort, as evidenced by a high prevalence of cavitary lesions and sputum-smear positivity in over half of patients, and the need for intensive care in nearly one-fifth of cases—figures that parallel international reports of tuberculosis during the COVID-19 pandemic [30]-[32].
This study is subject to several important limitations. First, as a single-center investigation based in a tertiary referral hospital, the cohort likely overrepresents severe or complex cases of TB and may not be generalizable to broader populations managed in primary or secondary care settings. Second, the absence of a pre-pandemic comparator group limits the ability to discern the specific impact of the COVID-19 pandemic on TB presentation, disease progression, and outcomes. Third, SARS-CoV-2 infection status—whether active, recent, or past—was not systematically documented at the time of TB diagnosis, limiting the capacity to assess possible interactions between the two infections. Although multiple international cohort studies and meta-analyses have shown that TB-COVID-19 co-infection is associated with more severe disease, including higher rates of respiratory failure, intensive care admission, and in-hospital mortality [33] [34], the present study cannot confirm such associations [33] [34]. These limitations highlight the need for well-designed, multicenter longitudinal studies with integrated microbiological surveillance to clarify the interaction and long-term impact of COVID-19 on TB epidemiology and outcomes.
Nevertheless, this retrospective analysis provides a noteworthy snapshot of TB management during an unprecedented global health emergency. The findings reveal not only the strain imposed by the COVID-19 pandemic on TB care, but also the adaptability and resilience of healthcare professionals in ensuring treatment initiation and continuity. These results should serve as a basis for strengthening TB services and infrastructures, reinforcing diagnostic capabilities, and safeguarding treatment adherence, particularly in anticipation of future health system disruptions.
Author’s Contribution
E.F.M. and M.O. are first authors with equal contribution to the whole manuscript. Conceptualization: E.F.M., M.O. and L.S. Methodology: E.F.M. and M.O. Data collection: M.O. Investigation: E.F.M., M.O. and L.S. Writing—Original Draft: E.F.M. and M.O. Writing—Review & Editing: E.F.M., M.O., F.C. and L.S. Supervision: L.S.
NOTES
*First authors.
#Corresponding author.