European Journal of Cardiovascular Medicine

Tuberculosis (TB) remains a major public health concern, particularly in low- and middle-income countries like India, which accounts for nearly one-fourth of global TB cases¹. The advent of the COVID-19 pandemic has introduced an additional burden to TB control programs, as both diseases primarily affect the lungs and share overlapping symptoms². This syndemic interaction between TB and COVID-19 presents unique clinical challenges, particularly in resource-limited settings³.

COVID-19 severity is influenced by factors such as age, diabetes, cardiovascular disease, and lung pathology⁴. Patients with TB, especially those with residual lung fibrosis or cavitary lesions, are hypothesized to be more susceptible to severe outcomes following SARS-CoV-2 infection⁵. Moreover, socioeconomic deprivation, malnutrition, and delayed access to healthcare—common among TB patients—may further exacerbate disease severity⁶.

Existing literature on the clinical course of COVID-19 in TB patients is limited, with most studies focusing on incidence rather than severity predictors. A systematic review by Tadolini et al. noted increased mortality among co-infected individuals, yet did not explore the influence of host and disease-related variables⁷. As India faces a dual epidemic of TB and COVID-19, identifying the predictors of severe disease in this vulnerable population is essential for triage, early intervention, and prioritization of care.

Despite policy-level guidelines from WHO and the Indian Council of Medical Research (ICMR) advocating integrated TB-COVID management⁸, there is a paucity of data from India evaluating specific risk factors that contribute to severe COVID-19 among TB patients. This study was designed to bridge this gap and to support clinical decision-making in high-burden settings.

This cross-sectional study was conducted at Mahadevappa Rampure Medical College, Kalaburagi, Karnataka, between January and June 2022. The study aimed to assess the demographic and clinical factors influencing the severity of COVID-19 among patients with a current or past diagnosis of tuberculosis. Ethical approval was obtained from the Institutional Ethics Committee (Ref: MRMC/IEC/2022, dated 04/04/2022). Eligible participants included adult patients (aged ≥18 years) with confirmed COVID-19 infection—either by RT-PCR or rapid antigen test—who had a documented history of active or treated TB.

Patients with incomplete clinical records or those who did not provide informed consent were excluded. Data were collected using a pre-tested structured proforma that included sociodemographic details, comorbidities (e.g., diabetes mellitus, hypertension, HIV), type and site of TB, radiological findings (e.g., presence of fibrocavitary lesions), COVID-19 vaccination status, and clinical outcomes (oxygen requirement, ICU admission, mortality). COVID-19 severity was classified according to the Ministry of Health and Family Welfare (MoHFW) guidelines as mild, moderate, or severe. Statistical analysis was performed using SPSS version 25.0.

Descriptive statistics (mean, standard deviation, and proportions) were used to summarize the data. Bivariate analysis was carried out using the chi-square test and t-test to explore associations between clinical variables and disease severity. Factors with p < 0.05 in univariate analysis were included in a multivariable logistic regression model to identify independent predictors of severe COVID-19. Results were reported as odds ratios (OR) with 95% confidence intervals (CI). Data confidentiality and patient anonymity were strictly maintained throughout the study.

Out of the 132 tuberculosis (TB) patients diagnosed with COVID-19, 45 (34.1%) developed moderate-to-severe disease based on MoHFW severity criteria. The mean age of patients was 52.8 ± 14.6 years, with 60.6% being male. Pulmonary TB was present in 104 (78.8%) patients, with 32% showing fibrocavitary lesions on chest imaging.

Comorbidities included diabetes mellitus in 42.4%, hypertension in 35.6%, and HIV in 5.3%. COVID-19 severity was significantly associated with age >60 years (OR = 3.2; 95% CI: 1.4–7.3), diabetes (OR = 2.7; 95% CI: 1.2–6.0), and cavitary pulmonary TB (OR = 2.9; 95% CI: 1.1–7.5). Patients who had received at least one dose of COVID-19 vaccine had significantly lower odds of severe disease (OR = 0.42; 95% CI: 0.18–0.98).

Table 1: Demographic and Clinical Profile of Study Participants

Table 2: Factors Associated with Moderate-to-Severe COVID-19

Table 3: COVID-19 Severity by TB Type and Comorbidities

Table 4: Vaccination Status and Clinical Outcomes

The present study aimed to evaluate the factors associated with severity of COVID-19 among patients with a current or past history of tuberculosis (TB). The findings highlight that age above 60 years, comorbid diabetes mellitus, and the presence of cavitary pulmonary lesions are significantly associated with moderate-to-severe COVID-19 outcomes. Additionally, COVID-19 vaccination emerged as a strong protective factor against severe disease. These findings have important implications for managing TB patients in the ongoing pandemic and for future outbreak preparedness.

TB and COVID-19, both affecting the respiratory system, represent a syndemic interaction—where co-existence intensifies morbidity and mortality beyond their individual effects. India, which bears the highest global TB burden, has simultaneously faced multiple COVID-19 waves, often overwhelming healthcare systems⁹. Co-infection poses diagnostic challenges due to overlapping symptoms such as fever, cough, and breathlessness, frequently delaying treatment for either or both conditions¹⁰.

Previous studies suggest that TB patients are not only more susceptible to contracting COVID-19 due to compromised immunity but are also more likely to experience poor outcomes [3,4]. Our study supports these findings by showing that nearly one-third of co-infected patients progressed to moderate or severe COVID-19.

Age >60 years significantly increased the odds of severe disease (OR = 3.2), consistent with global trends. Age-related immune senescence and higher prevalence of comorbidities may explain this association [5]. Moreover, diabetes mellitus, found in 42.4% of participants, was an independent predictor of severity (OR = 2.7). Diabetes impairs immune response, increases ACE2 receptor expression (used by SARS-CoV-2 for cell entry), and promotes inflammation, all of which contribute to adverse outcomes^{11, 12}.

These findings align with the meta-analysis by Singh et al., which reported that COVID-19 patients with diabetes had more than two-fold increased risk of severe infection and death¹³.

One of the novel findings of this study is the association between cavitary pulmonary TB and COVID-19 severity (OR = 2.9). Cavitary lesions signify advanced TB and are often accompanied by fibrosis, reduced lung reserve, and impaired gas exchange¹⁴. These pathophysiological changes likely predispose patients to hypoxia and respiratory failure during COVID-19, thereby increasing the need for oxygen therapy and ICU admission.

A multicentric study by Kumar et al. also reported that post-TB lung damage significantly influenced outcomes among COVID-19 patients, reinforcing our observations ¹⁵.

The most encouraging finding of this study is the protective association of COVID-19 vaccination against severe disease (OR = 0.42). This supports national and international data demonstrating reduced severity, hospitalization, and mortality in vaccinated individuals ¹⁶. In TB patients, who are immunologically vulnerable and often marginalized socioeconomically, vaccination serves as a critical layer of protection.

A South African cohort study by Jassat et al. demonstrated that vaccinated TB patients had a 40–60% reduction in severe COVID-19, similar to our findings ¹⁷. These results underline the importance of prioritizing TB patients for vaccination and reinforcing booster doses.

Our results are consistent with earlier reports from WHO and national data that indicate poorer prognosis in TB-COVID co-infection. A review by Tadolini et al. covering over 50 co-infected cases globally found mortality rates approaching 22%, especially among older patients with comorbidities ¹⁸. Similarly, Motta et al. highlighted that active TB status at the time of COVID-19 infection worsened clinical outcomes ¹⁹.

Furthermore, a systematic review by Sarkar et al. concluded that the co-infected group had higher ICU admission and mortality compared to patients with only COVID-19 ²⁰.

Our study emphasizes the urgent need for integrated TB and COVID-19 management protocols. Clinical triage tools must consider prior TB status, presence of cavitary disease, and metabolic comorbidities while assigning risk scores. Screening programs for TB patients should incorporate COVID-19 symptom surveillance and vaccination drives.

Additionally, as India plans to expand its digital health infrastructure under Ayushman Bharat, leveraging TB patient databases (e.g., Nikshay) for COVID-19 risk stratification could offer targeted benefits.

This study has certain limitations. First, the single-center design may restrict generalizability. Second, due to its cross-sectional nature, causality cannot be inferred. Third, laboratory markers such as CRP, D-dimer, and IL-6 were not consistently available across all participants and hence excluded from analysis. Finally, the study relied on clinical records, which may be subject to missing or incomplete data.

Nonetheless, the study offers significant insights by using a mixed dataset of active and past TB patients during a crucial period of the COVID-19 pandemic.

The study demonstrates that TB patients with older age, diabetes mellitus, and cavitary lung lesions are at significantly higher risk for severe COVID-19. Vaccination, however, provides substantial protection. These findings support prioritization strategies and integrated care models for managing co-infected patients.

AUTHORS CONTRIBUTION

Study conception and design: Dr. Ravikumar, Dr. Shivanand, Dr. Mohit Kulkarni

Data collection –Dr. Shivanand, Dr. Mohit Kulkarni

Analysis and Interpretation of results: Dr. Ravikumar, Dr. Pratibha Rao K

Draft and manuscript preparation: Dr Bhuvanendranath H, Dr. Ravikumar, Dr. Pratibha Rao K

FUNDING:

This research did not receive grant from any funding agency.

CONFLICTS OF INTEREST:

Nonea

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