DISCUSSION
Tuberculosis is most common infectious disease in developing countries. Immune system dysfunction, treatment with immunosuppressive drugs, chronic diseases such as diabetes, and chronic renal failure are known to increase susceptibility to tuberculosis. These risk factors are not mutually exclusive, and their coexistence can worsen in the course of the disease. However, because the immune dysfunction they cause varies, the correlation between comorbidities and disease susceptibility is complicated [17].
Coronaviruses have been known to cause occasional pandemics. The studies in the literature that examined correlations between SARS, MERS, H1N1, and reactivation of tuberculosis during these periods showed that cellular immunity associated with this infection was temporarily suppressed and reactivation of latent tuberculosis or a new TB infection occurred [11-15]. There is no such information on SARS-Cov-2 yet. We have done a retrospective study in our clinic and found that the number of patients diagnosed with TB has increased. Examination of the number of children diagnosed with TB in the pediatric pulmonology and pediatric infectious disease clinics at our hospital by year between 2017 and 2021 shows that three pediatric patients were diagnosed with tuberculosis and received treatment in 2017, four in 2018, eight in 2019, and 23 in 2020- April 2021. When we scanned the number of pediatric patients diagnosed with tuberculosis in Konya by years, we found that 21 children were diagnosed with tuberculosis in 2017, 21 children in 2018, 27 children in 2019, 33 children in 2020, and 13 children until April 2021. Despite the decrease in the child population in Konya, there was a remarkable increase in the number of pediatric tuberculosis cases (Table 3) [18,19].
We checked all our patients with TB by Covid-19 antibody (IgG+IgM) or PCR. Only eigth of the patients was positive. Of the eight patients with positive PCR or antibody, two (%25) had cavitary lesions, three (%37,5) had pleural effusion, and one (%12,5) had pleural and pericardial effusion. Remaining 15 patients with negative PCR or antibody have mild fenotipe including two (%13,3) had pleural effusion and three (%20) had cavitary lesion.
We could not test the presence of autoantibodies against interferon type 1 in any of them. Both innate and acquired immunity play important roles in the immune response against Mycobacterium tuberculosis. T lymphocytes, dendritic cells, Toll-like receptors, IFN-gamma, TNF-alpha, and IL-12 play important role immune response to Mycobacteria [20]. There is an increased susceptibility to tuberculosis in primary immunodeficiencies with defects in these cells and pathways.
The primary immunodeficiencies known to predispose to tuberculosis are T-cell deficiencies, chronic granulomatous disease and Mendelian susceptibility to mycobacterial diseases. The unexpectedly severe clinical findings of tuberculosis in our patients suggested primary immunodeficiency, while the immunological evaluation revealed a CVID diagnosis in one patient (patient #1) and mild immunological defects in the other patients that did not meet ESID criteria for a primary immunodeficiency. Lymphopenia was present in only one of our patients, and improvement at the follow-up suggested a temporary situation secondary to the infection.
Physical activity can affect NK cells; their number can change even throughout the day. We do not yet know the importance of the low NK cell count detected in four of our patients during the disease. but turn to normal levels at follow up (except in the # 1 patient). Consequently, the activation of TB seems to be due to the structure of the COVID-19 virus and its pathological characteristics.
There are few studies on COVID-19 and tuberculosis. Jain et al. showed that the risk of SARS-CoV-2 infection is increased in patients with latent tuberculosis and there is a susceptibility to severe COVID-19 pneumonia. Additionally, it is indicated that the COVID-19 pandemic leads to a decrease in admission to health facilities and to a delay in diagnosing tuberculosis [21]. Can Sarinoğlu et al.’ simultaneously requested COVID-19 and tuberculosis tests in 30 patients since March 2020 and found that 26.6% of 30 patients was immunosuppressed (malignancy, hematopoietic stem cell transplantation, positive HIV test). Two out of 30 patients had both COVID-19 PCR and tuberculosis test positive. One of these two patients had diabetes, hypertension, chronic obstructive lung disease, and chronic renal failure. The other patient had no underlying disease [22]. Our study also supports that a COVID-19 infection changes the individual’s immune system and causes tuberculosis infection.
In previous studies and case reports, it has been shown that covid-19 causes TB reactivation and newly diagnosed TB, but all the patients in this study were adult except one patient diagnosed with congenital TB. There have been no studies on children since the beginning of the pandemic period. Our patients had comorbidities such as immunodeficiency, however, none of our patients died [23-27].
The remarkable increase in the number of tuberculosis activation in the recent year suggests the role of COVID-19 infection. The clinical findings of the respiratory diseases that are secondary to infections progress similar to TB. Therefore, the diagnosis of TB may easily be missed. Since TB is a slowly progressing infection, there may be delays in diagnosis. It has been observed that latent TB infection can be activated even if the covid-19 infection is mild in children. Covid-19 infection is not as innocent as it seems for children either.
The experiences of our clinic and our country support the impression that the increase in recent year is due to increased TB cases associated with the pandemic. This should be kept in mind in case of cavity lesions and pleurisy. Moreover, the presence of a possible underlying immunodeficiency should be investigated in the case of complicated respiratory infections. The pathologic structure of the virus may be responsible of the increase, although the mechanism is not fully understood. Further research should be done on this topic.