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.