key: cord-1008624-3g3pcg60
authors: Parolina, Liubov; Pshenichnaya, Natalia; Vasilyeva, Irina; Lizinfed, Irina; Urushadze, Natalia; Guseva, Valeriya; Otpushchennikova, Olga; Dyachenko, Olga; Kharitonov, Pavel
title: Clinical characteristics of COVID-19 in TB patients and factors associated with the disease severity
date: 2022-04-26
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2022.04.041
sha: bd3fb104cbb1ff12a9890b14648ef0b95665952e
doc_id: 1008624
cord_uid: 3g3pcg60

Background Data on COVID-19 patients who have pulmonary tuberculosis (TB) is limited. In this study we compare the clinical characteristics of COVID-19/TB and COVID-19 only patients and analyze the links between the severity of COVID-19 disease and clinical characteristics of COVID-19/TB patients. Methods Retrospective, anonymized, cross-sectional study of 111 patients who met inclusion criteria for analysis (75 COVID-19/TB and 36 COVID-19 patients) was conducted. Results Patients in both groups (COVID-19/TB vs COVID-19) mainly suffered from fever (72.0% vs 100%, p < 0.001), fatigue (76.0% vs 94.4%, p = 0.018), chest pain (72.0% vs 36.1%, p < 0.001), followed by cough (60.0% vs 97.2%, p < 0.001) and dyspnea (44.0% vs 63.9%, p = 0.05). In group COVID-19/TB the most frequently reported comorbidities were chronic liver disease (17 [22.7%]), cardiovascular diseases (25 [33.3%]), and diseases of the nervous system (13 [17.3%]). Female gender, fever, dyspnea, pulmonary bilateral TB lesion, and 3 or more comorbidities have a statistic significant positive effect on severity of the disease among COVID-19/TB patients. Conclusion It is important to perform rapid molecular testing and CT to correctly distinguish COVID-19 and TB due to similar clinical characteristics of both diseases. Bilateral pulmonary TB lesion and comorbidity should be considered as risk factors for severe COVID-19.

Crohn's disease; 1 -skin cancer ; 1 -invasive aspergillosis; 1 -candidiasis among patients with 105 COVID-19 / TB and 2 patients with lung cancer among patients with COVID-19), chronic use of 106 corticosteroids (2 patients with bronchial asthma, 1 -with COPD among patients with COVID-107 19 / TB and 1 among patients with COVID-19), lack of a completed course of treatment for 108 COVID-19 in the institution (3 patients among patients with COVID-19/TB and 1 among  109 patients with COVID-19 were transferred to another hospital due to the bed load). 110

Inclusion criteria were: gender, age, hospital admission, one or more comorbidities, data on the 111 date of onset of the disease, laboratory tests at admission and discharge: erythrocytes, 112 hemoglobin, leukocytes, neutrophils, lymphocytes, AST, ALT, creatinine, urea, C -reactive 113 protein, fibrinogen, CT study based on a visual scale for assessing the extent of the lesion (CT0 = 114 no lesion, CT1 < 25%, CT2 = 25-50%, CT3 = 50-75%, CT 4 > 75% involvement respectively. This finding can be possibly linked to the age difference between the groups. As it 178 was observed from the previous data of COVID-19 patients, comorbidities increase the chances 179 of infection, and also the elderly, especially those in long-term care facilities, as well as people 180 of any age with serious underlying medical conditions are at a greater risk of getting COVID-19 181 (CDC, 2020). Perhaps, the older age of patients in the COVID-19 group explains the greater 182 number of comorbidities and death. 183

Signs and symptoms of the TB/COVID-19 and COVID-19 patients are summarized in Table 2 . 184

Confirmed and reported cases of COVID-19 have a wide range of symptoms, from mild 185 complaints, such as fever and cough, to more critical cases associated with difficulty in breathing 186 (CDC, 2020). Some of the most common symptoms include cough, fever, chills, shortness of 187 breath (SOB), muscle aches, sore throat, unexplained loss of taste or smell, diarrhea, and 188 headache (Maragakis, 2020 Characteristics of pulmonary tuberculosis in individuals who fell ill with COVID-19 are given in 196 Laboratory parameters also differed between the two groups (Table 4 ). Patients with TB had 214 higher platelet counts (ME 276 vs 185, p = 0.006), while patients without TB had higher levels 215 of abnormalities in urea (p < 0.001), creatinine (p < 0.001), C-reactive protein (p < 0.001), and 216 ALT (p < 0.001). 217

We analyzed the need for oxygen ( The features of the severity of patients in both groups were analyzed (Table 5) In severe cases of COVID-19, oxygen therapy methods were used: nasal cannula -2.6% in the 241 COVID-19/TB group vs 8.3% in the COVID-19 group; oxygen mask -28.9% vs 5.6%, 242 mechanical ventilation and ECMO did not occur in the COVID-19/TB group while being used in 243 the COVID-19 group (33.3% and 8.3%, respectively); oxygen therapy was performed in 31.6% 244 in the COVID-19/TB group vs 53.6% in the COVID-19 group (p < 0.001). 245

The univariate analysis of the COVID-19/TB data revealed the following statistically significant 246 factors influencing the severity of the disease ( Age was selected , as many studies had shown its effect on COVID-19 outcomes. 258

The final multivariable logistic regression model included female gender, fever, dyspnea, 259 disseminated TB, 3 or more comorbidities, and smoking status as independent contributors to 260 severity. The predictive model was statistically significant (p<0.001) based on the F-test. Identification of the relationship between tuberculosis and the severity and mortality from 286 COVID-19 is crucial for the development of measures for the prevention and timely diagnosis of 287 COVID-19 in patients with tuberculosis. Our study showed that the risk of developing severe 288 COVID-19 in TB patients was associated with factors such as female gender, smoking, fever, 289 dyspnea, disseminated TB, having 3 or more comorbidities, and patient age. When the structure 290 of the lung tissue is affected by tuberculosis, resistance to additional infectious agents, such as 291 viruses, decreases. In addition, it is known that tuberculosis is a secondary immunodeficiency. 292

All this can be the basis for a more severe course of the newly emerged disease. The data 293 obtained in the study suggest that strategies should be developed to reduce the risk of severe 294 The third result is that patients with TB and comorbidities appear to be at increased risk of 311 developing COVID-19 and having an adverse disease course. The significance of comorbidity 312 for mortality and the development of a serious condition in TB patients with the addition of 313 COVID-19 is widely discussed in the literature. In particular, it has been shown that old age, 314 diabetes, and respiratory diseases are the main factors increasing the mortality in patients with 315 COVID-19/TB coinfection (Stochino et al., 2020) . In the global study by the TB/COVID-19 316

Global Study Group (2021), the univariate analysis of mortality showed the statistical 317 significance having more than one comorbidity, type 2 diabetes mellitus, cardiovascular disease, 318 chronic respiratory disease and chronic renal disease. In our study, 69.3% of patients had at least 319 one additional disease. At the same time, in COVID-19/TB patients, as well as in patients 320 without TB, the main comorbidity was cardiovascular disease. Assessing the significance of 321 other comorbidities for the development of severe COVID-19 requires caution and a larger 322 observation group. 323

Our study had some limitations. First, our analysis included all cases of COVID-19/TB from 324 only TB hospitals in two regions of Russia, including cases of COVID-19. In other types of 325 hospitals or regions of the country, different results may be obtained. Second, although the 326 control group of patients without TB was recruited randomly, its size implies that the results 327 should be interpreted with caution. As more data becomes available, it will be important to 328 identify factors that influence mortality and complications in TB patients diagnosed with 329 COVID-19. Third, in the retrospective design of the study, analysis of symptoms was limited due 330 to the fact, that not all symptoms could be indicated in the paper history of the disease. In 331 addition, there was a significant age difference between the two groups. 332

In this study, we compared demographic, clinical, CT, and laboratory parameters of COVID- influencing mortality and severity in the COVID-19/TB cohort, to better understand the 349 relationship between TB and COVID-19. 350

The authors declare that they have no known competing financial interests or personal 352 relationships that could have appeared to influence the work reported in this paper. 353 

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