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Systemic immune profile in hospitalized patients with tuberculosis and Covid-19

Ridolfi, F.; Guimaraes, S. S.; Araujo-Pereira, M.; Bemfica, N. S.; De Oliveira, Q. M.; Xavier, M. S.; Roma, E. H.; SantAnna, F. M.; De Andrade, A. M.; Figueiredo, M. C.; Sterling, T. R.; Gordhan, B. G.; Kana, B. D.; Andrade, B. B.; Gomes-Silva, A.; Rolla, V. C.; Associative BRICS Research in Covid-19 and TB (ABRICOT) Research Group,

2025-06-06 infectious diseases
10.1101/2025.06.05.25329097 medRxiv
Show abstract

Tuberculosis (TB) and Covid-19 are respiratory diseases and their interaction could increase lung impairment and mortality. However, few cases of concomitant TB and Covid-19 have been reported, and biomarkers are still poorly described. This cross-sectional study included in-hospital adult (>18 years old) participants, with pulmonary TB (TB group), with Covid-19 (Covid-19 group), and with TB/Covid-19 co-infection (TB/Covid-19 group). We compared baseline demographic, clinical, laboratory, and inflammatory profile features across the groups. Inflammatory soluble factors were assessed via MILLIPLEX MAP Human Cytokine/Chemokine Premixed 29 Plex and Luminex Intelliflex xMAP. We used the Chi-square test for categorical variables, and the Mann-Whitney U or the Kruskal-Wallis tests for continuous variables. A random forest model evaluated the variables importance in discriminating the groups, assessed by the Mean Decrease Gini Index ([&ge;]1.5). Among the 76 participants included, 33 (43%) with pulmonary TB, 13 (17%) with TB/Covid-19, and 30 (39%) with Covid-19. Male participants were predominant in all groups. The TB and TB/Covid-19 groups had lower median body mass index (BMI) (18.4 [interquartile range (IQR) 16-22] and 19.4 [IQR 16.1-20.3], respectively) compared to the Covid-19 group (25.5 [IQR 22.0-31.7]; p<0.001). People living with HIV/AIDS were more frequent in TB (63%) and TB/Covid-19 (61%) groups than in Covid-19 (20%; p=0.001). Participants in the Covid-19 group had significantly more comorbidities (63%) than those in the TB (9%) and TB/Covid-19 (15%) groups (p<0.001). Comorbidities included HIV seropositivity, diabetes mellitus, chronic obstructive pulmonary disease, and hypertension. Cavitation on chest CT scan was observed in 45% of TB and 61% of TB/Covid-19 participants, but none in the Covid-19 group (p<0.001). Covid-19 participants exhibited lower platelet counts (p=0.004), higher creatinine (p<0.001), and higher urea levels (p=0.004). Random forest analysis identified urea, hemoglobin, hematocrit, and platelets as the best tests to discriminate TB/Covid-19 from the other groups (Area Under the Curve>0.70 in both cases). MCP-1 was significantly elevated in Covid-19 compared to TB and TB/Covid-19 (p=0.014). No inflammatory signature differentiated TB/Covid-19 from single infections. TB and Covid-19 are clinically similar and TB/Covid-19 co-infection is uncommon. Overall, the plasma inflammatory response could not differentiate Covid-19, TB and TB/Covid-19. Comorbidities, radiologic findings, and laboratory tests, such as urea, hemoglobin, hematocrit and platelets, may be useful tools to distinguish TB and TB/Covid-19, as well as Covid-19 and TB/Covid-19.

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