Characteristics and outcomes of in-hospital patients with Covid-19 and history of tuberculosis: A matched Case-Control from the Brazilian Covid-19 Registry

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Consequently, low and middle-income countries suffer from other endemic diseases, such as tuberculosis. This study was designed to compare Covid-19 manifestations and outcomes between patients with previously treated tuberculosis and controls without this condition. Methods: We performed a matched case-control study drawn from the Brazilian Covid-19 Registry data, including in-hospital patients aged 18 and over with laboratory-confirmed Covid-19 from March 1, 2020 to March 31, 2022. Cases were patients with a past history of tuberculosis. Controls were Covid-19 patients without tuberculosis history. Patients were matched by hospital, sex, presence of HIV and number of comorbidities, with a 1:4 ratio. Results: From 13,636 patients with laboratory-confirmed diagnosis of Covid-19 enrolled in this study, 80 had a history of tuberculosis. Statistical differences in history of chronic pulmonary obstructive disease (15% vs 3.2%), psychiatric disease (10% vs 3.5%,), chronic kidney disease (11.2% vs 2.8%) and solid-organ transplantation; (5% vs 0.9%, p<0.05 for all) were higher in patients with a past history of tuberculosis. Prior use of inhalatory medications (5% vs 0.6%,), oral corticoids (8.8% vs 1.9%), immunosuppressants (8.8% vs 1.9%,) and the use of illicit drugs were more common in the case group (6.2% vs 0.3% p<0.05for all). There were no significant differences in in-hospital mortality, mechanical ventilation, need for dialysis and ICU admission. Conclusions: Patients with a history of tuberculosis infection presented a higher frequency of use of illicit drugs, chronic pulmonary obstructive disease, psychiatric disease, chronic kidney disease, solid-organ transplantation, prior use of inhalatory medications, oral corticoids, and immunosuppressants. The outcomes were similar between cases and controls. Covid-19 Tuberculosis hospitalization infectious diseases Figures Figure 1 Background To reduce Covid-19 transmission and mortality rates, governments worldwide have strengthened the focus and expanded Covid-19 treatment in healthcare services [1,2]. Over the last two years, vaccination has advanced all over the world and, with that, the Covid-19 death toll has diminished [2]. However, even with a significant reduction in mortality rates, Covid-19 incidence is still substantial, with thousands of new daily cases in low and middle-income countries [3]. Even though Covid-19 control has shown improvements, it is likely that the virus will continue to cause infections [4]. Most countries in South America, for example, are still suffering from the disease itself and its consequences, especially considering new covariants that led to new infection waves [5]. This disease has required extreme attention from governments and health professionals, and the focus on Covid-19 has caused a negative impact on the control and prevention of other infectious diseases, such as tuberculosis (TB) [6]. As TB is endemic to those countries, the coinfection scenario becomes more likely. [6]. Tuberculosis can lead to severe lung disability and airflow impairment. Host inflammatory response to Mycobacterium tuberculosis infection can cause pulmonary lesions. Furthermore, immune cells, cytokines, and chemokines can lead to granuloma formation and tissue necrosis, with subsequent cavitation and fibrosis [7]. In countries with higher TB rates, such as Brazil, SARS-CoV-2 infection in patients with a history of TB are a concern for health authorities and clinicians. Studies point out that patients with a previous history of TB have a higher incidence of lung impairment [7] and have up to 2.5 fold chance of having chronic obstructive pulmonary disease (COPD) [8]. Furthermore, COPD leads to worse outcomes in Covid-19 [9] and a higher hospitalization rate.[10]. Even though knowledge about Covid-19 and possible coinfections has significantly grown, data regarding SARS-CoV 2 and its role in patients with a previous history of TB is still lacking, especially regarding patients that required hospitalization [11,12]. This information may help clinicians identify possible patients at risk for Covid-19 severity and death. Therefore, this study aimed to compare Covid-19 manifestations and outcomes between patients with a previous history ofI TB and controls without this condition. Methods Study design and subjects This study is a part of the multicentric cohort “Brazilian Covid-19 Registry”, which included data from Covid-19 patients admitted in 39 Brazilian hospitals [13]. Consecutive patients aged 18 and over with Covid-19 admitted to the participating hospitals from March 1, 2020 to March 31, 2022 were included in the study. All patients presented a laboratory confirmation of Covid-19 according to the World Health Organization guidance [14]. This manuscript adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Guideline [15]. For this study, a matched analysis was conducted comparing patients with a history of TB treatment with controls without any history of TB. Active and previous TB diagnoses and treatment were retrieved by medical records. Records that state an active diagnosis TB during the hospital stay or if it did not explicitly state a history of TB were excluded from the analysis. This study was approved by the Brazilian National Commission for Research Ethics (CAAE 30350820.5.1001.0008) and had internal approval of ethics boards from each hospital. Individual informed consent was waived due to the severity of the situation, and we sought to de-identify the data collected. We state that this study protocol conforms to the ethical guidelines of the Declaration of Helsinki. Data collection The Brazilian Covid-19 Registry collected demographic, clinical, laboratory and outcomes data from medical records by trained health professionals, and medical and nursing undergraduate students using the Research Electronic Data Capture (REDCap) tools [16,17] hosted by the Telehealth Center, University Hospital, Universidade Federal de Minas Gerais [18]. Statistical analysis For the present analysis, TB cases were matched to controls by age, sex, number of comorbidities, presence of HIV and hospital, with a 1:4 ratio. Selection of cases and controls are shown in Figure 1. Categorical data was presented as absolute numbers and proportions, and continuous variables were expressed as medians and interquartile ranges. Association between cases and controls were measured by the Chi-square and Fisher Exact tests to compare the distribution of categorical variables, and the Wilcoxon-Mann–Whitney test for continuous variables. Results were considered statistically significant if the p-value was <0.05. All statistical analysis was performed with R software (version 4.0.2). Outcomes Primary outcomes included: (i) invasive mechanical ventilation (IMV) requirement, (ii) need for dialysis and (iii) in-hospital mortality. Intensive Care Unit admission, length of in-hospital stay and time spent in the ICU were analyzed as secondary outcomes. Patient and public involvement This was an urgent public health research study in response to a Public Health Emergency of International Concern. Patients or the public were not involved in the design, conduct, interpretation or presentation of the results of this research. Results From 13,636 patients with laboratory-confirmed diagnosis of Covid-19, 80 presented a previous diagnosis of tuberculosis, an incidence of 0.006 (IC: 0.004 to 0.007) among the study’s population. When comparing clinical characteristics of those patients to matched controls, it was observed that chronic pulmonary obstructive disease (COPD) (15% vs 3.2%, p<0.001), psychiatric disease (10% vs 3.5%, p=0.034) and history of solid-organ transplantation (5% vs 0.9%, p=0.033) were more frequent in study cases. Also, regular home use of inhalatory medications (5% vs 0.6%, p=0.017), oral corticoids (8.8% vs 1.9%, p=0.006) and immunosuppressants (8.8% vs 1.9%, p=0.006) were more common in this group, as well as a higher frequency of illicit drug use when compared to controls(6.2% vs 0.3% p=0.002). [Table 1] Table 1 - Comparison between patients with treated TB and controls Treated TB N = 80 1 Controls N = 316 1 p-value 2 Women 49 (61.3%) 189 (59.8%) 0.915 Age (years) 58.5 (46.8, 69.0) 59.0 (45.8, 69.0) 0.999 Comorbidities Hypertension 28 (35.0%) 152 (48.1%) 0.048 Diabetes mellitus 16 (20.0%) 76 (24.1%) 0.536 COPD 12 (15.0%) 10 (3.2%) <0.001 Chronic kidney disease 9 (11.2%) 9 (2.8%) 0.004 Psychiatric disease 8 (10.0%) 11 (3.5%) 0.034 Obesity 6 (7.5%) 47 (14.9%) 0.122 Heart failure 6 (7.5%) 11 (3.5%) 0.125 Asthma 5 (6.2%) 19 (6.0%) 0.999 Transplant 4 (5.0%) 3 (0.9%) 0.033 Stroke 4 (5.0%) 10 (3.2%) 0.495 HIV infection 4 (5.0%) 10 (3.2%) 0.495 Coronary artery disease 3 (3.8%) 15 (4.7%) 0.999 Rheumatological disease 3 (3.8%) 4 (1.3%) 0.150 Cancer 3 (3.8%) 10 (3.2%) 0.731 Atrial fibrillation/flutter 2 (2.5%) 7 (2.2%) 0.999 Medications in use at Home Oral anticoagulant 1 (1.2%) 12 (3.8%) 0.480 Inhalatory corticoid 4 (5.0%) 2 (0.6%) 0.017 Oral corticoid 7 (8.8%) 6 (1.9%) 0.006 Immunosuppressants 7 (8.8%) 6 (1.9%) 0.006 Toxic habits Alcoholism 9 (11.2%) 17 (5.4%) 0.101 Illicit drugs 5 (6.2%) 1 (0.3%) 0.002 Current smoking 9 (11.2%) 19 (6.0%) 0.165 1 n (%); Median (IQR) 2 Pearson's Chi-squared test; Wilcoxon rank sum test; Fisher's exact test. COPD: chronic obstructive pulmonary disease; HIV When comparing the prevalence of symptoms presented at hospital admission, Covid-19 patients with and without a past diagnosis of TB had similar results, except for adynamia which was most frequent (35% vs 22.2%, p=0.025) and myalgia the least common (21.2% vs 33.9%, p=0.042) in cases [Table S1]. There was no difference in use of antibiotics (42.5% vs 44.4%, p=0.857), anticoagulants (85% vs 88.8%, p=0.456), antifungals (6.2% vs 3.5%, p=0.337) and corticoids (77.5% vs 81.8%, p=0.477) medications during patient stay [Table S1]. Also, when comparing laboratory findings, values of C-reactive protein (CRP) at hospital admission were lower in patients with a previous history of TB (58 vs 90, p=0.005) than in controls. [Table S2] No statistically significant differences were observed in regard to patient outcomes between the groups, such as ICU admission (41.2% vs 43.4%, p=0.831), mechanical ventilation requirement (28.7% vs 36.7%, p=0.483) and death (23.8% vs 24.8%, p=0.966). [Table 2] Table 2 - Outcomes comparison between patients with treated TB and controls Treated TB N = 80 1 Controls N = 316 1 p-value 2 In-hospital stay (days) 13.0 (6.0, 22.2) 9.0 (5.0, 19.0) 0.064 ICU admission 33 (41.2%) 137 (43.4%) 0.831 Time spent in the ICU (days) 12.0 (5.0, 17.0) 10.0 (5.0, 18.0) 0.853 Mechanical ventilation requirement 23 (28.7%) 106 (33.7%) 0.483 Time with mechanical ventilation 9.0 (6.0, 14.0) 13.0 (6.0, 20.2) 0.107 Dialysis 10 (12.5%) 39 (12.4%) 0.999 Septic shock 8 (10.0%) 57 (18.0%) 0.118 Acute heart failure 4 (5.0%) 6 (1.9%) 0.122 In-hospital death 19 (23.8%) 78 (24.8%) 0.966 1 n (%); Median (IQR) 2 Pearson's Chi-squared test; Wilcoxon rank sum test; Fisher's exact test. ICU: Intensive Care Unit Discussion Among all patients admitted to this multicenter cohort that analyzed data from 37 Brazilian hospitals, the frequency of tuberculosis was small, with a ratio of 6:1000 individuals. Nevertheless, our records allowed the comparison of individuals with a previous history of TB and its respective matched control group. In our data we have found significant differences between both groups, since the presence of COPD, psychiatric diseases, hypertension, previous solid organ transplant and the use of illicit drugs were higher in the TB group. These are known risk factors for tuberculosis. It was also possible to observe a substantial difference between the use of medications such as immunosuppressants, oral and inhalatory corticoids, which were also higher in the case group. We did not find significant differences in the outcomes such as in-hospital mortality, IMV requirement, need for dialysis and ICU admission. One of these differences was a higher frequency of COPD in patients with previous TB. The organism’s inflammatory response against Mycobacterium tuberculosis leads to cytokine and chemokine releases, which can cause lung damage, resulting in COPD [7]. This can be corroborated by the findings of the study, since patients with a history of tuberculosis had a higher incidence of COPD when compared to the control group (15% vs 3.2%, p <0.001). However, even with the higher rate of COPD patients in our case group, the frequency of dyspnea (58.8% vs 65.2%, p=0.347) and cough (62.5% vs 53.8%, p=0.203) were similarly reported by both groups in the acute phase of the disease. The awareness of the differences in study patients regarding the presence of comorbidities, such as COPD, and their role in the prognosis of Covid-19 in these subjects may be fundamental to improve patient care. Patients with COPD and Covid-19 have a higher risk of developing severe pneumonia, and the pathophysiological mechanism explaining this may be related to the greater availability of angiotensin-converting enzyme 2 (ACE2) receptors in the small airways [19]. SARS-CoV 2 has an invasion mechanism into the body cells by the recognition of the virus Spike protein predominantly by ACE2 receptors [20]. Another mechanism that explains the greater propensity to develop severe cases of pneumonia is the tissue damage caused by the disease itself, which results in poor underlying lung reserves [20]. However, ACE2 receptors appear to be more abundant in older male individuals, [21] which in itself may be a risk factor for developing severe forms of Covid-19 [22]. This study did not show tough a difference in outcomes of case and control groups, as far as acute phase is concerned. We have no information about the severity of COPD, which could have been relevant. It should be noted that patients in the case group also had higher rates of solid organ transplants (5% vs 0.9%, p =0.033). Tuberculosis is one of the most frequent complications of solid organ transplantation [23,24], mainly because the prevalence of latent TB is high Brasil [25]. The reports of hypertension were smaller in patients with history of TB when compared with controls (35% vs 48%, p=0.048). A metanalysis points out that there is no correlation between hypertension in TB and non-TB patients, studies shown a higher and lower frequency of TB [26]. Hypertension is risk factor for mortality in TB patients [27], however it was not found as an independent risk factor for Covid mortality [28]. In this study we found no difference in admission systolic blood pressure levels between groups (128 vs 123 mm/Hg, p =0.823). The rate of psychiatric diseases at baseline was also higher in patients with history of TB when compared to control (10% vs 3.5%, p=0.034). Despite the fact that the role of psychiatric diseases as a risk factor for developing TB is still under debate, schizophrenia and depression have shown to be possible risk factors for its development [29]. Both diseases share a strong relationship with social determinants, such as homelessness and poverty [29]. Unfortunately, our data did not retrieve social and economic variables to try to explore these issues in Covid-19 patients and those with a history of TB, but the association between psychiatric diseases and TB can reinforce that theory. Illicit drug use was also higher at baseline in patients with a history of TB. Illicit drugs are a risk for TB infection [29], the use of illicit drugs facilitate close physical contact and also is higher in the homeless population, a group also at risk for TB [30]. The use of powder or crack cocaine can lead to pulmonary edema, pneumonia, alveolar hemorrhage and other lung damage. This damage, associated with cocaine effect reducing alveolar macrophage response and proinflammatory responses facilitate the infection from M . tuberculosis [31]. The relation of illicit drugs and Covid-19 was pointed out by Wang et al (2021), substance abuse was related to an increase in hospitalization and death rates in Covid-19 patients. However, there was no difference between these outcomes in our groups [32]. Besides psychiatric diseases and illicit drug use, chronic kidney disease (CKD) also presented a higher frequency in our case group at baseline, compared with controls (11.2% vs 2.8% p=0.004). Chronic kidney disease leads to malnutrition, oxidative stress, and inflammation, which impairs cell-mediated immunity. This state of immunosuppression can result in the reactivation of latent tuberculosis infections and even new TB infections. Consequently, TB incidence is higher in CKD patients than in non-CKD [33]. Furthermore, CKD is found as a risk factor for Covid hospitalization, severity, and mortality [34]. Data published by the Brazilian Covid-19 Registry shows that elevated blood urea nitrogen at admission is a risk for death in COVID patients [35] and higher creatinine levels at admission lead to greater chances for renal replacement therapy [36]. This evidence reinforces that kidney impairment is a risk factor for COVID severity, however little is known of the physiopathology of CKD and COVID severity [34]. Since CKD is a risk factor for TB infection, we advise that the population at risk for CKD should have priority in vaccination and boosts shots against COVID and clinicians have to better screen these patients for the presence or a history of TB and other infections [37]. Patients with a history of TB had significantly higher home use of inhaled corticosteroids and oral corticosteroids than the control group at baseline. The higher rate inhaled and oral corticosteroids use may explain better outcomes than those expected, since the use of specific corticosteroids can lead to better outcomes such as lower rate of need for ventilatory support [38,39]. In-hospital use of corticosteroids did not differ between groups (77.5 vs 81.8, p=0.477). However, further studies are necessary to support that home use of corticosteroids can contribute to better outcomes in patients with previous diagnosis of TB. For this study, a few limitations were observed. First, all of our patients were retrieved through medical data, which resulted in a low number of patients with a history of TB. Second, this study was retrospective, this can lead to report bias from the medical records. In order to lessen the burden of this potential bias, data collected was audited for possible errors. Conclusion In this study, patients with a previous TB infection presented a higher frequency of illicit CKD, COPD, psychiatric disease, solid organ transplants and drug abuse when compared to controls. Furthermore, cases presented a higher home use of oral and inhalatory corticosteroids and immunosuppressants than controls. Covid-19 clinical presentation was similar between groups, except for adynamia, which was more prevalent in patients with treated TB, and myalgia, which was more frequently reported by controls. No statistically significant differences were observed between the groups in regard to ICU admission, hospital length of stay, time spent in the ICU, dialysis, need for mechanical ventilation and in-hospital death. Declarations Funding: Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG APQ-00208-20) and Instituto de Avaliação de Tecnologia em Saúde IATS/CNPQ. Conflicts of interest/competing interests: The authors declare no conflict of interest. Ethics approval and consent to participate: This study was approved by the Brazilian National Commission for Research Ethics (CAAE 30350820.5.1001.0008) and had internal approval of ethics boards from each hospital. Individual informed consent was waived due to the severity of the situation, and we de-identify the data collected. Availability of data and material: Data can be available upon request. Consent for publication: All authors approved the manuscript before submission. Authors' contributions: “Conceptualization, RLRC. and RC.; methodology, RLRC; DP; VC, RC and MM; software, MM; validation, MM; formal analysis, RLRC and MM.; investigation FC; GN; KR; LM; MC; MJ; MC; NB; NO and RA; resources, RLRC and MM; data curation, FC; GN; KR; LM; MC; MJ; MC; NB; NO and RA; writing—original draft preparation, RLRC; DP; VC; and RC.; writ-ing—review and editing, RLRC; DP; VC; VA; RC and MM; visualization, RLRC; supervision, RLRC and RC.; project administration, MM; funding acquisition, RLRC and MM. Acknowledgements: We would like to thank all the research teams from the hospitals that helped us in the Brazilian Covid-19 Registry. 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Tuberculosis and Chronic Kidney Disease: An Emerging Global Syndemic. Kidney Int. 2016 , 90 , 34–40. Jdiaa, S.S.; Mansour, R.; El Alayli, A.; Gautam, A.; Thomas, P.; Mustafa, R.A. COVID-19 and Chronic Kidney Disease: An Updated Overview of Reviews. J. Nephrol. 2022 , 35 , 69–85. Marcolino, M.S.; Pires, M.C.; Ramos, L.E.F.; Silva, R.T.; Oliveira, L.M.; Carvalho, R.L.R.; Mourato, R.L.S.; Sánchez-Montalvá, A.; Raventós, B.; Anschau, F.; et al. ABC2-SPH Risk Score for in-Hospital Mortality in COVID-19 Patients: Development, External Validation and Comparison with Other Available Scores. Int. J. Infect. Dis. 2021 , 110 , 281–308. Figueiredo, F. de A.; Ramos, L.E.F.; Silva, R.T.; Ponce, D.; de Carvalho, R.L.R.; Schwarzbold, A.V.; Maurílio, A. de O.; Scotton, A.L.B.A.; Garbini, A.F.; Farace, B.L.; et al. Development and Validation of the MMCD Score to Predict Kidney Replacement Therapy in COVID-19 Patients. BMC Med. 2022 , 20 , 324. Rovin, B.H.; Adler, S.G.; Barratt, J.; Bridoux, F.; Burdge, K.A.; Chan, T.M.; Cook, H.T.; Fervenza, F.C.; Gibson, K.L.; Glassock, R.J.; et al. Executive Summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. Kidney Int. 2021 , 100 , 753–779. Yu, L.-M.; Bafadhel, M.; Dorward, J.; Hayward, G.; Saville, B.R.; Gbinigie, O.; Van Hecke, O.; Ogburn, E.; Evans, P.H.; Thomas, N.P.B.; et al. Inhaled Budesonide for COVID-19 in People at High Risk of Complications in the Community in the UK (PRINCIPLE): A Randomised, Controlled, Open-Label, Adaptive Platform Trial. Lancet 2021 , 398 , 843–855. RECOVERY Collaborative Group; Horby, P.; Lim, W.S.; Emberson, J.R.; Mafham, M.; Bell, J.L.; Linsell, L.; Staplin, N.; Brightling, C.; Ustianowski, A.; et al. Dexamethasone in Hospitalized Patients with Covid-19. N. Engl. J. Med. 2021 , 384 , 693–704. Additional Declarations No competing interests reported. Supplementary Files suplementarymaterial.docx Cite Share Download PDF Status: Published Journal Publication published 19 Dec, 2024 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 14 Oct, 2024 Reviews received at journal 09 Oct, 2024 Reviewers agreed at journal 09 Sep, 2024 Reviews received at journal 17 Aug, 2024 Reviewers agreed at journal 14 Aug, 2024 Reviews received at journal 31 May, 2024 Reviewers agreed at journal 31 May, 2024 Reviewers invited by journal 31 May, 2024 Editor invited by journal 14 May, 2024 Editor assigned by journal 10 May, 2024 Submission checks completed at journal 08 May, 2024 First submitted to journal 03 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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18:53:41","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4365616/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4365616/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-024-10305-3","type":"published","date":"2024-12-19T15:56:53+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":56809125,"identity":"97ded0ba-f5ae-4649-abc6-b0e8a2e372dc","added_by":"auto","created_at":"2024-05-20 18:47:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":101394,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of Covid-19 Patients included in the study. TB: tuberculosis\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4365616/v1/ead9a96d8405447d4ccf3a20.png"},{"id":72201442,"identity":"f254eaa8-7aa9-46bb-ac98-7e1027c4b24b","added_by":"auto","created_at":"2024-12-23 16:05:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":727759,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4365616/v1/50d12410-3e55-480b-9e62-a767e81c4e8a.pdf"},{"id":56809124,"identity":"fc2a5d4f-3a53-44e3-adff-2626f8812f34","added_by":"auto","created_at":"2024-05-20 18:47:01","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":38946,"visible":true,"origin":"","legend":"","description":"","filename":"suplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-4365616/v1/026382e3ddd4d8a0de4cb8b7.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Characteristics and outcomes of in-hospital patients with Covid-19 and history of tuberculosis: A matched Case-Control from the Brazilian Covid-19 Registry","fulltext":[{"header":"Background","content":"\u003cp\u003eTo reduce Covid-19 transmission and mortality rates, governments worldwide have strengthened the focus and expanded Covid-19 treatment in healthcare services [1,2]. Over the last two years, vaccination has advanced all over the world and, with that, the Covid-19 death toll has diminished [2]. However, even with a significant reduction in mortality rates, Covid-19 incidence is still substantial, with thousands of new daily cases in low and middle-income countries [3].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Even though Covid-19 control has shown improvements, it is likely that the virus will continue to cause infections [4]. \u0026nbsp;Most countries in South America, for example, are still suffering from the disease itself and its consequences, especially considering new covariants that led to new infection waves [5]. This disease has required extreme attention from governments and health professionals, and the focus on Covid-19 has caused \u0026nbsp;a negative impact on the control and prevention of other infectious diseases, such as tuberculosis (TB) [6]. As TB is endemic to those countries, the coinfection scenario becomes more likely. [6].\u003c/p\u003e\n\u003cp\u003eTuberculosis can lead to severe lung disability and airflow impairment. Host inflammatory response to \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e infection can cause pulmonary lesions. Furthermore, immune cells, cytokines, and chemokines can lead to granuloma formation and tissue necrosis, \u0026nbsp;with subsequent cavitation and fibrosis [7].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn countries with higher TB rates, such as Brazil, SARS-CoV-2 infection in patients with a history of TB are \u0026nbsp;a concern for health authorities and clinicians. Studies point out that patients with a previous history of TB have a higher incidence of lung impairment [7] and have up to 2.5 fold chance of having \u0026nbsp; chronic obstructive pulmonary disease\u0026nbsp;(COPD) [8]. Furthermore, COPD leads to worse outcomes in Covid-19 [9] and a higher hospitalization rate.[10].\u003c/p\u003e\n\u003cp\u003eEven though knowledge about Covid-19 and possible coinfections has significantly grown, data regarding SARS-CoV 2 and its role in patients with a previous history of TB is still lacking, especially regarding patients that required hospitalization [11,12]. This information may help clinicians identify possible patients at risk for Covid-19 severity and death. Therefore, this study aimed to compare Covid-19 manifestations and outcomes between patients with a previous history ofI TB and controls without this condition.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cem\u003eStudy design and subjects\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a part of the multicentric cohort \u0026ldquo;Brazilian Covid-19 Registry\u0026rdquo;, which included data from Covid-19 patients admitted in 39 Brazilian hospitals [13]. Consecutive patients aged 18 and over with Covid-19 admitted to the participating hospitals from March 1, 2020 to March 31, 2022 were included in the study. All patients presented a laboratory confirmation of Covid-19 according to the World Health Organization guidance [14].\u003c/p\u003e\n\u003cp\u003eThis manuscript adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Guideline [15]. For this study, a matched analysis was conducted comparing patients with a history of TB treatment with controls without any history of TB. Active and previous TB diagnoses and treatment were retrieved by medical records. Records that state an active diagnosis TB during the hospital stay or if it did not explicitly state a history of TB were excluded from the analysis.\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Brazilian National Commission for Research Ethics (CAAE 30350820.5.1001.0008) and had internal approval of ethics boards from each hospital. Individual informed consent was waived due to the severity of the situation, and we sought to de-identify the data collected. We state that this study protocol conforms to the ethical guidelines of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eData collection\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe Brazilian Covid-19 Registry collected demographic, clinical, laboratory and outcomes data from medical records by trained health professionals, and medical and nursing undergraduate students using the Research Electronic Data Capture (REDCap) tools [16,17] hosted by the Telehealth Center, University Hospital, Universidade Federal de Minas Gerais [18].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFor the present analysis, TB cases were matched to controls by age, sex, number of comorbidities, presence of HIV and hospital, with a 1:4 ratio. Selection of cases and controls are shown in Figure 1.\u003c/p\u003e\n\u003cp\u003eCategorical data was presented as absolute numbers and proportions, and continuous variables were expressed as medians and interquartile ranges. Association between cases and controls were measured by the Chi-square and Fisher Exact tests to compare the distribution of categorical variables, and the Wilcoxon-Mann\u0026ndash;Whitney test for continuous variables. Results were considered statistically significant if the p-value was \u0026lt;0.05. All statistical analysis was performed with R software (version 4.0.2).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOutcomes\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePrimary outcomes included: \u0026nbsp;(i) invasive mechanical ventilation (IMV) requirement, (ii) need for dialysis and (iii) in-hospital mortality. Intensive Care Unit admission, length of in-hospital stay and time spent in the ICU were analyzed as secondary outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePatient and public involvement\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis was an urgent public health research study in response to a Public Health Emergency of International Concern. Patients or the public were not involved in the design, conduct, interpretation or presentation of the results of this research.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eFrom 13,636 patients with laboratory-confirmed diagnosis of Covid-19, 80 presented a previous diagnosis of tuberculosis, an incidence of 0.006 (IC: 0.004 to 0.007) among the study\u0026rsquo;s population. When comparing clinical characteristics of those patients to matched controls, it was observed that chronic pulmonary obstructive disease (COPD) (15% vs 3.2%, p\u0026lt;0.001), psychiatric disease (10% vs 3.5%, p=0.034) and history of solid-organ transplantation \u0026nbsp;(5% vs 0.9%, p=0.033) were more frequent in study cases. Also, regular home use of inhalatory medications (5% vs 0.6%, p=0.017), oral corticoids (8.8% vs 1.9%, p=0.006) and immunosuppressants (8.8% vs 1.9%, p=0.006) were more common in this group, as well as a higher frequency of illicit drug use when compared to controls(6.2% vs 0.3% p=0.002).\u0026nbsp;[Table 1]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 - Comparison between patients with treated TB and controls\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"604\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreated TB N = 80\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls N = 316\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003e\u003cstrong\u003eWomen\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e49 (61.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e189 (59.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e0.915\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u0026nbsp;\u003c/strong\u003e(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e58.5 (46.8, 69.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e59.0 (45.8, 69.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003e\u003cem\u003eComorbidities\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e28 (35.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e152 (48.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.048\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eDiabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e16 (20.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e76 (24.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e0.536\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eCOPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e12 (15.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e10 (3.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eChronic kidney disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e9 (11.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e9 (2.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003ePsychiatric disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e8 (10.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e11 (3.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.034\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eObesity\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e6 (7.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e47 (14.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e0.122\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eHeart failure\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e6 (7.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e11 (3.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eAsthma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e5 (6.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e19 (6.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eTransplant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e4 (5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e3 (0.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.033\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eStroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e4 (5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e10 (3.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e0.495\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eHIV infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e4 (5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e10 (3.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e0.495\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eCoronary artery disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e3 (3.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e15 (4.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eRheumatological disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e3 (3.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e4 (1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e0.150\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eCancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e3 (3.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e10 (3.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e0.731\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eAtrial fibrillation/flutter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e2 (2.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e7 (2.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedications in use at Home\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eOral anticoagulant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e12 (3.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e0.480\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eInhalatory corticoid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e4 (5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e2 (0.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.017\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eOral corticoid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e7 (8.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e6 (1.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eImmunosuppressants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e7 (8.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e6 (1.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003e\u003cstrong\u003eToxic habits\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eAlcoholism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e9 (11.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e17 (5.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e0.101\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eIllicit drugs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e5 (6.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e1 (0.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.125827814569536%\"\u003e\n \u003cp\u003eCurrent smoking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.11920529801324%\"\u003e\n \u003cp\u003e9 (11.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.357615894039736%\"\u003e\n \u003cp\u003e19 (6.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.397350993377483%\"\u003e\n \u003cp\u003e0.165\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003en (%); Median (IQR) \u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003ePearson\u0026apos;s Chi-squared test; Wilcoxon rank sum test; Fisher\u0026apos;s exact test.\u003c/p\u003e\n\u003cp\u003eCOPD: chronic obstructive pulmonary disease; HIV\u003c/p\u003e\n\u003cp\u003eWhen comparing the prevalence of symptoms presented at hospital admission, Covid-19 patients with and without a past diagnosis of TB had similar results, except for adynamia which was most frequent (35% vs 22.2%, p=0.025) and myalgia the least common (21.2% vs 33.9%, p=0.042) in cases [Table S1]. There was no difference in use of \u0026nbsp;antibiotics (42.5% vs 44.4%, p=0.857), anticoagulants (85% vs 88.8%, p=0.456), antifungals (6.2% vs 3.5%, p=0.337) and corticoids (77.5% vs 81.8%, p=0.477) medications during patient stay [Table S1]. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlso, when comparing laboratory findings, values of C-reactive protein (CRP) at hospital admission were lower in patients with a previous history of TB (58 vs 90, p=0.005) than in controls. [Table S2]\u003c/p\u003e\n\u003cp\u003eNo statistically significant differences were observed in regard to patient outcomes between the groups, such as ICU admission (41.2% vs 43.4%, p=0.831), mechanical ventilation requirement (28.7% vs 36.7%, p=0.483) and death (23.8% vs 24.8%, p=0.966).\u0026nbsp;[Table 2]\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2 - Outcomes comparison between patients with treated TB and controls\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.92845257903494%\"\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.63560732113145%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreated TB N = 80\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls N = 316\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.467554076539102%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.92845257903494%\"\u003e\n \u003cp\u003eIn-hospital stay (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.63560732113145%\"\u003e\n \u003cp\u003e13.0 (6.0, 22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\"\u003e\n \u003cp\u003e9.0 (5.0, 19.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.467554076539102%\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.92845257903494%\"\u003e\n \u003cp\u003eICU admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.63560732113145%\"\u003e\n \u003cp\u003e33 (41.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\"\u003e\n \u003cp\u003e137 (43.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.467554076539102%\"\u003e\n \u003cp\u003e0.831\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.92845257903494%\"\u003e\n \u003cp\u003eTime spent in the ICU (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.63560732113145%\"\u003e\n \u003cp\u003e12.0 (5.0, 17.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\"\u003e\n \u003cp\u003e10.0 (5.0, 18.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.467554076539102%\"\u003e\n \u003cp\u003e0.853\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.92845257903494%\"\u003e\n \u003cp\u003eMechanical ventilation requirement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.63560732113145%\"\u003e\n \u003cp\u003e23 (28.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\"\u003e\n \u003cp\u003e106 (33.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.467554076539102%\"\u003e\n \u003cp\u003e0.483\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.92845257903494%\"\u003e\n \u003cp\u003eTime with mechanical ventilation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.63560732113145%\"\u003e\n \u003cp\u003e9.0 (6.0, 14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\"\u003e\n \u003cp\u003e13.0 (6.0, 20.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.467554076539102%\"\u003e\n \u003cp\u003e0.107\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.92845257903494%\"\u003e\n \u003cp\u003eDialysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.63560732113145%\"\u003e\n \u003cp\u003e10 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\"\u003e\n \u003cp\u003e39 (12.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.467554076539102%\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.92845257903494%\"\u003e\n \u003cp\u003eSeptic shock\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.63560732113145%\"\u003e\n \u003cp\u003e8 (10.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\"\u003e\n \u003cp\u003e57 (18.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.467554076539102%\"\u003e\n \u003cp\u003e0.118\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.92845257903494%\"\u003e\n \u003cp\u003eAcute heart failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.63560732113145%\"\u003e\n \u003cp\u003e4 (5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\"\u003e\n \u003cp\u003e6 (1.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.467554076539102%\"\u003e\n \u003cp\u003e0.122\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.92845257903494%\"\u003e\n \u003cp\u003eIn-hospital death\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.63560732113145%\"\u003e\n \u003cp\u003e19 (23.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\"\u003e\n \u003cp\u003e78 (24.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.467554076539102%\"\u003e\n \u003cp\u003e0.966\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003en (%); Median (IQR) \u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003ePearson\u0026apos;s Chi-squared test; Wilcoxon rank sum test; Fisher\u0026apos;s exact test. ICU: Intensive Care Unit\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAmong all patients admitted to this multicenter cohort that analyzed data from 37 Brazilian hospitals, the frequency of tuberculosis was small, with a ratio of 6:1000 individuals. Nevertheless, our records allowed the comparison of individuals with a previous history of TB and its respective matched control group. In our data we have found significant differences between both groups, since the presence of COPD, psychiatric diseases, hypertension, previous solid organ transplant and the use of illicit drugs were higher in the TB group. These are known risk factors for tuberculosis. It was also possible to observe a substantial difference between the use of medications such as immunosuppressants, oral and inhalatory corticoids, which were also higher in the case group. We did not find significant differences in the outcomes such as in-hospital mortality, IMV requirement, need for dialysis and ICU admission.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOne of these differences was a higher frequency of COPD in patients with previous TB. The organism\u0026rsquo;s inflammatory response against \u003cem\u003e\u003cu\u003eMycobacterium tuberculosis\u003c/u\u003e\u003c/em\u003e leads to cytokine and chemokine releases, which can cause lung damage, resulting in COPD [7]. This can be corroborated by the findings of the study, since patients with a history of tuberculosis had a higher incidence of COPD when compared to the control group (15% vs 3.2%, p \u0026lt;0.001). However, even with the higher rate of COPD patients in our case group, the frequency of dyspnea (58.8% vs 65.2%, p=0.347) and cough (62.5% vs 53.8%, p=0.203) were similarly reported by both groups in the acute phase of the disease.\u003c/p\u003e\n\u003cp\u003eThe awareness of the differences in study patients regarding the presence of comorbidities, such as COPD, and their role in the prognosis of Covid-19 in these subjects may be fundamental to improve patient care. Patients with COPD and Covid-19 have a higher risk of developing severe pneumonia, and the pathophysiological mechanism explaining this may be related to the greater availability of angiotensin-converting enzyme 2 (ACE2) receptors in the small airways [19]. SARS-CoV 2 has an invasion mechanism into the body cells by the recognition of the virus Spike protein predominantly by ACE2 receptors [20]. Another mechanism that explains the greater propensity to develop severe cases of pneumonia is the tissue damage caused by the disease itself, which results in poor underlying lung reserves [20]. However, ACE2 receptors appear to be more abundant in older male individuals, [21] which in itself may be a risk factor for developing severe forms of Covid-19 [22]. This study did not show tough a difference in outcomes of case and control groups, as far as acute phase is concerned. We have no information about the severity of COPD, which could have been relevant.\u003c/p\u003e\n\u003cp\u003eIt should be noted that patients in the case group also had higher rates of solid organ transplants (5% vs 0.9%, p =0.033). Tuberculosis is one of the most frequent complications of solid organ transplantation [23,24], mainly because the prevalence of latent TB is high Brasil [25].\u003c/p\u003e\n\u003cp\u003eThe reports of hypertension were smaller in patients with history of TB when compared with controls (35% vs 48%, p=0.048). A metanalysis points out that there is no correlation between hypertension in TB and non-TB patients, studies shown a higher and lower frequency of TB [26]. \u0026nbsp; Hypertension is risk factor for mortality in TB patients [27], however it was not found as an independent risk factor for Covid mortality [28]. In this study we found no difference in admission systolic blood pressure levels between groups (128 vs 123 mm/Hg, p =0.823).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;The rate of psychiatric diseases at baseline was also higher in patients with history of \u0026nbsp;TB when compared to control (10% vs 3.5%, p=0.034). Despite the fact that the role of psychiatric diseases as a risk factor for developing TB is still under debate, schizophrenia and depression have shown to be possible risk factors for its development [29]. Both diseases share a strong relationship with social determinants, such as homelessness and poverty [29]. Unfortunately, our data did not retrieve social and economic variables to try to explore these issues in Covid-19 patients and those with a history of TB, but the association between psychiatric diseases and TB can reinforce that theory.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Illicit drug use was also higher at baseline in patients with a history of \u0026nbsp; TB. Illicit drugs are a risk for TB infection [29], the use of illicit drugs facilitate close physical contact and also is higher in the homeless population, a group also at risk for TB [30]. The use of powder or crack cocaine can lead to pulmonary edema, pneumonia, alveolar hemorrhage and other lung damage. This damage, associated with cocaine effect reducing alveolar macrophage response and proinflammatory responses facilitate the infection from \u003cem\u003e\u003cu\u003eM\u003c/u\u003e. \u003cu\u003etuberculosis\u003c/u\u003e\u003c/em\u003e [31]. The relation of illicit drugs and Covid-19 was pointed out by Wang et al (2021), substance abuse was related to an increase in hospitalization and death rates in Covid-19 patients. However, there was no difference between these outcomes in our groups [32].\u003c/p\u003e\n\u003cp\u003eBesides psychiatric diseases and illicit drug use, chronic kidney disease (CKD) also presented a higher frequency in our case group at baseline, compared with controls (11.2% vs 2.8% p=0.004). Chronic kidney disease leads to malnutrition, oxidative stress, and inflammation, which impairs cell-mediated immunity. This state of immunosuppression can result in the reactivation of latent tuberculosis infections and even new TB infections. Consequently, TB incidence is higher in CKD patients than in non-CKD [33].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurthermore, CKD is found as a risk factor for Covid hospitalization, severity, and mortality [34]. Data published by the Brazilian Covid-19 Registry shows that elevated blood urea nitrogen at admission is a risk for death in COVID patients\u0026nbsp;[35] and higher creatinine levels at admission lead to greater chances for renal replacement therapy\u0026nbsp;[36]. This evidence reinforces that kidney impairment is a \u0026nbsp;risk factor for COVID severity, however little is known of the physiopathology of CKD and COVID severity\u0026nbsp;[34]. Since CKD is a risk factor for TB infection, we advise that the population at risk for CKD should have priority in vaccination and boosts shots against COVID and clinicians have to better screen these patients for the presence or a history of TB and other infections\u0026nbsp;[37].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients with a history of TB had significantly higher home use of inhaled corticosteroids and oral corticosteroids than the control group at baseline. The higher rate inhaled and oral corticosteroids use may explain better outcomes than those expected, since the use of specific corticosteroids can lead to better outcomes such as lower rate of need for ventilatory support [38,39]. In-hospital use of corticosteroids did not differ between groups (77.5 vs 81.8, p=0.477). However, further studies are necessary to support that home use of corticosteroids can contribute to better outcomes in patients with previous diagnosis of TB.\u003c/p\u003e\n\u003cp\u003eFor this study, a few limitations were observed. First, all of our patients were \u0026nbsp;retrieved through medical data, which resulted in a low number of patients with a history of TB. Second, this study was retrospective, this can lead to report bias from the medical records. In order to lessen the burden of this potential bias, data collected was audited for possible errors. \u0026nbsp;\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this study, patients with a previous TB infection presented a higher frequency of illicit CKD, COPD, psychiatric disease, solid organ transplants and \u0026nbsp;drug abuse when compared to controls. Furthermore, cases presented a higher home use of \u0026nbsp;oral and inhalatory corticosteroids and immunosuppressants than controls. \u0026nbsp; Covid-19 clinical presentation was similar between groups, except for adynamia, which was more prevalent in patients with treated TB, and myalgia, which was more frequently reported by controls. No statistically significant differences were observed between the groups in regard to ICU admission, hospital length of stay, time spent in the ICU, dialysis, need for mechanical ventilation and in-hospital death.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding:\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Funda\u0026ccedil;\u0026atilde;o de Amparo \u0026agrave; Pesquisa do Estado de Minas Gerais (FAPEMIG APQ-00208-20) and Instituto de Avalia\u0026ccedil;\u0026atilde;o de Tecnologia em Sa\u0026uacute;de IATS/CNPQ.\u003c/p\u003e\n\u003cp\u003eConflicts of interest/competing interests:\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate:\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Brazilian National Commission for Research Ethics (CAAE 30350820.5.1001.0008) and had internal approval of ethics boards from each hospital. Individual informed consent was waived due to the severity of the situation, and we de-identify the data collected.\u003c/p\u003e\n\u003cp\u003eAvailability of data and material:\u003c/p\u003e\n\u003cp\u003eData can be available upon request.\u003c/p\u003e\n\u003cp\u003eConsent for publication:\u003c/p\u003e\n\u003cp\u003eAll authors approved the manuscript before submission.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Authors\u0026apos; contributions:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026ldquo;Conceptualization, RLRC. and RC.; methodology, RLRC; DP; VC, RC and MM; software, MM; validation, MM; formal analysis, RLRC and MM.; investigation FC; GN; KR; LM; MC; MJ; MC; NB; NO and RA; resources, RLRC and MM; data curation, FC; GN; KR; LM; MC; MJ; MC; NB; NO and RA; writing\u0026mdash;original draft preparation, RLRC; DP; VC; and RC.; writ-ing\u0026mdash;review and editing, RLRC; DP; VC; VA; RC and MM; visualization, RLRC; supervision, RLRC and RC.; project administration, MM; funding acquisition, RLRC and MM.\u003c/p\u003e\n\u003cp\u003eAcknowledgements:\u003c/p\u003e\n\u003cp\u003eWe would like to thank all the research teams from the hospitals that helped us in the Brazilian Covid-19 Registry.\u0026nbsp;In particular, the hospitals that compose this analysis: Hospital Metropolitano Odilon Behrens; Hospital da Unimed;Hospital Universit\u0026aacute;rio de Canoas; Hospital de Cl\u0026iacute;nicas de Porto Alegre; Hospital Santa Cruz; Hospital M\u0026aacute;rcio Cunha; Hospital Risoleta Tolentino Neves; Hospital S\u0026atilde;o Jo\u0026atilde;o de Deus; Hospital Eduardo de Menezes; and Hospital Metropolitano Doutor C\u0026eacute;lio de Castro.\u0026nbsp;Furthermore, we would like to thank the undergraduate students that helped in data collection, all hospital staff for taking care of our patients, and the Brazilian Covid-19 Registry team for the work and help.\u003c/p\u003e"},{"header":"References","content":"\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003ede Souza Melo, A.; da Penha Sobral, A.I.G.; Marinho, M.L.M.; Duarte, G.B.; Vieira, A.A.; Sobral, M.F.F. The Impact of Social Distancing on COVID-19 Infections and Deaths. \u003cem\u003eTropical Diseases, Travel Medicine and Vaccines\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e7\u003c/em\u003e, 1\u0026ndash;7.\u003c/li\u003e\n \u003cli\u003eWatson, O.J.; Barnsley, G.; Toor, J.; Hogan, A.B.; Winskill, P.; Ghani, A.C. Global Impact of the First Year of COVID-19 Vaccination: A Mathematical Modelling Study.\u0026nbsp;\u003cem\u003eLancet Infect. Dis.\u003c/em\u003e \u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e22\u003c/em\u003e, 1293\u0026ndash;1302.\u003c/li\u003e\n \u003cli\u003eWHO Coronavirus (COVID-19) Dashboard. Available online:\u003ca href=\"https://covid19.who.int/\"\u003e\u0026nbsp;\u003c/a\u003ehttps://covid19.who.int/ \u0026nbsp; (accessed on 30 Jan 2022)\u003c/li\u003e\n \u003cli\u003eMurray, C.J.L. COVID-19 Will Continue but the End of the Pandemic Is near.\u0026nbsp;\u003cem\u003eLancet\u003c/em\u003e 2022, \u003cem\u003e399\u003c/em\u003e, 417\u0026ndash;419.\u003c/li\u003e\n \u003cli\u003eMalta, M.; Vettore, M.V.; da Silva, C.M.F.P.; Silva, A.B.; Strathdee, S.A. The Foreseen Loss of the Battle against COVID-19 in South America: A Foretold Tragedy.\u0026nbsp;\u003cem\u003eEClinicalMedicine\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e39\u003c/em\u003e, 101068.\u003c/li\u003e\n \u003cli\u003eWHO Global tuberculosis report 2021. Available online:\u003ca href=\"https://www.who.int/publications/i/item/9789240037021\"\u003e\u0026nbsp;\u003c/a\u003ehttps://www.who.int/publications/i/item/9789240037021 (accessed on 30 Jan 2022)\u003c/li\u003e\n \u003cli\u003eRavimohan, S.; Kornfeld, H.; Weissman, D.; Bisson, G.P. Tuberculosis and Lung Damage: From Epidemiology to Pathophysiology.\u0026nbsp;\u003cem\u003eEur. Respir. Rev.\u003c/em\u003e \u003cstrong\u003e2018\u003c/strong\u003e, \u003cem\u003e27\u003c/em\u003e, 147\u003c/li\u003e\n \u003cli\u003eAmaral, A.F.S.; Coton, S.; Kato, B.; Tan, W.C.; Studnicka, M.; Janson, C.; Gislason, T.; Mannino, D.; Bateman, E.D.; Buist, S.; et al. Tuberculosis Associates with Both Airflow Obstruction and Low Lung Function: BOLD Results. \u003cem\u003eEur. Respir. J.\u003c/em\u003e \u003cstrong\u003e2015\u003c/strong\u003e, \u003cem\u003e46\u003c/em\u003e, 1104\u0026ndash;1112.\u003c/li\u003e\n \u003cli\u003eSanchez-Ramirez, D.C.; Mackey, D. Underlying Respiratory Diseases, Specifically COPD, and Smoking Are Associated with Severe COVID-19 Outcomes: A Systematic Review and Meta-Analysis.\u0026nbsp;\u003cem\u003eRespir. Med.\u003c/em\u003e \u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e171\u003c/em\u003e, 106096.\u003c/li\u003e\n \u003cli\u003eAveyard, P.; Gao, M.; Lindson, N.; Hartmann-Boyce, J.; Watkinson, P.; Young, D.; Coupland, C.A.C.; Tan, P.S.; Clift, A.K.; Harrison, D.; et al. Association between Pre-Existing Respiratory Disease and Its Treatment, and Severe COVID-19: A Population Cohort Study. \u003cem\u003eLancet Respir Med\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e9\u003c/em\u003e, 909\u0026ndash;923.\u003c/li\u003e\n \u003cli\u003eJassat, W.; Cohen, C.; Tempia, S.; Masha, M.; Goldstein, S.; Kufa, T.; Murangandi, P.; Savulescu, D.; Walaza, S.; Bam, J.-L.; et al. 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Immune Determinants of COVID-19 Disease Presentation and Severity.\u0026nbsp;\u003cem\u003eNat. Med.\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e27\u003c/em\u003e, 28\u0026ndash;33.\u003c/li\u003e\n \u003cli\u003eMalinis, M.; Koff, A. Mycobacterium Tuberculosis in Solid Organ Transplant Donors and Recipients.\u0026nbsp;\u003cem\u003eCurr. Opin. Organ Transplant.\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e26\u003c/em\u003e, 432\u0026ndash;439.\u003c/li\u003e\n \u003cli\u003eAbad, C.L.R.; Razonable, R.R. Mycobacterium Tuberculosis after Solid Organ Transplantation: A Review of More than 2000 Cases.\u0026nbsp;\u003cem\u003eClin. Transplant.\u003c/em\u003e \u003cstrong\u003e2018\u003c/strong\u003e, \u003cem\u003e32\u003c/em\u003e, e13259.\u003c/li\u003e\n \u003cli\u003eBrasil. Minist\u0026eacute;rio da Sa\u0026uacute;de. Secretaria de Vigil\u0026acirc;ncia em Sa\u0026uacute;de. Departamento de Doen\u0026ccedil;as de Condi\u0026ccedil;\u0026otilde;es Cr\u0026ocirc;nicas e Infec\u0026ccedil;\u0026otilde;es Sexualmente Transmiss\u0026iacute;veis. Protocolo de vigil\u0026acirc;ncia da infec\u0026ccedil;\u0026atilde;o latente pelo Mycobacterium tuberculosis no Brasil / Minist\u0026eacute;rio da Sa\u0026uacute;de, Secretaria de Vigil\u0026acirc;ncia em Sa\u0026uacute;de, Departamento de Doen\u0026ccedil;as de Condi\u0026ccedil;\u0026otilde;es Cr\u0026ocirc;nicas e Infec\u0026ccedil;\u0026otilde;es Sexualmente Transmiss\u0026iacute;veis. \u0026ndash; 2. ed. \u0026ndash; Bras\u0026iacute;lia: Minist\u0026eacute;rio da Sa\u0026uacute;de, 2022.\u003c/li\u003e\n \u003cli\u003eSeegert, A.B.; Rudolf, F.; Wejse, C.; Neupane, D. Tuberculosis and Hypertension-a Systematic Review of the Literature.\u0026nbsp;\u003cem\u003eInt. J. Infect. Dis.\u003c/em\u003e \u003cstrong\u003e2017\u003c/strong\u003e, \u003cem\u003e56\u003c/em\u003e, 54\u0026ndash;61.\u003c/li\u003e\n \u003cli\u003eChidambaram, V.; Gupte, A.; Wang, J.-Y.; Golub, J.E.; Karakousis, P.C. The Impact of Hypertension and Use of Calcium Channel Blockers on Tuberculosis Treatment Outcomes.\u0026nbsp;\u003cem\u003eClin. Infect. Dis.\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e73\u003c/em\u003e, e3409\u0026ndash;e3418.\u003c/li\u003e\n \u003cli\u003eD\u0026rsquo;Elia, L.; Giaquinto, A.; Zarrella, A.F.; Rendina, D.; Iaccarino Idelson, P.; Strazzullo, P.; Galletti, F. Hypertension and Mortality in SARS-COV-2 Infection: A Meta-Analysis of Observational Studies after 2 Years of Pandemic.\u0026nbsp;\u003cem\u003eEur. J. Intern. Med.\u003c/em\u003e \u003cstrong\u003e2023\u003c/strong\u003e, \u003cem\u003e108\u003c/em\u003e, 28\u0026ndash;36.\u003c/li\u003e\n \u003cli\u003eHayward, S.E.; Deal, A.; Rustage, K.; Nellums, L.B.; Sweetland, A.C.; Boccia, D.; Hargreaves, S.; Friedland, J.S. The Relationship between Mental Health and Risk of Active Tuberculosis: A Systematic Review.\u0026nbsp;\u003cem\u003eBMJ Open\u003c/em\u003e \u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e12\u003c/em\u003e, e048945.\u003c/li\u003e\n \u003cli\u003eDuarte, R.; L\u0026ouml;nnroth, K.; Carvalho, C.; Lima, F.; Carvalho, A.C.C.; Mu\u0026ntilde;oz-Torrico, M.; Centis, R. Tuberculosis, Social Determinants and Co-Morbidities (including HIV). \u003cem\u003ePulmonology\u003c/em\u003e \u003cstrong\u003e2018\u003c/strong\u003e, \u003cem\u003e24\u003c/em\u003e, 115\u0026ndash;119.\u003c/li\u003e\n \u003cli\u003eSilva, D.R.; Mu\u0026ntilde;oz-Torrico, M.; Duarte, R.; Galv\u0026atilde;o, T.; Bonini, E.H.; Arbex, F.F.; Arbex, M.A.; Augusto, V.M.; Rabahi, M.F.; Mello, F.C. de Q. Risk factors for tuberculosis: diabetes, smoking, alcohol use, and the use of other drugs. \u003cem\u003eJ. Bras. Pneumol.\u003c/em\u003e \u003cstrong\u003e2018\u003c/strong\u003e, \u003cem\u003e44\u003c/em\u003e, 145\u0026ndash;152.\u003c/li\u003e\n \u003cli\u003eWang, Q.Q.; Kaelber, D.C.; Xu, R.; Volkow, N.D. COVID-19 Risk and Outcomes in Patients with Substance Use Disorders: Analyses from Electronic Health Records in the United States.\u0026nbsp;\u003cem\u003eMol. Psychiatry\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e26\u003c/em\u003e, 30\u0026ndash;39.\u003c/li\u003e\n \u003cli\u003eRomanowski, K.; Clark, E.G.; Levin, A.; Cook, V.J.; Johnston, J.C. Tuberculosis and Chronic Kidney Disease: An Emerging Global Syndemic.\u0026nbsp;\u003cem\u003eKidney Int.\u003c/em\u003e \u003cstrong\u003e2016\u003c/strong\u003e, \u003cem\u003e90\u003c/em\u003e, 34\u0026ndash;40.\u003c/li\u003e\n \u003cli\u003eJdiaa, S.S.; Mansour, R.; El Alayli, A.; Gautam, A.; Thomas, P.; Mustafa, R.A. COVID-19 and Chronic Kidney Disease: An Updated Overview of Reviews.\u0026nbsp;\u003cem\u003eJ. Nephrol.\u003c/em\u003e \u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e35\u003c/em\u003e, 69\u0026ndash;85.\u003c/li\u003e\n \u003cli\u003eMarcolino, M.S.; Pires, M.C.; Ramos, L.E.F.; Silva, R.T.; Oliveira, L.M.; Carvalho, R.L.R.; Mourato, R.L.S.; S\u0026aacute;nchez-Montalv\u0026aacute;, A.; Ravent\u0026oacute;s, B.; Anschau, F.; et al.\u0026nbsp;ABC2-SPH Risk Score for in-Hospital Mortality in COVID-19 Patients: Development, External Validation and Comparison with Other Available Scores. \u003cem\u003eInt. J. Infect. Dis.\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e110\u003c/em\u003e, 281\u0026ndash;308.\u003c/li\u003e\n \u003cli\u003eFigueiredo, F. de A.; Ramos, L.E.F.; Silva, R.T.; Ponce, D.; de Carvalho, R.L.R.; Schwarzbold, A.V.; Maur\u0026iacute;lio, A. de O.; Scotton, A.L.B.A.; Garbini, A.F.; Farace, B.L.; et al. Development and Validation of the MMCD Score to Predict Kidney Replacement Therapy in COVID-19 Patients. \u003cem\u003eBMC Med.\u003c/em\u003e \u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e20\u003c/em\u003e, 324.\u003c/li\u003e\n \u003cli\u003eRovin, B.H.; Adler, S.G.; Barratt, J.; Bridoux, F.; Burdge, K.A.; Chan, T.M.; Cook, H.T.; Fervenza, F.C.; Gibson, K.L.; Glassock, R.J.; et al. Executive Summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. \u003cem\u003eKidney Int.\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e100\u003c/em\u003e, 753\u0026ndash;779.\u003c/li\u003e\n \u003cli\u003eYu, L.-M.; Bafadhel, M.; Dorward, J.; Hayward, G.; Saville, B.R.; Gbinigie, O.; Van Hecke, O.; Ogburn, E.; Evans, P.H.; Thomas, N.P.B.; et al. Inhaled Budesonide for COVID-19 in People at High Risk of Complications in the Community in the UK (PRINCIPLE): A Randomised, Controlled, Open-Label, Adaptive Platform Trial. \u003cem\u003eLancet\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e398\u003c/em\u003e, 843\u0026ndash;855.\u003c/li\u003e\n \u003cli\u003eRECOVERY Collaborative Group; Horby, P.; Lim, W.S.; Emberson, J.R.; Mafham, M.; Bell, J.L.; Linsell, L.; Staplin, N.; Brightling, C.; Ustianowski, A.; et al. Dexamethasone in Hospitalized Patients with Covid-19. \u003cem\u003eN. Engl. J. Med.\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e384\u003c/em\u003e, 693\u0026ndash;704.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Covid-19, Tuberculosis, hospitalization, infectious diseases","lastPublishedDoi":"10.21203/rs.3.rs-4365616/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4365616/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Covid-19 pandemic caused a negative impact on other infectious diseases control, prevention, and treatment. Consequently, low and middle-income countries suffer from other endemic diseases, such as tuberculosis. This study was designed to compare Covid-19 manifestations and outcomes between patients with previously treated tuberculosis and controls without this condition.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe performed a matched case-control study drawn from the Brazilian Covid-19 Registry data, including in-hospital patients aged 18 and over with laboratory-confirmed Covid-19 from March 1, 2020 to March 31, 2022. Cases were patients with a past history of tuberculosis. Controls were Covid-19 patients without tuberculosis history. Patients were matched by hospital, sex, presence of HIV and number of comorbidities, with a 1:4 ratio.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom 13,636 patients with laboratory-confirmed diagnosis of Covid-19 enrolled in this study, 80 had a history of tuberculosis. Statistical differences in history of chronic pulmonary obstructive disease (15% vs 3.2%), psychiatric disease (10% vs 3.5%,), chronic kidney disease (11.2% vs 2.8%) and solid-organ transplantation; (5% vs 0.9%, p\u0026lt;0.05 for all) were higher in patients with a past history of tuberculosis. Prior use of inhalatory medications (5% vs 0.6%,), oral corticoids (8.8% vs 1.9%), immunosuppressants (8.8% vs 1.9%,) and the use of illicit drugs were more common in the case group (6.2% vs 0.3% p\u0026lt;0.05for all). There were no significant differences in in-hospital mortality, mechanical ventilation, need for dialysis and ICU admission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients with a history of tuberculosis infection presented a higher frequency of use of illicit drugs, chronic pulmonary obstructive disease, psychiatric disease, chronic kidney disease, solid-organ transplantation, prior use of inhalatory medications, oral corticoids, and immunosuppressants. The outcomes were similar between cases and controls.\u003c/p\u003e","manuscriptTitle":"Characteristics and outcomes of in-hospital patients with Covid-19 and history of tuberculosis: A matched Case-Control from the Brazilian Covid-19 Registry","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-20 18:46:56","doi":"10.21203/rs.3.rs-4365616/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-14T18:18:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-09T18:45:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"180587170332839588641944006782516036976","date":"2024-09-09T10:09:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-17T05:32:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"206699498646670045959364083798062486563","date":"2024-08-14T11:25:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-31T14:50:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"333389031323606513067753750435923906583","date":"2024-05-31T14:24:44+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-31T08:36:29+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-05-14T11:33:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-10T12:26:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-08T12:43:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2024-05-03T18:45:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f9dcb4a9-b52f-4c1a-ad1e-a9062f48663e","owner":[],"postedDate":"May 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-23T15:58:59+00:00","versionOfRecord":{"articleIdentity":"rs-4365616","link":"https://doi.org/10.1186/s12879-024-10305-3","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2024-12-19 15:56:53","publishedOnDateReadable":"December 19th, 2024"},"versionCreatedAt":"2024-05-20 18:46:56","video":"","vorDoi":"10.1186/s12879-024-10305-3","vorDoiUrl":"https://doi.org/10.1186/s12879-024-10305-3","workflowStages":[]},"version":"v1","identity":"rs-4365616","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4365616","identity":"rs-4365616","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}