Clinical Outcomes of Covid-19 in Patients With Liver Cirrhosis - A Propensity-Matched Analysis From a Multicentric Brazilian Cohort

Clinical Outcomes of Covid-19 in Patients With Liver Cirrhosis - A Propensity-Matched Analysis From a Multicentric Brazilian Cohort | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical Outcomes of Covid-19 in Patients With Liver Cirrhosis - A Propensity-Matched Analysis From a Multicentric Brazilian Cohort Luanna Silva Monteiro Menezes, Pedro Ferrari Sales Cunha, Magda Carvalho Pires, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4746005/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Jan, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted 4 You are reading this latest preprint version Abstract Background Cirrhosis has been pointed out as a clinical entity that leads to worse clinical prognosis in COVID-19 patients. However, this concept is controversial in the literature. We aimed to evaluate clinical outcomes by comparing patients with cirrhosis to those without cirrhosis in a Brazilian cohort. Methods Data from 20,164 COVID-19 inpatients were collected from 41 hospitals in Brazil between March to September 2020 and March 2021 to August 2022. We compared 117 patients with cirrhosis to 632 matched controls. A propensity score model was used to adjust for potential confounding variables, incorporating some predictors: age, sex at birth, number of comorbidities, hospital of admission, whether it was an in-hospital clinical manifestation of COVID-19 and admission year. Closeness was defined as being within 0.16 standard deviations of the logit of the propensity score. Results The median age was 61 (IQR 50–70) years-old, and 63.4% were men. There were no significant differences in the self-reported symptoms. Patients with cirrhosis had lower median hemoglobin levels (10.8 vs 13.1 g/dl), lower platelets (127,000 vs 200,000 cells/mm3), and leukocytes counts, as well as lower median C-reactive protein (63.0 vs 76.0 p = 0.044) when compared to controls.They also had had higher mortality compared to matched controls (51.3% vs 21.7%, p < 0.001). They also had higher frequencies of admission in an intensive care unit (51.3% vs 38.0%, p = 0.007), invasive mechanical ventilation (43.9% vs 26.6%, p < 0.001), dialysis (17.9% vs 11.1%, p = 0.038), septic shock (23.9% vs 14.9%; p = 0.015) and institution of palliative care (19.7% vs 7.4%; p < 0.001). Conclusions This study has shown that COVID-19 inpatients with cirrhosis had significantly higher incidence of severe outcomes, as well as higher frequency of institution of palliative care when compared to matched controls. Our findings underscore the need for these patients to receive particular attention from healthcare teams and allocated resources. COVID-19 Liver Cirrhosis Patient Outcome Assessment Propensity Score Cohort Studies Figures Figure 1 BACKGROUND Liver cirrhosis has a variable prognosis and is associated with a rising global burden of morbidity and mortality. Its prevalence has approximately doubled since the 1990s. Epidemiological data related to chronic liver disease (CLD) are variable and scarce, particularly in low-income countries, suggesting that the actual numbers may be underestimated [ 1 ]. Despite these limitations, some data indicate that cirrhosis is the eighth leading cause of death in Brazil, representing a significant disease burden [ 2 ]. Acute-on-chronic liver failure (ACLF) refers to decompensated chronic liver disease, characterized by complications such as variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome. ACLF is associated with an acute inflammatory state that can lead to multiple organ failure and has a high 28-day mortality rate, exceeding 20%, compared to under 5% among patients with decompensated cirrhosis but without ACLF [ 3 , 4 ]. Many conditions can trigger organic dysfunctions in those patients, including both intrahepatic and extrahepatic conditions. During the COVID-19 pandemic, SARS-CoV-2 infection was a significant cause of ACLF, with studies showing worse prognosis and higher mortality among patients with chronic liver disease (CLD) [ 5 – 7 ]. CLD, especially cirrhosis, has also been demonstrated to be an independent risk factor for mortality in COVID-19 patients. Additionally, greater severity of underlying liver disease has been correlated with an increased likelihood of mortality in individuals with COVID-19 [ 8 ]. Vaccination has been shown to reduce this outcome in patients with CLD [ 9 ]. COVID-19 complications extend beyond the respiratory tract, affecting the cardiac, gastrointestinal, hepatic, renal, hematologic, and nervous systems [ 10 – 12 ]. Among patients with these complications, liver injury, indicated by elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), has been reported in a significant number of hospitalized COVID-19 patients, potentially indicating a poorer prognosis [ 13 ]. Direct liver damage by SARS-CoV-2 has been identified as one of the main factors contributing to ACLF and systemic inflammation in patients with pre-existing CLD [ 14 ]. There is a lack of robust evidence regarding the prognosis of Latin patients with CDL in the context of SARS-CoV-2 infection. Up to June 2024, Brazil reached 38,823,186 confirmed cases, with 712,349 deaths due to COVID-19 complications [ 15 ]. No robust Latin American studies have investigated the clinical outcomes of COVID-19 in patients with cirrhosis so far. Therefore, this study aimed to compare the clinical features and outcomes of COVID-19-infected Brazilian inpatients with and without cirrhosis across different phases of the pandemic. This research addresses a gap in understanding this issue within the Brazilian population, which comprises approximately 49% of South America's population. MATERIAL AND METHODS Study design and participants This study is part of a large multicenter retrospective Brazilian cohort (Brazilian COVID-19 Registry), which involved 41 hospitals, including private and public, in 18 cities from six Brazilian states (Bahia, Minas Gerais, Pernambuco, Rio Grande do Sul, Santa Catarina, São Paulo), comprising two periods: March to September 2020 and March 2021 to August 2022 [ 16 ]. This study included consecutive adult patients (≥ 18 years old) with laboratory-confirmed COVID-19 admitted to the participating hospitals. Positive cases were considered through the detection of SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR) tests in nasopharyngeal or oropharyngeal swab or serological tests [IgM] in the first phase of the study; and by RT-PCR in the second phase [ 16 , 17 ]. Patients admitted because of COVID-19 or those who developed first symptoms of COVID-19 infection during hospitalization and tested positive were included. Patients transferred from other hospitals, those younger than 18, and pregnant and puerperal women were excluded from the present analysis. Patients who reported having cirrhosis and had this comorbidity documented in their medical records were classified as "cases". Data collection Demographic data, clinical characteristics, laboratory results in hospital presentation, and outcomes were collected from the medical records by trained healthcare professionals and medical or nursing students to the Research Electronic Data Capture (REDCap®) electronic platform [ 18 , 19 ], hosted at the Telehealth Center of the University Hospital of the Universidade Federal de Minas Gerais [ 20 ]. To ensure reliability and monitor data quality, the database was routinely audited. Study protocol and definition details were published elsewhere [ 16 , 21 ]. For more details about the collected data, refer to Supplementary File 1. All clinical characteristics regarding the patient’s previous history were considered based on the records in the medical register. Outcomes The primary outcome was in-hospital mortality. Secondary outcomes included length of hospital stay, admission to the intensive care unit (ICU), invasive mechanical ventilation (IMV), renal replacement therapy, septic shock, nosocomial infection, acute heart failure, myocarditis, any type of bleeding, venous thromboembolism (VTE) and palliative care reference. Statistical analysis To mitigate potential confounding variables, a rigorous propensity score matching approach was employed to balance the baseline characteristics between patients with underlying cirrhosis and control patients (those without underlying cirrhosis). The propensity score model was estimated by logistic regression, incorporating a comprehensive set of predictors: age, sex at birth, number of comorbidities (hypertension, diabetes mellitus, obesity, coronary artery disease, heart failure, atrial fibrillation or flutter, chronic obstructive pulmonary disease, cancer, and previous stroke), hospital of admission, whether it was an in-hospital clinical manifestation of COVID-19 and admission year (2020 vs 2021–2022) [ 16 ]. This robust model ensures a meticulous adjustment for these potential confounders. Matching was conducted by identifying control group individuals whose propensity scores closely aligned with those of the cirrhotic patient group. Closeness was stringently defined as being within 0.16 standard deviations of the logit of the propensity score, which was measured on a scale from 0 to 1.00. This matching process was executed using the MatchIt package in R software. Following the matching process, a thorough descriptive analysis of data was performed. Categorical data were presented as absolute numbers and proportions. The Kolmogorov-Smirnov test was applied to verify data normality. All continuous variables had non-normal distribution and were expressed as median and interquartile ranges (IQR). The chi-square and Fisher’s exact tests were used to compare the distribution of categorical variables, while the Wilcoxon–Mann–Whitney test was used for continuous variables. Statistical analysis was performed using R software (version 4.0.2) with tidyverse, stringr, gtsummary and MatchIt packages. Statistical tests were conducted with an alpha level of 0.05 in two-sided tests, so results were considered statistically significant if p-value was < 0.05. Ethics statement This study was approved by the Brazilian National Commission for Research Ethics (CAAE 30350820.5.1001.0008). Individual informed consent was waived due to the pandemic situation and the use of data from medical records. RESULTS Demographic and clinical features The study included 749 patients. Of those, 117 patients had cirrhosis and 632 were matched controls (Fig. 1 ). The median age was 61 (IQR 50–70) years-old, and 63.4% were men. Both groups had similar demographic characteristics and comorbidities, except for hypertension and chronic kidney disease (CKD) - people with cirrhosis had a lower frequency of hypertension (40.2% vs 57.6%; p < 0.001) and a higher frequency of CKD (14.5% vs 6.6%; p = 0.004), when compared to their matched controls. Smoking (14.5% vs 5.1%, p < 0.001) and alcohol consumption (42.7% vs 8.4%, p < 0.001) were more frequent in the cirrhosis than in the control group. Other demographic characteristics are shown in Table 1 . Table 1 Demographics and clinical characteristics of Covid-19 patients with cirrhosis and matched controls without cirrhosis Variables Overall 1 N = 749 Study group 1 N = 117 Control group 1 N = 632 p-value 2 Age (years) 61.0 (50.0, 70.0) 61.0 (52.0, 70.0) 61.0 (49.0, 70.0) 0.469 Sex (male) 475 (63.4%) 80 (68.4%) 395 (62.5%) 0.225 Received vaccine (any number of doses) 3 76 (18.0%) 17 (27.4%) 59 (17.0%) 0.051 Hypertension 411 (54.9%) 47 (40.2%) 364 (57.6%) < 0.001 CAD 52 (6.9%) 8 (6.8%) 44 (7.0%) 0.961 Heart Failure 59 (7.9%) 12 (10.3%) 47 (7.4%) 0.298 Atrial fibrillation 26 (3.5%) 5 (4.3%) 21 (3.3%) 0.583 Ischemic stroke 32 (4.3%) 2 (1.7%) 30 (4.7%) 0.209 Chagas disease 9 (1.2%) 0 (0.0%) 9 (1.4%) 0.368 Asthma 42 (5.6%) 5 (4.3%) 37 (5.9%) 0.495 COPD 51 (6.8%) 12 (10.3%) 39 (6.2%) 0.107 Diabetes mellitus 232 (31.0%) 43 (36.8%) 189 (29.9%) 0.141 Obesity 93 (12.4%) 13 (11.1%) 80 (12.7%) 0.641 CKD 59 (7.9%) 17 (14.5%) 42 (6.6%) 0.004 Rheumatologic conditions 20 (2.7%) 0 (0.0%) 20 (3.2%) 0.057 HIV infection 13 (1.7%) 2 (1.7%) 11 (1.7%) > 0.999 Cancer 57 (7.6%) 12 (10.3%) 45 (7.1%) 0.240 Previous transplantation 12 (1.6%) 3 (2.6%) 9 (1.4%) 0.413 Illicit drugs use 14 (1.9%) 2 (1.7%) 12 (1.9%) > 0.999 Alcohol abuse 103 (13.8%) 50 (42.7%) 53 (8.4%) < 0.001 Current Smoking 49 (6.5%) 17 (14.5%) 32 (5.1%) < 0.001 Previous smoker 135 (18.0%) 23 (19.7%) 112 (17.7%) 0.617 CAD: coronary artery disease; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; HIV: human immunodeficiency virus 1 n (%); Median (IQR); 2 Statistical tests performed: chi-square test; Wilcoxon rank-sum test; Fisher's exact test. 3 Missing: 45.3% Patient's data upon hospital presentation There were no significant differences in the self-reported symptoms between patients with cirrhosis and controls (Table S1 ). Regarding objective changes in signs on physical examination upon hospital presentations, a higher incidence of abnormal mental status, with Glasgow Coma Scale of less than 15, was noted in the study group (16.2% vs 8.4%, p = 0.008). Regarding hemodynamic status, the group with cirrhosis had lower arterial pressure compared to the control group. This was evaluated using systolic blood pressure as a categorical variable (≥ 90 mmHg, adjusted for inotropic requirement), with 87.9% of the cirrhosis group meeting this criterion versus 95.4% of the control group (p = 0.008) (Table S1 ). Regarding laboratory exams, patients with cirrhosis had lower median hemoglobin levels (10.8 g/dl vs 13.1 g/dl; p < 0.001), lower platelets (127,000 cells/mm3 vs 200,000 cells/mm3; p < 0.001), leukocytes, neutrophils, and lymphocytes counts, and lower median C-reactive protein (63.0 vs 76.0 p = 0.044) when compared to controls. Median of bilirubin, activated partial thromboplastin time, international normalized ratio, and lactate levels upon hospital presentation were significantly higher in the CLD group (Table 2 ). AST was abnormal in both groups, but the cirrhotic group had a higher elevation than the controls (65.2 U/L vs 42.0 U/L; p < 0.001). Table 2 Laboratory exams of Covid-19 patients with cirrhosis and matched controls without cirrhosis upon hospital presentation Variables Overall 1 N = 749 Control group 1 N = 632 Study group 1 N = 117 p-value 2 Hemoglobin (g/dL) 12.7 (10.9, 14.3) 13.1 (11.4, 14.4) 10.8 (8.9, 12.4) < 0.001 Leukocytes (cells/mm³) 7,300.0 (5,335.0, 10,292.5) 7,440.0 (5,630.0, 10,410.0) 6,026.0 (3,810.0, 9,410.0) < 0.001 Neutrophils (cells/mm³) 5,430.0 (3,732.0, 8,089.5) 5,481.0 (3,940.0, 8,159.0) 4,347.0 (2,631.2, 7,202.8) < 0.001 Lymphocytes (cells/mm³) 1,020.0 (680.0, 1,530.0) 1,080.0 (727.5, 1,549.2) 850.5 (496.5, 1,306.5) < 0.001 Platelets (cells/mm³) 194,000 (143,000, 258,000) 200,000 (156,500, 262,000) 127,000 (73,250, 203,750) < 0.001 Total bilirubin (mg/dL) 0.6 (0.4, 0.9) 0.5 (0.3, 0.7) 1.2 (0.7, 2.3) < 0.001 aPTT (seconds)/control 1.0 (1.0, 1.2) 1.0 (1.0, 1.1) 1.1 (1.0, 1.4) < 0.001 INR 1.1 (1.0, 1.2) 1.1 (1.0, 1.2) 1.3 (1.2, 1.6) < 0.001 Creatinine (mg/dL) 0.9 (0.7, 1.3) 0.9 (0.7, 1.3) 1.0 (0.7, 1.5) 0.155 Ureia (mg/dL) 39.0 (28.0, 60.3) 38.0 (28.5, 58.0) 44.0 (26.5, 75.0) 0.321 C-reactive protein (mg/L) 74.3 (38.0, 136.2) 76.0 (39.4, 137.8) 63.0 (24.4, 104.4) 0.044 Lactate (mg/dL) 1.6 (1.1, 2.1) 1.5 (1.1, 2.0) 2.0 (1.5, 2.7) < 0.001 Aspartate aminotransferase (U/L) 43.0 (29.6, 73.0) 41.0 (28.0, 63.0) 60.0 (36.2, 116.9) < 0.001 Alanine aminotransferase (U/L) 33.0 (21.0, 59.5) 33.0 (21.0, 63.0) 32.0 (20.0, 47.0) 0.242 Bicarbonate 23.0 (20.1, 25.0) 23.0 (21.0, 25.1) 21.4 (17.2, 23.5) < 0.001 pH 7.4 (7.4, 7.5) 7.4 (7.4, 7.5) 7.4 (7.4, 7.5) 0.693 aPTT: activated partial thromboplastin time; INR: international normalized ratio; 1 Median (IQR); 2 Statistical tests performed: chi-square test; Wilcoxon rank-sum test; Fisher's exact test. Outcomes analysis In-hospital mortality was higher among patients with cirrhosis (51.3% vs 21.7%, p < 0.001), compared to matched controls. They also had a higher frequency of ICU admission (51.3% vs 38.0%, p = 0.007), IMV (26.6% vs 43.9%, p < 0.001), dialysis (17.9% vs 11.1%, p = 0.038), and septic shock (23.9% vs 14.9%; p = 0.015). Additionally, they were referred to palliative care more often than the control group (19.7% vs 7.4%; p < 0.001). On the other hand, patients with cirrhosis had a lower incidence of VTE when compared to the controls (0.9% vs 5.4%; p = 0.033), and the incidence of hemorrhages was similar in both groups (6.8% vs 3.8%; p = 0.139). The median length of stay was 10 days for the control group and 13 days for the CLD group (p = 0.106) (Table 3). DISCUSSION This study demonstrated a high mortality rate among inpatients with liver cirrhosis and concomitant COVID-19 infection – 51.3%, compared to 21.7% in the control group, which did not have liver disease. We also observed a higher frequency of other adverse outcomes in patients with cirrhosis, including intensive care admission, renal replacement therapy, nosocomial infection, and VTE, as well as a longer length of stay when compared to matched controls. Furthermore, we found that patients with cirrhosis were more often referred for palliative care. These findings align with previous research demonstrating a higher risk of mortality among patients with cirrhosis and COVID-19, as reported by Singh et al. in a cohort study conducted in the United States, which reported a relative risk (RR) of death 4.6 times higher for patients with cirrhosis [ 22 ]. In our study, we found that more than 50% of patients with cirrhosis have died, with 2.36-fold higher RR compared to those without cirrhosis. Ioannou et al. demonstrated in a large cohort involving veteran affairs that patients with cirrhosis and COVID-19 were more frequently hospitalized and had higher mortality than patients without cirrhosis [ 23 ]. However, there were no differences between both groups (cirrhosis and no cirrhosis) concerning mortality in the hospitalized subgroup analysis. Other studies reported higher 30-day mortality rates in cirrhotic patients [ 7 , 23 – 26 ], as well as higher mortality rates considering inpatient plus hospice deaths compared with patients with COVID-19 without cirrhosis [ 27 ]. Most of these included patients in the pandemic's pre-vaccination phase. Our findings extend these results, showing that even after vaccination efforts, patients with cirrhosis still have a worse prognosis. A large Swedish cohort study, which performed a propensity score-matching analysis, did not find a difference in the development of severe COVID-19 concerning mortality when comparing patients with and without cirrhosis [ 28 ]. Another cohort study, involving multiple European countries and using a large multinational database of patients with COVID-19, also conducted a propensity score-matched design [ 29 ]. This study included patients who had COVID-19 between March 2020 and March 2021 and found no difference in mortality after matching the cirrhosis group to the control group. The latter study included 70 patients with cirrhosis. These findings differ from our study, which also used propensity score-matched analysis to reduce bias due to other comorbidities, infection year, and other variables. Our findings are compatible with those from a large multinational cohort in the United Kingdom, which showed higher mortality in patients with cirrhosis and SARS-CoV-2 infection when compared to non-cirrhotic patients − 32% versus 8% [ 5 ]. However, after stratifying the cirrhosis group according to Child-Pugh stage-based classification and applying propensity score-matched models for each group, higher mortality rates were found in comparisons between Child B and Child C versus non-cirrhotic groups, while no difference was observed between Child A and the control group. Despite those controversial findings involving patients with cirrhosis and COVID-19, some recent studies have also shown that patients at different stages of liver disease may exhibit different responses. Mallet et al in a large French cohort found that patients with decompensated liver cirrhosis had a significantly higher mortality rate, whereas patients with mild liver disease or compensated cirrhosis were not at increased risk of COVID-19-related death [ 8 ]. Our study adds to this evidence by highlighting a high incidence of other severe outcomes, including ICU admission, septic shock, dialysis, respiratory failure, and IMV. In addition, we observed that respiratory failure occurred more frequently in patients with advanced CLD in line with previous data, which suggests that it remains the leading cause of death among that group of patients [ 5 ]. Some factors could contribute to higher mortality in the patients with cirrhosis. One of them is the increased incidence of CKD in the case group since it is well-known that renal impairment in patients with COVID-19 can lead to worse outcomes [ 30 , 31 ]. Furthermore, the higher incidence of smoking in the study group compared to the control group might also have contributed to the increased mortality, as smoking raises the risk of pulmonary lesions. Therefore, these patients may exhibit an exacerbated pulmonary response to COVID-19 infection. In our study, a higher number of patients with cirrhosis were eligible for palliative care than in the control group. This observation likely reflects the severity of ACLF in these patients. As a large number of cirrhotic patients often necessitated intensive care interventions, we suppose that there was a delay in the transition to palliative care and the limitation of life-sustaining treatments. This delay in palliative care referral could have contributed to the over intervention observed in the cirrhosis group, underscoring the importance of timely and proactive palliative care management in this vulnerable population during acute illness episodes. Cirrhosis is a prevalent disease in Brazil, especially alcohol-related hepatic cirrhosis [ 32 ]. Studies involving COVID-19 patients with underlying cirrhosis are scarce in Latin America. Thus, data from this study can help clinical professionals to better understand the characteristics of COVID-19 in this population. However, this study has some limitations. Our statistical analysis did not account for the clinical behavior given the different strains prevalent at various phases of the pandemic (including the impact of vaccination). Additionally, the stage of liver disease was not considered in the analysis due to a lack of registered data on this basis. Moreover, this is a retrospective observational cohort study, which inherently carries limitations in reviewing patient records. Nonetheless, periodic audits were conducted to ensure data quality. On the other hand, as a study strength, the utilization of advanced propensity score matching techniques enhances the robustness of our findings by minimizing selection bias and confounding effects, thus providing a more accurate estimation of the impact of cirrhosis on COVID-19 outcomes. This methodological rigor underscores the validity and reliability of our study's conclusions, contributing valuable insights to the existing body of knowledge. Furthermore, our study features an expressive number of patients across 41 different hospitals. The geographical diversity of hospitals across various regions of Brazil guarantees a diverse representation of the population in the study. Additionally, we analyzed data from the pre and post-vaccination phases. Most studies involving patients with cirrhosis were only developed in the first phase of the pandemic, with non-vaccinated patients. CONCLUSION This study includes 41 hospitals from the Northeast to the South of Brazil, representing a diverse cross-section of the large Brazilian population. We found that Brazilian COVID-19 inpatients with cirrhosis had significantly higher in-hospital mortality rates, and higher frequencies of ICU admission, IMV, dialysis, and other severe outcomes, as well as higher frequency of institution of palliative care when compared to the control group. Our findings underscore the need for these patients to receive particular attention from healthcare teams and allocated resources. Abbreviations ACLF acute-on-chronic liver failure ALT alanine aminotransferase aPTT activated partial thromboplastin time AST aspartate aminotransferase CAAE certificate of presentation of ethical review CAD coronary artery disease CKD chronic kidney disease CLD chronic liver disease COPD chronic obstructive pulmonary disease COVID 19-coronavirus Disease 19 HIV human immunodeficiency virus ICU intensive care unit IgM immunoglobulin M IMV invasive mechanical ventilation INR international normalized ratio IQR interquartile ranges REDCap® Research Electronic Data Capture RR relative risk RT PCR-real-time polymerase chain reaction S1 supplementary 1 SARSCoV 2-severe acute respiratory syndrome coronavirus 2 VTE venous thromboembolism Declarations Ethics approval and consent to participate This study was approved by the Ethics and Research Committee (CAAE 30350820.5.1001.0008) and had internal approval of ethics boards from each hospital. The study adhered to the Declaration of Helsinki. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This study was supported in part by Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), grant number APQ‑01154–21; and National Institute of Science and Technology for Health Technology Assessment (Instituto de Avaliação de Tecnologias em Saúde‑IATS); grant number 465518/2014‑1. The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. Authors' contributions Substantial contributions for the conception or design of the manuscript: Menezes, LSM; Ferrari, PSC; Valle, LR; Carvalho, RLR; Ferrari, Teresa Cristina A.; Marcolino, MS. Substantial contributions for data acquisition, analysis or interpretation: Menezes, LSM; Ferrari, PSC; Valle, LR; Carvalho, RLR; Marcolino, MS; Pires, MC; Flávia Carvalho Cardoso Costa; Ferreira, MAP; Guimaraes-Junior, MH; Francisco, S. C.; CARNEIRO, M; Aranha, FG; Silveira, DV. Writing original draft preparation: Menezes, LSM; Ferrari, PSC; Valle, LR; Carvalho, RLR; Marcolino, MS.; Writing - review and editing: Menezes, LSM; Ferrari, PSC; Valle, LR; Carvalho, RLR; Marcolino, MS; Ferrari, Teresa Cristina A.; Pires, MC; Francisco, S. C.; CARNEIRO, M; Aranha, FG.; Supervision: Menezes, LSM and Marcolino, MS.; Project administration: Marcolino, MS.; Revised the manuscript critically for important intellectual content: all authors. Final approval of the version to be published: all authors. Acknowledgements We would like to thank the hospitals, which are part of this collaboration, they are: Hospitais da Rede Mater Dei; Hospital das Clínicas da UFMG; Hospital de Clínicas de Porto Alegre; Hospital Santo Antônio; Hospital Eduardo de Menezes; Hospital Tacchini; Hospital Márcio Cunha; Hospital Metropolitano Dr. Célio de Castro; Hospital Metropolitano Odilon Behrens; Hospital Risoleta Tolentino Neves; Hospital Santa Rosália; Hospital Santa Cruz; Hospital São João de Deus; Hospital Semper; Hospital Unimed‑BH; Hospital Universitário Canoas; Hospital Universitário Santa Maria; Hospital Moinhos de Vento; Instituto Mário Penna; Hospital Nossa Senhora da Conceição; Hospital João XXIII; Hospital Regional Antônio Dias; Hospital Júlia Kubitschek; Hospital Cristo Redentor; Hospital Mãe de Deus; Hospital Regional do Oeste; Hospital das Clínicas da Faculdade de Medicina de Botucatu; Hospital das Clínicas da Universidade Federal de Pernambuco; Hospital Universitário Ciências Médicas; Hospital Bruno Born; Hospital SOS Cárdio; Hospital São Lucas da PUCRS; Orizonti‑Instituto de Saúde e Longevidade Ltda; Santa Casa de Misericórdia de Belo Horizonte; Universidade Federal do Rio Grande do Sul. 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Gao F, Zheng KI, Fan Y-C, Targher G, Byrne CD, Zheng M-H. ACE2: A Linkage for the Interplay Between COVID-19 and Decompensated Cirrhosis. Am J Gastroenterol. 2020;115:1544. Coronavírus Brasil. [cited 17 Jun 2024]. Available: https://covid.saude.gov.br/ . Marcolino MS, Ziegelmann PK, Souza-Silva MVR, Nascimento IJB, Oliveira LM, Monteiro LS, et al. Clinical characteristics and outcomes of patients hospitalized with COVID-19 in Brazil: Results from the Brazilian COVID-19 registry. Int J Infect Dis. 2021;107:300–10. Diseases C. Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases. World Health Organization; 19 Mar 2020 [cited 3 Mar 2024]. Available: https://www.who.int/publications/i/item/10665-331501 . Research electronic data capture. (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inf. 2009;42:377–81. The REDCap consortium. Building an international community of software platform partners. J Biomed Inf. 2019;95:103208. Soriano Marcolino M, Minelli Figueira R, Pereira Afonso Dos Santos J, Silva Cardoso C, Luiz Ribeiro A, Alkmim MB. The Experience of a Sustainable Large Scale Brazilian Telehealth Network. Telemed J E Health. 2016;22:899–908. Bicalho MAC, Aliberti MJR, Delfino-Pereira P, Chagas VS, Rosa PMdaS, Pires MC, et al. Clinical characteristics and outcomes of COVID-19 patients with preexisting dementia: a large multicenter propensity-matched Brazilian cohort study. BMC Geriatr. 2024;24:25. Singh S, Khan A. Clinical Characteristics and Outcomes of Coronavirus Disease 2019 Among Patients With Preexisting Liver Disease in the United States: A Multicenter Research Network Study. Gastroenterology. 2020;159:768–e7713. Ioannou GN, Liang PS, Locke E, Green P, Berry K, O’Hare AM, et al. Cirrhosis and Severe Acute Respiratory Syndrome Coronavirus 2 Infection in US Veterans: Risk of Infection, Hospitalization, Ventilation, and Mortality. Hepatology. 2021;74:322–35. Mendizabal M, Ridruejo E, Piñero F, Anders M, Padilla M, Toro LG, et al. Comparison of different prognostic scores for patients with cirrhosis hospitalized with SARS-CoV-2 infection. Ann Hepatol. 2021;25:100350. Nevola R, Criscuolo L, Beccia D, Delle Femine A, Ruocco R, Imbriani S, et al. Impact of chronic liver disease on SARS-CoV-2 infection outcomes: Roles of stage, etiology and vaccination. World J Gastroenterol. 2023;29:800–14. Iavarone M, D’Ambrosio R, Soria A, Triolo M, Pugliese N, Del Poggio P, et al. High rates of 30-day mortality in patients with cirrhosis and COVID-19. J Hepatol. 2020;73:1063–71. Bajaj JS, Garcia-Tsao G, Biggins SW, Kamath PS, Wong F, McGeorge S, et al. Comparison of mortality risk in patients with cirrhosis and COVID-19 compared with patients with cirrhosis alone and COVID-19 alone: multicentre matched cohort. Gut. 2021;70:531–6. Simon TG, Hagström H, Sharma R, Söderling J, Roelstraete B, Larsson E, et al. Risk of severe COVID-19 and mortality in patients with established chronic liver disease: a nationwide matched cohort study. BMC Gastroenterol. 2021;21:1–11. Brozat JF, Hanses F, Haelberger M, Stecher M, Dreher M, Tometten L, et al. COVID-19 mortality in cirrhosis is determined by cirrhosis-associated comorbidities and extrahepatic organ failure: Results from the multinational LEOSS registry. United Eur Gastroenterol J. 2022;10:409–24. Kumar R, Priyadarshi RN, Anand U. Chronic renal dysfunction in cirrhosis: A new frontier in hepatology. World J Gastroenterol. 2021;27:990–1005. Chung EYM, Palmer SC, Natale P, Krishnan A, Cooper TE, Saglimbene VM, et al. Incidence and Outcomes of COVID-19 in People With CKD: A Systematic Review and Meta-analysis. Am J Kidney Dis. 2021;78:804–15. Melo APS, França EB, Malta DC, Garcia LP, Mooney M, Naghavi M. Mortality due to cirrhosis, liver cancer, and disorders attributed to alcohol use: Global Burden of Disease in Brazil, 1990 and 2015. Rev Bras Epidemiol. 2017;20Suppl(01):61–74. Tables Table 3 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table3.docx SupplementaryMaterial.docx Cite Share Download PDF Status: Published Journal Publication published 15 Jan, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 18 Jul, 2024 Editor assigned by journal 18 Jul, 2024 Submission checks completed at journal 18 Jul, 2024 First submitted to journal 15 Jul, 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4746005","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":328739829,"identity":"2b46b99f-2353-4565-9f6f-ba8b5fb1d290","order_by":0,"name":"Luanna Silva Monteiro Menezes","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYBACPhReAgODHIg+8ACPFjYEkxmsxRisJYFoLUCQ2AC1DrcWieRnjwtq6qL5pfsPPni4xyZ9ftjhh0Bb7OR0G3BpSTM3nnHscO7MOYeZDRKepeVuvJ1mANSSbGx2AJeWBDNpHrYDuRtuJAPZBw7nbpydANJyIHEbTi3p36R5/tWBtLD/AGpJN5yd/oGAlhwzad42ZrAtDEAtCfLSOQRs4XlTJs3bB/TLjGRjoMPSDDdI5xQcSDDA7Rd+9vRt0jzf6nL7JRIffvxxwEZefnb65g8fKuzkcGnBBAZglQbEKgcB+QZSVI+CUTAKRsFIAAAaTF825wiCqgAAAABJRU5ErkJggg==","orcid":"","institution":"Universidade Federal de Minas Gerais","correspondingAuthor":true,"prefix":"","firstName":"Luanna","middleName":"Silva Monteiro","lastName":"Menezes","suffix":""},{"id":328739831,"identity":"195e8b0b-cfcc-44a3-9bcb-6684d7897b0a","order_by":1,"name":"Pedro Ferrari Sales Cunha","email":"","orcid":"","institution":"Hospital Metropolitano Odilon Behrens. R. Formiga","correspondingAuthor":false,"prefix":"","firstName":"Pedro","middleName":"Ferrari Sales","lastName":"Cunha","suffix":""},{"id":328739832,"identity":"b2f4e671-17b0-43cd-bf85-a57e69a4b28e","order_by":2,"name":"Magda Carvalho Pires","email":"","orcid":"","institution":"Universidade Federal de Minas Gerais","correspondingAuthor":false,"prefix":"","firstName":"Magda","middleName":"Carvalho","lastName":"Pires","suffix":""},{"id":328739833,"identity":"25848852-de7f-4b09-9318-9fa520df7c95","order_by":3,"name":"Lucas Rocha Valle","email":"","orcid":"","institution":"Universidade Federal de Minas Gerais","correspondingAuthor":false,"prefix":"","firstName":"Lucas","middleName":"Rocha","lastName":"Valle","suffix":""},{"id":328739838,"identity":"54ba3235-6c05-4e32-8f48-8b3d35880de9","order_by":4,"name":"Flávia Carvalho Cardoso Costa","email":"","orcid":"","institution":"Hospitais da Rede Mater Dei. Av. do Contorno","correspondingAuthor":false,"prefix":"","firstName":"Flávia","middleName":"Carvalho Cardoso","lastName":"Costa","suffix":""},{"id":328739840,"identity":"a4d8c310-a252-425d-ab9d-4d6dc32e70f9","order_by":5,"name":"Maria Angélica Pires Ferreira","email":"","orcid":"","institution":"Hospital de Clínicas de Porto Alegre. R. Ramiro Barcelos","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"Angélica Pires","lastName":"Ferreira","suffix":""},{"id":328739842,"identity":"74fcbe0a-631f-4411-bb98-112c0eb5f104","order_by":6,"name":"Milton Henriques Guimarães-Júnior","email":"","orcid":"","institution":"Hospital Márcio Cunha","correspondingAuthor":false,"prefix":"","firstName":"Milton","middleName":"Henriques","lastName":"Guimarães-Júnior","suffix":""},{"id":328739843,"identity":"add3f01c-29b7-4bfb-876f-28db3d8596b1","order_by":7,"name":"Saionara Cristina Francisco","email":"","orcid":"","institution":"Hospital Metropolitano Doutor Célio de Castro","correspondingAuthor":false,"prefix":"","firstName":"Saionara","middleName":"Cristina","lastName":"Francisco","suffix":""},{"id":328739844,"identity":"b5ac1138-a549-4e71-88c3-8d510f4ca165","order_by":8,"name":"Marcelo Carneiro","email":"","orcid":"","institution":"Hospital Santa Cruz. R. Fernando Abott","correspondingAuthor":false,"prefix":"","firstName":"Marcelo","middleName":"","lastName":"Carneiro","suffix":""},{"id":328739845,"identity":"fcd74aac-f75f-455f-b1f0-c6e2ef4bc698","order_by":9,"name":"Daniel Vitório Silveira","email":"","orcid":"","institution":"Hospital Unimed BH","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"Vitório","lastName":"Silveira","suffix":""},{"id":328739847,"identity":"087e829a-e7ae-4a07-9c52-bd507e0f18cb","order_by":10,"name":"Fernando Graça Aranha","email":"","orcid":"","institution":"Hospital SOS Cárdio","correspondingAuthor":false,"prefix":"","firstName":"Fernando","middleName":"Graça","lastName":"Aranha","suffix":""},{"id":328739849,"identity":"cc8b2551-6ccb-4d8d-a867-24baf810caa2","order_by":11,"name":"Rafael Lima Rodrigues Carvalho","email":"","orcid":"","institution":"Hospital Universitário","correspondingAuthor":false,"prefix":"","firstName":"Rafael","middleName":"Lima Rodrigues","lastName":"Carvalho","suffix":""},{"id":328739851,"identity":"774a8c2b-ec09-4672-ad28-4c537434bd69","order_by":12,"name":"Teresa Cristina Abreu Ferrari","email":"","orcid":"","institution":"Universidade Federal de Minas Gerais","correspondingAuthor":false,"prefix":"","firstName":"Teresa","middleName":"Cristina Abreu","lastName":"Ferrari","suffix":""},{"id":328739854,"identity":"b18c5c0e-d3d6-4955-9a4b-e3694054c32f","order_by":13,"name":"Milena Soriano Marcolino","email":"","orcid":"","institution":"Universidade Federal de Minas Gerais","correspondingAuthor":false,"prefix":"","firstName":"Milena","middleName":"Soriano","lastName":"Marcolino","suffix":""}],"badges":[],"createdAt":"2024-07-16 00:42:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4746005/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4746005/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-024-10424-x","type":"published","date":"2025-01-15T15:57:39+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":62729708,"identity":"52224c36-d4e3-4356-8df4-85125774747c","added_by":"auto","created_at":"2024-08-18 23:07:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":27628,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the patients included in this study\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4746005/v1/5270b6c9e24295bad971f9f3.png"},{"id":74285721,"identity":"7900e707-e8d4-4b15-9fde-66e36a8b6885","added_by":"auto","created_at":"2025-01-20 16:14:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":907242,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4746005/v1/524e1135-d8ae-4567-b6b5-2e1d1201feb7.pdf"},{"id":62729291,"identity":"d9ef41f8-6089-43dc-b149-ab34743af9e7","added_by":"auto","created_at":"2024-08-18 22:59:46","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16415,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.docx","url":"https://assets-eu.researchsquare.com/files/rs-4746005/v1/c7dee836fb869574e8ff511c.docx"},{"id":62729292,"identity":"36ef61ec-c62e-4931-bb96-c573f5ab2384","added_by":"auto","created_at":"2024-08-18 22:59:46","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":18630,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-4746005/v1/0266ce0ace0adcd41672d166.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eClinical Outcomes of Covid-19 in Patients With Liver Cirrhosis - A Propensity-Matched Analysis From a Multicentric Brazilian Cohort\u003c/p\u003e","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eLiver cirrhosis has a variable prognosis and is associated with a rising global burden of morbidity and mortality. Its prevalence has approximately doubled since the 1990s. Epidemiological data related to chronic liver disease (CLD) are variable and scarce, particularly in low-income countries, suggesting that the actual numbers may be underestimated [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Despite these limitations, some data indicate that cirrhosis is the eighth leading cause of death in Brazil, representing a significant disease burden [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAcute-on-chronic liver failure (ACLF) refers to decompensated chronic liver disease, characterized by complications such as variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome. ACLF is associated with an acute inflammatory state that can lead to multiple organ failure and has a high 28-day mortality rate, exceeding 20%, compared to under 5% among patients with decompensated cirrhosis but without ACLF [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Many conditions can trigger organic dysfunctions in those patients, including both intrahepatic and extrahepatic conditions.\u003c/p\u003e \u003cp\u003eDuring the COVID-19 pandemic, SARS-CoV-2 infection was a significant cause of ACLF, with studies showing worse prognosis and higher mortality among patients with chronic liver disease (CLD) [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. CLD, especially cirrhosis, has also been demonstrated to be an independent risk factor for mortality in COVID-19 patients. Additionally, greater severity of underlying liver disease has been correlated with an increased likelihood of mortality in individuals with COVID-19 [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Vaccination has been shown to reduce this outcome in patients with CLD [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCOVID-19 complications extend beyond the respiratory tract, affecting the cardiac, gastrointestinal, hepatic, renal, hematologic, and nervous systems [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Among patients with these complications, liver injury, indicated by elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), has been reported in a significant number of hospitalized COVID-19 patients, potentially indicating a poorer prognosis [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Direct liver damage by SARS-CoV-2 has been identified as one of the main factors contributing to ACLF and systemic inflammation in patients with pre-existing CLD [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere is a lack of robust evidence regarding the prognosis of Latin patients with CDL in the context of SARS-CoV-2 infection. Up to June 2024, Brazil reached 38,823,186 confirmed cases, with 712,349 deaths due to COVID-19 complications [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. No robust Latin American studies have investigated the clinical outcomes of COVID-19 in patients with cirrhosis so far.\u003c/p\u003e \u003cp\u003eTherefore, this study aimed to compare the clinical features and outcomes of COVID-19-infected Brazilian inpatients with and without cirrhosis across different phases of the pandemic. This research addresses a gap in understanding this issue within the Brazilian population, which comprises approximately 49% of South America's population.\u003c/p\u003e"},{"header":"MATERIAL AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eThis study is part of a large multicenter retrospective Brazilian cohort (Brazilian COVID-19 Registry), which involved 41 hospitals, including private and public, in 18 cities from six Brazilian states (Bahia, Minas Gerais, Pernambuco, Rio Grande do Sul, Santa Catarina, S\u0026atilde;o Paulo), comprising two periods: March to September 2020 and March 2021 to August 2022 [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study included consecutive adult patients (\u0026ge;\u0026thinsp;18 years old) with laboratory-confirmed COVID-19 admitted to the participating hospitals. Positive cases were considered through the detection of SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR) tests in nasopharyngeal or oropharyngeal swab or serological tests [IgM] in the first phase of the study; and by RT-PCR in the second phase [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Patients admitted because of COVID-19 or those who developed first symptoms of COVID-19 infection during hospitalization and tested positive were included.\u003c/p\u003e \u003cp\u003ePatients transferred from other hospitals, those younger than 18, and pregnant and puerperal women were excluded from the present analysis.\u003c/p\u003e \u003cp\u003ePatients who reported having cirrhosis and had this comorbidity documented in their medical records were classified as \"cases\".\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eDemographic data, clinical characteristics, laboratory results in hospital presentation, and outcomes were collected from the medical records by trained healthcare professionals and medical or nursing students to the Research Electronic Data Capture (REDCap\u0026reg;) electronic platform [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], hosted at the Telehealth Center of the University Hospital of the \u003cem\u003eUniversidade Federal de Minas Gerais\u003c/em\u003e [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. To ensure reliability and monitor data quality, the database was routinely audited. Study protocol and definition details were published elsewhere [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. For more details about the collected data, refer to Supplementary File 1. All clinical characteristics regarding the patient\u0026rsquo;s previous history were considered based on the records in the medical register.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eThe primary outcome was in-hospital mortality. Secondary outcomes included length of hospital stay, admission to the intensive care unit (ICU), invasive mechanical ventilation (IMV), renal replacement therapy, septic shock, nosocomial infection, acute heart failure, myocarditis, any type of bleeding, venous thromboembolism (VTE) and palliative care reference.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eTo mitigate potential confounding variables, a rigorous propensity score matching approach was employed to balance the baseline characteristics between patients with underlying cirrhosis and control patients (those without underlying cirrhosis). The propensity score model was estimated by logistic regression, incorporating a comprehensive set of predictors: age, sex at birth, number of comorbidities (hypertension, diabetes mellitus, obesity, coronary artery disease, heart failure, atrial fibrillation or flutter, chronic obstructive pulmonary disease, cancer, and previous stroke), hospital of admission, whether it was an in-hospital clinical manifestation of COVID-19 and admission year (2020 vs 2021\u0026ndash;2022) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. This robust model ensures a meticulous adjustment for these potential confounders.\u003c/p\u003e \u003cp\u003eMatching was conducted by identifying control group individuals whose propensity scores closely aligned with those of the cirrhotic patient group. Closeness was stringently defined as being within 0.16 standard deviations of the logit of the propensity score, which was measured on a scale from 0 to 1.00. This matching process was executed using the MatchIt package in R software.\u003c/p\u003e \u003cp\u003eFollowing the matching process, a thorough descriptive analysis of data was performed. Categorical data were presented as absolute numbers and proportions. The Kolmogorov-Smirnov test was applied to verify data normality. All continuous variables had non-normal distribution and were expressed as median and interquartile ranges (IQR). The chi-square and Fisher\u0026rsquo;s exact tests were used to compare the distribution of categorical variables, while the Wilcoxon\u0026ndash;Mann\u0026ndash;Whitney test was used for continuous variables.\u003c/p\u003e \u003cp\u003eStatistical analysis was performed using R software (version 4.0.2) with tidyverse, stringr, gtsummary and MatchIt packages. Statistical tests were conducted with an alpha level of 0.05 in two-sided tests, so results were considered statistically significant if p-value was \u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eEthics statement\u003c/h2\u003e \u003cp\u003e This study was approved by the Brazilian National Commission for Research Ethics (CAAE 30350820.5.1001.0008). Individual informed consent was waived due to the pandemic situation and the use of data from medical records.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eDemographic and clinical features\u003c/h2\u003e \u003cp\u003eThe study included 749 patients. Of those, 117 patients had cirrhosis and 632 were matched controls (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The median age was 61 (IQR 50\u0026ndash;70) years-old, and 63.4% were men.\u003c/p\u003e \u003cp\u003eBoth groups had similar demographic characteristics and comorbidities, except for hypertension and chronic kidney disease (CKD) - people with cirrhosis had a lower frequency of hypertension (40.2% vs 57.6%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and a higher frequency of CKD (14.5% vs 6.6%; p\u0026thinsp;=\u0026thinsp;0.004), when compared to their matched controls. Smoking (14.5% vs 5.1%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and alcohol consumption (42.7% vs 8.4%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were more frequent in the cirrhosis than in the control group. Other demographic characteristics are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographics and clinical characteristics of Covid-19 patients with cirrhosis and matched controls without cirrhosis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;749\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStudy group\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;117\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl group\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;632\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e61.0 (50.0, 70.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61.0 (52.0, 70.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e61.0 (49.0, 70.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.469\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e475 (63.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e80 (68.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e395 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.225\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReceived vaccine (any number of doses)\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e76 (18.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17 (27.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e59 (17.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e411 (54.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47 (40.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e364 (57.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e52 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (6.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e44 (7.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.961\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart Failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e59 (7.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e47 (7.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.298\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrial fibrillation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26 (3.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21 (3.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.583\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIschemic stroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e30 (4.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.209\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChagas disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (1.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9 (1.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.368\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsthma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e42 (5.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e37 (5.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.495\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOPD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e51 (6.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e39 (6.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.107\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e232 (31.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e43 (36.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e189 (29.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.141\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObesity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e93 (12.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (11.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e80 (12.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.641\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCKD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e59 (7.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17 (14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42 (6.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRheumatologic conditions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20 (2.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.057\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHIV infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e57 (7.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e45 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.240\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (1.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9 (1.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.413\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIllicit drugs use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (1.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12 (1.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol abuse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e103 (13.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50 (42.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e53 (8.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent Smoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e49 (6.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17 (14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e32 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e135 (18.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23 (19.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e112 (17.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.617\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eCAD: coronary artery disease; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; HIV: human immunodeficiency virus \u003csup\u003e1\u003c/sup\u003en (%); Median (IQR); \u003csup\u003e2\u003c/sup\u003e Statistical tests performed: chi-square test; Wilcoxon rank-sum test; Fisher's exact test. \u003csup\u003e3\u003c/sup\u003eMissing: 45.3%\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003ePatient's data upon hospital presentation\u003c/h2\u003e \u003cp\u003eThere were no significant differences in the self-reported symptoms between patients with cirrhosis and controls (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). Regarding objective changes in signs on physical examination upon hospital presentations, a higher incidence of abnormal mental status, with Glasgow Coma Scale of less than 15, was noted in the study group (16.2% vs 8.4%, p\u0026thinsp;=\u0026thinsp;0.008). Regarding hemodynamic status, the group with cirrhosis had lower arterial pressure compared to the control group. This was evaluated using systolic blood pressure as a categorical variable (\u0026ge;\u0026thinsp;90 mmHg, adjusted for inotropic requirement), with 87.9% of the cirrhosis group meeting this criterion versus 95.4% of the control group (p\u0026thinsp;=\u0026thinsp;0.008) (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRegarding laboratory exams, patients with cirrhosis had lower median hemoglobin levels (10.8 g/dl vs 13.1 g/dl; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), lower platelets (127,000 cells/mm3 vs 200,000 cells/mm3; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), leukocytes, neutrophils, and lymphocytes counts, and lower median C-reactive protein (63.0 vs 76.0 p\u0026thinsp;=\u0026thinsp;0.044) when compared to controls. Median of bilirubin, activated partial thromboplastin time, international normalized ratio, and lactate levels upon hospital presentation were significantly higher in the CLD group (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). AST was abnormal in both groups, but the cirrhotic group had a higher elevation than the controls (65.2 U/L vs 42.0 U/L; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory exams of Covid-19 patients with cirrhosis and matched controls without cirrhosis upon hospital presentation\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;749\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;632\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStudy group\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;117\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.7 (10.9, 14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.1 (11.4, 14.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.8 (8.9, 12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukocytes (cells/mm\u0026sup3;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7,300.0 (5,335.0, 10,292.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7,440.0 (5,630.0, 10,410.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,026.0 (3,810.0, 9,410.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophils (cells/mm\u0026sup3;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5,430.0 (3,732.0, 8,089.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5,481.0 (3,940.0, 8,159.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,347.0 (2,631.2, 7,202.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes (cells/mm\u0026sup3;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,020.0 (680.0, 1,530.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,080.0 (727.5, 1,549.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e850.5 (496.5, 1,306.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets (cells/mm\u0026sup3;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e194,000 (143,000, 258,000)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e200,000 (156,500, 262,000)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e127,000 (73,250, 203,750)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal bilirubin (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6 (0.4, 0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5 (0.3, 0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.2 (0.7, 2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eaPTT (seconds)/control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.0 (1.0, 1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0 (1.0, 1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.1 (1.0, 1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eINR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.1 (1.0, 1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.1 (1.0, 1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.3 (1.2, 1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9 (0.7, 1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9 (0.7, 1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0 (0.7, 1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.155\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUreia (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.0 (28.0, 60.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.0 (28.5, 58.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44.0 (26.5, 75.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.321\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC-reactive protein (mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74.3 (38.0, 136.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.0 (39.4, 137.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63.0 (24.4, 104.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactate (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.6 (1.1, 2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5 (1.1, 2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0 (1.5, 2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspartate aminotransferase (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43.0 (29.6, 73.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.0 (28.0, 63.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60.0 (36.2, 116.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlanine aminotransferase (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.0 (21.0, 59.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.0 (21.0, 63.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.0 (20.0, 47.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.242\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBicarbonate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.0 (20.1, 25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.0 (21.0, 25.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.4 (17.2, 23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.4 (7.4, 7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.4 (7.4, 7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.4 (7.4, 7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.693\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eaPTT: activated partial thromboplastin time; INR: international normalized ratio; \u003csup\u003e1\u003c/sup\u003eMedian (IQR); \u003csup\u003e2\u003c/sup\u003eStatistical tests performed: chi-square test; Wilcoxon rank-sum test; Fisher's exact test.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes analysis\u003c/h2\u003e \u003cp\u003eIn-hospital mortality was higher among patients with cirrhosis (51.3% vs 21.7%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), compared to matched controls. They also had a higher frequency of ICU admission (51.3% vs 38.0%, p\u0026thinsp;=\u0026thinsp;0.007), IMV (26.6% vs 43.9%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), dialysis (17.9% vs 11.1%, p\u0026thinsp;=\u0026thinsp;0.038), and septic shock (23.9% vs 14.9%; p\u0026thinsp;=\u0026thinsp;0.015). Additionally, they were referred to palliative care more often than the control group (19.7% vs 7.4%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). On the other hand, patients with cirrhosis had a lower incidence of VTE when compared to the controls (0.9% vs 5.4%; p\u0026thinsp;=\u0026thinsp;0.033), and the incidence of hemorrhages was similar in both groups (6.8% vs 3.8%; p\u0026thinsp;=\u0026thinsp;0.139). The median length of stay was 10 days for the control group and 13 days for the CLD group (p\u0026thinsp;=\u0026thinsp;0.106) (Table\u0026nbsp;3).\u003c/p\u003e "},{"header":"DISCUSSION","content":"\u003cp\u003eThis study demonstrated a high mortality rate among inpatients with liver cirrhosis and concomitant COVID-19 infection \u0026ndash; 51.3%, compared to 21.7% in the control group, which did not have liver disease. We also observed a higher frequency of other adverse outcomes in patients with cirrhosis, including intensive care admission, renal replacement therapy, nosocomial infection, and VTE, as well as a longer length of stay when compared to matched controls. Furthermore, we found that patients with cirrhosis were more often referred for palliative care.\u003c/p\u003e \u003cp\u003eThese findings align with previous research demonstrating a higher risk of mortality among patients with cirrhosis and COVID-19, as reported by Singh et al. in a cohort study conducted in the United States, which reported a relative risk (RR) of death 4.6 times higher for patients with cirrhosis [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In our study, we found that more than 50% of patients with cirrhosis have died, with 2.36-fold higher RR compared to those without cirrhosis. Ioannou et al. demonstrated in a large cohort involving veteran affairs that patients with cirrhosis and COVID-19 were more frequently hospitalized and had higher mortality than patients without cirrhosis [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, there were no differences between both groups (cirrhosis and no cirrhosis) concerning mortality in the hospitalized subgroup analysis. Other studies reported higher 30-day mortality rates in cirrhotic patients [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], as well as higher mortality rates considering inpatient plus hospice deaths compared with patients with COVID-19 without cirrhosis [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Most of these included patients in the pandemic's pre-vaccination phase. Our findings extend these results, showing that even after vaccination efforts, patients with cirrhosis still have a worse prognosis.\u003c/p\u003e \u003cp\u003eA large Swedish cohort study, which performed a propensity score-matching analysis, did not find a difference in the development of severe COVID-19 concerning mortality when comparing patients with and without cirrhosis [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Another cohort study, involving multiple European countries and using a large multinational database of patients with COVID-19, also conducted a propensity score-matched design [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. This study included patients who had COVID-19 between March 2020 and March 2021 and found no difference in mortality after matching the cirrhosis group to the control group. The latter study included 70 patients with cirrhosis. These findings differ from our study, which also used propensity score-matched analysis to reduce bias due to other comorbidities, infection year, and other variables. Our findings are compatible with those from a large multinational cohort in the United Kingdom, which showed higher mortality in patients with cirrhosis and SARS-CoV-2 infection when compared to non-cirrhotic patients \u0026minus;\u0026thinsp;32% versus 8% [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, after stratifying the cirrhosis group according to Child-Pugh stage-based classification and applying propensity score-matched models for each group, higher mortality rates were found in comparisons between Child B and Child C versus non-cirrhotic groups, while no difference was observed between Child A and the control group.\u003c/p\u003e \u003cp\u003eDespite those controversial findings involving patients with cirrhosis and COVID-19, some recent studies have also shown that patients at different stages of liver disease may exhibit different responses. Mallet et al in a large French cohort found that patients with decompensated liver cirrhosis had a significantly higher mortality rate, whereas patients with mild liver disease or compensated cirrhosis were not at increased risk of COVID-19-related death [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study adds to this evidence by highlighting a high incidence of other severe outcomes, including ICU admission, septic shock, dialysis, respiratory failure, and IMV. In addition, we observed that respiratory failure occurred more frequently in patients with advanced CLD in line with previous data, which suggests that it remains the leading cause of death among that group of patients [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSome factors could contribute to higher mortality in the patients with cirrhosis. One of them is the increased incidence of CKD in the case group since it is well-known that renal impairment in patients with COVID-19 can lead to worse outcomes [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Furthermore, the higher incidence of smoking in the study group compared to the control group might also have contributed to the increased mortality, as smoking raises the risk of pulmonary lesions. Therefore, these patients may exhibit an exacerbated pulmonary response to COVID-19 infection.\u003c/p\u003e \u003cp\u003eIn our study, a higher number of patients with cirrhosis were eligible for palliative care than in the control group. This observation likely reflects the severity of ACLF in these patients. As a large number of cirrhotic patients often necessitated intensive care interventions, we suppose that there was a delay in the transition to palliative care and the limitation of life-sustaining treatments. This delay in palliative care referral could have contributed to the over intervention observed in the cirrhosis group, underscoring the importance of timely and proactive palliative care management in this vulnerable population during acute illness episodes.\u003c/p\u003e \u003cp\u003eCirrhosis is a prevalent disease in Brazil, especially alcohol-related hepatic cirrhosis [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Studies involving COVID-19 patients with underlying cirrhosis are scarce in Latin America. Thus, data from this study can help clinical professionals to better understand the characteristics of COVID-19 in this population.\u003c/p\u003e \u003cp\u003eHowever, this study has some limitations. Our statistical analysis did not account for the clinical behavior given the different strains prevalent at various phases of the pandemic (including the impact of vaccination). Additionally, the stage of liver disease was not considered in the analysis due to a lack of registered data on this basis. Moreover, this is a retrospective observational cohort study, which inherently carries limitations in reviewing patient records. Nonetheless, periodic audits were conducted to ensure data quality.\u003c/p\u003e \u003cp\u003eOn the other hand, as a study strength, the utilization of advanced propensity score matching techniques enhances the robustness of our findings by minimizing selection bias and confounding effects, thus providing a more accurate estimation of the impact of cirrhosis on COVID-19 outcomes. This methodological rigor underscores the validity and reliability of our study's conclusions, contributing valuable insights to the existing body of knowledge. Furthermore, our study features an expressive number of patients across 41 different hospitals. The geographical diversity of hospitals across various regions of Brazil guarantees a diverse representation of the population in the study. Additionally, we analyzed data from the pre and post-vaccination phases. Most studies involving patients with cirrhosis were only developed in the first phase of the pandemic, with non-vaccinated patients.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis study includes 41 hospitals from the Northeast to the South of Brazil, representing a diverse cross-section of the large Brazilian population. We found that Brazilian COVID-19 inpatients with cirrhosis had significantly higher in-hospital mortality rates, and higher frequencies of ICU admission, IMV, dialysis, and other severe outcomes, as well as higher frequency of institution of palliative care when compared to the control group. Our findings underscore the need for these patients to receive particular attention from healthcare teams and allocated resources.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eACLF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eacute-on-chronic liver failure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eALT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ealanine aminotransferase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eaPTT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eactivated partial thromboplastin time\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAST\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003easpartate aminotransferase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCAAE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecertificate of presentation of ethical review\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCAD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecoronary artery disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCKD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003echronic kidney disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCLD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003echronic liver disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCOPD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003echronic obstructive pulmonary disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCOVID\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e19-coronavirus Disease 19\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehuman immunodeficiency virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIgM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eimmunoglobulin M\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIMV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einvasive mechanical ventilation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eINR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einternational normalized ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einterquartile ranges\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eREDCap\u0026reg;\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eResearch Electronic Data Capture\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003erelative risk\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePCR-real-time polymerase chain reaction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eS1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esupplementary 1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSARSCoV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e2-severe acute respiratory syndrome coronavirus 2\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVTE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003evenous thromboembolism\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics and Research Committee (CAAE 30350820.5.1001.0008) and had internal approval of ethics boards from each hospital. The study adhered to the Declaration of Helsinki.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported in part by Funda\u0026ccedil;\u0026atilde;o de Amparo \u0026agrave; Pesquisa do Estado de Minas Gerais (FAPEMIG), grant number APQ‑01154\u0026ndash;21; and National Institute of Science and Technology for Health Technology Assessment (Instituto de Avalia\u0026ccedil;\u0026atilde;o de Tecnologias em Sa\u0026uacute;de‑IATS); grant number 465518/2014‑1. The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSubstantial contributions for the conception or design of the manuscript: Menezes, LSM; Ferrari, PSC; Valle, LR; Carvalho, RLR; Ferrari, Teresa Cristina A.; Marcolino, MS.\u003c/p\u003e\n\u003cp\u003eSubstantial contributions for data acquisition, analysis or interpretation: \u0026nbsp;Menezes, LSM; Ferrari, PSC; Valle, LR; Carvalho, RLR; Marcolino, MS; Pires, MC; \u0026nbsp;Fl\u0026aacute;via Carvalho Cardoso Costa; Ferreira, MAP; Guimaraes-Junior, MH; Francisco, S. C.; CARNEIRO, M; Aranha, FG; Silveira, DV.\u003c/p\u003e\n\u003cp\u003eWriting original draft preparation: Menezes, LSM; Ferrari, PSC; Valle, LR; Carvalho, RLR; Marcolino, MS.;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWriting - review and editing: Menezes, LSM; Ferrari, PSC; Valle, LR; Carvalho, RLR; Marcolino, MS; Ferrari, Teresa Cristina A.; Pires, MC; Francisco, S. C.; CARNEIRO, M; Aranha, FG.;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSupervision: Menezes, LSM and Marcolino, MS.;\u003c/p\u003e\n\u003cp\u003eProject administration: Marcolino, MS.;\u003c/p\u003e\n\u003cp\u003eRevised the manuscript critically for important intellectual content: all authors. Final approval of the version to be published: all authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank the hospitals, which are part of this collaboration, they are: Hospitais da Rede Mater Dei; Hospital das Cl\u0026iacute;nicas da UFMG; Hospital de Cl\u0026iacute;nicas de Porto Alegre; Hospital Santo Ant\u0026ocirc;nio; Hospital Eduardo de Menezes; Hospital Tacchini; Hospital M\u0026aacute;rcio Cunha; Hospital Metropolitano Dr. C\u0026eacute;lio de Castro; Hospital Metropolitano Odilon Behrens; Hospital Risoleta Tolentino Neves; Hospital Santa Ros\u0026aacute;lia; Hospital Santa Cruz; Hospital S\u0026atilde;o Jo\u0026atilde;o de Deus; Hospital Semper; Hospital Unimed‑BH; Hospital Universit\u0026aacute;rio Canoas; Hospital Universit\u0026aacute;rio Santa Maria; Hospital Moinhos de Vento; Instituto M\u0026aacute;rio Penna; Hospital Nossa Senhora da Concei\u0026ccedil;\u0026atilde;o; Hospital Jo\u0026atilde;o XXIII; Hospital Regional Ant\u0026ocirc;nio Dias; Hospital J\u0026uacute;lia Kubitschek; Hospital Cristo Redentor; Hospital M\u0026atilde;e de Deus; Hospital Regional do Oeste; Hospital das Cl\u0026iacute;nicas da Faculdade de Medicina de Botucatu; Hospital das Cl\u0026iacute;nicas da Universidade Federal de Pernambuco; Hospital Universit\u0026aacute;rio Ci\u0026ecirc;ncias M\u0026eacute;dicas; Hospital Bruno Born; Hospital SOS C\u0026aacute;rdio; Hospital S\u0026atilde;o Lucas da PUCRS; Orizonti‑Instituto de Sa\u0026uacute;de e Longevidade Ltda; Santa Casa de Miseric\u0026oacute;rdia de Belo Horizonte; Universidade Federal do Rio Grande do Sul. We also thank all the clinical staff at those hospitals, all undergraduate students and members of the cohort, for their efforts in collecting data.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMurray CJL, Atkinson C, Bhalla K, Birbeck G, Burstein R, Chou D, et al. The state of US health, 1990\u0026ndash;2010: burden of diseases, injuries, and risk factors. JAMA. 2013;310:591\u0026ndash;608.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBittencourt PL, Codes L, Cesar HF, Gomes Ferraz ML. Public knowledge and attitudes toward liver diseases and liver cancer in the Brazilian population: a cross sectional study. Lancet Reg Health Am. 2023;23:100531.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEuropean Association for the Study of the Liver. Electronic address: [email protected], European Association for the Study of the Liver. EASL Clinical Practice Guidelines on acute-on-chronic liver failure. J Hepatol. 2023;79:461\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoreau R, Gao B, Papp M, Ba\u0026ntilde;ares R, Kamath PS. Acute-on-chronic liver failure: A distinct clinical syndrome. J Hepatol. 2021;75(Suppl 1):S27\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarjot T, Moon AM, Cook JA, Abd-Elsalam S, Aloman C, Armstrong MJ, et al. Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: An international registry study. J Hepatol. 2021;74:567\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim D, Adeniji N, Latt N, Kumar S, Bloom PP, Aby ES, et al. Predictors of Outcomes of COVID-19 in Patients With Chronic Liver Disease: US Multi-center Study. Clin Gastroenterol Hepatol. 2021;19:1469\u0026ndash;e147919.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGe J, Pletcher MJ, Lai JC, N3C Consortium. Outcomes of SARS-CoV-2 Infection in Patients With Chronic Liver Disease and Cirrhosis: A National COVID Cohort Collaborative Study. Gastroenterology. 2021;161:1487\u0026ndash;e15015.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMallet V, Beeker N, Bouam S, Sogni P, Pol S. Demosthenes research group. Prognosis of French COVID-19 patients with chronic liver disease: A national retrospective cohort study for 2020. J Hepatol. 2021;75:848\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGe J, Digitale JC, Pletcher MJ, Lai JC, N3C Consortium. Breakthrough SARS-CoV-2 infection outcomes in vaccinated patients with chronic liver disease and cirrhosis: A National COVID Cohort Collaborative study. Hepatology. 2023;77:834\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEl Moheb M, Naar L, Christensen MA, Kapoen C, Maurer LR, Farhat M, et al. Gastrointestinal Complications in Critically Ill Patients With and Without COVID-19. JAMA. 2020;324:1899\u0026ndash;901.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ, Balough EM, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020;395:1763\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020;77:683\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePhipps MM, Barraza LH, LaSota ED, Sobieszczyk ME, Pereira MR, Zheng EX, et al. Acute Liver Injury in COVID-19: Prevalence and Association with Clinical Outcomes in a Large U.S. Cohort. Hepatology. 2020;72:807.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGao F, Zheng KI, Fan Y-C, Targher G, Byrne CD, Zheng M-H. ACE2: A Linkage for the Interplay Between COVID-19 and Decompensated Cirrhosis. Am J Gastroenterol. 2020;115:1544.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoronav\u0026iacute;rus Brasil. [cited 17 Jun 2024]. Available: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://covid.saude.gov.br/\u003c/span\u003e\u003cspan address=\"https://covid.saude.gov.br/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarcolino MS, Ziegelmann PK, Souza-Silva MVR, Nascimento IJB, Oliveira LM, Monteiro LS, et al. Clinical characteristics and outcomes of patients hospitalized with COVID-19 in Brazil: Results from the Brazilian COVID-19 registry. Int J Infect Dis. 2021;107:300\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDiseases C. Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases. World Health Organization; 19 Mar 2020 [cited 3 Mar 2024]. Available: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.who.int/publications/i/item/10665-331501\u003c/span\u003e\u003cspan address=\"https://www.who.int/publications/i/item/10665-331501\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eResearch electronic data capture. (REDCap)\u0026mdash;A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inf. 2009;42:377\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThe REDCap consortium. Building an international community of software platform partners. 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Gastroenterology. 2020;159:768\u0026ndash;e7713.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIoannou GN, Liang PS, Locke E, Green P, Berry K, O\u0026rsquo;Hare AM, et al. Cirrhosis and Severe Acute Respiratory Syndrome Coronavirus 2 Infection in US Veterans: Risk of Infection, Hospitalization, Ventilation, and Mortality. Hepatology. 2021;74:322\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMendizabal M, Ridruejo E, Pi\u0026ntilde;ero F, Anders M, Padilla M, Toro LG, et al. Comparison of different prognostic scores for patients with cirrhosis hospitalized with SARS-CoV-2 infection. Ann Hepatol. 2021;25:100350.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNevola R, Criscuolo L, Beccia D, Delle Femine A, Ruocco R, Imbriani S, et al. Impact of chronic liver disease on SARS-CoV-2 infection outcomes: Roles of stage, etiology and vaccination. World J Gastroenterol. 2023;29:800\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIavarone M, D\u0026rsquo;Ambrosio R, Soria A, Triolo M, Pugliese N, Del Poggio P, et al. High rates of 30-day mortality in patients with cirrhosis and COVID-19. J Hepatol. 2020;73:1063\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBajaj JS, Garcia-Tsao G, Biggins SW, Kamath PS, Wong F, McGeorge S, et al. Comparison of mortality risk in patients with cirrhosis and COVID-19 compared with patients with cirrhosis alone and COVID-19 alone: multicentre matched cohort. Gut. 2021;70:531\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimon TG, Hagstr\u0026ouml;m H, Sharma R, S\u0026ouml;derling J, Roelstraete B, Larsson E, et al. Risk of severe COVID-19 and mortality in patients with established chronic liver disease: a nationwide matched cohort study. BMC Gastroenterol. 2021;21:1\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrozat JF, Hanses F, Haelberger M, Stecher M, Dreher M, Tometten L, et al. COVID-19 mortality in cirrhosis is determined by cirrhosis-associated comorbidities and extrahepatic organ failure: Results from the multinational LEOSS registry. United Eur Gastroenterol J. 2022;10:409\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumar R, Priyadarshi RN, Anand U. Chronic renal dysfunction in cirrhosis: A new frontier in hepatology. World J Gastroenterol. 2021;27:990\u0026ndash;1005.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChung EYM, Palmer SC, Natale P, Krishnan A, Cooper TE, Saglimbene VM, et al. Incidence and Outcomes of COVID-19 in People With CKD: A Systematic Review and Meta-analysis. Am J Kidney Dis. 2021;78:804\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMelo APS, Fran\u0026ccedil;a EB, Malta DC, Garcia LP, Mooney M, Naghavi M. Mortality due to cirrhosis, liver cancer, and disorders attributed to alcohol use: Global Burden of Disease in Brazil, 1990 and 2015. Rev Bras Epidemiol. 2017;20Suppl(01):61\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 3 is available in the Supplementary Files section.\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, Liver Cirrhosis, Patient Outcome Assessment, Propensity Score, Cohort Studies","lastPublishedDoi":"10.21203/rs.3.rs-4746005/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4746005/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCirrhosis has been pointed out as a clinical entity that leads to worse clinical prognosis in COVID-19 patients. However, this concept is controversial in the literature. We aimed to evaluate clinical outcomes by comparing patients with cirrhosis to those without cirrhosis in a Brazilian cohort.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eData from 20,164 COVID-19 inpatients were collected from 41 hospitals in Brazil between March to September 2020 and March 2021 to August 2022. We compared 117 patients with cirrhosis to 632 matched controls. A propensity score model was used to adjust for potential confounding variables, incorporating some predictors: age, sex at birth, number of comorbidities, hospital of admission, whether it was an in-hospital clinical manifestation of COVID-19 and admission year. Closeness was defined as being within 0.16 standard deviations of the logit of the propensity score.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe median age was 61 (IQR 50\u0026ndash;70) years-old, and 63.4% were men. There were no significant differences in the self-reported symptoms. Patients with cirrhosis had lower median hemoglobin levels (10.8 vs 13.1 g/dl), lower platelets (127,000 vs 200,000 cells/mm3), and leukocytes counts, as well as lower median C-reactive protein (63.0 vs 76.0 p\u0026thinsp;=\u0026thinsp;0.044) when compared to controls.They also had had higher mortality compared to matched controls (51.3% vs 21.7%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). They also had higher frequencies of admission in an intensive care unit (51.3% vs 38.0%, p\u0026thinsp;=\u0026thinsp;0.007), invasive mechanical ventilation (43.9% vs 26.6%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), dialysis (17.9% vs 11.1%, p\u0026thinsp;=\u0026thinsp;0.038), septic shock (23.9% vs 14.9%; p\u0026thinsp;=\u0026thinsp;0.015) and institution of palliative care (19.7% vs 7.4%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis study has shown that COVID-19 inpatients with cirrhosis had significantly higher incidence of severe outcomes, as well as higher frequency of institution of palliative care when compared to matched controls. Our findings underscore the need for these patients to receive particular attention from healthcare teams and allocated resources.\u003c/p\u003e","manuscriptTitle":"Clinical Outcomes of Covid-19 in Patients With Liver Cirrhosis - A Propensity-Matched Analysis From a Multicentric Brazilian Cohort","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-18 22:59:41","doi":"10.21203/rs.3.rs-4746005/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-18T13:44:10+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-18T13:05:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-18T09:15:48+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2024-07-16T00:40:52+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":"ba8d1b8b-5b3f-40af-adcc-c5b6ee3c2ff0","owner":[],"postedDate":"August 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-01-20T16:10:01+00:00","versionOfRecord":{"articleIdentity":"rs-4746005","link":"https://doi.org/10.1186/s12879-024-10424-x","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2025-01-15 15:57:39","publishedOnDateReadable":"January 15th, 2025"},"versionCreatedAt":"2024-08-18 22:59:41","video":"","vorDoi":"10.1186/s12879-024-10424-x","vorDoiUrl":"https://doi.org/10.1186/s12879-024-10424-x","workflowStages":[]},"version":"v1","identity":"rs-4746005","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4746005","identity":"rs-4746005","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}