COVID-19 and Nonalcoholic Fatty Liver Disease (CovidFAT)

Th17 Immune Response in Patients With COVID-19 and Nonalcoholic Fatty Liver Disease

COVID-19 is currently the leading public health problem, associated with a high risk of complications and death in risk groups of patients. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with a prevalence of 30% in the Western population and is also recognized as an independent risk factor for the development of severe COVID-19. In the pathogenesis of COVID-19, the key role is played by the hyperreactivity of the immune response, the so-called cytokine storm leading to the development of severe forms of pneumonia, acute respiratory and multiorgan failure. The aim of this study is to investigate the clinical course, outcomes, and profile of inflammatory response in patients with COVID-19 and NAFLD.

Study Overview

• Status: Completed
• Conditions: Covid19; NAFLD
• Intervention / Treatment: Diagnostic test: Th17 cytokine profile; Diagnostic test: Screening for the components of metabolic syndrome; Diagnostic test: Evaluation of the degree of steatosis

Detailed Description

SARS-CoV-2 virus infection is currently the leading public health problem, associated with a high risk of complications and death in at-risk groups. Risk factors for the development of severe forms of COVID-19 include components of the metabolic syndrome (obesity, diabetes, dyslipidemia, and arterial hypertension), which are also associated with the development of nonalcoholic fatty liver disease (NAFLD). According to previously published, but mostly retrospective studies, NAFLD is a possible risk factor for the development of severe COVID-19. . In the pathogenesis of COVID-19, the key role is played by the hyperreactivity of the immune response, the so-called cytokine storm. According to recent research, activation of the Th17 system could play a key role in the regulation of this excessive inflammatory response. Furthermore, Th17 lymphocytes and cytokines are important in the development and progression of NAFLD. The question is whether, due to Th17 hyperreactivity, patients with NAFLD are at higher risk of developing severe forms of the disease and what is the profile of the Th17 immune response to SARS-CoV-2 infection in this group of patients.

• Study Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

• Croatia
  • Zagreb, Croatia, 10000
    • University Hospital for Infectious Diseases Zagreb

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

120 patients diagnosed with and hospitalized for severe COVID-19 (60 patients with NAFLD, 60 patients without NAFLD).

Description

Inclusion Criteria:

• Adult patients diagnosed with COVID-19

Exclusion Criteria:

• Immunosuppression
• Consumption of alcohol > 20 g/day
• HIV
• Chronic viral hepatitis
• Presence of other chronic liver disease (hemochromatosis, Wilson's disease, toxic hepatitis, deficiency of alpha-1-antitrypsin, liver autoimmune disease)
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
NAFLD; patients diagnosed with NAFLD and hospitalized due to the severe COVID-19	Diagnostic test: Th17 cytokine profile; Screening for the components of metabolic syndrome; Diagnostic test: Screening for the components of metabolic syndrome; Anthropometric measures including height, weight, waist circumference and hip circumference will be measured in all patients. Results of the routine laboratory tests as part of the standard diagnostic procedure will be collected: CRP, leukocyte count, ratio neutrophils and lymphocytes, hemoglobin, platelet count, urea, creatinine, bilirubin, AST, ALT, GGT, ALP, albumins, fasting glucose.; Diagnostic test: Evaluation of the degree of steatosis; The degree of steatosis will be estimated using the ultrasound and a method for grading steatosis will be measuring the degree of ultrasound attenuation by hepatic fat using a process based on simultaneous transient elastography (TE) which measures the degree of steatosis.
non-NAFLD; patients hospitalized due to the with severe COVID-19 without NAFLD	Diagnostic test: Th17 cytokine profile; Screening for the components of metabolic syndrome; Diagnostic test: Screening for the components of metabolic syndrome; Anthropometric measures including height, weight, waist circumference and hip circumference will be measured in all patients. Results of the routine laboratory tests as part of the standard diagnostic procedure will be collected: CRP, leukocyte count, ratio neutrophils and lymphocytes, hemoglobin, platelet count, urea, creatinine, bilirubin, AST, ALT, GGT, ALP, albumins, fasting glucose.; Diagnostic test: Evaluation of the degree of steatosis; The degree of steatosis will be estimated using the ultrasound and a method for grading steatosis will be measuring the degree of ultrasound attenuation by hepatic fat using a process based on simultaneous transient elastography (TE) which measures the degree of steatosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Th17 cytokines concentrations	Measurement of Th17 cytokines concentration in serum of patients by multiplex technology	Day of hospital admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Staging of liver steatosis	The degree of steatosis will be estimated using the controlled attenuation parameter (CAP) in patients with NAFLD.	Day of hospital discharge (expected maximum of 28 days)
Duration of hospitalization	Days of hospitalization	Day of hospital discharge (expected maximum of 28 days)
Remission of respiratory symptoms	Time to independence from oxygen therapy in days	Day of hospital discharge (expected maximum of 28 days)
28 days survival	Number of subjects surviving at 28 days from hospitalization	Day of hospital discharge (expected maximum of 28 days)
Rate of high flow oxygen therapy or non-invasive ventilation	Requirement for high flow oxygen therapy during the initial hospitalisation	Day of hospital discharge (expected maximum of 28 days)
Secondary infections	Presence/absence of secondary infection during hospitalization	Day of hospital discharge (expected maximum of 28 days)
Rate of invasive mechanical ventilation	Requirement of invasive mechanical ventilation	Day of hospital discharge (expected maximum of 28 days)
Rate of pulmonary thromboembolism	Presence of pulmonary thromboembolism diagnosed with MSCT pulmonary angiography on clinical suspicion	Day of hospital discharge (expected maximum of 28 days)

Collaborators and Investigators

• Sponsor: University Hospital for Infectious Diseases, Croatia
• Investigators: Principal Investigator: Neven Papic, MD, PhD, School of Medicine, University of Zagreb, Croatia

Publications and helpful links

General Publications

• Mocibob L, Susak F, Situm M, Viskovic K, Papic N, Vince A. COVID-19 and Pulmonary Thrombosis-An Unresolved Clinical Puzzle: A Single-Center Cohort Study. J Clin Med. 2022 Nov 29;11(23):7049. doi: 10.3390/jcm11237049.
• Papic N, Samadan L, Vrsaljko N, Radmanic L, Jelicic K, Simicic P, Svoboda P, Lepej SZ, Vince A. Distinct Cytokine Profiles in Severe COVID-19 and Non-Alcoholic Fatty Liver Disease. Life (Basel). 2022 May 26;12(6):795. doi: 10.3390/life12060795.
• Susak F, Vrsaljko N, Vince A, Papic N. TGF Beta as a Prognostic Biomarker of COVID-19 Severity in Patients with NAFLD-A Prospective Case-Control Study. Microorganisms. 2023 Jun 13;11(6):1571. doi: 10.3390/microorganisms11061571.
• Vrsaljko N, Samadan L, Viskovic K, Mehmedovic A, Budimir J, Vince A, Papic N. Association of Nonalcoholic Fatty Liver Disease With COVID-19 Severity and Pulmonary Thrombosis: CovidFAT, a Prospective, Observational Cohort Study. Open Forum Infect Dis. 2022 Feb 9;9(4):ofac073. doi: 10.1093/ofid/ofac073. eCollection 2022 Apr.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 15, 2022

Study Registration Dates

• First Submitted: July 24, 2021
• First Submitted That Met QC Criteria: July 27, 2021
• First Posted (Actual): July 29, 2021

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 27, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Liver Diseases; COVID-19; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: UHID07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No