Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease (CHESS2101): A multicenter study.

BACKGROUND & AIMS: The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. METHODS: This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. RESULTS: A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0-48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m2 (IQR 23.8-28.1 kg/m2). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. CONCLUSIONS: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. LAY SUMMARY: The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.

Severe Acute Respiratory Syndrome Coronavirus-2 Infection in Children With Liver Transplant and Native Liver Disease: An International Observational Registry Study.

OBJECTIVE: Increased mortality risk because of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry. METHODS: In this multicenter observational cohort study, we collected data from 91 patients <21 years (LD 44, LT 47) with laboratory-confirmed SARS-CoV2 infection between April 21 and September 17, 2020. RESULTS: Patients with LD were more likely to require admission (70% vs 43% LT, P = 0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, P = 0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS-C); all recovered without LT. Two LD patients had MIS-C alone and 1 patient died. Bivariable logistic-regression analysis found that patients with nonalcoholic fatty LD (NAFLD) (odds ratio [OR] 5.6, P = 0.02) and LD (OR 6.1, P = 0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death). CONCLUSIONS: Although not directly comparable, LT recipients had lower odds of severe SARS-CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS-CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS-CoV2 infection.

Extrapulmonary complications of COVID-19: A multisystem disease?

The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently declared a pandemic by the World Health Organization. In addition to its acute respiratory manifestations, SARS-CoV-2 may also adversely affect other organ systems. To date, however, there is a very limited understanding of the extent and management of COVID-19-related conditions outside of the pulmonary system. This narrative review provides an overview of the current literature about the extrapulmonary manifestations of COVID-19 that may affect the urinary, cardiovascular, gastrointestinal, hematological, hematopoietic, neurological, or reproductive systems. This review also describes the current understanding of the extrapulmonary complications caused by COVID-19 to improve the management and prognosis of patients with COVID-19.

Association and Interaction Between Serum Interleukin-6 Levels and Metabolic Dysfunction-Associated Fatty Liver Disease in Patients With Severe Coronavirus Disease 2019.

Background and Aim: Circulating levels of interleukin (IL)-6, a well-known inflammatory cytokine, are often elevated in coronavirus disease-2019 (COVID-19). Elevated IL-6 levels are also observed in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Our study aimed to describe the association between circulating IL-6 levels and MAFLD at hospital admission with risk of severe COVID-19. Methods: A total of 167 patients with laboratory-confirmed COVID-19 from three Chinese hospitals were enrolled. Circulating levels of IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured at admission. All patients were screened for fatty liver by computed tomography. Forty-six patients were diagnosed as MAFLD. Results: Patients with MAFLD (n = 46) had higher serum IL-6 levels (median 7.1 [interquartile range, 4.3-20.0] vs. 4.8 [2.6-11.6] pg/mL, p = 0.030) compared to their counterparts without MAFLD (n = 121). After adjustment for age and sex, patients with MAFLD had a ~2.6-fold higher risk of having severe COVID-19 than those without MAFLD. After adjustment for age, sex and metabolic co-morbidities, increased serum IL-6 levels remained associated with higher risk of severe COVID-19, especially among infected patients with MAFLD (adjusted-odds ratio 1.14, 95% CI 1.05-1.23; p = 0.002). There was a significant interaction effect between serum IL-6 levels and MAFLD for risk of severe COVID-19 (p for interaction = 0.008). Conclusions: Patients with MAFLD and elevated serum IL-6 levels at admission are at higher risk for severe illness from COVID-19.

Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: An international registry study.

BACKGROUND & AIMS: Chronic liver disease (CLD) and cirrhosis are associated with immune dysregulation, leading to concerns that affected patients may be at risk of adverse outcomes following SARS-CoV-2 infection. We aimed to determine the impact of COVID-19 on patients with pre-existing liver disease, which currently remains ill-defined. METHODS: Between 25th March and 8th July 2020, data on 745 patients with CLD and SARS-CoV-2 (including 386 with and 359 without cirrhosis) were collected by 2 international registries and compared to data on non-CLD patients with SARS-CoV-2 from a UK hospital network. RESULTS: Mortality was 32% in patients with cirrhosis compared to 8% in those without (p <0.001). Mortality in patients with cirrhosis increased according to Child-Pugh class (A [19%], B [35%], C [51%]) and the main cause of death was from respiratory failure (71%). After adjusting for baseline characteristics, factors associated with death in the total CLD cohort were age (odds ratio [OR] 1.02; 1.01-1.04), Child-Pugh A (OR 1.90; 1.03-3.52), B (OR 4.14; 2.4-7.65), or C (OR 9.32; 4.80-18.08) cirrhosis and alcohol-related liver disease (OR 1.79; 1.03-3.13). Compared to patients without CLD (n = 620), propensity-score-matched analysis revealed significant increases in mortality in those with Child-Pugh B (+20.0% [8.8%-31.3%]) and C (+38.1% [27.1%-49.2%]) cirrhosis. Acute hepatic decompensation occurred in 46% of patients with cirrhosis, of whom 21% had no respiratory symptoms. Half of those with hepatic decompensation had acute-on-chronic liver failure. CONCLUSIONS: In the largest such cohort to date, we demonstrate that baseline liver disease stage and alcohol-related liver disease are independent risk factors for death from COVID-19. These data have important implications for the risk stratification of patients with CLD across the globe during the COVID-19 pandemic. LAY SUMMARY: This international registry study demonstrates that patients with cirrhosis are at increased risk of death from COVID-19. Mortality from COVID-19 was particularly high among patients with more advanced cirrhosis and those with alcohol-related liver disease.

Data sharing during COVID-19 pandemic: what to take away.

INTRODUCTION: In light of the viral outbreak of SARS-CoV-2 that monopolized the focus of the scientific community and general public alike for the past 6 months, one of the greatest contributors in the battle against this pandemic was the international sharing of information. Whether regarding the viral genome, incubation periods, method of transmission, symptoms, dangerous behaviors, age groups at risk, all information was valuable, all data was shared as soon as possible. AREAS COVERED: Considering that the most severely impacted group of patients are already suffering from other conditions, accessing the impact that metabolic associated fatty liver disease (MAFLD), obesity, and diabetes has on patients by sharing information between different healthcare facilities is of vital importance. However, the value behind open information sharing would remain significant even without a viral outbreak and should there be a more efficient infrastructure in place, the global exchange of data can become more practical and less arduous. EXPERT OPINION: Since the sharing of data by individual researchers is often motivated by personal benefits, this observed international collaboration is conditional at best, and the widespread misinformation during this pandemic could be an indication of a certain lack of consensus within the scientific community itself.

Radiomics-based model for accurately distinguishing between severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) and influenza A infected pneumonia.

Clinicians have been faced with the challenge of differentiating between severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) infected pneumonia (NCP) and influenza A infected pneumonia (IAP), a seasonal disease that coincided with the outbreak. We aim to develop a machine-learning algorithm based on radiomics to distinguish NCP from IAP by texture analysis based on computed tomography (CT) imaging. Forty-one NCP and 37 IAP patients admitted from January to February 6, 2019 admitted to two hospitals in Wenzhou, China. All patients had undergone chest CT examination and blood routine tests prior to receiving medical treatment. NCP was diagnosed by real-time RT-PCR assays. Eight of 56 radiomic features extracted by LIFEx were selected by least absolute shrinkage and selection operator regression to develop a radiomics score and subsequently constructed into a nomogram to predict NCP with area under the operating characteristics curve of 0.87 (95% confidence interval: 0.77-0.93). The nomogram also showed excellent calibration with Hosmer-Lemeshow test yielding a nonsignificant statistic (P = .904). The novel nomogram may efficiently distinguish between NCP and IAP patients. The nomogram may be incorporated to existing diagnostic algorithm to effectively stratify suspected patients for SARS-CoV-2 pneumonia.

Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study).

BACKGROUND AND AIMS: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. METHODS: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19. RESULTS: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1-3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9-38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p < 0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC 0.94, HR = 19.2 (95 CI 2.3-163.3), p < 0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis patients. CONCLUSIONS: SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.

Metabolic-associated fatty liver disease is associated with severity of COVID-19.

The Corona Virus Disease 2019 (COVID-19) pandemic has attracted increasing worldwide attention. While metabolic-associated fatty liver disease (MAFLD) affects a quarter of world population, its impact on COVID-19 severity has not been characterized. We identified 55 MAFLD patients with COVID-19, who were 1:1 matched by age, sex and obesity status to non-aged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients without MAFLD. Our results demonstrate that in patients aged less than 60 years with COVID-19, MAFLD is associated with an approximately fourfold increase (adjusted odds ratio 4.07, 95% confidence interval 1.20-13.79, P = .02) in the probability for severe disease, after adjusting for confounders. Healthcare professionals caring for patients with COVID-19 need to be aware that there is a positive association between MAFLD and severe illness with COVID-19.

Diabetes as a risk factor for greater COVID-19 severity and in-hospital death: A meta-analysis of observational studies.

AIMS: To estimate the prevalence of established diabetes and its association with the clinical severity and in-hospital mortality associated with COVID-19. DATA SYNTHESIS: We systematically searched PubMed, Scopus and Web of Science, from 1st January 2020 to 15th May 2020, for observational studies of patients admitted to hospital with COVID-19. Meta-analysis was performed using random-effects modeling. A total of 83 eligible studies with 78,874 hospitalized patients with laboratory-confirmed COVID-19 were included. The pooled prevalence of established diabetes was 14.34% (95% CI 12.62-16.06%). However, the prevalence of diabetes was higher in non-Asian vs. Asian countries (23.34% [95% CI 16.40-30.28] vs. 11.06% [95% CI 9.73-12.39]), and in patients aged ≥60 years vs. those aged <60 years (23.30% [95% CI 19.65-26.94] vs. 8.79% [95% CI 7.56-10.02]). Pre-existing diabetes was associated with an approximate twofold higher risk of having severe/critical COVID-19 illness (n = 22 studies; random-effects odds ratio 2.10, 95% CI 1.71-2.57; I2 = 41.5%) and ~threefold increased risk of in-hospital mortality (n = 15 studies; random-effects odds ratio 2.68, 95% CI 2.09-3.44; I2 = 46.7%). Funnel plots and Egger's tests did not reveal any significant publication bias. CONCLUSIONS: Pre-existing diabetes is significantly associated with greater risk of severe/critical illness and in-hospital mortality in patients admitted to hospital with COVID-19.