ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic underlines a persistent threat of respiratory tract infectious diseases and warrants preparedness for a rapid response. At present, COVID-19 has had a serious social impact and imposed a heavy global burden on public health. The exact pathogenesis of COVID-19 has not been fully elucidated. Since the outbreak of COVID-19, a renewed attention has been brought to Toll-like receptors (TLRs). Available data and new findings have demonstrated that the interaction of human TLRs and SARS-CoV-2 is a vital mediator of COVID-19 immunopathogenesis. TLRs such as TLR2, 4, 7 and 8 are potentially important in viral combat and activation of immunity in patients with COVID-19. Therapeutics targeting TLRs are currently considered promising options against the pandemic. A number of TLR-targeting immunotherapeutics are now being investigated in preclinical studies and different phases of clinical trials. In addition, innovative vaccines based on TLRs under development could be a promising approach for building a new generation of vaccines to solve the current challenges. In this review, we summarize recent progress in the role of TLRs in COVID-19, focusing the new candidate drugs targeting TLRs, the current technology and potential paths forward for employing TLR agonists as vaccine adjuvants.Copyright © 2023 The Scandinavian Foundation for Immunology.
ABSTRACT
Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) on children with underlying liver disease (LD) is unknown. We aim to report outcomes for pediatric patients with LD from the joint North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and the Society of Pediatric Liver Transplantation (SPLIT) SARS-CoV2 registry Methods: We collected data from patients younger than 21 years with LD from 6 countries and laboratory-confirmed SARS-CoV2 infection reported to a multicenter observational cohort study between April 2020 and May 2021. Results: Seventy-three (59% male,55% white, 23% Hispanic) children with a median age of 9 years were reported in the registry. The most common causes of LD were biliary atresia (22%) followed by autoimmune hepatitis (16%) and non-alcoholic fatty liver disease (16%). Five patients (7%) presented in acute liver failure (ALF);all recovered without the need for a liver transplant. Four patients presented with multisystem inflammatory syndrome in children (2 with ALF, 2 without ALF) with one death reported. The most common presenting symptoms were constitutional (49%) including fever and fatigue followed by respiratory symptoms (47%). Twenty two percent (n=16) of patients were asymptomatic at the time of diagnosis. Twentythree percent had radiologic evidence of pneumonia and 14% reported co-infections. Median peak INR was 1.4, peak total bilirubin 2.9 (mg/dl), peak ALT 129 (IU/l) and nadir albumin 3.1 (g/dl). Sixty-four percent of patients required hospitalization;40% (n=19) in the ICU and 60% (n=28) non-ICU for a median of 6 and 7 days, respectively. Twenty-two percent of patients required respiratory support including mechanical ventilation (n=6), high-frequency oscillatory ventilation (n=3), highflow nasal cannula (n=5) and regular nasal cannula (n=2) for a median of 6 days. Nine patients required vasoactive agents, 3 required renal replacement therapy and 2 patients required ECMO. Sixty-six percent did not receive any SARSCoV2 directed treatment. Twelve (16%) patients developed new liver-related complications including ascites (n=9), GI bleeding (n=2), encephalopathy (n=3), progression of endstage liver disease (n=2) and infection (n=1). There were a total of 3 (4.1%) deaths (20yr, 17yr and 6month of age at time of death) reported secondary to acute on chronic liver failure with respiratory failure and multiorgan failure Conclusion: Contrary to healthy children, almost 2/3rd pediatric patients with LD testing positive for SARS-CoV2 required hospitalization with death reported in 4% of cases. Acute liver failure is rare with SARS-CoV2 infection with recovery reported without the need for liver transplantation. Close monitoring is needed due to an increased risk of underlying liver disease complications and death, particularly in children with end-stage liver disease awaiting transplantation.
ABSTRACT
BACKGROUND AND AIM: Coronavirus disease 2019 (COVID-19) has attracted increasing worldwide attention. While diabetes is known to aggravate COVID-19 severity, it is not known whether nondiabetic patients with metabolic dysfunction are also more prone to more severe disease. The association of metabolic associated fatty liver disease (MAFLD) with COVID-19 severity in nondiabetic patients was investigated here. METHODS: The study cohort comprised 65 patients with (i.e. cases) and 65 patients without MAFLD (i.e. controls). Each case was randomly matched with one control by sex (1:1) and age (+/-5 years). The association between the presence of MAFLD (as exposure) and COVID-19 severity (as the outcome) was assessed by binary logistic regression analysis. RESULTS: In nondiabetic patients with COVID-19, the presence of MAFLD was associated with a four-fold increased risk of severe COVID-19;the risk increased with increasing numbers of metabolic risk factors. The association with COVID-19 severity persisted after adjusting for age, sex, and coexisting morbid conditions. CONCLUSION: Health-care professionals caring for nondiabetic patients with COVID-19 should be cognizant of the increased likelihood of severe COVID-19 in patients with MAFLD.