CONNFERENCE UPDATE: AASLD 2020
Endothelial-mediated hypercoagulability is associated with liver injury in COVID-19
Hepatocellular liver injury has been associated with severe illness and death among COVID-19 patients, but the mechanisms leading to these undesirable outcomes have remained unknown. While liver enzyme derangement appears to be mild in COVID-19 patients, hepatic dysfunction may still have significant impact on the systemic disease pathophysiology of COVID-19 due to the liver’s central role in drug metabolism, coagulation, and the production of albumin and acute-phase reactants.1 According to Dr. Matthew McConnell, Yale School of Medicine, United States, liver injury has been observed in 40-60% of COVID-19 patients hospitalized in the Yale health system. Multivariate analysis revealed an association between abnormal liver tests and severe COVID-19 implications including ICU admission, mechanical ventilation and death.2
In particular, vascular thrombosis, a condition where a vein is obstructed by a blood clot, is commonly observed in the livers of COVID-19 patients. Dr. McConnell and his team hypothesized that COVID-19’s unique coagulopathy, which is primarily the result of endothelial inflammation and platelet activation, could cause liver injury by inducing microvascular thrombosis in the liver. From the Yale-New Haven Hospital Connecticut, 68 patients who had COVID-19 confirmed by polymerase chain reaction (PCR) were recruited into a study to have their coagulation parameters measured and liver status tested. For consistency purposes, the liver tests were performed 5 days before and after coagulation parameters assessments, and their peak values were recorded. In the absence of liver tests within this window, the closest possible liver test result was recorded. In addition to individual parameters, thromboelastography (TEG) was also performed and was defined as having 2 parameters of hypercoagulability.
Depending on their alanine transaminase (ALT) levels, the patients were categorized into groups of having ALT >3 times the upper limit of normal (ULN) or <3 times the ULN. In patients with ALT >3 times ULN, factor VIII, fibrinogen and factor II were found to be significantly elevated in the plasma (p<0.05). A significantly higher proportion of these patients also had a hypercoagulable TEG profile (p<0.05), suggesting that thrombosis may play an important role in the commonly observed hepatocellular liver injury among COVID-19 patients.
To better understand this interaction, the researchers have further cultured primary human liver sinusoidal endothelial cells (LSECs) with interleukin 6 (IL6) and soluble IL6 receptor (IL6R) to simulate the activation of the IL6 trans-signalling pathway that is implicated in the pathogenesis of COVID-19. In previous studies, an increased level of factor VIII and other coagulation markers was found to be a well-established risk factor for deep venous thrombosis, and an elevated IL6 was found to be an independent factor associated with factor VIII levels.3
In the simulated environment, Dr. McConnell and his team similarly found that an IL6/IL6R stimulation has significantly increased the level of factor VIII and von Willebrand factor mRNA expression among LSECs (p<0.01 and p<0.05, respectively). The IL6/IL6R complex also induced the activation of signal transducer and activator of transcription (STAT) 1 and 3 transcription factors (p<0.01), which are known to induce factor VIII expression. Together, these data suggested that a majority of COVID-19 patients are of a prothrombotic LSEC phenotype, and that the commonly observed liver injury may be caused by an elevated level of factor VIII which is mediated by the IL6 trans-signalling pathway implicated in COVID-19 pathogenesis.
By defining a specific mechanism of liver injury among COVID-19 patients, a therapeutic target towards the liver-related COVID-19 complications may be identified in the future. Based on the results of the studies, Dr. McConnell concluded that, “Procoagulant endotheliopathy occurs in COVID-19 patients and is associated with liver injury, and that IL6 trans-signaling is a driver of endotheliopathy via the activation of STAT3.”
Safeguard children’s health from Omicron-associated complications with BNT162b2
The fifth wave of Coronavirus disease 2019 (COVID-19) has caused more than a million people being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Omicron BA.2, predominant) and over 9,000 COVID-19-associated deaths in Hong Kong.1 Children, a subgroup of the population who had experienced more favorable outcomes vs. the older adults during the first 4 waves of the pandemic, were reported to have disproportionately higher hospitalization rates under the Omicron era.2 Some studies revealed that seizure and laryngotracheobronchitis, or croup, were common severe complications which led to pediatric hospitalization.2 The findings highlighted the importance of COVID-19 vaccination among children, but those aged <5 years were still not eligible for this mitigation measure. In an interview with Omnihealth Practice, Dr. Leung, Sze-Yin Agnes presented the latest safety and efficacy data of BNT162b2 among children aged ≥6 months and encouraged parents to arrange COVID-19 vaccination for their children to reduce the negative impact of this pandemic in young children.
Addition of molnupiravir in the evolving SARS-CoV-2 treatment landscape
At a symposium organized by the Hong Kong Society for Infectious Diseases, Dr. Marissa Grifasi Williams kicked off the symposium by sharing how the evolution of virus has changed the management of SARS-CoV-2, highlighting the current guidelines to recommend molnupiravir as an oral therapy for the coronavirus disease 2019 (COVID-19). She further discussed the MOVe-OUT trial, which demonstrated that molnupiravir reduced the risk of hospitalization or death in at-risk and unvaccinated COVID-19 adults. Concluding her presentation, Dr. Williams featured the additional data of molnupiravir from the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2022, validating that molnupiravir was effective in clearing the virus as early as 3 days, as well as improving symptoms. Then, Dr. Yap, Yat-Hin Desmond shared his experience in managing COVID-19 patients with renal failure in Hong Kong.
Multi-peptide CoVac-1 vaccine induces T-cell immunity in immunoglobulin-deficient cancer patients
In the American Association for Cancer Research (AACR) annual meeting 2022, Dr. Claudia Tandler from the University of Tübingen, Germany, discussed the safety and immunogenicity of a novel multi-peptide vaccine, CoVac-1, for the induction of a (SARS-CoV-2) T-cell immunity in cancer patients with dis
BNT162b2 boosters and beyond: Strategies to overcome waning immune responses against omicron variant
During the fifth wave of Coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [B.1.1.529 (Omicron), predominant] infected over a million people and claimed more than 9,000 lives in Hong Kong.1 Elderly people aged ≥60 years were the most vulnerable population and accounted for ≥95% of the total death cases.1 Among the deceased, most were unvaccinated (>70%), or had received only 1 dose of COVID-19 vaccine, and/or were with known chronic diseases.1 Even for people who have received 2 doses of vaccines, increasing evidence showed that protection against severe COVID-19 would be reduced due to the waning immune responses against the Omicron variant.2 As such, in an interview with Omnihealth Practice, Professor HUNG, Fan-Ngai Ivan, addressed the rising concern about Omicron and presented the latest data showing that BNT162b2 boosters are still highly effective against the new threat. He also provided some updates on the development of new Omicron-adapted vaccines for conferring better protection to people.
Emerging from covid-19 predicament: An update on its management and vaccination
The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has afflicted more than 200 million people, with a death toll of more than 4 million people worldwide.1 As of September 29, 2021, Hong Kong has recorded 12,210 COVID-19 cases with 213 deaths.2 Although the situation in Hong Kong has been stabilized since the end of the fourth wave of epidemic in May 2021, the emergence of variants, especially the Delta variants, could be another threat to our society.3,4 In a lecture held by the Macau Association of Health Service Executives (MAHSE), Professor Hung, Fan-Ngai Ivan addressed the concerns over the emergence of the Delta variant and provided an update on the COVID-19 management and vaccination.
Latest updates: Six-month safety and efficacy of BNT162b2 mRNA COVID-19 vaccine
In brief With up to 6 months of follow-up in an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy study, the 6-month safety and efficacy data of BNT162b2 mRNA COVID-19 have been updated and summarized in this report.1 Background The current outbreak of the novel coron
The myths and facts of COVID-19 vaccination and boosters: Current strategies and foresight
Since launching the COVID-19 Vaccination Program in Hong Kong, over 50% of the total population has received the 1st vaccine dose.1 Currently, some studies point out that the immunogenicity varies greatly across the COVID-19 vaccines locally available, sparking controversy on the pro
Breaking the myths: Consensus statements from local rheumatologists recommend covid-19 vaccination in patients with autoimmune rheumatic diseases
In brief The Hong Kong Society of Rheumatology (HKSR) published a set of consensus statements for Coronavirus Disease 2019 (COVID-19) vaccination in adult patients with autoimmune rheumatic diseases (ARDs). This statement serves as a guide to local rheumatologists and other specialists, nurses, he
High prevalence of thrombotic complications found in ICU-admitted COVID-19 patients, systematic screening warranted
Ever since the report of the very first case of coronavirus disease 2019 (COVID-19) in Wuhan back in December 2019, increasing evidence indicates that COVID-19 is associated with a high thrombotic risk.1,2 While the underlying mechanism of thrombus formation among COVID-19 patients had been well-inv
Long-term neurologic symptoms emerge in 1 out of 3 patients hospitalized with COVID-19
With confirmed cases of the 2019 coronavirus disease (COVID-19) on the rise, neurological symptoms and syndromes have been reported by a significant proportion of patients in addition to the predominant respiratory symptoms.1-3 A recent study from Italy further demonstrated that long-term neurologic