Liver injury, characterized predominantly by elevated aspartate aminotransferase and alanine aminotransferase, is a common feature of coronavirus disease 2019 (COVID-19) symptoms caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Additionally, SARS-CoV-2 infection is associated with acute-on-chronic liver failure in patients with cirrhosis and has a notably elevated mortality in patients with alcohol-related liver disease compared to other etiologies. Direct viral infection of the liver with SARS-CoV-2 remains controversial, and alternative pathophysiologic explanations for its hepatic effects are an area of active investigation. In this review, we discuss the effects of SARS-CoV-2 and the inflammatory environment it creates on endothelial cells and platelets more generally and then with a hepatic focus. In doing this, we present vascular inflammation and thrombosis as a potential mechanism of liver injury and liver-related complications in COVID-19.

Covid-19 and Liver Injury: Role of Inflammatory Endotheliopathy, Platelet Dysfunction, and Thrombosis.

BACKGROUND: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may positively or negatively impact outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the association of ARB or ACEI use with coronavirus disease 2019 (COVID-19)-related outcomes in US Veterans with treated hypertension using an active comparator design, appropriate covariate adjustment, and negative control analyses. METHODS AND FINDINGS: In this retrospective cohort study of Veterans with treated hypertension in the Veterans Health Administration (01/19/2020-08/28/2020), we compared users of (A) ARB/ACEI vs. non-ARB/ACEI (excluding Veterans with compelling indications to reduce confounding by indication) and (B) ARB vs. ACEI among (1) SARS-CoV-2+ outpatients and (2) COVID-19 hospitalized inpatients. The primary outcome was all-cause hospitalization or mortality (outpatients) and all-cause mortality (inpatients). We estimated hazard ratios (HR) using propensity score-weighted Cox regression. Baseline characteristics were well-balanced between exposure groups after weighting. Among outpatients, there were 5.0 and 6.0 primary outcomes per 100 person-months for ARB/ACEI (n = 2,482) vs. non-ARB/ACEI (n = 2,487) users (HR 0.85, 95% confidence interval [CI] 0.73-0.99, median follow-up 87 days). Among outpatients who were ARB (n = 4,877) vs. ACEI (n = 8,704) users, there were 13.2 and 14.8 primary outcomes per 100 person-months (HR 0.91, 95%CI 0.86-0.97, median follow-up 85 days). Among inpatients who were ARB/ACEI (n = 210) vs. non-ARB/ACEI (n = 275) users, there were 3.4 and 2.0 all-cause deaths per 100 person months (HR 1.25, 95%CI 0.30-5.13, median follow-up 30 days). Among inpatients, ARB (n = 1,164) and ACEI (n = 2,014) users had 21.0 vs. 17.7 all-cause deaths, per 100 person-months (HR 1.13, 95%CI 0.93-1.38, median follow-up 30 days). CONCLUSIONS: This observational analysis supports continued ARB or ACEI use for patients already using these medications before SARS-CoV-2 infection. The novel beneficial association observed among outpatients between users of ARBs vs. ACEIs on hospitalization or mortality should be confirmed with randomized trials.

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Angiotensin II receptor blocker or angiotensin-converting enzyme inhibitor use and COVID-19-related outcomes among US Veterans.

Interaction effects between angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and steroid or antiviral therapies in COVID-19: A population-based study.

Stroke in patients with COVID-19 has received increasing attention throughout the global COVID-19 pandemic, perhaps due to the substantial disability and mortality that can result when the two conditions co-occur. We reviewed the existing literature and found that the proposed pathomechanism underlying COVID-19-associated ischemic stroke is broadly divided into the following three categories: vasculitis, endothelialitis, and endothelial dysfunction; hypercoagulable state; and cardioembolism secondary to cardiac dysfunction. There has been substantial debate as to whether there is a causal link between stroke and COVID-19. However, the distinct phenotype of COVID-19-associated strokes, with multivessel territory infarcts, higher proportion of large vessel occlusions, and cryptogenic stroke mechanism, that emerged in pooled analytic comparisons with non-COVID-19 strokes is compelling. Further, in this article, we review the various treatment approaches that have emerged as they relate to the proposed pathomechanisms. Finally, we briefly cover the logistical challenges, such as delays in treatment, faced by providers and health systems; the innovative approaches utilized, including the role of tele-stroke; and the future directions in COVID-19-associated stroke research and healthcare delivery.

/pdf/pathomechanisms-and-treatment-implications-for-stroke-in-1voj1u2u.pdf

Pathomechanisms and Treatment Implications for Stroke in COVID-19: A Review of the Literature

Background An understanding and appreciation of scientific research is a key quality of the modern clinician. Yet the Medical Schools Council has previously reported a reduction in the number of clinicians performing research. To explore the reasons for this difficulty, this multicentre, cross-sectional study aims to determine the medical student involvement and perceptions of research and research-orientated careers. It will additionally identify perceived barriers and incentives to participating in research as a student. Methods and analysis This cross-sectional study of medical students at UK medical schools recognised by the General Medical Council will be administered using an online questionnaire. This will be disseminated nationally over a 2-month period through collaborative university medical school and student networks. The primary outcome is to determine the extent to which medical students are currently involved in research. Secondary outcomes include identifying the personal and demographic factors involved in incentivising and deterring medical students from becoming involved in research during medical school. This will be achieved using a selection of Likert scale, multiple-choice and free text questions. Ordinal logistic regression analysis will be performed to understand the association between specific factors and student involvement in research. This study will also characterise the proportion of medical students who are currently interested in conducting research in the future. Ethics and dissemination Ethics approval has been obtained from the Medical Sciences Interdivisional Research Ethics Committee, Oxford, England. The results will be disseminated via publication in a peer-reviewed medical journal and may be presented at local, regional, national and international conferences by medical student collaborators.

https://bmjopen.bmj.com/content/bmjopen/11/9/e050104.full.pdf

Cross-sectional Survey of Medical student Attitudes to Research and Training pathways (SMART) in the UK: study protocol.

https://journals.sagepub.com/doi/pdf/10.1177/1470320320987118

The controversy of using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in COVID-19 patients.

A 68-year-old man was referred to the general surgeons on account of his abdominal pain of unknown cause. He had contracted COVID-19, 9 days prior. CT chest abdomen and pelvis revealed an extensive thrombus extending from the portal vein to the superior mesenteric vein. Further investigation ruled out haematological causes, and COVID-19 was determined to be the cause. He was treated with an extended course of therapeutic dose low molecular weight heparin under the guidance of the haematology team. He was discharged once he was clinically stable and pain-free, with a plan to be followed up by both the surgeons and haematologists. This case highlights the different ways in which COVID-19 presents, and the need for clearer guidance on the treatment and prevention of thromboembolism in COVID-19.

https://casereports.bmj.com/content/bmjcr/14/6/e244049.full.pdf

Superior mesenteric vein and portal vein thrombosis in a patient with COVID-19: a rare case.

We read with great interest the study by Swaminathan et al , which aimed to determine the effect of personal protective equipment (PPE) on the physical and mental well-being of patient-facing staff during the COVID-19 pandemic.1 It has been widely evidenced that COVID-19 has a profound impact on an individual’s physical and mental well-being,2 yet it is unclear to what extent PPE is a contributing factor. While we agree that the authors have provided valuable insight into this matter, we have some questions related to the design and reporting of this study.

The authors state that ‘the impact on mental well-being was studied with a …

https://pmj.bmj.com/content/postgradmedj/early/2020/12/29/postgradmedj-2020-139583.full.pdf

Letter to the Editor: Impact of enhanced personal protective equipment on the physical and mental well-being of healthcare workers during COVID-19.

We read with great interest the letter published by Ooi et al , which discussed the impact of removal of points for additional educational achievements from the UK Foundation Programme (UKFP) application score for the 2023 cohort.1 Educational achievement points can be gained through additional degrees or publications, and account for seven points in the 100-point application score for medical undergraduates. The UKFP’s reasoning for removal of additional educational achievement points, as highlighted in their letter published on 30 November 2020, was that their inclusion has resulted in less differentiation between candidates in recent years, and that there are inconsistencies in opportunities to obtain additional degrees.2 However, there was no direct reasoning for removal of points for publications.

In 1993, the General Medical Council (GMC) set out Tomorrow’s Doctors , which highlighted the outcomes and standards for undergraduate medical education. In 2018, the GMC updated their primary outcomes for graduates to (1) professional values and behaviours, (2) professional skills, and (3) professional knowledge. As part of their professional knowledge outcome, they highlight clinical research and scholarship as a key principle, including the importance of interpreting evidence and appraising literature to identify answers to clinical problems, and also designing studies to promote evidence-based medicine.

Engagement in research is important for medical undergraduates and clinical trainees as found by the Research for all report that was published by the Royal College of Physicians in 2015.3 The report showed that doctors are committed …

https://pmj.bmj.com/content/postgradmedj/early/2021/02/15/postgradmedj-2021-139793.full.pdf

Factors influencing the engagement in research of medical undergraduates and clinical trainees.

ABSTRACT The compartmentalised eukaryotic cell demands accurate targeting of proteins to the organelles in which they function, whether membrane-bound (like the nucleus) or non-membrane-bound (like the nucleolus). Nucleolar targeting relies on positively charged localisation signals and has received rejuvenated interest since the widespread recognition of liquid–liquid phase separation (LLPS) as a mechanism contributing to nucleolus formation. Here, we exploit a new genome-wide analysis of protein localisation in the early-branching eukaryote Trypanosoma brucei to analyse general nucleolar protein properties. T. brucei nucleolar proteins have similar properties to those in common model eukaryotes, specifically basic amino acids. Using protein truncations and addition of candidate targeting sequences to proteins, we show both homopolymer runs and distributed basic amino acids give nucleolar partition, further aided by a nuclear localisation signal (NLS). These findings are consistent with phase separation models of nucleolar formation and physical protein properties being a major contributing mechanism for eukaryotic nucleolar targeting, conserved from the last eukaryotic common ancestor. Importantly, cytoplasmic ribosome proteins, unlike mitochondrial ribosome proteins, have more basic residues – pointing to adaptation of physicochemical properties to assist segregation.

Milad Jeilani

Papers

The controversy of using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in COVID-19 patients.

Superior mesenteric vein and portal vein thrombosis in a patient with COVID-19: a rare case.

Letter to the Editor: Impact of enhanced personal protective equipment on the physical and mental well-being of healthcare workers during COVID-19.

Factors influencing the engagement in research of medical undergraduates and clinical trainees.

Nucleolar targeting in an early-branching eukaryote suggests a general mechanism for ribosome protein sorting