COVID-19 and liver dysfunction: A systematic review and meta-analysis of retrospective studies

Recently, Coronavirus Disease 2019 (COVID-19) pandemic is the most significant global health crisis. In this study, we conducted a meta-analysis to find the association between liver injuries and the severity of COVID-19 disease. Online databases, including PubMed, Web of Science, Scopus, and Science direct, were searched to detect relevant publications up to 16 April 2020. Depending on the heterogeneity between studies, a fixed- or random-effects model was applied to pool data. Publication bias Egger's test was also performed. Meta-analysis of 20 retrospective studies (3428 patients), identified that patients with a severe manifestation of COVID-19 exhibited significantly higher levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin values with prolonged prothrombin time. Furthermore, lower albumin level was associated with a severe presentation of COVID-19. Liver dysfunction was associated with a severe outcome of COVID-19 disease. Close monitoring of the occurrence of liver dysfunction is beneficial in early warning of unfavorable outcomes.     

The impact of COVID-19 on liver injury in various age

The coronavirus disease 2019 (COVID-19) disease was first detected in December 2019 in Wuhan, China. This disease is currently one of the most important global health problems. The novel coronavirus COVID-19 is a respiratory illness, that has caused a deadly pandemic that is spreading rapidly around the world. It is not only a respiratory system virus that causes severe lung disease, but also a systemic disease agent that can affect all systems. People with COVID-19 disease usually have respiratory signs, however, the liver disorder is not an uncommon presentation. In addition, many studies around the world have revealed that the liver is injured to various degrees in patients with severe acute respiratory syndrome coronavirus 2 disease. This review mainly focuses on the impact of COVID-19 on Liver Injury at various ages.     

Hepatic manifestations of coronavirus disease 2019 infection: Clinical and laboratory perspective

The novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has become a global challenge of unprecedented nature since December 2019. Although most patients with COVID-19 exhibit mild clinical manifestations and upper respiratory tract involvement, in approximately 5%-10% of patients, the disease is severe and involves multiple organs, leading to multi-organ dysfunction and failure. The liver and gastrointestinal tract are also frequently involved in COVID-19. In the context of liver involvement in patients with COVID-19, many key aspects need to be addressed in both native and transplanted organs. This review focuses on the clinical presentations and laboratory abnormalities of liver function tests in patients with COVID-19 with no prior liver disease, patients with pre-existing liver diseases and liver transplant recipients. A brief overview of the history of COVID-19 and etiopathogenesis of the liver injury will also be described as a prelude to better understanding the above aspects.     

COVID-19-induced liver injury in adult patients: A brief overview

Coronavirus disease has spread worldwide since 2019, causing important pandemic issues and various social health problems to date. Little is known about the origin of this virus and the effects it has on extra-pulmonary organs. The different mechanisms of the virus and the influence it has on humans are still being studied, with hopes of finding a cure for the disease and the pathologies associated with the infection. Liver damage caused by coronavirus disease 2019 (COVID-19) is sometimes underestimated and has been of important clinical interest in the past few years. Hepatic dysfunctions can manifest in different forms which can sometimes be mild and without specific signs and symptoms or be severe with important clinical implications. There are several studies that have tried to explain the mechanism of entry (hepatotropism) of the virus into hepatocytes and the effects the virus has on this important organ. What clearly emerges from the current literature is that hepatic injury represents an important clinical aspect in the management of patients infected with COVID-19, especially in frail patients and those with comorbidities. The aim of our brief overview is to summarize the current literature regarding the forms of hepatic damage, complications, mechanisms of pathology, clinical features of liver injury, influence of comorbidities and clinical management in patients with COVID-19 infection.     

Impact of the COVID-19 pandemic on pathological autopsy practices in Japan

During the coronavirus disease 2019 (COVID-19) pandemic, autopsies have provided valuable insights into the pathogenesis of COVID-19. The precise effect of this pandemic on autopsy procedures in Japan, especially in instances unrelated to COVID-19, has not yet been established. Therefore, we conducted a questionnaire survey from December 2020 to January 2021 regarding the status of pathological autopsy practices in Japan during the first year of the COVID-19 pandemic. The questionnaire was sent to 678 medical facilities with pathologists, of which 227 responded. In cases where a confirmed diagnosis of COVID-19 was not made at the time of autopsy, many facilities counted them as suspected COVID-19 cases if pneumonia was suspected clinically. At around half of the sites, autopsies were prohibited for suspected COVID-19 cases. In addition, the number of autopsies of non-COVID-19 cases during the pandemic period was also investigated, and a significant decrease was observed compared with the incidence in the pre-pandemic period. The COVID-19 pandemic has affected not only the autopsies of COVID-19 cases but also the entire practice of pathological autopsies. It is necessary to establish a system that supports the implementation of pathological autopsy practices during the pandemic of an emerging infectious disease.     

Effects of COVID-19 on children with autism

The coronavirus disease 2019 (COVID-19) pandemic affects all countries and populations worldwide, significantly impacting people with autism with a high risk of morbidity and mortality due to COVID-19. Approximately 25% of children with autism have an asymptomatic or symptomatic immune deficiency or dysfunction. In addition, they frequently have various comorbid conditions that increase the severity of COVID-19. In addition, severe COVID-19 during pregnancy may increase the risk of autism in the offspring. Furthermore, severe acute respiratory syndrome coronavirus 2 could target human nervous system tissues due to its neurotrophic effects. The COVID-19 pandemic intensely impacts many patients and families in the autism community, especially the complex management of autism-associated disorders during the complete lockdown. During the complete lockdown, children with autism had difficulties coping with the change in their routine, lack of access to special education services, limited physical space available, and problems related to food and sleep. Additionally, children with autism or intellectual disabilities are more liable to be abused by others during the pandemic when the standard community supports are no longer functioning to protect them. Early detection and vaccination of children with autism against COVID-19 are highly indicated. They should be prioritized for testing, vaccination, and proper management of COVID-19 and other infectious diseases. In this review, we discuss the various effects of COVID-19 on children with autism, the difficulties they face, the increased risk of infection during pregnancy, how to alleviate the impact of COVID-19, and how to correct the inequalities in children with autism.     

COVID-19 in dialysis units: A comprehensive review

The coronavirus disease 2019 (COVID-19) pandemic has been challenging for healthcare professionals worldwide. One of the populations affected by the pandemic are patients on renal replacement therapy, as kidney disease is an independent risk factor for severe COVID-19 and maintenance dialysis (a life-sustaining therapy) cannot be interrupted in the vast majority of cases. Over the past months, several authors and medical societies have published recommendations and guidelines on the management of this population. This article is a comprehensive review regarding the measures to prevent, contain and deal with a COVID-19 pandemic in the dialysis setting. We recapitulate the epidemiology and pathophysiology of COVID-19 in kidney dysfunction and present the main recommendations concerning the screening of healthcare personnel, dialysis patients and visitors as well as measures to improve the safety of the dialysis facilities’ environments. In addition to preventive measures, this article briefly describes actions directed towards management of an outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within a dialysis facility, the management of complications in dialysis patients with COVID-19 and overall data regarding the management of children with kidney disease.     

Pharmacological approach for the reduction of inflammatory and prothrombotic hyperactive state in COVID-19 positive patients by acting on complement cascade

The novel Coronavirus SARS-CoV-2 is the viral pathogen responsible for the ongoing global pandemic, COVID-19 (Coronavirus disease 2019). To date, the data recorded indicate 1.62 Mln deaths and 72.8 Mln people infected (WHO situation report Dec 2020). On December 27, the first anti-COVID-19 vaccinations started in Europe. There are no direct antivirals against SARS-CoV-2. Understanding the pathophysiological and inflammatory/immunological processes of SARS-CoV-2 infection is essential to identify new drug therapies. In the most severe COVID-19 cases, an unregulated immunological/inflammatory system results in organ injury that can be fatal to the host in some cases. Pharmacologic approaches to normalize the unregulated inflammatory/immunologic response is an important therapeutic solution. Evidence associates a non-regulation of the “complement system” as one of the causes of generalized inflammation causing multi-organ dysfunction. Serum levels of a complement cascade mediator, factor “C5a”, have been found in high concentrations in the blood of COVID-19 patients with severe disease. In this article we discuss the correlation between complement system and COVID-19 infection and pharmacological solutions directed to regulate.     

Impact of COVID-19 pandemic on patients with rare disease in Hong Kong

The COVID-19 pandemic has had significant health, social, and economic consequences internationally. While the pandemic has direct implications on infected patients and families, there is a need to examine the pandemic's effect on patients with non-COVID-19-related diseases. This study examines the impact of the COVID-19 pandemic on 272 rare disease patients with 89 distinct rare diseases in Hong Kong using a cross-sectional online survey between April 10 and April 29, 2020 from the patient and caregiver perspective. The pandemic has impacted patient's health status in 46%, service use patterns in 71%, mental health in 79%, daily living in 82%, social life in 92%, and financial status in 81% of patients. Patient's health status, medical and rehabilitation, and mental health were more impacted by the COVID-19 pandemic in the group of patients with any level of dependency according to the Barthel Index for Activities of Daily Living compared with that in the group of patients who are fully independent (p < 0.0001; p < 0.0001; p = 0.0420). This study is the first study to examine the impact of COVID-19 pandemic on the rare disease population in Hong Kong, and demonstrates the pandemic's effect on service and resource utilization, and patient's physical and mental well-being.     

Impact of COVID-19 on liver disease: From the experimental to the clinic perspective

Coronavirus disease 2019 (COVID-19) has caused a global pandemic unprecedented in over a century. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a predominantly respiratory infection, various degrees of liver function abnormalities have been reported. Pre-existing liver disease in patients with SARS-CoV-2 infection has not been comprehensively evaluated in most studies, but it can critically compromise survival and trigger hepatic decompensation. The collapse of the healthcare services has negatively impacted the diagnosis, monitoring, and treatment of liver diseases in non-COVID-19 patients. In this review, we aim to discuss the impact of COVID-19 on liver disease from the experimental to the clinic perspective.     

Autoimmune complications of COVID-19

Coronavirus disease 2019 (COVID-19) is still propagating a year after the start of the pandemic. Besides the complications patients face during the COVID-19 disease period, there is an accumulating body of evidence concerning the late-onset complications of COVID-19, of which autoimmune manifestations have attracted remarkable attention from the first months of the pandemic. Autoimmune hemolytic anemia, immune thrombocytopenic purpura, autoimmune thyroid diseases, Kawasaki disease, Guillain-Barre syndrome, and the detection of autoantibodies are the cues to the discovery of the potential of COVID-19 in inducing autoimmunity. Clarification of the pathophysiology of COVID-19 injuries to the host, whether it is direct viral injury or autoimmunity, could help to develop appropriate treatment.     

Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19)

Angiotensin-converting enzyme 2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID-19). ACE2 is abundantly expressed in a variety of cells residing in many different human organs. In human physiology, ACE2 is a pivotal counter-regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin–angiotensin–aldosterone system (RAAS) and the main substrate of ACE2. Many factors have been associated with both altered ACE2 expression and COVID-19 severity and progression, including age, sex, ethnicity, medication, and several co-morbidities, such as cardiovascular disease and metabolic syndrome. Although ACE2 is widely distributed in various human tissues and many of its determinants have been well recognised, ACE2-expressing organs do not equally participate in COVID-19 pathophysiology, implying that other mechanisms are involved in orchestrating cellular infection resulting in tissue damage. Reports of pathologic findings in tissue specimens of COVID-19 patients are rapidly emerging and confirm the established role of ACE2 expression and activity in disease pathogenesis. Identifying pathologic changes caused by SARS-CoV-2 infection is crucially important as it has major implications for understanding COVID-19 pathophysiology and the development of evidence-based treatment strategies. Currently, many interventional strategies are being explored in ongoing clinical trials, encompassing many drug classes and strategies, including antiviral drugs, biological response modifiers, and RAAS inhibitors. Ultimately, prevention is key to combat COVID-19 and appropriate measures are being taken accordingly, including development of effective vaccines. In this review, we describe the role of ACE2 in COVID-19 pathophysiology, including factors influencing ACE2 expression and activity in relation to COVID-19 severity. In addition, we discuss the relevant pathological changes resulting from SARS-CoV-2 infection. Finally, we highlight a selection of potential treatment modalities for COVID-19. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Changing Patterns of Medical Visits and Factors Associated with No-show in Patients with Rheumatoid Arthritis during COVID-19 Pandemic

BackgroundThe main barrier to the effective rheumatoid arthritis (RA) therapy is poor adherence. Coronavirus disease 2019 (COVID-19) pandemic have led to a significant change in the pattern and the number of medical visits. We assessed changing patterns of medical visits and no-show, and identified factors associated with no-show in patients with RA during COVID-19 pandemic.MethodsRA patients treated with disease-modifying antirheumatic drugs at least 6 months who had been in remission or those with mild disease activity were observed for 6 months from February to July 2020. No-show was defined as a missed appointment that was not previously cancelled by the patient and several variables that might affect no-show were examined.ResultsA total of 376 patients and 1,189 appointments were evaluated. Among 376 patients, 164 patients (43.6%) missed appointment more than one time and no-show rate was 17.2% during COVID-19 pandemic. During the observation, face-to-face visits gradually increased and no-show gradually decreased. The logistic regression analysis identified previous history of no-show (adjusted odds ratio [OR], 2.225; 95% confidence interval [CI], 1.422–3.479; P < 0.001) and fewer numbers of comorbidities (adjusted OR, 0.749; 95% CI, 0.584–0.961; P = 0.023) as the independent factors associated with no-show.ConclusionMonthly analysis showed that the no-show rate and the pattern of medical visits gradually changed in patients with RA during COVID-19 pandemic. Moreover, we found that previous history of no-show and fewer numbers of comorbidities as the independent factors associated with no-show.     

An overview of COVID-19 in solid organ transplantation

BackgroundThe COVID-19 pandemic has influenced the field of solid organ transplantation (SOT) in many ways. COVID-19 has led to programmatic impacts and changes in donor and recipient selection. Several studies have evaluated the course, optimal treatment, and prevention of COVID-19 in SOT recipients.ObjectivesTo review the literature on COVID-19 in SOT recipients.SourcesPubMed, Web of Science, and Google Scholar were searched. The search was restricted to articles published between January 1, 2019 and December 1, 2021.ContentThe COVID-19 pandemic initially led to a decreased volume of solid organ transplants. However, transplant volumes at most centres have rebounded. Donor selection remains an incompletely defined issue. Several reports suggest that donor-derived SARS-CoV-2 infections occur only in lung transplant recipients and that other organs from SARS-CoV-2 PCR-positive donors could potentially be safely used. However, these data are limited to case series. Transplantation for end-stage lung disease after COVID-19 infection is increasingly common and has been performed with acceptable outcomes. In acute COVID-19 in a transplant candidate, transplantation should be delayed when feasible. After adjustment, mortality after COVID-19 appear similar in SOT recipients compared to the general population, with notable increased use of antiviral and anti-inflammatory treatment options. Prevention of COVID-19 is key in SOT recipients. Vaccination of SOT recipients and anyone who is in contact with SOT recipients is one of the cornerstones of prevention. Nonpharmacological interventions such as face coverings, hand hygiene, and physical distancing remain ever important as well.ImplicationsThe COVID-19 pandemic continues to have an important impact on SOT candidates and recipients. Prevention of infection is the most important measure and requires careful attention to approaches to vaccination and messaging of the ongoing need for face coverings, physical distancing, and hand hygiene.     

Does eNOS derived nitric oxide protect the young from severe COVID-19 complications?

The COVID-19 pandemic poses an imminent threat to humanity, especially to the elderly. The molecular mechanisms underpinning the age-dependent disparity for disease progression is not clear. COVID-19 is both a respiratory and a vascular disease in severe patients. The damage endothelial system provides a good explanation for the various complications seen in COVID-19 patients. These observations lead us to suspect that endothelial cells are a barrier that must be breached before progression to severe disease. Endothelial intracellular defences are largely dependent of the activation of the interferon (IFN) system. Nevertheless, low type I and III IFNs are generally observed in COVID-19 patients suggesting that other intracellular viral defence systems are also activated to protect the young. Intriguingly, Nitric oxide (NO), which is the main intracellular antiviral defence, has been shown to inhibit a wide array of viruses, including SARS-CoV-1. Additionally, the increased risk of death with diseases that have underlying endothelial dysfunction suggest that endothelial NOS-derived nitric oxide could be the main defence mechanism. NO decreases dramatically in the elderly, the hyperglycaemic and the patients with low levels of vitamin D. However, eNOS derived NO occurs at low levels, unless it is during inflammation and co-stimulated by bradykinin. Regrettably, the bradykinin-induced vasodilation also progressively declines with age, thereby decreasing anti-viral NO production as well. Intriguingly, the inverse correlation between the percentage of WT eNOS haplotype and death per 100K population could potentially explain the disparity of COVID-19 mortality between Asian and non-Asian countries. These changes with age, low bradykinin and NO, may be the fundamental reasons that intracellular innate immunity declines with age leading to more severe COVID-19 complications.     

Effect of SARS-CoV-2 infection on the liver

There have been numerous concerns about the disease and how it affects the human body since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic began in December 2019. The impact of SARS-CoV-2 on the liver is being carefully investigated due to an increase in individuals with hepatitis and other liver illnesses, such as alcoholic liver disease. Additionally, the liver is involved in the metabolism of numerous drugs used to treat comorbidities and coronavirus disease 2019 (COVID-19). Determining how SARS-CoV-2 affects the liver and what factors place individuals with COVID-19 at a higher risk of developing liver problems are the two main objectives of this study. This evaluation of the literature included research from three major scientific databases. To provide an update on the current impact of COVID-19 on the liver, data was collected and relevant information was incorporated into the review. With more knowledge about the effect of the disease on the liver, better management and therapeutics can be developed, and education can ultimately save lives and reduce the long-term impact of the pandemic on our population.     

Could oxytocin reduce autoimmune disease in COVID-19?

Disruption of immune and neuroendocrine system function has been shown to play a key role in COVID-19. Oxytocin is vitally important for the immune and neuroendocrine systems. However, oxytocin dysfunction might occur in COVID-19 leading to autoimmune disease. Intranasal oxytocin may be effective in turning off an overactive immune system. This could be a powerful approach to avoid possible autoimmune diseases after COVID-19.     

Dysregulation of glutamine/glutamate metabolism in COVID-19 patients: A metabolism study in African population and mini meta-analysis

Coronavirus disease 2019 (COVID-19) remains a serious global threat. The metabolic analysis had been successfully applied in the efforts to uncover the pathological mechanisms and biomarkers of disease severity. Here we performed a quasi-targeted metabolomic analysis on 56 COVID-19 patients from Sierra Leone in western Africa, revealing the metabolomic profiles and the association with disease severity, which was confirmed by the targeted metabolomic analysis of 19 pairs of COVID-19 patients. A meta-analysis was performed on published metabolic data of COVID-19 to verify our findings. Of the 596 identified metabolites, 58 showed significant differences between severe and nonsevere groups. The pathway enrichment of these differential metabolites revealed glutamine and glutamate metabolism as the most significant metabolic pathway (Impact = 0.5; −log10P = 1.959). Further targeted metabolic analysis revealed six metabolites with significant intergroup differences, with glutamine/glutamate ratio significantly associated with severe disease, negatively correlated with 10 clinical parameters and positively correlated with SPO₂ (r_s= 0.442, p = 0.005). Mini meta-analysis indicated elevated glutamate was related to increased risk of COVID-19 infection (pooled odd ratio [OR] = 2.02; 95% confidence interval [CI]: 1.17–3.50) and severe COVID-19 (pooled OR = 2.28; 95% CI: 1.14–4.56). In contrast, elevated glutamine related to decreased risk of infection and severe COVID-19, the pooled OR were 0.30 (95% CI: 0.20–0.44), and 0.44 (95% CI: 0.19–0.98), respectively. Glutamine and glutamate metabolism are associated with COVID-19 severity in multiple populations, which might confer potential therapeutic target of COVID-19, especially for severe patients.     

COVID-19 and the antiphospholipid syndrome

Coronavirus disease 2019 (COVID-19) has resulted in a global pandemic. Most COVID-19 patients are asymptomatic or have flu-like symptoms. However, around 15% of the patients may have severe disease, including unilateral or bilateral pneumonia with acute respiratory distress syndrome and progressive hypoxemia that may require mechanical ventilation assistance. A systemic inflammatory response syndrome occurs in the most severe forms of COVID-19, with multiorgan involvement which can be life threatening caused by a cytokine storm. Although what best characterizes COVID-19 are the manifestations of the respiratory system, it has been shown that it also acts at the cardiovascular level, producing coagulation abnormalities, which causes thrombotic events mainly in the arteries/arterioles, microcirculation and venous system, and potentially increased mortality risk. This multiorgan vascular disease overlaps with other known microangiopathies, such as thrombotic microangiopathy or paroxysmal nocturnal hemoglobinuria, where complement overactivation plays an important role in the pathophysiology of thrombosis. Furthermore, coagulopathy secondary to COVID-19 occurs in the context of an uncontrolled inflammatory response, reminiscent of APS, especially in its catastrophic form. This review summarizes the current knowledge regarding the relationship between COVID-19 and the APS.     

Potential risk factors for acute grief during the COVID-19 pandemic: The mediating role of avoidance processes

Bereavement during the COVID-19 pandemic may have some unique characteristics that become potential risk factors (e.g., absence of grief rituals, no opportunity to say goodbye to the deceased and loneliness caused by social distancing) for acute grief. Avoidance processes could be significant mediators in the context of the pandemic. The current study aimed to investigate whether and how these COVID-19-related risk factors were related to acute grief severity. Bereaved adults (n = 319) who lost significant others during the COVID-19 pandemic completed a self-report questionnaire package measuring COVID-19-related factors, grief severity and depressive and anxious avoidance. Regression analyses suggested that among the three potential risk factors (loneliness, grief rituals and opportunity to say goodbye), loneliness was significantly associated with acute grief after controlling for basic demographic and loss-related information. Structural equation models suggested that depressive avoidance and anxious avoidance partially mediated the associations of loneliness with acute grief severity. The findings indicate that dealing with loss during the COVID-19 pandemic warrants further exploration concerning how potential environmental risk factors may impede adaptation to loss. Depressive and anxious avoidance processes may play important roles in grief interventions for isolated and lonely bereaved people.