Liver dysfunction during COVID-19 pandemic: Contributing role of associated factors in disease progression and severity

In December 2019, a new strain of coronavirus was discovered in China, and the World Health Organization declared it a pandemic in March 2020. The majority of people with coronavirus disease 19 (COVID-19) exhibit no or only mild symptoms such as fever, cough, anosmia, and headache. Meanwhile, approximately 15% develop a severe lung infection over the course of 10 d, resulting in respiratory failure, which can lead to multi-organ failure, coagulopathy, and death. Since the beginning of the pandemic, it appears that there has been consideration that pre-existing chronic liver disease may predispose to deprived consequences in conjunction with COVID-19. Furthermore, extensive liver damage has been linked to immune dysfunction and coagulopathy, which leads to a more severe COVID-19 outcome. Besides that, people with COVID-19 frequently have abnormal liver function, with more significant elevations in alanine aminotransferase and aspartate aminotransferase in patients with severe COVID-19 compared to those with mild/moderate disease. This review focuses on the pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the liver, as well as the use of liver chemistry as a prognostic tool during COVID-19. We also evaluate the findings for viral infection of hepatocytes, and look into the potential mechanisms behind SARS-CoV-2-related liver damage.     

Liver transplantation in the era of COVID-19

Liver transplantation is considered the ultimate solution for patients with end-stage chronic liver disease or acute liver failure. Patients with liver transplant need special care starting from preoperative preparation, surgical intervention ending with postoperative care. Transplanted patients have to receive immunosuppressive therapy to prevent rejection. Such a state of immune suppression could predispose to different types of infections in liver transplant recipients. Currently, the world is suffering a pandemic caused by a new strain of the coronavirus family called COVID-19. Certain infection control precautions are needed to protect immunocompromised and vulnerable patients, including liver transplant candidates and recipients from acquiring COVID-19 infection. Restricting non-transplant elective surgical procedures, managing transplant patients in separate outpatient clinics, and in-patient wards can prevent transmission of infection both to patients and healthcare workers. Telemedicine can help in the triage of patients to screen for symptoms of COVID-19 before their regular appointment. Management of immunosuppressive therapy and drug-drug interactions in liver transplant recipients infected with COVID-19 should be cautiously practiced to prevent rejection and effectively treat the underlying infection. In this report, we are trying to summarize available evidence about different aspects of the management of liver transplant candidates and recipients in the era of COVID-19.     

Insomnia,Poor Sleep Quality and Sleep Duration,and Risk for COVID-19 Infection and Hospitalization

BackgroundMedical comorbidities increase the risk of severe acute COVID-19 illness. Although sleep problems are common after COVID-19 infection, it is unclear whether insomnia, poor sleep quality, and extremely long or short sleep increase risk of developing COVID-19 infection or hospitalization.MethodsThe study used a cross-sectional survey of a diverse sample of 19,926 US adults.ResultsCOVID-19 infection and hospitalization prevalence rates were 40.1% and 2.9%, respectively. Insomnia and poor sleep quality were reported in 19.8% and 40.1%, respectively. In logistic regression models adjusted for comorbid medical conditions and sleep duration but excluding participants who reported COVID-19-associated sleep problems, poor sleep quality, but not insomnia, was associated with COVID-19 infection (adjusted odds ratio [aOR] 1.16; 95% CI, 1.07-1.26) and COVID-19 hospitalization (aOR 1.50; 95% CI, 1.18-1.91). In comparison with habitual sleep duration of 7-8 hours, sleep durations <7 hours (aOR 1.14; 95% CI, 1.06-1.23) and sleep duration of 12 hours (aOR 1.61; 95% CI, 1.12-2.31) were associated with increased odds of COVID-19 infection. Overall, the relationship between COVID-19 infection and hours of sleep followed a quadratic (U-shaped) pattern. No association between sleep duration and COVID-19 hospitalization was observed.ConclusionIn a general population sample, poor sleep quality and extremes of sleep duration are associated with greater odds of having had a COVID-19 infection; poor sleep quality was associated with an increased requirement of hospitalization for severe COVID-19 illness. These observations suggest that inclusion of healthy sleep practices in public health messaging may reduce the impact of the COVID-19 pandemic.     

Transient increase in platelet counts associated with COVID-19 infection during TPO-RA as the second-line treatment in children with ITP

The thrombopoietin receptor agonists (TPO-RA) were recommended for primary immune thrombocytopenia (ITP) during the pandemic of COVID-19. However, the incidence of thrombocytosis and thrombosis was sporadically reported in the chronic immune thrombocytopenia (CITP) patients receiving TPO-RA during the COVID-19 infection. With the local prevalence of COVID-19 in December 2022 in the Beijing area, we got more powerful evidence about the change in platelet (Plt) counts associated with COVID-19 infection. A single-centre observational cohort study was performed from the beginning of December 2022 to the end of February 2023 to enrol CITP children treated with TPO-RA alone as the second-line treatment and suffering from the COVID-19 infection in December 2022. The Plt counts before, during and after COVID-19 infection were collected. In total, 67 (34 males and 33 females) patients with 8.10 (2.15, 15.70) years of age were enrolled. Sixty-three patients who had responded to the TPO-RA showed a transient increase in Plt counts after the infection of COVID-19. The time of starting to increase was on Day 3 (2, 7), and to the peak level on Day 14 (7, 19) of infection with the peak Plt count was 289 (88, 1974) × 10⁹/L. With at least 2 months observation period from COVID-19 infection, the Plt counts of 100% (63/63) patients declined to the baseline on Day 25 (14, 41). The phenomenon of transient increase in Plt counts has been shown in the CITP children who responded to TPO-RA when suffering from COVID-19 infection.     

COVID-19 and pediatric fatty liver disease: Is there interplay?

The rapid global spread of coronavirus disease 2019 (COVID-19) infection has become a major health issue with higher morbidity and mortality rates. Besides respiratory symptoms, a growing body of evidence indicates a variety of gastrointestinal manifestations including liver involvement. In this regard, several data supported an association between COVID-19 infection and liver injury in adults, while in children there is compelling but currently limited evidence. In particular, patients with COVID-19 have shown a higher risk of liver injury (mainly expressed as increased transaminase levels or hepatic steatosis). Conversely, a greater risk of more severe forms of COVID-19 infection has been observed in subjects with pre-existing chronic liver diseases. The dramatic interplay between COVID-19 and liver damage has been related to the inflammatory pathways chronically active in patients with nonalcoholic fatty liver disease and acutely in those affected by COVID-19, but other different pathogenic mechanisms have also been supposed. Of note, patients with previous metabolic comorbidities also had a higher risk of severe COVID-19 infection. This emphasizes the pathogenic interrelation of the inflammatory pathways with a dysregulated metabolic milieu in COVID-19 patients. Taking into account the prognostic role of fatty liver in COVID-19 patients and its intrinsic relationship with metabolic abnormalities even in childhood, a strict monitoring of this condition is recommended. We aimed to summarize the most recent evidence regarding the potential interplay between pediatric fatty liver and COVID-19.     

Insulin resistance in COVID-19 and diabetes

BackgroundThe epidemiology of COVID-19 and its association with cardiometabolic disorders is poorly understood. This is a narrative review that investigates the effects of COVID-19 infection on insulin resistance in patients with diabetes.MethodsAn online search of all published literature was done via PubMed and Google Scholar using the MeSH terms “COVID-19,” “SARS-CoV-2,” “coronavirus,” “insulin resistance,” and “diabetes.” Only articles that were directly applicable to insulin resistance in COVID-19 and diabetes was reviewed.ResultsCurrent data shows an increased risk of mortality in patients with diabetes and COVID-19 compared to those without diabetes. COVID-19 triggers insulin resistance in patients, causing chronic metabolic disorders that were non-existent prior to infection.ConclusionPatients with diabetes are more susceptible to COVID-19 infection than those without diabetes. ACE2 expression decreases with infection, exaggerating Ang II activity with subsequent insulin resistance development, an exaggerated immune response and severe SARS-COV-2 infection.     

Community-acquired Respiratory Virus Cases Mimic COVID-19 on Lung Computed Tomography

We herein report four patients with community-acquired respiratory virus (CRV) infection. Although they had no history of contact with any individual with coronavirus disease 2019 (COVID-19), they were suspected of having COVID-19 based on findings of high-resolution computed tomography (CT) of the lungs. Among the four patients, two were infected with rhinovirus, one with metapneumovirus, and one with influenza A. Their chest CT findings were similar to those of COVID-19 patients reported in previous studies. Both CRV infection and COVID-19 can show various patterns on chest CT. CRV infection is thus indistinguishable from COVID-19 based on CT findings alone.     

Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection with the Delta (B.1.617.2) variant: second interim results of a living systematic review and meta-analysis, 1 January to 25 August 2021

The Delta variant has become the dominant strain of SARS-CoV-2. We summarised the evidence on COVID-19 vaccine effectiveness (VE) identified in 17 studies that investigated VE against different endpoints. Pooled VE was 63.1% (95% confidence interval (CI): 40.9–76.9) against asymptomatic infection, 75.7% (95% CI: 69.3–80.8) against symptomatic infection and 90.9% (95% CI: 84.5–94.7) against hospitalisation. Compared with the Alpha variant, VE against mild outcomes was reduced by 10–20%, but fully maintained against severe COVID-19.     

Rapid Recovery in COVID-19 Patients with Chronic Hepatitis B Virus Infection Treated with Tenofovir Disoproxil Fumarate

The coronavirus disease 2019 (COVID-19) pandemic continues worldwide. We report here two cases of chronic hepatitis B patients with acute respiratory syndrome coronavirus 2 infection treated with tenofovir disoproxil fumarate who demonstrated a favorable outcome. This report adds some evidence that concurrent HBV infection may not worsen COVID-19 infection and tenofovir disoproxil fumarate treatment may have partial positive effect on COVID-19 rapid recovery.     

Efficacy of naproxen in the management of patients hospitalized with COVID-19 infection: A randomized,double-blind,placebo-controlled,clinical trial

Background and aimsThe current study was done to examine the efficacy of naproxen in the management of patients with COVID-19 infection.MethodsThis randomized, double-blind, placebo-controlled, clinical trial was done on hospitalized adult patients with confirmed COVID-19 infection. Patients were randomly assigned to receive either naproxen (two capsules per day each containing 500 mg naproxen sodium) or placebo (containing starch) for five days along with the routine treatment that was nationally recommended for COVID-19 infection. Clinical symptoms of COVID-19 infection, the time to clinical improvement, blood pressure, laboratory parameters, and death due to COVID-19 infection were considered as the outcome variables in the present study.ResultsTreatment with naproxen improved cough and shortness of breath in COVID-19 patients; such that, compared with placebo, naproxen intake was associated with 2.90 (95% CI: 1.10–7.66) and 2.82 (95% CI: 1.05–7.55) times more improvement in cough and shortness of breath, respectively. In addition, naproxen administration resulted in a significant increase in mean corpuscular volume (MCV) and had a preventive effect on the reduction of systolic blood pressure in COVID-19 patients.ConclusionTreatment with naproxen can improve cough and shortness of breath in COVID-19-infected patients. Further studies are required to confirm our findings.     

Heterogeneity in presentation of hyperglycaemia during COVID-19 pandemic: A proposed classification

Diabetes and hyperglycemia occurring during COVID-19 era have implications for COVID-19 related morbidity/mortality. In this brief review, we have attempted to categorise and classify such heterogenous hyperglycemic states. During COVID-19 pandemic broadly two types of hyperglycemia were seen: one in patients without COVID-19 infection and second in patients with COVID-19 infection. Patients not inflicted with COVID-19 infection and diagnosed with either type 2 diabetes mellitus (T2DM) or type 1 diabetes mellitus (T1DM) show more severe hyperglycemia and more ketoacidosis, respectively. In former, it could be attributed to weight gain, decreased exercise, stress and in both type of diabetes, due to delayed diagnosis during lockdown and pandemic. In patients with COVID-19 and associated pneumonia, altered glucose metabolism leading to hyperglycemia could be due to corticosteroids, cytokine storm, damage to pancreatic beta cells, or combination of these factors. Some of these patients present with diabetic ketoacidosis, hyperglycemic hyperosmolar state or both. We have provided a framework for categorisation of hyperglycemic states, which could be consolidated/revised in future based on new research data.     

COVID-19 and hepatorenal syndrome

Coronavirus disease 2019 (COVID-19) is a highly infectious disease which emerged into a global pandemic. Although it primarily causes respiratory symptoms for affected patients, COVID-19 was shown to have multi-organ manifestations. Elevated liver enzymes appear to be commonly observed during the course of COVID-19, and there have been numerous reports of liver injury secondary to COVID-19 infection. It has been established that patients with pre-existing chronic liver disease (CLD) are more likely to have poorer outcomes following COVID-19 infection compared to those without CLD. Co-morbidities such as diabetes, hypertension, obesity, cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD, and a substantial population may also live with some degree of frailty. The mechanisms of how COVID-19 induces liver injury have been postulated. Hepatorenal syndrome (HRS) is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause, and is usually a marker of severe decompensated liver disease. Select reports of HRS following acute COVID-19 infection have been presented, although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published data. Evidence discussing the management of HRS in high-dependency care and intensive care contexts is only emerging. In this article, we provide an overview on the speculative pathophysiological mechanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario.     

COVID-19 in Liver Transplant Recipients

Background and AimsCoronavirus disease 2019 (COVID-19) has infected over 93 million people worldwide as of January 14, 2021. Various studies have gathered data on liver transplant patients infected with COVID-19. Here, we discuss the presentation of COVID-19 in immunosuppressed patients with prior liver transplants. We also evaluate patient outcomes after infection.MethodsWe searched the PubMed database for all studies focused on liver transplant patients with COVID-19.ResultsWe identified eight studies that evaluated COVID-19 infection in liver transplant patients (n=494). Hypertension was the most prevalent comorbidity in our cohort. Calcineurin inhibitors were the most common immunosuppressant medications in the entire cohort. The average time from liver transplant to COVID-19 infection in our cohort was 74.1 months. Fever and cough, at 70% and 62% respectively, were the most common symptoms in our review. In total, 50% of the patients received hydroxychloroquine as treatment for COVID-19. The next most prevalent treatment was azithromycin, given to 30% of patients in our cohort. In total, 80% of the patients were admitted to a hospital and 17% required intensive care unit-level care, with 21% having required mechanical ventilation. Overall mortality was 17% in our review.ConclusionsGiven the immunocompromised status of liver transplant patients, more intensive surveillance is necessary for severe cases of COVID-19 infection. As liver transplantations have been restricted during the COVID-19 pandemic, further investigation is warranted for studying the risk of COVID-19 infection in liver transplant patients.     

Management of an endoscopy center during the outbreak of COVID-19: Experience from West China Hospital

Since the outbreak of the coronavirus disease 2019 (COVID-19), various measures have been taken to protect against the infection. As droplet and contact transmission are the main routes of COVID-19 infection, endoscopy centers are considered to be high-risk areas for exposure to COVID-19. We have undertaken severalcountermeasures in our endoscopic center during the pandemic, and have gained significant experience in terms of prevention and control of COVID-19. We here present our experience and strategies adopted for preventing hospital infection in our endoscopy center during the COVID-19 pandemic. We describe our management of the environment, endoscope, patients, and medical staff, and our self-made masks.     

Impact of COVID-19 on Patients Hospitalized With Deep Vein Thrombosis and/or Pulmonary Embolism: A Nationwide Analysis

The Coronavirus disease 2019 (COVID-19) infection predisposes patients to develop deep vein thrombosis (DVT) and pulmonary embolism (PE). In this study, we compared the in-hospital outcomes of patients with DVT and/or PE with concurrent COVID-19 infection vs those with concurrent flu infection. The National Inpatient Sample from 2019 to 2020 was analyzed to identify all adult admissions diagnosed with DVT and PE. These patients were then stratified based on whether they had concomitant COVID-19 or flu. We identified 62,895 hospitalizations with the diagnosis of DVT and/or PE with concomitant COVID-19, and 8155 hospitalizations with DVT and/or PE with concomitant flu infection. After 1:1 propensity score match, the incidence of cardiac arrest and inpatient mortality were higher in the COVID-19 group. The incidence of cardiogenic shock was higher in the flu group. Increased age, Hispanic race, diabetes, chronic kidney disease, arrhythmia, liver disease, coagulopathy, and rheumatologic diseases were the independent predictors of mortality in patients with DVT and/or PE with concomitant COVID-19.     

COVID-19 and comorbidities of hepatic diseases in a global perspective

The worldwide outbreak of coronavirus disease 2019 (COVID-19) has challenged the priorities of healthcare system in terms of different clinical management and infection transmission, particularly those related to hepatic-disease comorbidities. Epidemiological data evidenced that COVID-19 patients with altered liver function because of hepatitis infection and cholestasis have an adverse prognosis and experience worse health outcomes. COVID-19-associated liver injury is correlated with various liver diseases following a severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) infection that can progress during the treatment of COVID-19 patients with or without pre-existing liver disease. SARS-CoV-2 can induce liver injury in a number of ways including direct cytopathic effect of the virus on cholangiocytes/hepatocytes, immune-mediated damage, hypoxia, and sepsis. Indeed, immediate cytopathogenic effects of SARS-CoV-2 via its potential target, the angiotensin-converting enzyme-2 receptor, which is highly expressed in hepatocytes and cholangiocytes, renders the liver as an extra-respiratory organ with increased susceptibility to pathological outcomes. But, underlying COVID-19-linked liver disease pathogenesis with abnormal liver function tests (LFTs) is incompletely understood. Hence, we collated COVID-19-associated liver injuries with increased LFTs at the nexus of pre-existing liver diseases and COVID-19, and defining a plausible pathophysiological triad of COVID-19, hepatocellular damage, and liver disease. This review summarizes recent findings of the exacerbating role of COVID-19 in pre-existing liver disease and vice versa as well as international guidelines of clinical care, management, and treatment recommendations for COVID-19 patients with liver disease.     

Impact of diabetes on the severity of COVID-19 infection in pregnant women - A single-center descriptive study

Background and aimsPregnant women have significant morbidity and mortality due to COVID-19 infection. Pregnancy and diabetes are known risk factors for severe COVID 19 infection. Understanding the interactions between COVID-19 and diabetes in pregnancy is crucial in developing appropriate therapeutic approaches. India, like many other countries, has a very high prevalence of diabetes and COVID-19 infected cases. Such studies are minimal worldwide and none from India to the best of our knowledge.Materials and methodsWe did a retrospective cross-sectional study. 856 COVID-19 infected pregnant women were included in the study. We estimated the impact of diabetes on the severity of COVID-19 infected pregnant women and compared the outcomes with the non-diabetic group.ResultsPrevalence of diabetes in pregnancy in the present study was 15.43%(n = 132/856). Prevalence of diabetes in non-severe infection was 14%(n = 115/818), severe infection was 44.73%(n = 17/38), and in maternal deaths was 75% (n = 6/8). The age-adjusted odds ratio for diabetes for severe infection was 4.492 (95% CI = 2.277–8.865, p < 0.001). COVID-19 infected pregnant women with diabetes were at higher risk for Cesarean section (78.3%) and ICU admission for newborns (14.81%)ConclusionDiabetes in pregnant women is strongly associated with the severity of COVID-19 infection. The prevalence of diabetes in pregnancy increases as the severity of COVID-19 infection increases. Diabetes is associated with more adverse outcomes in mothers and newborns. It is necessary to identify pregnant women with diabetes and prioritize them in public health interventions like vaccination.     

Long COVID-19: A Primer for Cardiovascular Health Professionals,on Behalf of the CCS Rapid Response Team

It is now widely recognized that COVID-19 illness can be associated with significant intermediate and potentially longer-term physical limitations. The term, “long COVID-19” is used to define any patient with persistent symptoms after acute COVID-19 infection (ie, after 4 weeks). It is postulated that cardiac injury might be linked to symptoms that persist after resolution of acute infection, as part of this syndrome. The Canadian Cardiovascular Society Rapid Response Team has generated this document to provide guidance to health care providers on the optimal management of patients with suspected cardiac complications of long COVID-19.     

Binge drinking alcohol and circadian misalignment in night shift nurses is associated with decreased resiliency to COVID-19 infection

Background

Nurses and other first responders are at high risk of exposure to the SARS-CoV2 virus, and many have developed severe COVID-19 infection. A better understanding of the factors that increase the risk of infection after exposure to the virus could help to address this. Although several risk factors such as obesity, diabetes, and hypertension have been associated with an increased risk of infection, many first responders develop severe COVID-19 without established risk factors. As inflammation and cytokine storm are the primary mechanisms in severe COVID-19, other factors that promote an inflammatory state could increase the risk of COVID-19 in exposed individuals. Alcohol misuse and shift work with subsequent misaligned circadian rhythms are known to promote a pro-inflammatory state and thus could increase susceptibility to COVID-19. To test this hypothesis, we conducted a prospective, cross-sectional observational survey-based study in nurses using the American Nursing Association network.

Method

We used validated structured questionnaires to assess alcohol consumption (the Alcohol Use Disorders Identification Test) and circadian typology or chronotype (the Munich Chronotype Questionnaire Shift -MCTQ-Shift).

Results

By latent class analysis (LCA), high-risk features of alcohol misuse were associated with a later chronotype, and binge drinking was greater in night shift workers. The night shift was associated with more than double the odds of COVID-19 infection of the standard shift (OR 2.67, 95% CI: 1.18 to 6.07). Binge drinkers had twice the odds of COVID-19 infection of those with low-risk features by LCA (OR: 2.08, 95% CI: 0.75 to 5.79).

Conclusion

Working night shifts or binge drinking may be risk factors for COVID-19 infection among nurses. Understanding the mechanisms underlying these risk factors could help to mitigate the impact of COVID-19 on our at-risk healthcare workforce.     

Clinical characteristics of older patients infected with COVID-19: A descriptive study

ObjectivesSince the outbreak of 2019 novel coronavirus (COVID-19), which has spread in the world rapidly. Population have a susceptibility to COVID-19, older people were more susceptible to have a variety diseases than younger, including COVID-19 infection with no doubt. This study focused on older patients with COVID-19 infection and analyzed the epidemiological and clinical characteristics of them.MethodsWe collected information on confirmed older patient transferred by Beijing Emergency Medical Service (EMS) to the designated hospitals from Jan 20 to Feb 29, 2020. The information including demographic, epidemiological, clinical, classification of severity and outcomes. All cases were categorized into three groups and compared the difference between aged 50–64 years, 65–79 years and older than 80 years.Results56.7 % of elderly confirmed patients were male, fever (78.3 %), cough (56.7 %), dyspnea (30.0 %), and fatigue (23.3 %) were common symptoms of COVID-19 infection. Classification of severity has statistically significant differences between the three groups, compared with middle-aged patients and aged 65–79 years group, older than 80 years group had significant statistical differences in contacted to symptomatic case in 14 days. As of Feb 29, 38.3 % patients had discharged and 53.3 % patients remained in hospital in our study, the fatality of COVID-19 infection in elderly was 8.3 %.ConclusionsThe COVID-19 infection is generally susceptible with a relatively high fatality rate in older patients, we should pay more attention to the elderly patients with COVID-19 infection.