世界病毒学杂志(英文版)最新文献

Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019 (COVID-19) vaccination protocols. All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations, e.g., BNT162b2, mRNA-1273, and ChAdOx1-S, can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration. Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination. The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies. Novel vaccine delivery platforms, e.g., mRNA-containing lipid nanoparticles and adenoviral vectors, contribute to the inflammatory background that leads to an exaggerated immune response, while patterns of molecular mimicry between the spike (S) protein and prominent liver antigens may account for the autoimmune presentation. Immune mediators triggered by vaccination or vaccine ingredients per se, including autoreactive antibodies, cytokines, and cytotoxic T-cell populations, may inflict hepatocellular damage through well-established pathways. We aim to review available data associated with immune-mediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.

The intestinal lumen harbors a diverse consortium of microorganisms that participate in reciprocal crosstalk with intestinal immune cells and with epithelial and endothelial cells, forming a multi-layered barrier that enables the efficient absorption of nutrients without an excessive influx of pathogens. Despite being a lung-centered disease, severe coronavirus disease 2019 (COVID-19) affects multiple systems, including the gastrointestinal tract and the pertinent gut barrier function. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can inflict either direct cytopathic injury to intestinal epithelial and endothelial cells or indirect immune-mediated damage. Alternatively, SARS-CoV-2 undermines the structural integrity of the barrier by modifying the expression of tight junction proteins. In addition, SARS-CoV-2 induces profound alterations to the intestinal microflora at phylogenetic and metabolomic levels (dysbiosis) that are accompanied by disruption of local immune responses. The ensuing dysregulation of the gut-lung axis impairs the ability of the respiratory immune system to elicit robust and timely responses to restrict viral infection. The intestinal vasculature is vulnerable to SARS-CoV-2-induced endothelial injury, which simultaneously triggers the activation of the innate immune and coagulation systems, a condition referred to as "immunothrombosis" that drives severe thrombotic complications. Finally, increased intestinal permeability allows an aberrant dissemination of bacteria, fungi, and endotoxin into the systemic circulation and contributes, to a certain degree, to the over-exuberant immune responses and hyper-inflammation that dictate the severe form of COVID-19. In this review, we aim to elucidate SARS-CoV-2-mediated effects on gut barrier homeostasis and their implications on the progression of the disease.

Background: Understanding the transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers (HCWs) and their social contacts is crucial to plan appropriate risk-reduction measures.

Aim: To analyze the socio-demographic risk factors and transmission of SARS-CoV-2 infection among HCWs in two tertiary care hospitals in Dubai, United Arab Emirates.

Methods: The demographic and clinical characteristics were available for all HCWs in both facilities from the human resources department. A cross-sectional survey was conducted from January-April 2022 among HCWs who tested positive through Reverse Transcriptase Polymerase Chain Reaction of the nasopharyngeal swab for SARS-CoV-2 between March 2020 and August 2021 in two tertiary-level hospitals. The survey included questions on demographics, work profile, characteristics of coronavirus disease 2019 (COVID-19), and infection among their household or co-workers. The survey also checked the knowledge and perception of participants on the infection prevention measures related to SARS-CoV-2.

Results: Out of a total of 346 HCWs infected with SARS-CoV-2, 286 (82.7%) HCWs consented to participate in this study. From the sample population, 150 (52.5%) of participants were female, and a majority (230, 80.4%) were frontline HCWs, including 121 nurses (121, 42.4%). Only 48 (16.8%) participants were fully vaccinated at the time of infection. Most infected HCWs (85%) were unaware of any unprotected exposure and were symptomatic at the time of testing (225, 78.7%). Nearly half of the participants (140, 49%) had co-infection among household, and nearly one-third (29.5%) had co-infection among three or more household. Another 108 (37.8%) participants reported cross-infection among co-workers. The frontline HCWs were significantly more infected (25.1% vs 8.6%, P < 0.001) compared to non-frontline HCWs. Another significant risk factor for a high infection rate was male sex (P < 0.001). Among the infected frontline HCWs, a significantly higher proportion were male and shared accommodation with family (P < 0.001). COVID-19 vaccination significantly reduced the infection rate (83.2% vs 16.8, P < 0.001) among HCWs. Most participants (99.3%) were aware about importance of appropriate use of personal protective equipment. However, only 70% agreed with the efficacy of the COVID-19 vaccination in preventing an infection and severe disease.

Conclusion: The risk profiling of the HCWs infected with SARS-CoV-2 found that working at frontline and being male increase the rate of infection. COVID-19 vaccination can effectively reduce the rate of transmission of SARS-CoV-2 among HCWs.

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.

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.

The liver has many significant functions, such as detoxification, the urea cycle, gluconeogenesis, and protein synthesis. Systemic diseases, hypoxia, infections, drugs, and toxins can easily affect the liver, which is extremely sensitive to injury. Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage. The primary regulator of intracellular pH in the liver is the Na⁺/H⁺ exchanger (NHE). Physiologically, NHE protects hepatocytes from apoptosis by making the intracellular pH alkaline. Severe acute respiratory syndrome coronavirus 2 increases local angiotensin II levels by binding to angiotensin-converting enzyme 2. In severe cases of coronavirus disease 2019, high angi-otensin II levels may cause NHE overstimulation and lipid accumulation in the liver. NHE overstimulation can lead to hepatocyte death. NHE overstimulation may trigger a cytokine storm by increasing proinflammatory cytokines in the liver. Since the release of proinflammatory cytokines such as interleukin-6 increases with NHE activation, the virus may indirectly cause an increase in fibrinogen and D-dimer levels. NHE overstimulation may cause thrombotic events and systemic damage by increasing fibrinogen levels and cytokine release. Also, NHE overstimulation causes an increase in the urea cycle while inhibiting vitamin D synthesis and gluconeogenesis in the liver. Increasing NHE3 activity leads to Na⁺ loading, which impairs the containment and fluidity of bile acid. NHE overstimulation can change the gut microbiota composition by disrupting the structure and fluidity of bile acid, thus triggering systemic damage. Unlike other tissues, tumor necrosis factor-alpha and angiotensin II decrease NHE3 activity in the intestine. Thus, increased luminal Na⁺ leads to diarrhea and cytokine release. Severe acute respiratory syndrome coronavirus 2-induced local and systemic damage can be improved by preventing virus-induced NHE overstimulation in the liver.

Towards the end of 2019, a new type of coronavirus, severe acute respiratory syndrome, emerged in the city of Wuhan in China's Hubei Province. The first occurrence was described as a case of pneumonia. Coronavirus disease 2019 (COVID-19) can progress primarily with symptoms varying from a mild upper respiratory tract infection to severe pneumonia, acute respiratory distress syndrome, and death. Determining the mechanisms of action of this virus, which can affect all systems including gastrointestinal, is vital for predicting the progression of the disease and managing its treatment. It is important to demonstrate the mechanisms of action of COVID-19 in patients without a previously known chronic or systemic disease. Although there is still no specific treatment for the virus, various algorithms have been created. As a result of the applied algorithms, the response to the treatment was satisfactory in some patients, while unexpected side effects occurred in some patients. It helps to clarify whether the unwanted effects that occur are due to the effect of the disease or the side effects of the drugs used in the treatment. There is currently increasing interest in COVID-19 interaction with liver tissue. Therefore, we would like to discuss the details of liver injury/dysfunction in the current literature.

Background: Empirical use of potentially hepatotoxic drugs in the management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is considered as one of the major etiopathogenetic factors for liver injury. Recent evidence has shown that an underlying genetic factor may also occur. Hence, it is important to understand the host genetics and iatrogenic-based mechanisms for liver dysfunction to make timely remedial measures.

Aim: To investigate drug-induced and genetic perspectives for the development of coronavirus disease 2019 (COVID-19)-related liver injury.

Methods: Reference Citation Analysis, PubMed, Google Scholar and China National Knowledge Infrastructure were searched by employing the relevant MeSH keywords and pertaining data of the duration, site and type of study, sample size with any subgroups and drug-induced liver injury outcome. Genetic aspects were extracted from the most current pertinent publications.

Results: In all studies, the hepatic specific aminotransferase and other biochemical indices were more than their prescribed upper normal limit in COVID-19 patients and were found to be significantly related with the gravity of disease, hospital stay, number of COVID-19 treatment drugs and worse clinical outcomes. In addition, membrane bound O-acyltransferase domain containing 7 rs641738, rs11385942 G>GA at chromosome 3 gene cluster and rs657152 C>A at ABO blood locus was significantly associated with severity of livery injury in admitted SARS-CoV-2 patients.

Conclusion: Hepatic dysfunction in SARS-CoV-2 infection could be the result of individual drugs or due to drug-drug interactions and may be in a subset of patients with a genetic propensity. Thus, serial estimation of hepatic indices in hospitalized SARS-CoV-2 patients should be done to make timely corrective actions for iatrogenic causes to avoid clinical deterioration. Additional molecular and translational research is warranted in this regard.

The incidence of human immunodeficiency virus (HIV)-infected cases that need total joint replacement (TJR) is generally rising. On the other hand, modern management of HIV-infected cases has enabled them to achieve longevity while increasing the need for arthroplasty procedures due to the augmented dege-nerative joint disease and fragility fractures, and the risk of osteonecrosis. Although initial investigations on joint replacement in HIV-infected cases showed a high risk of complications, the recent ones reported acceptable outcomes. It is a matter of debate whether HIV-infected cases are at advanced risk for adverse TJR consequences; however, the weak immune profile has been associated with an increased probability of complications. Likewise, surgeons and physicians should be aware of the complication rate after TJR in HIV-infected cases and include an honest discussion of the probable unwelcoming complication with their patients contemplating TJR. Therefore, a fundamental review and understanding of the interaction of HIV and arthroplasty are critical.

As the outbreak evolves, our understanding of the consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) on the liver has grown. In this review, we discussed the hepatotropic nature of SARS-CoV-2 and described the distribution of receptors for SARS-CoV-2 (e.g., angiotensin-converting enzyme 2) in the vascular endothelium and cholangiocytes of the liver. Also, we proposed mechanisms for possible viral entry that mediate liver injury, such as liver fibrosis. Due to SARS-CoV-2-induced liver damage, many COVID-19 patients develop liver dysfunction, mainly characterized by moderately elevated serum aminotransferase levels. Patients with chronic liver disease (CLD), such as cirrhosis, hepatocellular carcinoma, nonalcoholic fatty liver disease, and viral hepatitis, are also sensitive to SARS-CoV-2 infection. We discussed the longer disease duration and higher mortality following SARS-CoV-2 infection in CLD patients. Correspondingly, relevant risk factors and possible mechanisms were proposed, including cirrhosis-related immune dysfunction and liver deco-mpensation. Finally, we discussed the potential hepatotoxicity of COVID-19-related vaccines and drugs, which influence the treatment of CLD patients with SARS-CoV-2 infection. In addition, we suggested that COVID-19 vaccines in terms of immunogenicity, duration of protection, and long-term safety for CLD patients need to be further researched. The diagnosis and treatment for liver injury caused by COVID-19 were also analyzed in this review.