Expression of SARS-Cov-2 Entry Factors in Patients with Chronic Hepatitis.

Chronic hepatitis (CH) of dysmetabolic or viral etiology has been associated with poor prognosis in patients who experienced the severe acute respiratory coronavirus virus-2 (SARS-Cov-2) infection. We aimed to explore the impact of SARS-Cov-2 infection on disease severity in a group of patients with CH. Forty-two patients with CH of different etiology were enrolled (median age, 56 years; male gender, 59%). ACE2 and TMPRSS2 were measured in plasma samples of all patients by ELISA and in the liver tissue of a subgroup of 15 patients by Western blot. Overall, 13 patients (31%) experienced SARS-Cov-2 infection: 2/15 (15%) had CHB, 5/12 (39%) had CHC, and 6/15 (46%) had non-alcoholic fatty liver disease (NAFLD). Compared to viral CH patients, NAFLD subjects showed higher circulating ACE2 levels (p = 0.0019). Similarly, hepatic expression of ACE2 was higher in subjects who underwent SARS-Cov-2 infection compared to the counterpart, (3.24 ± 1.49 vs. 1.49 ± 1.32, p = 0.032). Conversely, hepatic TMPRSS2 was significantly lower in patients who experienced symptomatic COVID-19 disease compared to asymptomatic patients (p = 0.0038). Further studies are necessary to understand the impact of COVID-19 in patients with pre-existing liver diseases.

Autoimmune hepatitis triggered by SARS-CoV-2 vaccination.

The development of autoimmune diseases has been reported after SARS-CoV-2 infection. Vaccination against SARS-CoV-2 could also trigger auto-immunity, as it has been described with other vaccines. An aberrant immune response induced by molecular mimicry and bystander activation, especially in predisposed individuals, is a potential mechanism. We report the case of a 76-year-old woman with Hashimoto thyroiditis and prior COVID-19 infection who developed severe autoimmune hepatitis (with typical features including strongly positive anti-smooth muscle antibody and markedly elevated immunoglobulins G, as well as typical histological findings) following SARS-CoV-2 vaccination (mRNA-1273 SARS-CoV-2 vaccine, Moderna®). The link between SARS-CoV-2 vaccination and the development of autoimmune diseases needs to be further investigated. Although a causality relationship cannot be proven, caution may be warranted when vaccinating individuals with known autoimmune diseases.

COVID-19 and liver disease: An update. / Actualización en COVID-19 y enfermedad hepática.

The SARS-CoV-2 pandemic has proven to be a serious challenge for the Spanish healthcare system. The impact of the virus on the liver is not well known, but in patients with chronic liver disease, mostly in advanced stages, it can critically compromise survival and trigger decompensation. Treatment in this subpopulation is complex due to the potential hepatotoxicity of some of the medicinal products used. Moreover, the pandemic has also negatively impacted patients with liver disease who have not contracted COVID-19, since the reallocation of human and material resources to the care of patients with the virus has resulted in a decrease in the treatment, diagnosis and follow-up of patients with liver disease, which will surely have negative consequences in the near future. Efficient reorganization of hepatology units is a priority to minimise the impact of the pandemic on a population as vulnerable as liver disease patients.

Impact of COVID-19 in patients with concurrent co-infections: A systematic review and meta-analyses.

The burden and impact of secondary superadded infections in critically ill coronavirus disease 2019 (COVID-19) patients is widely acknowledged. However, there is a dearth of information regarding the impact of COVID-19 in patients with tuberculosis, HIV, chronic hepatitis, and other concurrent infections. This review was conducted to evaluate the consequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in patients with concurrent co-infections based on the publications reported to date. An extensive comprehensive screening was conducted using electronic databases up to 3rd September 2020 after obtaining registration with PROSPERO (CRD420202064800). The observational studies or interventional studies in English, evaluating the impact of SARS-CoV-2 in patients with concurrent infections are included for the meta-analyses. Our search retrieved 20 studies, with a total of 205,702 patients. Patients with tuberculosis (RR = 2.10; 95% CI, 1.75-2.51; I2 = 0%), influenza (RR = 2.04; 95% CI, 0.15-28.25, I2 = 99%) have an increased risk of mortality during a co-infection with SARS-CoV-2. No significant impact is found in people living with HIV (RR = 0.99; 95% CI, 0.82-1.19; I2 = 30%), Chronic hepatitis (RR = 1.15; 95% CI, 0.73-1.81; I2 = 10%). Several countries (Brazil, Paraguay, Argentina, Peru, Colombia, and Singapore) are on the verge of a dengue co epidemic (cumulative 878,496 and 5,028,380 cases of dengue and COVID-19 respectively). The impact of COVID-19 in patients of concurrent infections with either tuberculosis or influenza is detrimental. The clinical outcomes of COVID-19 in HIV or chronic hepatitis patients are comparable to COVID-19 patients without these concurrent infections.

Impact of COVID-19 in Patients with Concurrent Co-Infections: A Systematic Review and Meta-Analyses (preprint)

Background: The burden and impact of secondary superadded infections in critically ill coronavirus disease (COVID-19) patients is widely acknowledged. However, there is a dearth of information regarding the impact of COVID-19 in patients with tuberculosis, HIV, chronic hepatitis, and other concurrent infections. This review was conducted to evaluate the consequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in patients with concurrent co-infections based on the publications reported to date.Methods: An extensive comprehensive screening was conducted using electronic databases up to 3rd September 2020 after obtaining registration with PROSPERO (CRD420202064800). The observational studies or interventional studies in English, evaluating the impact of SARS-CoV-2 in patients with concurrent infections are included for the meta-analyses.Results: Our search retrieved 20 studies, with a total of 205,702 patients. Patients with Tuberculosis (RR =2.10, 95% CI: 1.75 to 2.51, I 2 =0%), Influenza (RR =2.04, 95% CI: 0.15 to 28.25, I 2 =99%) have an increased risk of mortality during a co-infection with SARS-CoV-2. No significant impact is found in people living with HIV (RR =0.99, 95% CI: 0.82 to 1.19, I 2 =30%), Chronic hepatitis (RR =1.15, 95% CI: 0.73 to 1.81, I 2 =10%). Several countries (Brazil, Paraguay, Argentina, Peru, Colombia, and Singapore) are on the verge of a Dengue co epidemic (cumulative 878496 and 5028380 cases of Dengue and Covid-19 respectively).Conclusions: The impact of COVID-19 in patients of concurrent infections with either Tuberculosis or Influenza is detrimental. The clinical outcomes of COVID-19 in HIV or Chronic hepatitis patients are comparable to COVID-19 patients without these concurrent infections.Funding Statement: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Declaration of Interests: None.

Molecular Basis of Kidney Defects in COVID-19 Patients (preprint)

Background: Kidney damage is considered to be one of the risk factors for severity and mortality among COVID-19 patients. However, molecular nature of such observations remains unknown. Hypothesis: Altered gene expressions due to infection and in chronic kidney disease could explain severity in COVID-19 with kidney defects. Methods: We collected gene expression data from publicly available resources Gene Expression Omnibus CKD, Enrichr for deregulated genes in SARS-CoV infected cells in vitro, DisGeNET and others and carried out enrichment analysis using Enrichr. Result: Number of common genes altered in chronic kidney disease (CKD) and SARS-CoV infected cells was 2834. Enrichment analysis revealed that biological processes related viral life cycle and growth, cytokines, immunity, interferon, inflammation, apoptosis, autophagy, oxidative stress and others were significantly enriched with common deregulated genes. Similarly, significantly enriched pathways related to viral and bacterial infections, immunity and inflammation, cell cycle, ubiquitin mediated proteolysis, signaling pathways like Relaxin signaling pathway, mTOR signaling pathway, IL-17 signaling pathway, NF-kappa B signaling pathway were enriched with the common deregulated genes. These processes and pathways are known to be related to kidney damage. DisGeNET terms enriched include and related to Dengue fever, chronic Hepatitis, measles, retroviridae infections, respiratory syncytial virus Infections and many others. Kidney dysfunction related terms ischemia of kidney, renal fibrosis and diabetic nephropathy. Conclusion: Common deregulated genes in SARS-CoV infected cells and chronic kidney disease, as well as their enrichment with molecular processes and pathways relevant for viral pathogenesis and renal dysfunctions, could explain the severity of COVID-19 with kidney disease. This observation not only provides molecular relation of severity in COVID-19 with renal dysfunctions but might also help in the management and treatment targets for these cases.