The COVID-19 pandemic is one of the greatest threats to human health in the 21 st century with more than 257 million cases and over 5.17 million deaths reported worldwide (as of November 23, 2021. Various agents were initially proclaimed to be effective against SARS-CoV-2, the etiological agent of COVID-19. Hydroxychloroquine, lopinavir/ritonavir, and ribavirin are all examples of therapeutic agents, whose efficacy against COVID-19 was later disproved. Meanwhile, concentrated efforts of researchers and clinicians worldwide have led to the identification of novel therapeutic options to control the disease including PAXLOVID™ (PF-07321332). Although COVID-19 cases are currently treated using a comprehensive approach of anticoagulants, oxygen, and antibiotics, the novel Pfizer agent PAXLOVID™ (PF-07321332), an investigational COVID-19 oral antiviral candidate, significantly reduced hospitalization time and death rates, based on an interim analysis of the phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) randomized, double-blind study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness. The scheduled interim analysis demonstrated an 89% reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset (primary endpoint). However, there still exists a great need for the development of additional treatments, as the recommended therapeutic options are insufficient in many cases. Thus far, mRNA and vector vaccines appear to be the most effective modalities to control the pandemic. In the current review, we provide an update on the progress that has been made since April 2020 in clinical trials concerning the effectiveness of therapies available to combat COVID-19. We focus on currently recommended therapeutic agents, including steroids, various monoclonal antibodies, remdesivir, baricitinib, anticoagulants and PAXLOVID™ summarizing the latest original studies and meta-analyses. Moreover, we aim to discuss other currently and previously studied agents targeting COVID-19 that either show no or only limited therapeutic activity. The results of recent studies report that hydroxychloroquine and convalescent plasma demonstrate no efficacy against SARS-CoV-2 infection. Lastly, we summarize the studies on various drugs with incoherent or insufficient data concerning their effectiveness, such as amantadine, ivermectin, or niclosamide.
Adiponectin is the adipokine associated with insulin sensitization, reducing liver gluconeogenesis, and increasing fatty acid oxidation and glucose uptake. Adiponectin is present in the kidneys, mainly in the arterial endothelium and smooth muscle cells, as well as in the capillary endothelium, and might be considered as a marker of many negative factors in chronic kidney disease. The last few years have brought a rising body of evidence that adiponectin is a multipotential protein with anti-inflammatory, metabolic, anti-atherogenic, and reactive oxygen species (ROS) protective actions. Similarly, adiponectin has shown many positive and direct actions in kidney diseases, and among many kidney cells. Data from large cross-sectional and cohort studies showed a positive correlation between serum adiponectin and mortality in chronic kidney disease. This suggests a complex interaction between local adiponectin action, comorbidities, and uremic milieu. In this review we discuss the role of adiponectin in chronic kidney disease.
Background/Aims: Chronic kidney disease CKD patients on intermittent hemodialysis IHD are exposed to SARS-CoV-2 infection and carry a risk of developing severe symptoms. The aim of this study was to evaluate the humoral and cellular immunity induced by two doses of mRNA vaccines, the Pfizer-BioNTech (Comirnaty) COVID-19 Vaccine and the Moderna (mRNA-1273) COVID-19 vaccine. Patients and methods: The study included 281 patients from five dialysis centers in northern Poland. Within 2 weeks prior to the first dose of the vaccine, a blood sample was collected for an evaluation of SARS-CoV-2 antibodies. Thirty to forty-five days after the second dose of the vaccine, a blood sample was taken to evaluate humoral and cellular response. Results: Patients with stage 5 CKD on IHD were characterized by a considerable SARS-CoV-2 vaccine-induced seroconversion rate. The strongest factors influencing the antibodies AB level after vaccination were a pre-vaccination history of SARS-CoV-2 infection, age, the neutrophil-to-lymphocyte ratio NLR, neutrophil absolute count, and the hemoglobin level. Cellular immunity was higher in patients with a pre-vaccination history of SARS-CoV-2 infection. Cellular immunity depended on the albumin level. Positive cellular response to vaccination was a positive factor reducing all-cause mortality, except for COVID-19 mortality (no such deaths were reported during our follow-up). Cellular immunity and humoral immunity were positively mutually dependent. High levels of albumin and hemoglobin, low neutrophil count, and a reduced NLR, translated into better response to vaccination. Conclusions: Patients with stage 5 CKD on IHD were characterized by a considerable SARS-CoV-2 vaccine-induced seroconversion rate and a good rate of cellular immunity. The factors that change with exacerbating inflammation and malnutrition (albumin, hemoglobin, neutrophil count, the NLR) affected the efficacy of the vaccination.
The intestinal microflora is extremely important, not only in the processes of absorption, digestion and biosynthesis of vitamins, but also in shaping the immune and cognitive functions of the human body. Several studies demonstrate a correlation between microbiota composition and such events as graft rejection, kidney interstitial fibrosis, urinary tract infections, and diarrhoea or graft tolerance. Some of those changes might be directly linked with pathologies such as colonization with pathogenic bacterial strains. Gut microbiota composition also plays an important role in metabolic complications and viral infections after transplantation. From the other side, gut microbiota might induce graft tolerance by promotion of T and B regulatory cells. Graft tolerance induction is still an extremely important issue regarding transplantology and might allow the reduction or even avoidance of immunosuppressive treatment. Although there is a rising evidence of the pivotal role of gut microbiota in aspects of kidney transplantation there is still a lack of knowledge on the direct mechanisms of microbiota action. Furthermore, some of those negative effects could be reversed by probiotics of faecal microbiota trapoinsplantation. While diabetes and hypertension as well as BKV and CMV viremia are common and important complications of transplantation, both worsening the graft function and causing systemic injuries, it opens up potential clinical treatment options. As has been also suggested in the current review, some bacterial subsets exhibit protective properties. However, currently, there is a lack of evidence on pro- and prebiotic supplementation in kidney transplant patients. In the current review, we describe the effect of the microbiota on the transplanted kidney in renal transplant recipients.
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