Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?

Despite the need for novel, effective therapeutics for the COVID-19 pandemic, no curative regimen is yet available, therefore patients are forced to rely on supportive and nonspecific therapies. Some SARS-CoV-2 proteins, like the 3 C-like protease (3CLpro) or the major protease (Mpro), have been identified as promising targets for antiviral drugs. The Mpro has major a role in protein processing as well as pathogenesis of the virus, and could be a useful therapeutic target. The antiviral drug nirmatrelvir can keep SARS-CoV-2 from replicating through inhibiting Mpro. Nirmatrelvir was combined with another HIV protease inhibitor, ritonavir, to create Paxlovid (Nirmatrelvir/Ritonavir). The metabolizing enzyme cytochrome P450 3 A is inhibited by ritonavir to lengthen the half-life of nirmatrelvir, so rintonavir acts as a pharmacological enhancer. Nirmatrelvir exhibits potent antiviral activity against current coronavirus variants, despite significant alterations in the SARS-CoV-2 viral genome. Nevertheless, there are still several unanswered questions. This review summarizes the current literature on nirmatrelvir and ritonavir efficacy in treating SARS-CoV-2 infection, and also their safety and possible side effects.

Hepatic Disorders and COVID-19: From Pathophysiology to Treatment Strategy.

Following the SARS-CoV-2 outbreak and the subsequent development of the COVID-19 pandemic, organs such as the lungs, kidneys, liver, heart, and brain have been identified as priority organs. Liver diseases are considered a risk factor for high mortality from the COVID-19 pandemic. Besides, liver damage has been demonstrated in a substantial proportion of patients with COVID-19, especially those with severe clinical symptoms. Furthermore, antiviral medications, immunosuppressive drugs after liver transplantation, pre-existing hepatic diseases, and chronic liver diseases such as cirrhosis have also been implicated in SARS-CoV-2-induced liver injury. As a result, some precautions have been taken to prevent, monitor the virus, and avoid immunocompromised and susceptible individuals, such as liver and kidney transplant recipients, from being infected with SARS-CoV-2, thereby avoiding an increase in mortality. The purpose of this review was to examine the impairment caused by SARS-CoV-2 infection and the impact of drugs used during the pandemic on the mortality range and therefore the possibility of preventive measures in patients with liver disease.

Current evidence of COVID-19 vaccination-related cardiovascular events.

Currently, the world is recovering from the shock of the coronavirus disease 2019 (COVID-19) pandemic; however, this situation is still fragile. Health authorities recommend administering COVID-19 vaccines as the safest and most reliable tool for eliminating COVID-19. Subsequent to the extensive administration of the COVID-19 vaccines, a series of cardiovascular adverse effects have been reported. This comprehensive review aimed to provide an update on the etiology, pathophysiology, clinical features, and management of the cardiovascular adverse events associated with COVID-19 vaccines, including myocarditis, pericarditis, thrombosis with thrombocytopenia syndrome, myocardial infarction, cardiac arrhythmias, hypertension, and stress-induced cardiomyopathy. The benefits of COVID-19 vaccination far outweigh the reported adverse events. It would be clinically important to provide diagnostic scoring systems to differentiate COVID-19-related cardiovascular adverse events from other causes and develop therapeutic approaches for their management. Further evaluation of cardiovascular adverse events of the COVID-19 vaccines is crucial for implementing vaccination programs and developing safer and more reliable vaccines.

Diagnostic accuracy of clinically applied nanoparticle-based biosensors at detecting SARS-CoV-2 RNA and surface proteins in pharyngeal swabs compared to RT-PCR as a reference test.

INTRODUCTION: Nanoparticle-based biosensors (NPBs) are point-of-care diagnostic platforms that can be used for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high accuracy. AREAS COVERED: EBSCOhost Web, Embase, ProQuest, PubMed/MEDLINE, Scopus, Web of Science, and WHO Global Literature on Coronavirus Disease 2019 (COVID-19) were searched for relevant records published from 1 November 2019 to 30 April 2022. Records reporting original data on the accuracy of clinically applied nanoparticle-based biosensors at detecting SARS-CoV-2 RNA and surface proteins from pharyngeal swab specimens were considered. Findings were reported based on the PRISMA 2020 statement. The QUADAS-2 tool was used for assessment of quality and risk of bias among the included studies. EXPERT OPINION: A total of 50 relevant records were identified, of which 13 were included. The included studies explored the diagnostic performance of 13 clinically applied distinct nanoparticle-based biosensors in a total of 789 pharyngeal swabs collected from 376 COVID-19 patients and 413 otherwise healthy individuals. The mean sensitivity, specificity, and accuracy were 97.07%, 94.43%, and 96.91%, respectively, in comparison to RT-qPCR as the reference test. Considering their ease-of-operation, portability, low-cost manufacturing, NPBs could be considered suitable candidate diagnostic platforms for substituting RT-qPCR.

Severe acute respiratory syndrome coronavirus 2 infection: Role of interleukin-6 and the inflammatory cascade.

Since December 2019, a novel coronavirus that represents a serious threat to human lives has emerged. There is still no definite treatment for severe cases of the disease caused by this virus, named coronavirus disease 2019 (COVID-19). One of the most considered treatment strategies targets the exaggerated immune regulator, and interleukin (IL)-6 is a crucial pro-inflammatory mediator. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases show an elevated level of IL-6 related to disease severity. IL-6 activity can be inhibited by the following: IL-6 itself, IL-6 signaling pathways such as Janus kinase and signal transducer and activator of transcription (JAK-STAT), gp130, IL-6R, and downstream activated ILs, such as IL-17 and IL-6 cytokine. Currently, according to these studies and their results, IL-6 blockade with anti-IL-6 or its receptor antibodies such as tocilizumab in COVID-19 is beneficial in severe cases and may reduce the mortality rate. JAK-STAT inhibitors block the cytokine storm by inhibiting several crucial pro-inflammatory mediators such as TNF-α and IL-6 and have shown various results in clinical trials. IL-6 induces IL-17 secretion, and IL-17 is involved in the pathogenesis of inflammatory processes. Clinical trials of anti-IL-17 drugs are currently recruiting, and anti-gp130 antibody is preclinical. However, this agent has shown positive effects in inflammatory bowel disease clinical trials and could be tested for SARS-CoV-2. This study aimed to review the role of IL-6 in the cytokine storm and studies regarding IL-6 and blockade of its inflammatory pathways in COVID-19 to determine if any of these agents are beneficial for COVID-19 patients.

Vitamin supplementation as a potential adjunctive therapeutic approach for COVID-19: biological and clinical plausibility.

The recent pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19) has introduced itself into the human population in the 21st century after the coronavirus diseases SARS-CoV and Middle East respiratory syndrome (MERS-CoV). Major investigations are underway worldwide in the search for pharmaceutical interventions for COVID-19 and many agents are administered in off-label routes. Several cases are under study to check or restrict clinical manifestations of COVID-19. According to the fact that the efficacy of some micro-nutrients like vitamins is proven to treat or prevent infectious diseases because of their antimicrobial and immunomodulatory activity, the potential role of vitamins in the COVID-19 treatment or prevention must be considered.

Extrapulmonary Clinical Manifestations in COVID-19 Patients.

COVID-19 manifestations in symptomatic patients can be in the form of pneumonia, acute respiratory syndrome, and multiple organ dysfunction as well. Renal complications, gastrointestinal dysfunctions, endocrine system disorders, myocardial dysfunction and arrhythmia, neurological dysfunctions, dermatological symptoms, hematological manifestations, and thromboinflammation are among the reported extrapulmonary complications. Moreover, the presence of coagulopathy, excessive and dysregulated immune responses, and autoimmunity by COVID-19 patients is considerable. The pathogenesis of infection entails the entry of the virus via receptors on cells, principally angiotensin-converting enzyme 2 receptors. Direct virus damage coupled with indirect effects of viral infection including thromboinflammation, dysfunction of the immune system, and dysregulation of the renin-angiotensin system leads to multiple organ failure. This review outlines the extrapulmonary organ-specific complications and their pathophysiology and epidemiology.

Neutrophils, Crucial, or Harmful Immune Cells Involved in Coronavirus Infection: A Bioinformatics Study.

The latest member of the Coronaviridae family, called SARS-CoV-2, causes the Coronavirus Disease 2019 (COVID-19). The disease has caused a pandemic and is threatening global health. Similar to SARS-CoV, this new virus can potentially infect lower respiratory tract cells and can go on to cause severe acute respiratory tract syndrome, followed by pneumonia and even death in many nations. The molecular mechanism of the disease has not yet been evaluated until now. We analyzed the GSE1739 microarray dataset including 10 SARS-positive PBMC and four normal PBMC. Co-expression network analysis by WGCNA suggested that highly preserved 833 turquoise module with genes were significantly related to SARS-CoV infection. ELANE, ORM2, RETN, BPI, ARG1, DEFA4, CXCL1, and CAMP were the most important genes involved in this disease according to GEO2R analysis as well. The GO analysis demonstrated that neutrophil activation and neutrophil degranulation are the most activated biological processes in the SARS infection as well as the neutrophilia, basophilia, and lymphopenia predicted by deconvolution analysis of samples. Thus, using Serpins and Arginase inhibitors during SARS-CoV infection may be beneficial for increasing the survival of SARS-positive patients. Regarding the high similarity of SARS-CoV-2 to SARS-CoV, the use of such inhibitors might be beneficial for COVID-19 patients.