SARS-CoV-2-associated organs failure and inflammation: a focus on the role of cellular and viral microRNAs.

SARS-CoV-2 has been responsible for the recent pandemic all over the world, which has caused many complications. One of the hallmarks of SARS-CoV-2 infection is an induced immune dysregulation, in some cases resulting in cytokine storm syndrome, acute respiratory distress syndrome and many organs such as lungs, brain, and heart that are affected during the SARS-CoV-2 infection. Several physiological parameters are altered as a result of infection and cytokine storm. Among them, microRNAs (miRNAs) might reflect this poor condition since they play a significant role in immune cellular performance including inflammatory responses. Both host and viral-encoded miRNAs are crucial for the successful infection of SARS-CoV-2. For instance, dysregulation of miRNAs that modulate multiple genes expressed in COVID-19 patients with comorbidities (e.g., type 2 diabetes, and cerebrovascular disorders) could affect the severity of the disease. Therefore, altered expression levels of circulating miRNAs might be helpful to diagnose this illness and forecast whether a COVID-19 patient could develop a severe state of the disease. Moreover, a number of miRNAs could inhibit the expression of proteins, such as ACE2, TMPRSS2, spike, and Nsp12, involved in the life cycle of SARS-CoV-2. Accordingly, miRNAs represent potential biomarkers and therapeutic targets for this devastating viral disease. In the current study, we investigated modifications in miRNA expression and their influence on COVID-19 disease recovery, which may be employed as a therapy strategy to minimize COVID-19-related disorders.

Dynamic alterations in white blood cell counts and SARS-CoV-2 shedding in saliva: an infection predictor parameter.

Introduction: The recent coronavirus (COVID-19) outbreak posed a global threat and quickly escalated to a pandemic. However, accurate information on potential relationships between SARS-CoV-2 shedding in body fluids, especially saliva, and white blood cell (WBC) count is limited. In the present study we investigated the potential correlation between alterations in blood cell counts and viral shedding in saliva in a cohort of COVID-19 patients. Method: In this preliminary clinical research, 24 age-matched COVID-19 patients without comorbidities, 12 (50%) men and 12 (50%) women, were followed up for a period of 5 days to investigate whether changes in the level of viral shedding in saliva might parallel with temporal alterations in WBC count. Viral shedding in saliva was qualitatively measured by performing SARS-CoV-2 rapid antigen tests on patient saliva samples, using SARS-CoV-2 Rapid Antigen Test Kit (Roche, Basel, Switzerland). These patients were classified into two groups with sputum and non-sputum cough. WBCs counts including leukocyte (LYM), neutrophil (NEU), and LYM counts were recorded for each patient on days 1, 3, and 5. Results: The results of the present study showed that the levels of WBC, LYM, and NEU as well as erythrocyte sedimentation rate (ESR) increased significantly on the 5th day compared to the first day in both groups with sputum. However, the levels of C-reactive protein (CRP), Neutrophil-to-Lymphocyte Ratio (NLR) and lactate dehydrogenase (LDH) did not show significant changes. Conclusion: This study proves that investigating the change in the number of blood LYMs as well as laboratory parameters such as CRP, LDH, and ESR as biomarkers is an accurate indicator to detect the amount of viral shedding in people with sputum and non-sputum. The results of our study denote that the measured parameters exhibit the intensity of viral shedding in people with sputum.

Immune-checkpoint expression in antigen-presenting cells (APCs) of cytomegaloviruses infection after transplantation: as a diagnostic biomarker.

Cytomegalovirus (CMV), a member of the Herpesviridae family, mostly causes only slight feverish symptoms or can be asymptomatic in immunocompetent individuals. However, it is known to be particularly a significant cause of morbidity in immunocompromised patients, including transplant recipients, whose immune system has been weakened due to the consumption of immunosuppressor drugs. Therefore, the diagnosis of CMV infection after transplantation is crucial. New diagnostic methods for the quick detection of CMV have been developed as a result of understanding the clinical importance of invasive CMV. Antigen-presenting cells (APCs) and T cells are important components of the immune system and it may be possible to diagnose viral infections using immunological markers, such as lymphocytosis, cytotoxic T lymphocytes (CTL), and serum cytokine levels. Moreover, PD-1, CTLA 4, and TIGIT, which are expressed on certain T cells and antigen-presenting cells, are over-expressed during the infection. The assessment of CMV infection based on T cell and APC activity, and the expression of immunological checkpoints, can be helpful for the diagnosis of transplant patients at risk for CMV infection. In this review, we will investigate how immune checkpoints affect immune cells and how they impair organ transplantation after CMV infection.

Interleukin-2 and Oncolytic Virotherapy: A New Perspective in Cancer Therapy.

By triggering immune responses in malignancies that have generally been linked to poor outcomes, immunotherapy has recently shown effectiveness. On the other hand, tumors provide an environment for cells that influence the body's immunity against cancer. Malignant cells also express large amounts of soluble or membrane-bound ligands and immunosuppressive receptors. In this regard, the combination of oncolytic viruses with pro-inflammatory or inflammatory cytokines, including IL-2, can be a potential therapy for some malignancies. Indeed, oncolytic viruses cause the death of cancerous cells and destroy the tumor microenvironment. They result in the local release of threat signals and antigens associated with tumors. As a result, it causes lymphocyte activity and the accumulation of antigenpresenting cells which causes them to accumulate in the tumor environment and release cytokines and chemokines. In this study, we reviewed the functions of IL-2 as a crucial type of inflammatory cytokine in triggering immune responses, as well as the effect of its release and increased expression following combination therapy with oncolytic viruses in the process of malignant progression, as an essential therapeutic approach that should be taken into consideration going forward.

PBMC MicroRNAs: Promising Biomarkers for the Differential Diagnosis of COVID-19 Patients with Abnormal Coagulation Indices.

MicroRNAs, or miRNAs, may involve in coagulation and inflammation pathways caused by severe Coronavirus disease (COVID-19). Accordingly, this attempt was made to explore the behavior of peripheral blood mononuclear cells (PBMCs) miRNAs as effective biomarkers to diagnose COVID-19 patients with normal and abnormal coagulation indices. We selected the targeted miRNAs (miR-19a-3p, miR-223-3p, miR-143-5p, miR-494-3p and miR-301a-5p) according to previous reports, whose PBMC levels were then determined by real-time PCR. Receiver operating characteristic (ROC) curve was obtained to clarify the diagnostic potency of studied miRNAs. The differentially expressed miRNA profiles and corresponding biological activities were predicted in accordance with bioinformatics data. Targeted miRNAs' expression profiles displayed a significant difference between COVID-19 subjects with normal and abnormal coagulation indices. Moreover, the average miR-223-3p level expressed in COVID-19 cases with normal coagulation indices was significantly lower than that in healthy controls. Based on data from ROC analysis, miR-223-3p and miR-494-3p are promising biomarkers to distinguish the COVID-19 cases with normal or abnormal coagulation indices. Bioinformatics data highlighted the prominent role of selected miRNAs in the inflammation and TGF-beta signaling pathway. The differences existed in the expression profiles of selected miRNAs between the groups introduced miR-494-3p and miR-223-3p as potent biomarkers to prognosis the incidence of COVID-19.

A comprehensive review of COVID-19 symptoms and treatments in the setting of autoimmune diseases.

After the first reporting of the index case of Severe Acute Respiratory Syndrome (SARS)-CoV-2-associated disease at the end of December 2019, the virus spread quickly throughout the world, prompting the WHO on 11 March 2020 to declare the disease a global pandemic. The coronavirus disease 2019 (COVID-19) pandemic, raises concerns for all people, mainly for susceptible population. People with pre-existing diseases, especially individuals with autoimmune disorders, are more at the risk of SARS-CoV-2 infection because of compromised immune system due to frequent use of immunosuppressive drugs and steroids. Patients with autoimmune diseases and their physicians have concerns about these patients' healthcare, since they are at a higher risk for COVID-19 infection, may show severe complications of COVID-19, and may experience probable flares of their pre-existing disease. Even though there have been several studies discussing the relation between COVID-19 and various types of autoimmune diseases, it cannot be ascertained that all patients with autoimmune diseases experience more severe complications of COVID-19 and have more hospitalization or mortality rate. The situation depends on each patient's condition, such as the type and the severity of the underlying autoimmune disease and the kind of treatment they receive. In the present review, we have discussed the effects of COVID-19 pandemic on patients with different autoimmune diseases and their relative concerns about their treatments. As a result, we have reviewed further considerations that should be taken into account for these patients during the pandemic or when they are infected with COVID-19.

Monoclonal antibodies in cervical malignancy-related HPV.

Despite many efforts to treat HPV infection, cervical cancer survival is still poor for several reasons, including resistance to chemotherapy and relapse. Numerous treatments such as surgery, radiation therapy, immune cell-based therapies, siRNA combined with various drugs, and immunotherapy are being studied and performed to provide the best treatment. Depending on the stage and size of the tumor, methods such as radical hysterectomy, pelvic lymphadenectomy, or chemotherapy can be utilized to treat cervical cancer. While accepted, these treatments lead to interruptions in cellular pathways and immune system homeostasis. In addition to a low survival rate, cervical neoplasm incidence has been rising significantly. However, new strategies have been proposed to increase patient survival while reducing the toxicity of chemotherapy, including targeted therapy and monoclonal antibodies. In this article, we discuss the types and potential therapeutic roles of monoclonal antibodies in cervical cancer.

The role of antigen-presenting cells in the pathogenesis of COVID-19.

Coronavirus Disease 2019 (COVID-19) is one of the three lethal coronavirus outbreaks in the recent two decades and a serious threat to global health all over the world. The principal feature of the COVID-19 infection is the so-called "cytokine storm" exaggerated molecular response to virus distribution, which plays massive tissue and organ injury roles. Immunological treatments, including monoclonal antibodies and vaccines, have been suggested as the main approaches in treating and preventing this disease. Therefore, a proper investigation of the roles of antigen-presenting cells (APCs) in the aforementioned immunological responses appears essential. The present review will provide detailed information about APCs' role in the infection and pathogenesis of SARS-CoV-2 and the effect of monoclonal antibodies in diagnosis and treatment.

SARS-CoV-2: Receptor and Co-receptor Tropism Probability.

The recent pandemic which arose from China, is caused by a pathogenic virus named "severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2)". Its rapid global expansion has inflicted an extreme public health concern. The attachment of receptor-binding domains (RBD) of the spike proteins (S) to the host cell's membrane, with or without the help of other cellular components such as proteases and especially co-receptors, is required for the first stage of its pathogenesis. In addition to humans, angiotensin-converting enzyme 2 (ACE2) is found on a wide range of vertebrate host's cellular surface. SARS-CoV-2 has a broad spectrum of tropism; thus, it can infect a vast range of tissues, organs, and hosts; even though the surface amino acids of the spike protein conflict in the receptor-binding region. Due to the heterogeneous ACE2 distribution and the presence of different domains on the SARS-CoV-2 spike protein for binding, the virus entry into diverse host cell types may depend on the host cells' receptor presentation with or without co-receptors. This review investigates multiple current types of receptor and co-receptor tropisms, with other molecular factors alongside their respective mechanisms, which facilitate the binding and entry of SARS-CoV-2 into the cells, extending the severity of the coronavirus disease 2019 (COVID-19). Understanding the pathogenesis of COVID-19 from this perspective can effectively help prevent this disease and provide more potent treatment strategies, particularly in vulnerable people with various cellular-level susceptibilities.

The effect of Wnt/ß-catenin signaling on PD-1/PDL-1 axis in HPV-related cervical cancer.

Infection with high-risk human papillomavirus (HPV), including HPV-16 and HPV-18, is the main cause of malignancies, such as cervical cancer. Viral oncoproteins encoded by HPV are expressed in HPV-positive cancers and associated with the early cancer stages and the transformation of normal cells. The signaling pathways involved in the transformation of normal cells to cancerous form and the subsequently expressed programmed cell death-ligand 1 (PD-L1) on the surface of the transformed cells lead to a disruption in recognition of tumor cells by the immune cell system, including T lymphocytes and dendritic cells which lead to the development of cervical cancer malignancy. These cells also produce modest levels of cytokines during exhaustion, tumor-infiltrating T CD4+ cells with high levels of PD-1 and CD39 release considerable quantities of cytokines. The Wnt/ß-catenin signaling pathway, which controls the expression of genes involved in the tumor cells' markers, is demonstrated to be one of the most potent cancer stimulants. It leads to the evasion of the tumor cells from immune cell detection and ultimately avoids being recognized by dendritic cells or T-cells. PD-L1, as an inhibitory immune checkpoint, is essential for controlling immune system activity by inhibiting T-cells' inflammatory function. In the present review, we looked into how Wnt/ß-catenin affects the expression of PD-L1 and related genes like c-MYC in cancer cells and its role in the development of HPV-induced malignancy. We hypothesized that blocking these pathways could be a potential immunotherapy and cancer prevention method.

The role of Th17 cells in viral infections.

The present review provides an overview of recent advances regarding the function of Th17 cells and their produced cytokines in the progression of viral diseases. Viral infections alone do not lead to virus-induced malignancies, as both genetic and host safety factors are also involved in the occurrence of malignancies. Acquired immune responses, through the differentiation of Th17 cells, form the novel components of the Th17 cell pathway when reacting with viral infections all the way from the beginning to its final stages. As a result, instead of inducing the right immune responses, these events lead to the suppression of the immune system. In fact, the responses from Th17 cells during persistent viral infections causes chronic inflammation through the production of IL-17 and other cytokines which provide a favorable environment for tumor growth and its development. Additionally, during the past decade, these cells have been understood to be involved in tumor progression and metastasis. However, further research is required to understand Th17 cells' immune mechanisms in the vast variety of viral diseases. This review aims to determine the roles and effects of the immune system, especially Th17 cells, in the progression of viral diseases; which can be highly beneficial for the diagnosis and treatment of these infections.

SARS-CoV-2 infection: The role of PD-1/PD-L1 and CTLA-4 axis.

The outbreak of SARS-CoV-2 in Wuhan of China in December 2019 and its worldwide spread has turned into the COVID-19 pandemic. Respiratory disorders, lymphopenia, cytokine cascades, and the immune responses provoked by this virus play a major and fundamental role in the severity of the symptoms and the immunogenicity which it causes. Owing to the decrease in the inflammatory responses' regulation in the immune system and the sudden increase in the secretion of cytokines, it seems that an investigation of inhibitory immune checkpoints can influence theories regarding this disease's treatment methods. Acquired cell-mediated immune defense's T-cells have a key major contribution in clearing viral infections thus reducing the severity of COVID-19's symptoms. The most important diagnostic feature in individuals with COVID-19 is lymphocyte depletion, most importantly, T-cells. Due to the induction of interferon-γ (INF-γ) production by neutrophils and monocytes, which are abundantly present in the peripheral blood of the individuals with COVID-19, the expression of inhibitory immune checkpoints including, PD-1 (programmed death), PD-L1 and CTLA4 on the T-cells' surface is enhanced. The purpose of this review is to discuss the functions of these checkpoints and their effects on the dysfunction and exhaustion of T-cells, making them almost ineffective in individuals with COVID-19, especially in the cases with extreme symptoms.