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.

A case report of rhino-facial mucormycosis in a non-diabetic patient with COVID-19: a systematic review of literature and current update.

BACKGROUND: COVID-19 disease may be associated with a wide range of bacterial and fungal infections. We report a patient with COVID-19 infection who developed rhino-facial mucormycosis during treatment with corticosteroids. CASE PRESENTATION: A 59-year-old non-diabetic male patient was admitted with a diagnosis of COVID-19 based on positive RT-PCR and CT of the lungs. Due to sever lung involvement, he was treated with methylprednisolone. The patient was re-admitted to hospital, due to nasal obstruction and left side facial and orbital swelling, several days after discharge. In sinus endoscopic surgery, debridement was performed and the specimens were sent to pathology and mycology laboratories. A nasal biopsy showed wide hyphae without septa. The sequenced PCR product revealed Rhizopus oryzae. Despite all medical and surgical treatment, the patient died. In addition, the characteristics of patients with COVID-19-associated mucormycosis were reviewed in 44 available literatures. In most studies, diabetes mellitus was the most common predisposing factor for mucormycosis. CONCLUSION: Our report highlights the need for assessing the presence of mucormycosis in patients with COVID-19 and also it shows that physicians should consider the potential for secondary invasive fungal infections in COVID-19 cases.

Coronavirus Disease 2019: A Brief Review of the Clinical Manifestations and Pathogenesis to the Novel Management Approaches and Treatments.

The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19) in China, which spread to the rest of the world, led the World Health Organization to classify it as a global pandemic. COVID-19 belongs to the Bettacoronavirus genus of the Coronaviridae family, and it mainly spreads through the respiratory tract. Studies have now confirmed a human-to-human transmission as the primary pathway of spread. COVID-19 patients with a history of diseases such as respiratory system diseases, immune deficiency, diabetes, cardiovascular disease, and cancer are prone to adverse events (admission to the intensive care unit requiring invasive ventilation or even death). The current focus has been on the development of novel therapeutics, including antivirals, monoclonal antibodies, and vaccines. However, although there is undoubtedly an urgent need to identify effective treatment options against infection with COVID-19, it is equally important to clarify management protocols for the other significant diseases from which these patients may suffer, including cancer. This review summarizes the current evidence regarding the epidemiology, pathogenesis, and management of patients with COVID-19. It also aims to provide the reader with insights into COVID-19 in pregnant patients and those with cancer, outlining necessary precautions relevant to cancer patients. Finally, we provide the available evidence on the latest potent antiviral drugs and vaccines of COVID-19 and the ongoing drug trials.

Arginase 1 (Arg1) as an Up-Regulated Gene in COVID-19 Patients: A Promising Marker in COVID-19 Immunopathy.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic. It is well-established that SARS-CoV-2 infection can lead to dysregulated immune responses. Arginase-1 (Arg1), which has a pivotal role in immune cells, can be expressed in most of the myeloid cells, e.g., neutrophils and macrophages. Arg1 has been associated with the suppression of antiviral immune responses. METHODS: Whole blood was taken from 21 COVID-19 patients and 21 healthy individuals, and after RNA extraction and complementary DNA (cDNA) synthesis, gene expression of Arg1 was measured by real-time PCR. RESULTS: The qPCR results showed that the expression of Arg1 was significantly increased in COVID-19 patients compared to healthy individuals (p < 0.01). The relative expression analysis demonstrated there were approximately 2.3 times increased Arg1 expression in the whole blood of COVID-19 patients. Furthermore, the receiver operating characteristic (ROC) analysis showed a considerable diagnostic value for Arg1 expression in COVID-19 (p = 0.0002 and AUC = 0.8401). CONCLUSION: Arg1 might be a promising marker in the pathogenesis of the disease, and it could be a valuable diagnostic tool.

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.

The roles of signaling pathways in SARS-CoV-2 infection; lessons learned from SARS-CoV and MERS-CoV.

The number of descriptions of emerging viruses has grown at an unprecedented rate since the beginning of the 21st century. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is the third highly pathogenic coronavirus that has introduced itself into the human population in the current era, after SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Molecular and cellular studies of the pathogenesis of this novel coronavirus are still in the early stages of research; however, based on similarities of SARS-CoV-2 to other coronaviruses, it can be hypothesized that the NF-κB, cytokine regulation, ERK, and TNF-α signaling pathways are the likely causes of inflammation at the onset of COVID-19. Several drugs have been prescribed and used to alleviate the adverse effects of these inflammatory cellular signaling pathways, and these might be beneficial for developing novel therapeutic modalities against COVID-19. In this review, we briefly summarize alterations of cellular signaling pathways that are associated with coronavirus infection, particularly SARS-CoV and MERS-CoV, and tabulate the therapeutic agents that are currently approved for treating other human diseases.

Novel insights into the treatment of SARS-CoV-2 infection: An overview of current clinical trials.

The emergence of the global pandemic caused by the novel SARS-CoV-2 virus has motivated scientists to find a definitive treatment or a vaccine against it in the shortest possible time. Current efforts towards this goal remain fruitless without a full understanding of the behavior of the virus and its adaptor proteins. This review provides an overview of the biological properties, functional mechanisms, and molecular components of SARS-CoV-2, along with investigational therapeutic and preventive approaches for this virus. Since the proteolytic cleavage of the S protein is critical for virus penetration into cells, a set of drugs, such as chloroquine, hydroxychloroquine, camostat mesylate have been tested in clinical trials to suppress this event. In addition to angiotensin-converting enzyme 2, the role of CD147 in the viral entrance has also been proposed. Mepolizumab has shown to be effective in blocking the virus's cellular entrance. Antiviral drugs, such as remdesivir, ritonavir, oseltamivir, darunavir, lopinavir, zanamivir, peramivir, and oseltamivir, have also been tested as treatments for COVID-19. Regarding preventive vaccines, the whole virus, vectors, nucleic acids, and structural subunits have been suggested for vaccine development. Mesenchymal stem cells and natural killer cells could also be used against SARS-CoV-2. All the above-mentioned strategies, as well as the role of nanomedicine for the diagnosis and treatment of SARS-CoV-2 infection, have been discussed in this review.

An Overview on SARS-CoV-2 (COVID-19) and Other Human Coronaviruses and Their Detection Capability via Amplification Assay, Chemical Sensing, Biosensing, Immunosensing, and Clinical Assays.

A novel coronavirus of zoonotic origin (SARS-CoV-2) has recently been recognized in patients with acute respiratory disease. COVID-19 causative agent is structurally and genetically similar to SARS and bat SARS-like coronaviruses. The drastic increase in the number of coronavirus and its genome sequence have given us an unprecedented opportunity to perform bioinformatics and genomics analysis on this class of viruses. Clinical tests like PCR and ELISA for rapid detection of this virus are urgently needed for early identification of infected patients. However, these techniques are expensive and not readily available for point-of-care (POC) applications. Currently, lack of any rapid, available, and reliable POC detection method gives rise to the progression of COVID-19 as a horrible global problem. To solve the negative features of clinical investigation, we provide a brief introduction of the general features of coronaviruses and describe various amplification assays, sensing, biosensing, immunosensing, and aptasensing for the determination of various groups of coronaviruses applied as a template for the detection of SARS-CoV-2. All sensing and biosensing techniques developed for the determination of various classes of coronaviruses are useful to recognize the newly immerged coronavirus, i.e., SARS-CoV-2. Also, the introduction of sensing and biosensing methods sheds light on the way of designing a proper screening system to detect the virus at the early stage of infection to tranquilize the speed and vastity of spreading. Among other approaches investigated among molecular approaches and PCR or recognition of viral diseases, LAMP-based methods and LFAs are of great importance for their numerous benefits, which can be helpful to design a universal platform for detection of future emerging pathogenic viruses.

Covid-19: Perspectives on Innate Immune Evasion.

The ongoing outbreak of Coronavirus disease 2019 infection achieved pandemic status on March 11, 2020. As of September 8, 2020 it has caused over 890,000 mortalities world-wide. Coronaviral infections are enabled by potent immunoevasory mechanisms that target multiple aspects of innate immunity, with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) able to induce a cytokine storm, impair interferon responses, and suppress antigen presentation on both MHC class I and class II. Understanding the immune responses to SARS-CoV-2 and its immunoevasion approaches will improve our understanding of pathogenesis, virus clearance, and contribute toward vaccine and immunotherepeutic design and evaluation. This review discusses the known host innate immune response and immune evasion mechanisms driving SARS-CoV-2 infection and pathophysiology.

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.