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Coronavirus disease 2019 (COVID-19) has affected not only individual lives but also the world and global systems, both natural and human-made. Besides millions of deaths and environmental challenges, the rapid spread of the infection and its very high socioeconomic impact have affected healthcare, economic status and wealth, and mental health across the globe. To better appreciate the pandemic's influence, multidisciplinary and interdisciplinary approaches are needed. In this chapter, world-leading scientists from different backgrounds share collectively their views about the pandemic's footprint and discuss challenges that face the international community., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The recent emergence of the Omicron variant has raised concerns on vaccine efficacy and the urgent need to study more efficient vaccination strategies. Here we observed that an mRNA vaccine booster in individuals vaccinated with two doses of inactivated vaccine significantly increased the plasma level of specific antibodies that bind to the receptor-binding domain (RBD) or the spike (S) ectodomain (S1 + S2) of both the G614 and the Omicron variants, compared to two doses of homologous inactivated vaccine. The level of RBD- and S-specific IgG antibodies and virus neutralization titers against variants of concern in the heterologous vaccination group were similar to that in individuals receiving three doses of homologous mRNA-vaccine or a boost of mRNA vaccine after infection, but markedly higher than that in individuals receiving three doses of a homologous inactivated vaccine. This heterologous vaccination regime furthermore significantly enhanced the RBD-specific memory B cell response and S1-specific T cell response, compared to two or three doses of homologous inactivated vaccine. Our study demonstrates that mRNA vaccine booster in individuals vaccinated with inactivated vaccines can be highly beneficial, as it markedly increases the humoral and cellular immune responses against the virus, including the Omicron variant., (© 2022. The Author(s).)

On November 26th, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), B.1.1.529, was designated by the World Health Organization (WHO), named Omicron, and classified as a variant of concern (VOC). The news raised an international alarm about a new wave of coronavirus disease 2019 (Covid-19) outbreak, since Omicron has a large group of mutations which may affect the way it spread, cause disease, and escape from the immunity. Therefore, it is essential to take a closer look at how it has emerged, how it may sustain the pandemic, and how we can act correspondingly, both nationally and internationally, to help control the spreading of the disease.

Introduction: In November 26th, 2021 a new strain of SARS-CoV-2 was designated by the World Health Organization as a variant of concern and named Omicron. The news broadcasted a global wave of panic and anxiety while many, like 2 years ago, were making themselves ready for the holiday season. After almost a month of its designation, countries from all 6 continents have been reported Omicron from their genomic sequences. This triggered an international alarm about a new era in the Covid-19 pandemic, where despite the vast amount of vaccinations, a surge in new cases and hospitalizations are reported from all over the world., Methods: Scientific literature published from November 26, 2021 to March 21, 2022 have been searched and retrieved by using "SARS-COV-2", "Omicron", "B.1.1.529", "Covid-19", and "global community" keywords from "PubMed", "Web o "Google Scholar", and "MedRxiv" databases., Results: Omicron have been evolved to spread faster than previous variants of concern, but it infects people lesser than other variants, Delta for example. Omicron can also escape vaccine-induced immunity more than previous SARS-CoV-2 variants., Discussion: Despite possible lower lethal risks than previous strains, Omicron may provide populations with a higher community transmission and a higher hospitalization load, which potentially overwhelm already exhausted health care systems. Therefore, we need to get used to the "New Normal" and maintain health recommendations to help decrease spreading of the virus and buy more time for the scientists to dive deeper into potential ways of tackling Covid-19, more than ever., (© 2022 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

The search for developing effective vaccines against SARS-CoV-2 began with the start of the COVID-19 pandemic, and the first vaccine dose was administered in December 2020. Today, full vaccination of most of the world's population is considered the most important means to overcome the COVID-19 pandemic. Vaccination has been associated with various struggles. Some adverse reactions have resulted in the discontinuation of the specific vaccines use in some countries. Countries in poor regions have faced difficulties supplying enough vaccine doses, and the emergence of new variants of concern has resulted in reduced effectiveness of available vaccines against COVID-19. The mix-and-match strategy, using heterologous vaccines in the first and second doses, might successfully solve the mentioned struggles. Moreover, this strategy has been associated with higher cellular and humoral immune responses without significantly increasing the adverse reactions. Hence, this strategy can help improve the vaccines' effectiveness, and act as a solution for vaccine shortage in poor regions., (© 2021 Wiley Periodicals LLC.)

The entire world has been suffering from the coronavirus disease 2019 (COVID-19) pandemic since March 11, 2020. More than a year later, the COVID-19 vaccination brought hope to control this viral pandemic. Here, we review the unknowns of the COVID-19 vaccination, such as its longevity, asymptomatic spread, long-term side effects, and its efficacy on immunocompromised patients. In addition, we discuss challenges associated with the COVID-19 vaccination, such as the global access and distribution of vaccine doses, adherence to hygiene guidelines after vaccination, the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, and vaccine resistance. Despite all these challenges and the fact that the end of the COVID-19 pandemic is still unclear, vaccines have brought great hope for the world, with several reports indicating a significant decline in the risk of COVID19-related infection and hospitalizations., (© 2021 Wiley Periodicals LLC.)

The coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS- CoV-2) with an estimated fatality rate of less than 1%. The SARS-CoV-2 accessory proteins ORF3a, ORF6, ORF7a, ORF7b, ORF8, and ORF10 possess putative functions to manipulate host immune mechanisms. These involve interferons, which appear as a consensus function, immune signaling receptor NLRP3 (NLR family pyrin domain-containing 3) inflammasome, and inflammatory cytokines such as interleukin 1β (IL-1β) and are critical in COVID-19 pathology. Outspread variations of each of the six accessory proteins were observed across six continents of all complete SARS-CoV-2 proteomes based on the data reported before November 2020. A decreasing order of percentage of unique variations in the accessory proteins was determined as ORF3a > ORF8 > ORF7a > ORF6 > ORF10 > ORF7b across all continents. The highest and lowest unique variations of ORF3a were observed in South America and Oceania, respectively. These findings suggest that the wide variations in accessory proteins seem to affect the pathogenicity of SARS-CoV-2., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Coronavirus disease 2019 (COVID-19) has a devastating impact on global populations triggered by a highly infectious viral sickness, produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The third major cause of mortality in the United States, following heart disease and cancer in 2020, was undoubtedly COVID-19. The centers for disease control and prevention (CDC) and the world health organization (WHO) separately developed a categorization system for differentiating new strains of SARS-CoV-2 into variants of concern (VoCs) and variants of interest (VoIs) with the continuing development of various strains SARS-CoV-2. By December 2021, five of the SARS-CoV-2 VoCs were discovered from the onset of the pandemic depending on the latest epidemiologic report by the WHO: Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529). Mutations in the receptor-binding domain (RBD) and n-terminal domain (NTD) have been found throughout all five identified VoCs. All strains other than the delta mutant are often found with the N501Y mutation situated on the RBD, resulting in higher binding between the spike protein and angiotensin-converting enzyme 2 (ACE2) receptors, enhanced viral adhesion, and following the entrance to host cells. The introduction of these new strains of SRAS-CoV-2 is likely to overcome the remarkable achievements gained in restricting this viral disease to the point where it is presented with remarkable vaccine developments against COVID-19 and strong worldwide mass immunization initiatives. Throughout this literature review, the effectiveness of current COVID-19 vaccines for managing and prohibiting SARS-CoV-2 strains is thoroughly described., (Copyright © 2021. Published by Elsevier Masson SAS.)

Coronavirus disease 2019 (COVID-19) is still propagating a year after the start of the pandemic. Besides the complications patients face during the COVID-19 disease period, there is an accumulating body of evidence concerning the late-onset complications of COVID-19, of which autoimmune manifestations have attracted remarkable attention from the first months of the pandemic. Autoimmune hemolytic anemia, immune thrombocytopenic purpura, autoimmune thyroid diseases, Kawasaki disease, Guillain-Barre syndrome, and the detection of autoantibodies are the cues to the discovery of the potential of COVID-19 in inducing autoimmunity. Clarification of the pathophysiology of COVID-19 injuries to the host, whether it is direct viral injury or autoimmunity, could help to develop appropriate treatment., (© 2021 Wiley Periodicals LLC.)

Although significant research has been done to find effective drugs against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), no definite effective drug exists. Thus, research has now shifted towards immunomodulatory agents other than antivirals. In this review, we aim to describe the latest findings on the role of type I interferon (IFN)-mediated innate antiviral response against SARS-CoV-2 and discuss the use of IFNs as a medication for COVID-19. A growing body of evidence has indicated a promoting active but delayed IFNs response to SARS-CoV-2 and Middle East respiratory syndrome coronavirus in infected bronchial epithelial cells. Studies have demonstrated that IFNs' administration before the viral peak and the inflammatory phase of disease could offer a highly protective effect. However, IFNs' treatment during the inflammatory and severe stages of the disease causes immunopathology and long-lasting harm for patients. Therefore, it is critical to note the best time window for IFNs' administration. Further investigation of the clinical effectiveness of interferon for patients with mild to severe COVID-19 and its optimal timing and route of administration can be beneficial in finding a safe and effective antiviral therapy for the COVID-19 disease., (© 2021 Wiley Periodicals LLC.)

Coronavirus disease 2019 (COVID-19) has resulted in a global pandemic, challenging both the medical and scientific community for the development of novel vaccines and a greater understanding of the effects of the SARS-CoV-2 virus. COVID-19 has been associated with a pronounced and out-of-control inflammatory response. Studies have sought to understand the effects of inflammatory response markers to prognosticate the disease. Herein, we aimed to review the evidence of 11 groups of systemic inflammatory markers for risk-stratifying patients and prognosticating outcomes related to COVID-19. Numerous studies have demonstrated the effectiveness of neutrophil to lymphocyte ratio (NLR) in prognosticating patient outcomes, including but not limited to severe disease, hospitalization, intensive care unit (ICU) admission, intubation, and death. A few markers outperformed NLR in predicting outcomes, including 1) systemic immune-inflammation index (SII), 2) prognostic nutritional index (PNI), 3) C-reactive protein (CRP) to albumin ratio (CAR) and high-sensitivity CAR (hsCAR), and 4) CRP to prealbumin ratio (CPAR) and high-sensitivity CPAR (hsCPAR). However, there are a limited number of studies comparing NLR with these markers, and such conclusions require larger validation studies. Overall, the evidence suggests that most of the studied markers are able to predict COVID-19 prognosis, however NLR seems to be the most robust marker., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Karimi, Shobeiri, Kulasinghe and Rezaei.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic coronavirus disease 2019 (COVID-19) that exhibits an overwhelming contagious capacity over other human coronaviruses (HCoVs). This structural snapshot describes the structural bases underlying the pandemic capacity of SARS-CoV-2 and explains its fast motion over respiratory epithelia that allow its rapid cellular entry. Based on notable viral spike (S) protein features, we propose that the flat sialic acid-binding domain at the N-terminal domain (NTD) of the S1 subunit leads to more effective first contact and interaction with the sialic acid layer over the epithelium, and this, in turn, allows faster viral 'surfing' of the epithelium and receptor scanning by SARS-CoV-2. Angiotensin-converting enzyme 2 (ACE-2) protein on the epithelial surface is the primary entry receptor for SARS-CoV-2, and protein-protein interaction assays demonstrate high-affinity binding of the spike protein (S protein) to ACE-2. To date, no high-frequency mutations were detected at the C-terminal domain of the S1 subunit in the S protein, where the receptor-binding domain (RBD) is located. Tight binding to ACE-2 by a conserved viral RBD suggests the ACE2-RBD interaction is likely optimal. Moreover, the viral S subunit contains a cleavage site for furin and other proteases, which accelerates cell entry by SARS-CoV-2. The model proposed here describes a structural basis for the accelerated host cell entry by SARS-CoV-2 relative to other HCoVs and also discusses emerging hypotheses that are likely to contribute to the development of antiviral strategies to combat the pandemic capacity of SARS-CoV-2., (© 2020 Federation of European Biochemical Societies.)

Kawasaki-like disease (KLD) and multisystem inflammatory syndrome in children (MIS-C) are considered as challenges for pediatric patients under the age of 18 infected with coronavirus disease 2019 (COVID-19). A systematic search was performed on July 2, 2020, and updated on December 1, 2020, to identify studies on KLD/MIS-C associated with COVID-19. The databases of Scopus, PubMed, Web of Science, Embase, and Scholar were searched. The hospitalized children with a presentation of Kawasaki disease (KD), KLD, MIS-C, or inflammatory shock syndromes were included. A total number of 133 children in 45 studies were reviewed. A total of 74 (55.6%) cases had been admitted to pediatric intensive care units (PICUs). Also, 49 (36.8%) patients had required respiratory support, of whom 31 (23.3%) cases had required mechanical ventilation/intubation, 18 (13.5%) cases had required other oxygen therapies. In total, 79 (59.4%) cases had been discharged from hospitals, 3 (2.2%) had been readmitted, 9 (6.7%) had been hospitalized at the time of the study, and 9 (6.7%) patients had expired due to the severe heart failure, shock, brain infarction. Similar outcomes had not been reported in other patients. Approximately two-thirds of the children with KLD associated with COVID-19 had been admitted to PICUs, around one-fourth of them had required mechanical ventilation/intubation, and even some of them had been required readmissions. Therefore, physicians are strongly recommended to monitor children that present with the characteristics of KD during the pandemic as they can be the dominant manifestations in children with COVID-19., (© 2021 Wiley Periodicals LLC.)

Autophagy-dependent cell death is a prominent mechanism that majorly contributes to homeostasis by maintaining the turnover of organelles under stressful conditions. Several viruses, including coronaviruses (CoVs), take advantage of cellular autophagy to facilitate their own replication. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta-coronavirus (β-CoVs) that mediates its replication through a dependent or independent ATG5 pathway using specific double-membrane vesicles that can be considered as similar to autophagosomes. With due attention to several mutations in NSP6, a nonstructural protein with a positive regulatory effect on autophagosome formation, a potential correlation between SARS-CoV-2 pathogenesis mechanisms and autophagy can be expected. Certain medications, albeit limited in number, have been indicated to negatively regulate autophagy flux, potentially in a way similar to the inhibitory effect of β-CoVs on the process of autophagy. However, there is no conclusive evidence to support their direct antagonizing effect on CoVs. Off-target accumulation of a major fraction of FDA-approved autophagy modulating drugs may result in adverse effects. Therefore, medications that have modulatory effects on autophagy could be considered as potential lead compounds for the development of new treatments against this virus. This review discusses the role of autophagy/virophagy in controlling SARS-CoV-2, focusing on the potential therapeutic implications., (© 2021 International Federation for Cell Biology.)

The current Coronavirus Disease 19 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) shows similar pathology to MERS and SARS-CoV, with a current estimated fatality rate of 1.4%. Open reading frame 10 (ORF10) is a unique SARS-CoV-2 accessory protein, which contains eleven cytotoxic T lymphocyte (CTL) epitopes each of nine amino acids in length. Twenty-two unique SARS-CoV-2 ORF10 variants have been identified based on missense mutations found in sequence databases. Some of these mutations are predicted to decrease the stability of ORF10 in silico physicochemical and structural comparative analyses were carried out on SARS-CoV-2 and Pangolin-CoV ORF10 proteins, which share 97.37% amino acid (aa) homology. Though there is a high degree of ORF10 protein similarity of SARS-CoV-2 and Pangolin-CoV, there are differences of these two ORF10 proteins related to their sub-structure (loop/coil region), solubility, antigenicity and shift from strand to coil at aa position 26 (tyrosine). SARS-CoV-2 ORF10, which is apparently expressed in vivo since reactive T cell clones are found in convalescent patients should be monitored for changes which could correlate with the pathogenesis of COVID-19., Competing Interests: Declaration of competing interest The authors do not have any conflicts of interest to declare., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Immune evasion is one of the unique characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attributed to its ORF8 protein. This protein modulates the adaptive host immunity through down-regulation of MHC-1 (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the host's interferon-mediated antiviral response. To understand the host's immune perspective in reference to the ORF8 protein, a comprehensive study of the ORF8 protein and mutations possessed by it have been performed. Chemical and structural properties of ORF8 proteins from different hosts, such as human, bat, and pangolin, suggest that the ORF8 of SARS-CoV-2 is much closer to ORF8 of Bat RaTG13-CoV than to that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 in SARS-CoV-2 can be grouped into four classes based on their predicted effects (Hussain et al., 2021) [1]. Based on the geo-locations and timescale of sample collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were found upon sequence similarity analyses and consideration of the amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of the rapidly evolving SARS-CoV-2 through the ORF8., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a pandemic since March 2020. The exact pathogenesis of SARS-CoV-2 and the role of each component of the innate and adaptive immune system is still unknown. However, available data from other coronavirus families, such as SARS-CoV and the Middle East respiratory syndrome and also new findings could be useful for a better understanding of SARS-CoV-2. Toll-like receptors (TLR) play an important role in recognition of viral particles and activation of the innate immune system. Activation of TLR pathways leads to secretion of pro-inflammatory cytokines, such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α, as well as type 1 interferon. Different TLRs, like TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, and TLR9 are potentially important in COVID-19 infection. It is also worth mentioning that we should bear in mind both the beneficial and harmful effects of TLR in confronting COVID-19 infection. TLRs could be a potential target in controlling the infection in the early stages of disease and production of vaccine against SARS-CoV-2., (© 2021 Wiley Periodicals LLC.)

Introduction: The world is witnessing the spread of one of the members of Coronaviruses (CoVs) family, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the 21st century. Considering the short time spent after its prevalence, limited information is known about the effect of the virus mechanism on different organs of the body; meanwhile the lack of specific treatment and vaccine for this virus has exposed millions of people to a big challenge., Areas Covered: The review article aims to describe the general and particular characteristics of CoVs, their classification, genome structure, host cell infection, cytokine storm, anti-viral treatments, and inhibition of COVID-19-related ER-mitochondrial stress. In addition, it refers to drugs such as Chloroquine/Hydroxychloroquine, Lopinavir/Ritonavir, darunavir, ribavirin, remdesivir, and favipiravir, which have undergone clinical trials for coronavirus disease 2019 (COVID-19) treatment. This analysis was derived from an extensive scientific literature search including Pubmed, ScienceDirect, and Google Scholar performed., Expert Opinion: The effectiveness rate and complications of these drugs can reveal new insights into the potential therapeutic goals for the disease. Moreover, lifestyle change can effectively prevent SARS-CoV-2 infection., (Copyright © 2021. Published by Elsevier Masson SAS.)

Due to the rapidly spreading of novel coronavirus disease (COVID-19) worldwide, there is an urgent need to develop efficient vaccines and specific antiviral treatments. Pathways of the viral entry into cells are interesting subjects for targeted therapy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The present study aims to provide a systematic evaluation of the most recent in vitro and in vivo investigations targeting SARS-CoV-2 cell entry. A systematic search was carried out in major medical sources, including MEDLINE (through PubMed), Web of Science, Scopus, and EMBASE. Combinations of the following search terms were used: SARS-CoV-2, in vitro, in vivo, preclinical, targeted therapy, and cell entry. A modified version of the Consolidated Standards of Reporting Trials and Systematic Review Centre for Laboratory Animal Experimentation assessment tools were applied for evaluating the risk of bias of in vitro and in vivo studies, respectively. A narrative synthesis was performed as a qualitative method for the data synthesis of each outcome measure. A total of 2,649 articles were identified through searching PubMed, Web of Science, Scopus, EMBASE, Google Scholar, and Biorxiv. Finally, 22 studies (one in vivo study and 21 in vitro studies) were included. The spike (S) glycoprotein of the SARS-CoV-2 was the main target of investigation in 19 studies. SARS-CoV-2 can enter into the host cells through endocytosis or independently. SARS-CoV-2 S protein utilizes angiotensin-converting enzyme 2 or CD147 as its cell-surface receptor to attach host cells. It consists of S1 and S2 subunits. The S1 subunit mediates viral attachment to the host cells, while the S2 subunit facilitates virus-host membrane fusion. The cleavage of the S1-S2 protein, which is required for the conformational changes of the S2 subunit and processing of viral fusion, is regulated by the host proteases, including cathepsin L (during endocytosis) and type II membrane serine protease (independently). Targeted therapy strategies against SARS-CoV-2 cell entry mechanisms fall into four main categories: strategies targeting virus receptors on the host, strategies neutralizing SARS-CoV-2 spike protein, strategies targeting virus fusion to host cells, and strategies targeting endosomal and non-endosomal dependent pathways of virus entry. Inhibition of the viral entry by targeting host or virus-related components remains the most potent strategy to prevent and treat COVID-19. Further high-quality investigations are needed to assess the efficacy of the proposed targets and develop specific antivirals against SARS-CoV-2., (© 2020 Wiley Periodicals LLC.)

COVID-19 has led to a pandemic, affecting almost all countries in a few months. In this work, we applied selected deep learning models including multilayer perceptron, random forest, and different versions of long short-term memory (LSTM), using three data sources to train the models, including COVID-19 occurrences, basic information like coded country names, and detailed information like population, and area of different countries. The main goal is to forecast the outbreak in nine countries (Iran, Germany, Italy, Japan, Korea, Switzerland, Spain, China, and the USA). The performances of the models are measured using four metrics, including mean average percentage error (MAPE), root mean square error (RMSE), normalized RMSE (NRMSE), and R 2 . The best performance was found for a modified version of LSTM, called M-LSTM (winner model), to forecast the future trajectory of the pandemic in the mentioned countries. For this purpose, we collected the data from January 22 till July 30, 2020, for training, and from 1 August 2020 to 31 August 2020, for the testing phase. Through experimental results, the winner model achieved reasonably accurate predictions (MAPE, RMSE, NRMSE, and R 2 are 0.509, 458.12, 0.001624, and 0.99997, respectively). Furthermore, we stopped the training of the model on some dates related to main country actions to investigate the effect of country actions on predictions by the model., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Rahele Kafieh et al.)

Although it is estimated that COVID-19 life-threatening conditions may be diagnosed in less than 1:1000 infected individuals below the age of 50, but the real impact of this pandemic on pediatric patients with different types of primary immunodeficiency (PID) is not elucidated. The current prospective study on a national registry of PID patients showed that with only 1.23 folds higher incidence of infections, these patients present a 10-folds higher mortality rate compared to population mainly in patients with combined immunodeficiency and immune dysregulation. Therefore, further management modalities against COVID-19 should be considered to improve the survival rate in these two PID entities using hematopoietic stem cell transplantation and immunomodulatory agents.

Background: Since the beginning of the novel coronavirus (SARS-CoV-2) disease outbreak, there has been an increasing interest in finding a potential therapeutic agent for the disease. Considering the matter of time, the computational methods of drug repurposing offer the best chance of selecting one drug from a list of approved drugs for the life-threatening condition of COVID-19. The present systematic review aims to provide an overview of studies that have used computational methods for drug repurposing in COVID-19., Methods: We undertook a systematic search in five databases and included original articles in English that applied computational methods for drug repurposing in COVID-19., Results: Twenty-one original articles utilizing computational drug methods for COVID-19 drug repurposing were included in the systematic review. Regarding the quality of eligible studies, high-quality items including the use of two or more approved drug databases, analysis of molecular dynamic simulation, multi-target assessment, the use of crystal structure for the generation of the target sequence, and the use of AutoDock Vina combined with other docking tools occurred in about 52%, 38%, 24%, 48%, and 19% of included studies. Studies included repurposed drugs mainly against non-structural proteins of SARS-CoV2: the main 3C-like protease (Lopinavir, Ritonavir, Indinavir, Atazanavir, Nelfinavir, and Clocortolone), RNA-dependent RNA polymerase (Remdesivir and Ribavirin), and the papain-like protease (Mycophenolic acid, Telaprevir, Boceprevir, Grazoprevir, Darunavir, Chloroquine, and Formoterol). The review revealed the best-documented multi-target drugs repurposed by computational methods for COVID-19 therapy as follows: antiviral drugs commonly used to treat AIDS/HIV (Atazanavir, Efavirenz, and Dolutegravir Ritonavir, Raltegravir, and Darunavir, Lopinavir, Saquinavir, Nelfinavir, and Indinavir), HCV (Grazoprevir, Lomibuvir, Asunaprevir, Ribavirin, and Simeprevir), HBV (Entecavir), HSV (Penciclovir), CMV (Ganciclovir), and Ebola (Remdesivir), anticoagulant drug (Dabigatran), and an antifungal drug (Itraconazole)., Conclusions: The present systematic review provides a list of existing drugs that have the potential to influence SARS-CoV2 through different mechanisms of action. For the majority of these drugs, direct clinical evidence on their efficacy for the treatment of COVID-19 is lacking. Future clinical studies examining these drugs might come to conclude, which can be more useful to inhibit COVID-19 progression., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The novel coronavirus disease (COVID-19) profoundly influences T-cell immunity. The counts of total T cells and T-cell subsets, especially CD4+ and CD8+ T cells, are decreased in patients with COVID-19. Also, the function of these cells becomes less effective as the expression of immune inhibitory receptors, such as Tim3 and PD-1, increases over time during the disease. Kinetic analyses show that the T-cell profile changes dynamically, so does the COVID-19 stages. As COVID-19 continues to deteriorate and progresses to severe/critical condition, the lymphocyte count steadily decreases. Therefore, the ability of COVID-19 to escape the immune system might lie in its power to profoundly diminish T-cell effective function, which is necessary for the establishment of a robust antiviral immunity. Also, COVID-19 is associated with increased numbers of monocytes and macrophages, and as the disease progresses from a mild form to a severe/critical condition, the macrophage population becomes denser. Monitoring the expression of cytokines associated with macrophage activation, mainly interleukin (IL)-6 and IL-10, indicates that the course of COVID-19 consists of two stages and the transition between disease stages occurs by the end of the first week after onset of symptoms. At the initial stage, the immune military recognizes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as nonself and thus fires macrophages at the lungs against the virus. The first flame can control disease progression effectively. However, a trained immunocompetent system would maintain the fire of macrophages over an extended time. It lies in its immune memory in tissue-resident macrophages, especially alveolar macrophages, making a professionally trained immune system more likely to be feared by COVID-19 than an untrained immune system. In this manner, the trained immunocompetent system commits such a failure that causes the lungs to come down rapidly. The fact that younger age groups, including neonates and children, are less susceptible to COVID-19 than older age groups reflects that the natural affinities of the immune system that has not been trained thoroughly would be standard in combatting against COVID-19 whereas the higher affinities of the trained immune system for rapid activation of immune responses might raise faults - the lungs come down.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third coronavirus causing an outbreak in the twenty-first century. It is related to a contagious coronavirus disease (COVID-19), which its high pace of spreading allowed it to lie to the whole world and be turned into a pandemic only a few months after the identification of the first case. Currently, the reverse transcription-polymerase chain reaction (RT-PCR) test of throat swap is the gold standard of diagnosis; however, several studies have reported false-negative results with non-ideal sensitivity. Because this pandemic constitutes a significant burden on global healthcare systems and due to the high transmission rate of the virus, an accurate diagnosis algorithm is needed to reduce the missing case number. A comprehensive clinical examination and taking a history of all systems (not just limited to the respiratory system) combined with hematologic laboratory tests and chest imaging can lead to a sensitive diagnosis, severity assessment, and RT-PCT test interpretation. This chapter focuses on clinical characteristics, hematologic laboratory, and chest imaging features in COVID-19.

Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22-42, aa 79-84, and aa 330-393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the findings propose a possible SARS-CoV-2 transmission flow across these nineteen species.

New coronavirus disease 2019 (COVID-19) has succeeded in surprising the world with infecting more than 12 million people and claiming 560,000 lives in only six months. COVID-19 is associated with a spectrum of respiratory symptoms, especially dyspnea. Patients who progress to severe or critical condition display peripheral and posterior lung lesions bilaterally. These patients require admission to the intensive care unit (ICU); therefore, they are prone to ICU-related complications during disease and after recovery. Respiratory physiotherapy techniques, in particular, active techniques, might help the improvement of airway clearance and lung capacity in addition to the reduction of breathing effort during the active disease. In parallel, it might lead to the prevention of disabilities, resulting from infection and extended hospitalization in patients who recovered from COVID-19. This supports physiotherapy both as a prophylactic and therapeutic strategy for COVID-19.

Nowadays, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused novel coronavirus disease (COVID-19) pandemic, is the worldwide challenge. The virus is highly contagious, and clinical consequences were very divers. It is estimated that if no effective action is taken, COVID-19 could plague 90% of the world's population and kill over 40 million people. So, it is essential to understand the virus pathogenicity and follow the preventive methods to control the high morbidity and mortality rates. Meanwhile our current knowledge of COVID-19 is still limited, despite hard efforts of scientists and clinicians during last few months. In this review article, we have collected the latest data about characteristics, pathogenesis, clinical manifestations, and diagnostic methods of SARS-CoV-2., (© 2020 Wiley Periodicals LLC.)

Coronavirus disease (COVID-19) reached pandemic proportions at the beginning of 2020 and continues to be a worldwide concern. End organ damage and acute respiratory distress syndrome are the leading causes of death in severely or critically ill patients. The elevated cytokine levels in severe patients in comparison with mildly affected patients suggest that cytokine release syndrome (CRS) occurs in the severe form of the disease. In this paper, the significant role of pro-inflammatory cytokines, including IL-1, IL-6, and TNF-alpha, and their mechanism of action in the CRS cascade is explained. Potential therapeutic approaches involving anti-IL-6 and anti-TNF-alpha antibodies to fight COVID-19 and reduce mortality rate in severe cases are also discussed.

The coronavirus disease (Covid-19) pandemic is the most serious event of the year 2020, causing considerable global morbidity and mortality. The goal of this review is to provide a comprehensive summary of reported associations between inter-individual immunogenic variants and disease susceptibility or symptoms caused by the coronavirus strains severe acute respiratory syndrome-associated coronavirus, severe acute respiratory syndrome-associated coronavirus-2, and two of the main respiratory viruses, respiratory syncytial virus and influenza virus. The results suggest that the genetic background of the host could affect the levels of proinflammatory and anti-inflammatory cytokines and might modulate the progression of Covid-19 in affected patients. Notably, genetic variations in innate immune components such as toll-like receptors and mannose-binding lectin 2 play critical roles in the ability of the immune system to recognize coronavirus and initiate an early immune response to clear the virus and prevent the development of severe symptoms. This review provides promising clues related to the potential benefits of using immunotherapy and immune modulation for respiratory infectious disease treatment in a personalized manner.

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the world's scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic's consequences and prevent recurrences of similar pandemics.

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the worlds scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemics consequences and prevent recurrences of similar pandemics.