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COVID-19 has created a global pandemic with high morbidity and mortality in 2020. Novel coronavirus (nCoV), also known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), is responsible for this deadly disease. International Committee on Taxonomy of Viruses (ICTV) has declared that nCoV is highly genetically similar to SARS-CoV epidemic in 2003 (89% similarity). Limited number of clinically validated Human-nCoV protein interaction data is available in the literature. With this hypothesis, the present work focuses on developing a computational model for nCoV-Human protein interaction network, using the experimentally validated SARS-CoV-Human protein interactions. Initially, level-1 and level-2 human spreader proteins are identified in SARS-CoV-Human interaction network, using Susceptible-Infected-Susceptible (SIS) model. These proteins are considered as potential human targets for nCoV bait proteins. A gene-ontology based fuzzy affinity function has been used to construct the nCoV-Human protein interaction network at 99.98% specificity threshold. This also identifies the level-1 human spreaders for COVID-19 in human protein-interaction network. Level-2 human spreaders are subsequently identified using the SIS model. The derived host-pathogen interaction network is finally validated using 7 potential FDA listed drugs for COVID-19 with significant overlap between the known drug target proteins and the identified spreader proteins., Comment: Total number of pages is 12. Total number of figures is 7. Total number of tables is 1

Background Evidence suggests that the outbreak of the coronavirus disease 2019 (COVID-19) and the prevention/control measures for COVID-19 may cause insomnia during the acute phase of COVID-19 pandemic in China. However, it is unclear whether insomnia sustains during the later phases of the pandemic. Methods We searched PubMed/Medline, EMBASE, PsycINFO and China National Knowledge Infrastructure from the 27th December 2019 to the 2nd February 2021. As early stage studies on COVID-19 pandemic in China were defined as those conducted prior to April 1st, 2020, while late stage studies were those conducted after April 1st, 2020. Results A total of 98 studies with 193,889 participants were included. The pooled prevalence of insomnia symptoms among all populations was 39.1% (95% CI 36.2–42.0%); the pooled prevalence of insomnia symptoms during the early and late stages of COVID-19 in China were 37.0% (95% CI 34.1–39.9%) and 41.8% (95% CI 33.6–50.0%), respectively. Importantly, there was no significant difference regarding the prevalence of insomnia symptoms between the early and late stages of COVID-19. Meta-regression showed that healthcare workers, COVID-19 patients, patients with chronic medical conditions and patients with mental disorders had a higher prevalence of insomnia symptoms compared to the general population. This association remained significant in healthcare workers and patients with chronic medical conditions after adjusting for age, gender, areas of high or low prevalence of COVID-19 cases, anxiety and depression. Conclusions Over one third of our sample present insomnia symptoms during the early stage of COVID-19 pandemic in China. Interestingly, prevalence of insomnia symptoms sustains high during the late stage of the pandemic despite the control of the disease and the amelioration of its adverse effects. Our findings suggest that insomnia symptoms related to COVID-19 appear to persist of over time.

Angiotensin-converting enzyme 2 (ACE2), also known as peptidyl-dipeptidase A, belongs to the dipeptidyl carboxydipeptidases family has emerged as a potential antiviral drug target against SARS-CoV-2. Most of the ACE2 inhibitors discovered till now are chemical synthesis; suffer from many limitations related to stability and adverse side effects. However, natural, and selective ACE2 inhibitors that possess strong stability and low side effects can be replaced instead of those chemicals' inhibitors. To envisage structurally diverse natural entities as an ACE2 inhibitor with better efficacy, a 3D structure-based-pharmacophore model (SBPM) has been developed and validated by 20 known selective inhibitors with their correspondence 1166 decoy compounds. The validated SBPM has excellent goodness of hit score and good predictive ability, which has been appointed as a query model for further screening of 11,295 natural compounds. The resultant 23 hits compounds with pharmacophore fit score 75.31 to 78.81 were optimized using in-silico ADMET and molecular docking analysis. Four potential natural inhibitory molecules namely D-DOPA (Amb17613565), L-Saccharopine (Amb6600091), D-Phenylalanine (Amb3940754), and L-Mimosine (Amb21855906) have been selected based on their binding affinity (-7.5, -7.1, -7.1, and -7.0 kcal/mol), respectively. Moreover, 250 ns molecular dynamics (MD) simulations confirmed the structural stability of the ligands within the protein. Additionally, MM/GBSA approach also used to support the stability of molecules to the binding site of the protein that also confirm the stability of the selected four natural compounds. The virtual screening strategy used in this study demonstrated four natural compounds that can be utilized for designing a future class of potential natural ACE2 inhibitor that will block the spike (S) protein dependent entry of SARS-CoV-2 into the host cell.

Background Extracorporeal membrane oxygenation (ECMO) is a valuable rescue therapy to treat refractory hypoxemia caused by influenza. The present meta-analysis aimed to compare the clinical characteristics and outcomes of ECMO between COVID-19 and influenza. Methods We searched the PubMed, Cochrane Library, SCOPUS, and Web of Science databases from inception to May 1, 2021. The included studies compared the clinical characteristics and outcomes of ECMO between adults with COVID-19 and those with influenza. Results The study included four retrospective cohorts involving a total of 129 patients with COVID-19 and 140 with influenza who were treated using ECMO. Clinical characteristics were similar between the COVID-19 and influenza groups, including body mass index (BMI), diabetes mellitus, hypertension, and immunocompromised status. A higher proportion of patients with COVID-19 on ECMO were male (75.9% vs. 62.9%; P = 0.04). There was no difference between the groups in terms of illness severity based on sequential organ failure assessment (SOFA) score or serum pH. Patients with COVID-19 had a longer mean duration of mechanical ventilation before ECMO (6.63 vs. 3.38 days; P

Coronaviruses are a large family of viruses that cause illnesses ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and the 2019 novel coronavirus infection (COVID-19). Currently, there is no analyzed data to examine the outbreak of COVID-19 by continent and no determination of prevalence trends; this article reviews COVID-19 epidemiology and immunology. Original research, reviews, governmental databases, and treatment guidelines are analyzed to present the epidemiology and immunology of COVID-19. Reports from patients who were COVID-19 infected showed typical symptoms of neutrophilia, lymphopenia, and increased systemic inflammatory proteins of IL-6 and C reactive protein (CRP). These observations agree with the results of severe conditions of MERS or lethal cases of SARS, in which there is an increased presence of neutrophils and macrophages in the airways. Additionally, analyzed data showed that Europe (49.37%), the Americas (27.4%), and Eastern Mediterranean (10.07%) had the most cumulative total per 100,000 population confirmed cases, and Africa (6.9%), Western Pacific (3.46%), and South-East Asia (2.72%) had the lowest cumulative total per 100,000 population confirmed cases. In general, the trend lines showed that the number of confirmed cases (cumulative total) and deaths (cumulative total) would decrease eventually.

Various boron-containing drugs have been approved for clinical use over the past two decades, and more are currently in clinical trials. The increasing interest in boron-containing compounds is due to their unique binding properties to biological targets; for example, boron substitution can be used to modulate biological activity, pharmacokinetic properties, and drug resistance. In this perspective, we aim to comprehensively review the current status of boron compounds in drug discovery, focusing especially on progress from 2015 to December 2020. We classify these compounds into groups showing anticancer, antibacterial, antiviral, antiparasitic and other activities, and discuss the biological targets associated with each activity, as well as potential future developments., Graphical abstract Boron derivatives are playing an increasingly important role on drug discovery campaigns. Here, we reviewed the use and pharmacological properties of boronic acids as therapeutic agents for various diseases.Image 1

Recent reports have suggested COVID-19 relapse or reinfection may lead to readmission, which may cause a diagnostic challenge between recently infected patients and reinfections. Compounding this problem is the post-viral lung sequela that may be expected after COVID-19 pneumonia, similar to both SARS and MERS. Although chest imaging may play a role in the diagnosis of primary SARS-CoV-2 infection, reinfection or relapse of COVID-19 will have similar imaging findings. A "new-baseline" imaging can be obtained from COVID-19 patients at the time of hospital discharge or clinical recovery. This new reference can not only determine if readmissions are from relapse or reinfection of COVID-19, resolving COVID-19 or potentially a different viral infection (influenza), but also for long term sequela of COVID-19 lung infection. Strategic use of imaging before discharge may be helpful in the subset of the population at the highest risk of a secondary viral infection such as influenza. Determining the residual abnormalities in post-discharge imaging can guide us in the long-term management of patients for many years to come.

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air-blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment., Graphical abstract Nanomedicine has demonstrated great potential in achieving specific targeting and amplifying therapeutic efficiency. This review focuses on the recent breakthroughs and targeting strategies to provide insights into nanomedicine for acute respiratory distress syndrome treatment.Image 1

OBJECTIVES: This study describes the utilization of a pediatric emergency department (ED) during the early months of the COVID-19 pandemic in the initial U.S. epicenter, including the impact on visit acuity and incidences of common diagnoses. STUDY DESIGN: We performed an observational retrospective review of patients younger than 18 years old seen in a New York City pediatric ED from March 7th to May 6th 2020, and during the same time period in 2018 and 2019. Demographics, visit details, diagnoses, and dispositions were compared. Validated algorithms were utilized to create practical diagnosis groupings and to determine the probability of a visit requiring emergent evaluation. RESULTS: ED visits during the pandemic decreased by 56% to an average daily census of 67 patients, from an anticipated 152. Admission rates rose from 13.3% to 17.4% (p

Background: Evidence suggests lungs as the organ most affected by coronavirus disease 2019 (COVID-19). The literature on previous coronavirus infections reports that patients may experience persistent impairment in respiratory function after being discharged. Our objective was to determine the prevalence of restrictive pattern, obstructive pattern and altered diffusion in patients post-COVID-19 infection and to describe the different evaluations of respiratory function used with these patients. Methods: A systematic review was conducted in five databases. Studies that used lung function testing to assess post-infection COVID-19 patients were included for review. Two independent reviewers analysed the studies, extracted the data and assessed the quality of evidence. Results: Of the 1973 reports returned by the initial search, seven articles reporting on 380 patients were included in the data synthesis. In the sensitivity analysis, we found a prevalence of 0.39 (CI 0.24–0.56, p

COVID-19 patients have presented with a wide range of neurological disorders, among which stroke is the most devastating. We have reviewed current studies, case series, and case reports with a focus on COVID-19 patients complicated with stroke, and presented the current understanding of stroke in this patient population. As evidenced by increased D-dimer, fibrinogen, factor VIII and von Willebrand factor, SARS-CoV-2 infection induces coagulopathy, disrupts endothelial function, and promotes hypercoagulative state. Collectively, it predisposes patients to cerebrovascular events. Additionally, due to the unprecedented strain on the healthcare system, stroke care has been inevitably compromised. The underlying mechanism between COVID-19 and stroke warrants further study, so does the development of an effective therapeutic or preventive intervention.

The current coronavirus disease 2019 pandemic has exceeded any epidemiologic prevision, but increasing information suggests some analogies with the major viral outbreaks in the last century, and a general warning has been issued on the possibility that coinfections can make the differential diagnosis and treatment difficult, especially in tropical countries. Some reports have noted that the presence of high dengue antibodies can give a false-negative result when testing for severe acute respiratory syndrome coronavirus 2. Mucocutaneous manifestations are very frequent, with an apparent overlap among different pathogens. However, strong clinicopathologic correlation might provide some clues to address differentials. Waiting for laboratory and instrumental results, the timing and distribution of skin lesions is often pathognomonic. Histopathologic findings characterize certain reaction patterns and provide insights on pathogenetic mechanisms. Unfortunately, skin assessment, especially invasive examinations such as biopsy, takes a back seat in severely ill patients. A literature retrieval was performed to collect information from other epidemics to counteract what has become the most frightening disease of our time.

Early in the SARS-CoV-2 pandemic, convalescent plasma (CP) therapy was proposed as a treatment for severely ill patients. We conducted a CP treatment protocol under the Mayo Clinic Extended Access Program at University Hospital Brooklyn (UHB). Potential donors were screened with a lateral flow assay (LFA) for IgM and IgG antibodies against the SARS-CoV-2 S1 receptor-binding domain (RBD). Volunteers that were LFA positive were tested with an ELISA to measure IgG titers against the RBD. Subjects with titers of at least 1:1024 were selected to donate. Most donors with positive LFA had acceptable titers and were eligible to donate. Out of 171 volunteers, only 65 tested positive in the LFA (38.0%), and 55 (32.2%) had titers of at least 1:1024. Before our donation program started, 31 CP units were procured from the New York Blood Center (NYBC). Among the 31 CP units that were obtained from the NYBC, 25 units (80.6%) were positive in the LFA but only 12 units (38.7%) had titers of at least 1:1024. CP was administered to 28 hospitalized COVID-19 patients. Patients who received low titer CP, high titer CP and patients who did not receive CP were followed for 45 days after presentation. Severe adverse events were not associated with CP transfusion. Death was a less frequent outcome for patients that received high titer CP (>1:1024) 38.6% mortality, than patients that received low titer CP (≤1:1024) 77.8% mortality.

Globally, SARS-CoV-2 has emerged as threat to life and economy. Researchers are trying to find a cure against this pathogen but without much success. Several attempts have been made to understand the atomic level details of SARS-CoV-2 in the past few months. However, one review with all structural details for drug and vaccine development has been missing. Hence, this review aims to summarize key functional roles played by various domains of SARS-CoV-2 genome during its entry into the host, replication, repression of host immune response and overall viral life cycle. Additionally, various proteins of SARS-CoV-2 for finding a potent inhibitor have also been highlighted. To mitigate this deadly virus, an understanding of atomic level information, pathogenicity mechanisms and functions of different proteins in causing the infection is imperative. Thus, these structural details would finally pave the way for development of a potential drug/vaccine against the disease caused by SARS-CoV-2.

Background A pandemic caused by SARS-CoV-2 infection (COVID-19) has rapidly spread across the globe. Although many articles have established the clinical characteristics of adult COVID-19 patients so far, limited data are available for children. The aim of this study was to reveal the clinical features, laboratory findings and nucleic acid test results of ten pediatric cases. Methods In this retrospective single-center cohort study, pediatric cases with COVID-19 infection were consecutively enrolled in one hospital in Huangshi, China from January 1 to March 11, 2020. Results A total of 10 children with COVID-19 were recruited. Of them, four were the asymptomatic type, one was the mild type, and five were the moderate type (including two subclinical ones). All patients were from family clusters. Only fever, nasal discharge and nasal congestion were observed. Lymphopenia and leukopenia were uncommon in our sample but elevated levels of lactate dehydrogenase (LDH) and alpha-hydroxybutyrate dehydrogenase (α-HBDH) were observed frequently. Of these laboratory test variables, no statistical difference was identified between asymptomatic and symptomatic patients. Abnormalities in radiological data were detected in five patients, and representative findings of chest CT images were patchy shadows and ground-glass opacities. There were two cases whose oropharyngeal nucleic acid tests reversed to positive after one negative result, and two patients whose oropharyngeal swabs tested negative but rectal swabs showed positive. Conclusions Clinical symptoms were mild in children with COVID-19. Increased levels of LDH and α-HBDH were potential clinical biomarkers for pediatric cases. More attention should be paid to the SARS-CoV-2 viral assessment of rectal swabs before patients are discharged.

Background: The aim of this research is to assess the predictive accuracy of the Infectious Diseases Seeker (IDS) – an innovative tool for prompt identification of the causative agent of infectious diseases during outbreaks – when field epidemiological data collected from a novel outbreak of unknown origin are analysed by the tool. For this reason, it has been taken into account the novel coronavirus disease (COVID-19) outbreak, which began in China at the end of December 2019, has rapidly spread around the globe, and it has led to a public health emergency of international concern (PHEIC), declared to the 30th of January 2020 by the World Health Organization (WHO). Methods: The IDS takes advantage of an off-line database, built before the COVID-19 pandemic, which represents a pivotal characteristic for working without an internet connection. The software has been tested using the epidemiological data available in different and progressive stages of the COVID-19 outbreak. As a comparison, the results of the tests performed using the epidemiological data from the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) epidemic in 2002 and Middle East Respiratory Syndrome coronavirus (MERS-CoV) epidemic in 2012, are shown. Results: The overall outcomes provided by the software are comforting, as a matter of the fact that IDS has identified with a good accuracy the SARS and MERS epidemics (over 90%), while, as expected, it has not provided erroneous and equivocal readings after the elaboration COVID-19 epidemic data. Conclusions: Even though IDS has not recognized the COVID-19 epidemic, it has not given to the end user a false result and wrong interpretation, as expected by the developers. For this reason, IDS reveals itself as useful software to identify a possible epidemic or outbreak. Thus, the intention of developers is to plan, once the software will be released, dedicated updates and upgrades of the database (e.g., SARS-CoV-2) in order to keep this tool increasingly useful and applicable to reality.

With the COVID-19 pandemic now ongoing for close to a year, people all over the world are still waiting for a vaccine to become available. The initial focus of accelerated global research and development efforts to bring a vaccine to market as soon as possible was on novel platform technologies that promised speed but had limited history in the clinic. In contrast, recombinant protein vaccines, with numerous examples in the clinic for many years, missed out on the early wave of investments from government and industry. Emerging data are now surfacing suggesting that recombinant protein vaccines indeed might offer an advantage or complement to the nucleic acid or viral vector vaccines that will likely reach the clinic faster. Here, we summarize the current public information on the nature and on the development status of recombinant subunit antigens and adjuvants targeting SARS-CoV-2 infections., Graphical abstract Unlabelled Image, Highlights • Recombinant protein vaccines constitute a proven, well-established vaccine development platform • Multiple expression systems are available to scale-up production • Various adjuvants are being used to elicit the desired immune response • Recombinant protein vaccines are suitable for production in low-resource countries • Recombinant protein COVID-19 vaccinesmay offer a better solution in the long-term

SARS-CoV-2 is the deadly virus behind COVID-19, the disease that went on to ravage the world and caused the biggest pandemic 21st century has witnessed so far. On the face of ongoing death and destruction, the urgent need for the discovery of a vaccine against the virus is paramount. This study resorted to the emerging discipline of immunoinformatics in order to design a multi-epitope mRNA vaccine against the spike glycoprotein of SARS-CoV-2. Various immunoinformatics tools were utilized to predict T and B lymphocyte epitopes. The epitopes were channeled through a filtering pipeline comprised of antigenicity, toxicity, allergenicity, and cytokine inducibility evaluation with the goal of selecting epitopes capable of generating both T and B cell-mediated immune responses. Molecular docking simulation between the epitopes and their corresponding MHC molecules was carried out. 13 epitopes, a highly immunogenic adjuvant, elements for proper sub-cellular trafficking, a secretion booster, and appropriate linkers were combined for constructing the vaccine. The vaccine was found to be antigenic, almost neutral at physiological pH, non-toxic, non-allergenic, capable of generating a robust immune response and had a decent worldwide population coverage. Based on these parameters, this design can be considered a promising choice for a vaccine against SARS-CoV-2., Graphical abstract Unlabelled Image, Highlights • SARS-CoV-2, the causative agent for COVID-19, has caused the biggest pandemic 21st century has witnessed so far. • Here, immunoinformatics was used for designing a muti-epitope mRNA vaccine against the spike glycoprotein of SARS-CoV-2. • Through stringent selection of T and B cell epitopes and other necessary elements, a vaccine was constructed in silico. • Proposed mechanism of its synthesis, delivery and action has also been presented. • The vaccine was found to be immunogenic, almost neutral, non-toxic, non-allergenic and has a decent worldwide coverage.

The emergence of a new coronavirus disease (coronavirus disease 2019 [COVID-19]) has raised global concerns regarding the health and safety of a vulnerable population. Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incites a profound inflammatory response leading to tissue injury and organ failure. COVID-19 is characterized by the bidirectional relationship between inflammation and thrombosis. The clinical syndrome is propelled by inflammation producing acute lung injury, large-vessel thrombosis, and in situ microthrombi that may contribute to organ failure. Myocardial injury is common, but true myocarditis is rare. Elderly patients, those with established cardiovascular disease, and mechanically ventilated patients face the highest mortality risk. Therapies for COVID-19 are evolving. The antiviral drug remdesivir, dexamethasone, transfusion of convalescent plasma, and use of antithrombotic therapy are promising. Most require additional prospective studies. Although most patients recover, those who survive severe illness may experience persistent physical and psychological disabilities., Central Illustration, Highlights • Severe acute respiratory syndrome coronavirus 2 infection (COVID-19) is a global pandemic affecting millions of people worldwide. • Clinical sequelae result largely from an intense inflammatory response triggering large-vessel and microvascular thrombosis. • No therapy has been universally effective for COVID-19, but systemic anticoagulation, remdesivir, and corticosteroids hold promise. • Long-term sequelae of COVID-19 are variable and incompletely defined, but physical and psychological disabilities can persist.

The novel coronavirus disease 2019 (COVID-19) is one of the biggest public health crises globally. Although Africa did not display the worst-case scenario compared to other continents, fears were still at its peak since Africa was already suffering from a heavy load of other life-threatening infectious diseases such as HIV/AIDS and malaria. Other factors that were anticipated to complicate Africa's outcomes include the lack of resources for diagnosis and contact tracing along with the low capacity of specialized management facilities per capita. The current review aims at assessing and generating discussions on the realities, and pros and cons of the WHO COVID-19 interim guidance 2020.5 considering the known peculiarities of the African continent. A comprehensive evaluation was done for COVID-19-related data published across PubMed and Google Scholar (date of the last search: August 17, 2020) with emphasis on clinical management and psychosocial aspects. Predefined filters were then applied in data screening as detailed in the methods. Specifically, we interrogated the WHO 2020.5 guideline viz-a-viz health priority and health financing in Africa, COVID-19 case contact tracing and risk assessment, clinical management of COVID-19 cases as well as strategies for tackling stigmatization and psychosocial challenges encountered by COVID-19 survivors. The outcomes of this work provide links between these vital sub-themes which may impact the containment and management of COVID-19 cases in Africa in the long-term. The chief recommendation of the current study is the necessity of prudent filtration of the global findings along with regional modelling of the global care guidelines for acting properly in response to this health threat on the regional level without exposing our populations to further unnecessary adversities.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic and contagious coronavirus that caused a global pandemic with 5.2 million fatalities to date. Questions concerning serologic features of long-term immunity, especially dominant epitopes mediating durable antibody responses after SARS-CoV-2 infection, remain to be elucidated. Objective We aimed to dissect the kinetics and longevity of immune responses in coronavirus disease 2019 (COVID-19) patients, as well as the epitopes responsible for sustained long-term humoral immunity against SARS-CoV-2. Methods We assessed SARS-CoV-2 immune dynamics up to 180 to 220 days after disease onset in 31 individuals who predominantly experienced moderate symptoms of COVID-19, then performed a proteome-wide profiling of dominant epitopes responsible for persistent humoral immune responses. Results Longitudinal analysis revealed sustained SARS-CoV-2 spike protein–specific antibodies and neutralizing antibodies in COVID-19 patients, along with activation of cytokine production at early stages after SARS-CoV-2 infection. Highly reactive epitopes that were capable of mediating long-term antibody responses were shown to be located at the spike and ORF1ab proteins. Key epitopes of the SARS-CoV-2 spike protein were mapped to the N-terminal domain of the S1 subunit and the S2 subunit, with varying degrees of sequence homology among endemic human coronaviruses and high sequence identity between the early SARS-CoV-2 (Wuhan-Hu-1) and current circulating variants. Conclusion SARS-CoV-2 infection induces persistent humoral immunity in COVID-19–convalescent individuals by targeting dominant epitopes located at the spike and ORF1ab proteins that mediate long-term immune responses. Our findings provide a path to aid rational vaccine design and diagnostic development.

Highlight: • It was proven that renal injury in Corona Virus Disease 2019 (COVID-19) patients has been a real concern. • There are three possible mechanisms of renal injury in COVID-19 infection: direct viral mediated, prolonged cytokine storm mediated, and drug-induced renal injury. • There is no targeted drug therapy in the treatment of renal injury, while Chinese Herbal Medicine can be a potential solution. • Huang Qi, Fu Ling, Di Huang, Shan Yao and Bai Zhu are the core herbs in Chinese Herbal Medicine to treat renal injury. • Chinese Herbal Medicine may act on PTGS2, PTGS1, IL6 and CASP3, etc., to prevent the pharmacological and non-pharmacological COVID-19 related renal injury., Clinical studies have shown that renal injury in Corona Virus Disease 2019 (COVID-19) patients has been a real concern, which is associated with high mortality and an inflammation/apoptosis-related causality. Effective target therapy for renal injury has yet been developed. Besides, potential anti-COVID-19 medicines have also been reported to cause adverse side effects to kidney. Chinese Herbal Medicine (CHM), however, has rich experience in treating renal injury and has successfully applied in China in the battle of COVID-19. Nevertheless, the molecular mechanisms of CHM treatment are still unclear. In this study, we searched prescriptions in the treatment of renal injury extensively and the potential mechanisms to treat COVID-19 related renal injury were investigated. The association rules analysis showed that the core herbs includes Huang Qi, Fu Ling, Bai Zhu, Di Huang, Shan Yao. TCM herbs regulate core pathways, such as AGE-RAGE, PI3K-AKT, TNF and apoptosis pathway, etc. The ingredients (quercetin, formononetin, kaempferol, etc.,) from core herbs could modulate targets (PTGS2 (COX2), PTGS1 (COX1), IL6, CASP3, NOS2, and TNF, etc.), and thereby prevent the pharmacological and non-pharmacological renal injury comparable to that from COVID-19 infection. This study provides therapeutic potentials of CHM to combat COVID-19 related renal injury to reduce complications and mortality.

Se is a micronutrient essential for human health. Sub-optimal Se status is common, occurring in a significant proportion of the population across the world including parts of Europe and China. Human and animal studies have shown that Se status is a key determinant of the host response to viral infections. In this review, we address the question whether Se intake is a factor in determining the severity of response to coronavirus disease 2019 (COVID-19). Emphasis is placed on epidemiological and animal studies which suggest that Se affects host response to RNA viruses and on the molecular mechanisms by which Se and selenoproteins modulate the inter-linked redox homeostasis, stress response and inflammatory response. Together these studies indicate that Se status is an important factor in determining the host response to viral infections. Therefore, we conclude that Se status is likely to influence human response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and that Se status is one (of several) risk factors which may impact on the outcome of SARS-CoV-2 infection, particularly in populations where Se intake is sub-optimal or low. We suggest the use of appropriate markers to assess the Se status of COVID-19 patients and possible supplementation may be beneficial in limiting the severity of symptoms, especially in countries where Se status is regarded as sub-optimal.

Middle East respiratory syndrome (MERS) is a threat to public health worldwide. A vaccine against the causative agent of MERS, MERS-coronavirus (MERS-CoV), is urgently needed. We previously identified a peptide ligand, Co4B, which can enhance antigen (Ag) delivery to the nasal mucosa and promote Ag-specific mucosal and systemic immune responses following intranasal immunization. MERS-CoV infects via the respiratory route; thus, we conjugated the Co4B ligand to the MERS-CoV spike protein receptor-binding domain (S-RBD), and used this to intranasally immunize C57BL/6 and human dipeptidyl peptidase 4-transgenic (hDPP4-Tg) mice. Ag-specific mucosal immunoglobulin (Ig) A and systemic IgG, together with virus-neutralizing activities, were highly induced in mice immunized with Co4B-conjugated S-RBD (S-RBD-Co4B) compared to those immunized with unconjugated S-RBD. Ag-specific T cell-mediated immunity was also induced in the spleen and lungs of mice intranasally immunized with S-RBD-Co4B. Intranasal immunization of hDPP4-Tg mice with S-RBD-Co4B reduced immune cell infiltration into the tissues of virus-challenged mice. Finally, S-RBD-Co4B-immunized mice exhibited were better protected against infection, more likely to survive, and exhibited less body weight loss. Collectively, our results suggest that S-RBD-Co4B could be used as an intranasal vaccine candidate against MERS-CoV infection.

The outbreak of the COVID-19 pandemic has cost five million lives to date, and was caused by a positive-sense RNA virus named SARS-CoV2. The lack of drugs specific to SARS-CoV2, leads us to search for an effective and specific therapeutic approach. Small interfering RNA (siRNA) is able to activate the RNA interference (RNAi) pathway to silence the specific targeted gene and inhibit the viral replication, and it has not yet attracted enough attention as a SARS-CoV2 antiviral agent. It could be a potential weapon to combat this pandemic until the completion of full scale, effective mass vaccination. For this study, specific siRNAs were designed using a web-based bioinformatics tool (siDirect2.0) against 14 target sequences. These might have a high probability of silencing the essential proteins of SARS-CoV2. such as: 3CLpro/Mpro/nsp5, nsp7, Rd-Rp/nsp12, ZD, NTPase/HEL or nsp13, PLpro/nsp3, envelope protein (E), spike glycoprotein (S), nucleocapsid phosphoprotein (N), membrane glycoprotein (M), ORF8, ORF3a, nsp2, and its respective 5′ and 3′-UTR. Among these potential drug targets, the majority of them contain highly conserved sequences; the rest are chosen on the basis of their role in viral replication and survival. The traditional vaccine development technology using SARS-CoV2 protein takes 6–8 months; meanwhile the virus undergoes several mutations in the candidate protein chosen for vaccine development. By the time the protein-based vaccine reaches the market, the virus would have undergone several mutations, such that the antibodies against the viral sequence may not be effective in restricting the newly mutated viruses. However, siRNA technology can make sequences based on real time viral mutation status. This has the potential for suppressing SARS-CoV2 viral replication, through RNAi technology.

Graphical abstract, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emerged pathogen that has caused coronavirus disease 2019 (COVID-19), the worst pandemic of our times leading to tremendous loss of human life and unprecedented measures of social distancing. COVID-19 symptom manifestations range from asymptomatic disease to severe and lethal outcomes. Lack of previous exposure and immunity to SARS-CoV-2, and high infectivity of the virus have contributed to its broad spread across the globe. In the absence of specific adaptive immunity, innate immune mechanisms are crucial for efficient antiviral defenses and control of the infection. Accumulating evidence now suggests that the remarkable heterogeneity in COVID-19 disease manifestations is due to variable degrees of impairment of innate immune mechanisms. In this review, we summarize recent findings describing both viral and host intrinsic factors that have been linked to defective innate immune responses and account for severe COVID-19. We also discuss emerging therapeutic opportunities for targeting innate immunity for the treatment of COVID-19.

COVID-19 is still a deadly disease that remains yet a major challenge for humans. In recent times, many large pharmaceutical and non-pharmaceutical companies have invested a lot of time and cost in fighting this disease. In this regard, today's scientific knowledge shows that designing and producing an effective vaccine is the best possible way to diminish the disease burden and dissemination or even eradicate the disease. Due to the urgent need, many vaccines are now available earlier than scheduled. New technologies have also helped to produce much more effective vaccines, although the potential side effects must be taken into account. Thus, in this review, the types of vaccines and vaccine designs made against COVID-19, the vaccination programs, as well as the delivery methods and molecules that have been used to deliver some vaccines that need a carrier will be described.

Africa is endowed with a profoundly rich and diverse system of plants and other bio-resources out of which, by traditional medicine practice, the people have satisfied their healthcare needs right from antiquity. In contemporary times, it has become necessary to modernize this traditional medical care system via scientific studies. Validation of the efficacy of health-enhancement products and drugs from plants and other bio-resources is predicated on diligent and intensive research accompanied by rigorous and conclusive clinical trials. Africa has eminently qualified human resources but due to the finance-intensive nature of medical research, individual African states on their own cannot fund the level of research desired for dealing with such serious issues as the COVID-19 pandemic. A collaboration among African states guided by a Mutual Pan-African support paradigm (MPASP) is a unique strategy for achieving success in any such a high-impact global project as the use of traditional medicine against COVID-19 and emerging pandemics; and this is hereby advocated.

The Middle East respiratory syndrome coronavirus (MERS-CoV), belonging to the family Coronaviridae and genus Betacoronavirus, has been recognized as a highly pathogenic virus. Due to the lack of therapeutic or preventive agents against MERS-CoV, developing an effective vaccine is essential for preventing a viral outbreak. To address this, we developed a recombinant S1 subunit of MERS-CoV spike protein fused with the human IgG4 Fc fragment (LV-MS1-Fc) in Chinese hamster ovary (CHO) cells. Thereafter, we identified the baculovirus gp64 signal peptide-directed secretion of LV-MS1-Fc protein in the extracellular fluid. To demonstrate the immunogenicity of the recombinant LV-MS1-Fc proteins, BALB/c mice were inoculated with 2.5 μg of LV-MS1-Fc. The inoculated mice demonstrated a significant humoral immune response, measured via total IgG and neutralizing antibodies. In addition, human dipeptidyl peptidase-4 (DPP4) transgenic mice vaccinated with LV-MS1-Fc showed the protective capacity of LV-MS1-Fc against MERS-CoV with no inflammatory cell infiltration. These data showed that the S1 and Fc fusion protein induced potent humoral immunity and antigen-specific neutralizing antibodies in mice, and conferred protection against coronavirus viral challenge, indicating that LV-MS1-Fc is an effective vaccine candidate against MERS-CoV infection.

Background Although Qing-Fei-Pai-Du decoction (QFPDD) is extensively used clinically to treat COVID-19 patients, the mechanism by which it modulates the immunological and metabolic functions of liver tissue remains unknown. Purpose The purpose of this study is to investigate the mechanism of action of QFPDD in the treatment of mice with coronavirus-induced pneumonia by combining integrated hepatic single-cell RNA sequencing and untargeted metabolomics. Methods We developed a human coronavirus pneumonia model in BALB/c mice by infecting them with human coronavirus HCoV-229E with stimulating them with cold-damp environment. We initially assessed the status of inflammation and immunity in model mice treated with or without QFPDD by detecting peripheral blood lymphocytes and inflammatory cytokines. Then, single-cell RNA sequencing and untargeted metabolomics were performed on mouse liver tissue. Results HCoV-229E infection in combination with exposure to a cold-damp environment significantly decreased the percentage of peripheral blood lymphocytes (CD4+ and CD8+ T cells, B cells) in mice, which was enhanced by QFPDD therapy. Meanwhile, the levels of inflammatory cytokines such as IL-6, TNF-α, and IFN-γ were significantly increased in mouse models but significantly decreased by QFPDD treatment. Single-cell RNA sequencing analysis showed that QFPDD could attenuate disease-associated alterations in gene expression, core transcriptional regulatory networks, and cell-type composition. Computational predictions indicated that QFPDD rectified the observed aberrant patterns of cell-cell communication. Additionally, the metabolic profiles of liver tissue in the Model group were distinct from mice in the Control group, and QFPDD significantly regulated hepatic purine metabolism. Conclusion To the best of our knowledge, this study is the first to integrate hepatic single-cell RNA sequencing and untargeted metabolomics into a TCM formula and these valuable findings indicate that QFPDD can improve immune function and reduce liver injury and inflammation., Graphical abstract Image, graphical abstract

Several researchers benefited from the EU supported project Sus-tainable Process Integration Laboratory - SPIL funded as project No. CZ.02.1.01/0.0/0.0/15_003/0000456, by Czech Republic Operational Programme Research and Development, Education, Priority 1: Strengthening capacity for quality research, based on the SPIL project.This work was also partly supported by the Ministerio de Ciencia e Innovacion (Espana) /FEDER under the RTI2018-098913-B100 project, by the Consejeria de Economia, Innovacion, Ciencia y Empleo (Junta de Andalucia) and FEDER under CV20-45250 and A-TIC-080-UGR18 projects., The first known case of Coronavirus disease 2019 (COVID-19) was identified in December 2019. It has spread worldwide, leading to an ongoing pandemic, imposed restrictions and costs to many countries. Predicting the number of new cases and deaths during this period can be a useful step in predicting the costs and facilities required in the future. The purpose of this study is to predict new cases and deaths rate one, three and seven-day ahead during the next 100 days. The motivation for predicting every n days (instead of just every day) is the investigation of the possibility of computational cost reduction and still achieving reasonable performance. Such a scenario may be encountered in real-time forecasting of time series. Six different deep learning methods are examined on the data adopted from the WHO website. Three methods are LSTM, Convolutional LSTM, and GRU. The bidirectional extension is then considered for each method to forecast the rate of new cases and new deaths in Australia and Iran countries. This study is novel as it carries out a comprehensive evaluation of the aforementioned three deep learning methods and their bidirectional extensions to perform prediction on COVID-19 new cases and new death rate time series. To the best of our knowledge, this is the first time that Bi-GRU and Bi-Conv-LSTM models are used for prediction on COVID-19 new cases and new deaths time series. The evaluation of the methods is presented in the form of graphs and Friedman statistical test. The results show that the bidirectional models have lower errors than other models. A several error evaluation metrics are presented to compare all models, and finally, the superiority of bidirectional methods is determined. This research could be useful for organisations working against COVID-19 and determining their long-term plans., European Commission CZ.02.1.01/0.0/0.0/15_003/0000456, Czech Republic Operational Programme Research and Development, Education, Priority 1: Strengthening capacity for quality research, based on the SPIL project, Ministerio de Ciencia e Innovacion (Espana) /FEDER RTI2018-098913-B100, Junta de Andalucia, European Commission CV20-45250 A-TIC-080-UGR18

Graphical abstract, Congruous coronavirus drug targets and analogous lead molecules must be identified as quickly as possible to produce antiviral therapeutics against human coronavirus (HCoV SARS 3CLpro) infections. In the present communication, we bear recognized a HIT candidate for HCoV SARS 3CLpro inhibition. Four Parametric GA-MLR primarily based QSAR model (R2:0.84, R2adj:0.82, Q2loo: 0.78) was once promoted using a dataset over 37 structurally diverse molecules along QSAR based virtual screening (QSAR-VS), molecular docking (MD) then molecular dynamic simulation (MDS) analysis and MMGBSA calculations. The QSAR-based virtual screening was utilized to find novel lead molecules from an in-house database of 100 molecules. The QSAR-vS successfully offered a hit molecule with an improved PEC50 value from 5.88 to 6.08. The benzene ring, phenyl ring, amide oxygen and nitrogen, and other important pharmacophoric sites are revealed via MD and MDS studies. Ile164, Pro188, Leu190, Thr25, His41, Asn46, Thr47, Ser49, Asn189, Gln191, Thr47, and Asn141 are among the key amino acid residues in the S1 and S2 pocket. A stable complex of a lead molecule with the HCoV SARS 3CLpro was discovered using MDS. MM-GBSA calculations resulted from MD simulation results well supported with the binding energies calculated from the docking results. The results of this study can be exploited to develop a novel antiviral target, such as an HCoV SARS 3CLpro Inhibitor.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the “WHO handbook for guideline development”, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT)., Graphical Abstract ga1

We evaluated enveloped virus-like particles (eVLPs) expressing various forms of the Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein and several adjuvants in an effort to identify a highly potent Coronavirus disease 2019 (COVID-19) vaccine candidate. eVLPs expressing a modified prefusion form of SARS-CoV-2 spike protein were selected as they induced high antibody binding titers and neutralizing activity after a single injection in mice. Formulation of SARS-CoV-2 S eVLPs with aluminum phosphate resulted in balanced induction of IgG2 and IgG1 isotypes and antibody binding and neutralization titers were undiminished for more than 3 months after a single immunization. A single dose of this candidate, named VBI-2902a, protected Syrian golden hamsters from challenge with SARS-CoV-2 and supports the on-going clinical evaluation of VBI-2902a as a highly potent vaccine against COVID-19.

Purpose Our purpose was to conduct a comprehensive systematic review of all existing literature regarding imaging findings on chest CT as well as associated clinical features in pregnant patients diagnosed with COVID-19. Materials & methods A literature search was conducted on April 21, 2020 and updated on July 24, 2020 using PubMed, Embase, World Health Organization, and Google Scholar. Only studies which described chest CT findings of COVID-19 in pregnant patients were included for analysis. Results A total of 67 articles and 427 pregnant patients were analyzed. The most frequently encountered pulmonary findings on chest CT of pregnant patients diagnosed with COVID-19 were ground-glass opacities (77.2%, 250/324), posterior involvement (72.5%, 50/69), multilobar involvement (71.8%, 239/333), bilateral lung involvement (69.4%, 231/333), peripheral distribution (68.1%, 98/144), and consolidation (40.9%, 94/230). Pregnant patients were also found to present more frequently with consolidation (40.9% vs. 21.0–31.8%) and pleural effusion (30.0% vs. 5.0%). Clinical findings included antepartum fever (198 cases), lymphopenia (128 cases), and neutrophilia (97 cases). Of the 251 neonates delivered to mothers with COVID-19, 96.8% of the neonates had negative RT-PCR and/or IgG antibody testing. In the eight cases (3.2%) of reported neonatal infection, tests were either conducted up to 72 h after birth or were found negative on all subsequent RT-PCR tests. Conclusion Pregnant patients appear to present with more advanced COVID-19 CT findings than those of the general adult population. The changes in laboratory values found in pregnant patients also mirror those found in the general patient population. Lastly, results from neonatal testing suggest low risk of vertical transmission. Summary statement The initial chest CT scans of 427 pregnant patients with COVID-19 showed higher rates of consolidation and pleural effusion in comparison to the general population., Highlights • Pregnant patients with COVID-19 were most often found to have bilateral, peripheral lung involvement. • Pregnant patients with COVID-19 frequently presented with consolidation (40.9%) and pleural effusion (30.0%). • Adoption of a standardized lexicon for reporting findings of COVID-19 is recommended to avoid heterogeneous and inconsistent use of morphological descriptors.

Although the use of corticosteroids is not recommended in the World Health Organization statement for the treatment of coronavirus disease 2019 (COVID-19), steroid therapy may be indicated for critical cases in specific situations. Here, we report the successful treatment of 11 cases of severe COVID-19 pneumonia with favipiravir and methylprednisolone. All cases were severe and patients required oxygen administration or had a blood oxygen saturation ≤93% on room air. All were treated with favipiravir and methylprednisolone, and 10 of 11 patients responded well and required no further oxygen supplementation or ventilator management. This study shows the importance of the early-stage use of a combination of favipiravir and methylprednisolone in severe cases to achieve a favorable clinical outcome.

The World Health Organization (WHO) has declared the COVID-19 an international health emergency due to the severity of infection progression, which became more severe due to its continuous spread globally and the unavailability of appropriate therapy and diagnostics systems. Thus, there is a need for efficient devices to detect SARS-CoV-2 infection at an early stage. Nowadays, the reverse transcription polymerase chain reaction (RT-PCR) technique is being applied for detecting this virus around the globe; however, factors such as stringent expertise, long diagnostic times, invasive and painful screening, and high costs have restricted the use of RT-PCR methods for rapid diagnostics. Therefore, the development of cost-effective, portable, sensitive, prompt and selective sensing systems to detect SARS-CoV-2 in biofluids at fM/pM/nM concentrations would be a breakthrough in diagnostics. Immunosensors that show increased specificity and sensitivity are considerably fast and do not imply costly reagents or instruments, reducing the cost for COVID-19 detection. The current developments in immunosensors perhaps signify the most significant opportunity for a rapid assay to detect COVID-19, without the need of highly skilled professionals and specialized tools to interpret results. Artificial intelligence (AI) and the Internet of Medical Things (IoMT) can also be equipped with this immunosensing approach to investigate useful networking through database management, sharing, and analytics to prevent and manage COVID-19. Herein, we represent the collective concepts of biomarker-based immunosensors along with AI and IoMT as smart sensing strategies with bioinformatics approach to monitor non-invasive early stage SARS-CoV-2 development, with fast point-of-care (POC) diagnostics as the crucial goal. This approach should be implemented quickly and verified practicality for clinical samples before being set in the present times for mass-diagnostic research.

Objective High-dose intravenous vitamin C (HIVC) is a major concern when treating patients with coronavirus disease 2019 (COVID-19). The aim of this study was to assess the clinical efficacy of HIVC on hyperinflammation in patients with severe COVID-19. Methods This retrospective cohort study included hospitalized patients with severe COVID-19, a subset of whom was treated with HIVC. The medical records were screened for demographic data, laboratory findings, and medications, as well as initial and repeated values of multiple inflammatory markers for analysis. Results A high percentage of patients presented with hyperinflammation based on inflammatory marker levels above the upper limit of normal (high-sensitivity C-reactive protein, 80.1%; interleukin-6, 91.5%; and tumor necrosis factor-α, 67.4%). Eighty-five (36%) patients received HIVC therapy. After treatment with HIVC, the levels of inflammatory markers displayed a significant decrease compared with those of patients without HIVC. Furthermore, the percentages of reduction in inflammatory marker levels were higher in patients receiving HIVC compared with those in patients treated without HIVC. Stepwise multiple linear regression analysis revealed that HIVC was independently associated with percentages of reduction in levels of inflammatory markers. Conclusions HIVC has the potential benefit of attenuating hyperinflammation by reducing inflammatory marker levels in patients with severe COVID-19.

Severe acute respiratory virus syndrome 2 (SARS-CoV-2) has led to a worldwide pandemic. Early studies in solid organ transplant (SOT) recipients suggested a wide variety of presentations, however, there remains a paucity of robust data in this population. We conducted a systematic review and meta-analysis of SOT recipients with SARS-CoV-2 infection from January 1st t October 9th, 2020. Pooled incidence of symptoms, treatments and outcomes were assessed. Two hundred and fifteen studies were included for systematic review and 60 for meta-analysis. We identified 2,772 unique SOT recipients including 1,500 kidney, 505 liver, 141 heart and 97 lung. Most common presenting symptoms were fever and cough in 70.2% and 63.8% respectively. Majority (81%) required hospital admission. Immunosuppressive medications, especially antimetabolites, were decreased in 76.2%. Hydroxychloroquine and interleukin six antagonists were administered in59.5% and 14.9% respectively, while only few patients received remdesivir and convalescent plasma. Intensive care unit admission was 29% from amongst hospitalized patients. Only few studies reported secondary infections. Overall mortality was 18.6%. Our analysis shows a high incidence of hospital admission in SOT recipients with SARS-CoV-2 infection. As management of SARS-CoV-2 continues to evolve, long-term outcomes among SOT recipients should be assessed in future studies., Highlights • High rate of hospital and ICU admission amongst SOT recipients with COVID-19 • Fever maybe absent in up to 30% of SOT recipients with COVID-19. • Majority of centers held anti-metabolites in SOT patients with COVID-19. • Overall mortality in SOT recipients with COVID-19 was 20%.

Setting up treatment strategies is the highest concern today to reduce the fatality of COVID-19. Due to a very new kind of virus attack, no specific treatment has been discovered to date. The most crucial way to dominate the disease severity is now the repurposing of drugs. In this review, we focused on the current treatment approaches targeting the crucial causative factors for the disease burden through cytokine storm or cytokine release syndrome. Several vaccines have been developed and have been applied already for prevention purposes, and several are on the way to be developed, although the effects and side effects are under observation. Presently, regulation of the immune response through intervention treatment methods has been adjusted on the basis of the COVID-19 severity stage and generally includes vaccines, immunotherapies including convalescent plasma and immunoglobulin treatment, monoclonal antibodies, cytokine therapy, complement inhibition, regenerative medicine, and repurposed anti-inflammatory and immune-regulatory drugs. Combination therapy is not acceptable in all respects because there is no concrete evidence in clinical trials or in vivo data. Target-specific drug therapies, such as inhibition of cytokine-producing signaling pathways, could be an excellent solution and thus reduce the severity of inflammation and disease severity. Therefore, gathering information about the mechanism of disease progression, possible goals, and drug efficacy of immune-based approaches to combat COVID-19 in the context of orderly review analysis is consequential.

The recent emergence of coronavirus disease-2019 (COVID-19) as a global pandemic has prompted scientists to address an urgent need for defining mechanisms of disease pathology and treatment. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, employs angiotensin converting enzyme 2 (ACE2) as its primary target for cell surface attachment and likely entry into the host cell. Thus, understanding factors that may regulate the expression and function of ACE2 in the healthy and diseased body is critical for clinical intervention. Over 66% of all adults in the United States are currently using a prescription drug and while earlier findings have focused on possible upregulation of ACE2 expression through the use of renin angiotensin system (RAS) inhibitors, mounting evidence suggests that various other widely administered drugs used in the treatment of hypertension, heart failure, diabetes mellitus, hyperlipidemias, coagulation disorders, and pulmonary disease may also present a varied risk for COVID-19. Specifically, we summarize mechanisms on how heparin, statins, steroids and phytochemicals, besides their established therapeutic effects, may also interfere with SARS-CoV-2 viral entry into cells. We also describe evidence on the effect of several vitamins, phytochemicals, and naturally occurring compounds on ACE2 expression and activity in various tissues and disease models. This comprehensive review aims to provide a timely compendium on the potential impact of commonly prescribed drugs and pharmacologically active compounds on COVID-19 pathology and risk through regulation of ACE2 and RAS signaling.

The nCOVID-19 pandemic initiated its course of contagion from the city of Wuhan and now it has spread all over the globe. SARS-CoV-2 is the causative virus and the infection as well as its symptoms are distributed across the multi-organ perimeters. Interactions between the host and virus governs the induction of 'cytokine storm' resulting various immunopathological consequences leading to death. Till now it has caused tens of millions of casualties and yet no credible cure has emerged to vision. This article presents a comprehensive overview on the two most promising remedial approaches that are being attempted for the management, treatment, and plausible cure of nCOVID-19. In this context, chemotherapeutic approach primarily aims to interrupt the interactions between the host and the virus causing inhibition of its entry into the host cell and/or its proliferation and suppressing the inflammatory milieu in the infected patients. On the other side, immunotherapeutic approaches aim to modulate the host immunity by fine tuning the inflammatory signaling cascades to achieve phylaxis from the virus and restoring immune-homeostasis. Considering most of the path-breaking findings, combinatorial therapy involving of chemotherapeutics as well as vaccine could usher to be a hope for all of us to eradicate the crisis.

A phage library displaying 1010 variants of the fibronectin type III (FN3) domain was affinity selected with the biotinylated form of the receptor binding domain (RBD, residues 319-541) of the SARS-CoV-2 virus spike protein. Nine binding FN3 variants (i.e. monobodies) were recovered, representing four different primary structures. Soluble forms of the monobodies bound to several different preparations of the RBD and the S1 spike subunit, with affinities ranging from 3 to 14 nM as measured by bio-layer interferometry. Three of the four monobodies bound selectively to the RBD of SARS-CoV-2, with the fourth monobody showing slight cross-reactivity to the RBD of SARS-CoV-1 virus. Examination of binding to the spike fragments and its trimeric form revealed that the monobodies recognise at least three overlapping epitopes on the RBD of SARS-CoV-2. While pairwise tests failed to identify a monobody pair that could bind simultaneously to the RBD, one monobody could simultaneously bind to the RBD with the ectodomain of the cellular receptor angiotensin converting enzyme 2 (ACE2). All four monobodies successfully bound the RBD after overexpression in Chinese hamster ovary (CHO) cells as fusions to the Fc domain of human IgG1.

Highlights • SARS-CoV-2 can infect multiple organs leading to their dysfunction, so a pleiotropic therapy would be advantageous. • MSC: MSC can simultaneously address injuries in multiple organs and promote their repair. • MSC, immunomodulators by excellence, may counteract infection and cytokine storm in COVID-19 patients. • MSC therapy is being tested in clinical trials for COVID-19 patients and proved to be safe and effective so far. • More clinical studies, addressing MSC use for COVID-19, with bigger cohorts and suitable controls are welcome., The devastating global impact of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has prompted scientists to develop novel strategies to fight Coronavirus Disease of 2019 (COVID-19), including the examination of pre-existing treatments for other viral infections in COVID-19 patients. This review provides a reasoned discussion of the possible use of Mesenchymal Stromal Cells (MSC) or their products as a treatment in SARS-CoV-2-infected patients. The main benefits and concerns of using this cellular therapy, guided by preclinical and clinical data obtained from similar pathologies will be reviewed. MSC represent a highly immunomodulatory cell population and their use may be safe according to clinical studies developed in other pathologies. Notably, four clinical trials and four case reports that have already been performed in COVID-19 patients obtained promising results. The clinical application of MSC in COVID-19 is very preliminary and further investigational studies are required to determine the efficacy of the MSC therapy. Nevertheless, these preliminary studies were important to understand the therapeutic potential of MSC in COVID-19. Based on these encouraging results, the United States Food and Drug Administration (FDA) authorized the compassionate use of MSC, but only in patients with Acute Respiratory Distress Syndrome (ARDS) and a poor prognosis. In fact, patients with severe SARS-CoV-2 can present infection and tissue damage in different organs, such as lung, heart, liver, kidney, gut and brain, affecting their function. MSC may have pleiotropic activities in COVID-19, with the capacity to fight inflammation and repair lesions in several organs.

The aim of this study was to evaluate hyperferritinemia could be a predicting factor of mortality in hospitalized patients with coronavirus disease-2019 (COVID-19).A total of 100 hospitalized patients with COVID-19 in intensive care unit (ICU) were enrolled and classified into moderate (The amount of ferritin was significantly higher in critical group compared with moderate and severe groups. The median of ferritin concentration was about three times higher in death group than survival group (1722.25 μg/L vs. 501.90 μg/L,The ferritin measured at admission may serve as an independent factor for predicting in-hospital mortality in patients with COVID-19 in ICU.El objetivo de este estudio fue evaluar si la hiperferritinemia podría ser un factor predictivo de la mortalidad en pacientes hospitalizados con enfermedad por coronavirus de 2019 (COVID-19).Se incluyó un total de 100 pacientes hospitalizados con COVID-19 en la unidad de cuidados intensivos (UCI), clasificándose como grupos moderado (n = 17), grave (n = 40) y crítico (n = 43). Se recopiló la información clínica y de laboratorio, comparándose los niveles de ferritina entre los diferentes grupos. Se evaluó la asociación entre ferritina y mortalidad mediante un análisis de regresión logística. Además, se evaluó la eficacia del valor predictivo utilizando la curva ROCLa cantidad de ferritina fue significativamente superior en el grupo de pacientes críticos en comparación con el grupo de pacientes graves. La media de concentración de ferritina fue cerca de 3 veces superior en el grupo de muerte que en el grupo de supervivientes (1.722,25 μg/L vs. 501,90 μg/L, El valor de ferritina medido durante el ingreso puede servir de factor independiente para prevenir la mortalidad intrahospitalaria en los pacientes de COVID-19 en la UCI.

Graphical abstract, Highlights • A year since the first report of the SARS-CoV-2, over 57 million cases have been diagnosed, and over 1.37 million have died worldwide. • An uncontrolled inflammatory response linked to a cytokine storm has been associated with pulmonary inflammation severity. • The genetic drifting of SARS-CoV-2 has been extremely slow, increasing the prospect of designing vaccines against all viral clades. • None of the therapeutic approaches currently used appears to be decisive for the treatment of COVID-19. • Three vaccines have demonstrated efficacy superior to 90%. Two of these vaccines, BNT162b2 and mRNA-1273, were based on an RNA platform, while Sputnik V was based on a non-replicating viral vector platform., Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) results in diverse outcomes. The symptoms appear to be more severe in males older than 65 and people with underlying health conditions; approximately one in five individuals could be at risk worldwide. The virus’s sequence was rapidly established days after the first cases were reported and identified an RNA virus from the Coronaviridae family closely related to a Betacoronavirus virus found in bats in China. SARS-CoV-2 is the seventh coronavirus known to infect humans, and with the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), the only ones to cause severe diseases. Lessons from these two previous outbreaks guided the identification of critical therapeutic targets such as the spike viral proteins promoting the virus’s cellular entry through the angiotensin-converting enzyme 2 (ACE2) receptor expressed on the surface of multiple types of eukaryotic cells. Although several therapeutic agents are currently evaluated, none seems to provide a clear path for a cure. Also, various types of vaccines are developed in record time to address the urgency of efficient SARS-CoV-2 prevention. Currently, 58 vaccines are evaluated in clinical trials, including 11 in phase III, and 3 of them reported efficacy above 90%. The results so far from the clinical trials suggest the availability of multiple effective vaccines within months.