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Objective: Following a significant relaxation of restrictions in China on December 7, 2022, after a surge in SARS-CoV-2 infections, an uptick in women presenting with menstrual disorders was observed in clinics. This study aimed to explore the alterations in menstrual characteristics and associated factors post SARS-CoV-2 infection. Methods: A cross-sectional online survey was conducted among 869 non-amenorrheic adult Chinese females (aged 18–53) to study the changes in menstrual characteristics and other infection-related factors post initial SARS-CoV-2 infection. The reported menstrual changes (group A) were compared to the reported no menstrual changes (group B). Data collected included basic individual-level information such as age, height, weight, menstrual history, reproductive and menstrual disorders, chronic diseases, SARS-CoV-2 vaccination status, COVID-19 symptoms, and changes in menstrual characteristics (regularity, period volume, and degree of dysmenorrhea) post SARS-CoV-2 infection. Results: Of the 869 participants, 442 (50.9%, group A) reported alterations in at least one menstrual characteristic; 171 (19.7%) experienced an extended menstrual cycle, and 122 (14.0%) reported a decrease in menstrual volume. Participants who reported menstrual changes (group A) were more likely to have pre-existing chronic diseases (7.7% vs. 3.0%, P = 0.003) and exhibit more symptoms of COVID-19 during the acute (4.94 vs. 4.03, P < 0.001) and recovery (4.37 vs. 3.41, P < 0.001) phases. These participants were also more likely to report fever as a COVID-19 symptom (93.4% vs. 86.9%, P = 0.001) and experienced a longer duration of fever (2.25 vs. 1.96 days, P = 0.001) as compared to group B. Notably, group A with chronic diseases, fewer vaccine doses, and more COVID-19-related symptoms experienced more frequent menstrual changes post COVID-19 (P < 0.05) than group B. Conclusion: Participants with chronic diseases, fewer vaccination doses, and more COVID-19-related symptoms may experience more frequent menstrual changes post COVID-19 infection according to the self-report results in this study. [ABSTRACT FROM AUTHOR]

Drugs that cure COVID-19 have been marketed; however, this disease continues to ravage the world without becoming extinct, and thus, drug discoveries are still relevant. Since Mpro has known advantages as a drug target, such as the conserved nature of the active site and the absence of homologous proteins in the body, it receives the attention of many researchers. Meanwhile, the role of traditional Chinese medicine (TCM) in the control of epidemics in China has also led to a focus on natural products, with the hope of finding some promising lead molecules through screening. In this study, we selected a commercial library of 2526 natural products from plants, animals and microorganisms with known biological activity for drug discovery, which had previously been reported for compound screening of the SARS CoV-2 S protein, but had not been tested on Mpro. This library contains compounds from a variety of Chinese herbs, including Lonicerae Japonicae Flos, Forsythiae Fructus and Scutellariae Radix, which are derived from traditional Chinese medicine prescriptions that have been shown to be effective against COVID-19. We used the conventional FRET method for the initial screening. After two rounds of selection, the remaining 86 compounds were divided into flavonoids, lipids, phenylpropanoids, phenols, quinones, alkaloids, terpenoids and steroids according to the skeleton structures, with inhibition rates greater than 70%. The top compounds in each group were selected to test the effective concentration ranges; the IC50 values were as follows: (−)–gallocatechin gallate (1.522 ± 0.126 μM), ginkgolic acid C15:1 (9.352 ± 0.531 μM), hematoxylin (1.025 ± 0.042 μM), fraxetin (2.486 ± 0.178 μM), wedelolactone (1.003 ± 0.238 μM), hydroxytyrosol acetate (3.850 ± 0.576 μM), vanitiolide (2.837 ± 0.225 μM), β,β–dimethylacrylalkannin (2.731 ± 0.308 μM), melanin (7.373 ± 0.368 μM) and cholesteryl sodium sulfate (2.741 ± 0.234μM). In the next step, we employed two biophysical techniques, SPR and nanoDSF, to obtain KD/Kobs values: hematoxylin (0.7 μM), (−)–gallocatechin gallate (126 μM), ginkgolic acid C15:1 (227 μM), wedelolactone (0.9770 μM), β,β–dimethylacrylalkannin (1.9004 μM,), cholesteryl sodium sulfate (7.5950 μM) and melanin (11.5667 μM), which allowed better assessments of the binding levels. Here, seven compounds were the winners. Then, molecular docking experiments were specially performed by AutoDock Vina to analyze the mode of interactions within Mpro and ligands. We finally formulated the present in silico study to predict pharmacokinetic parameters as well as drug-like properties, which is presumably the step that tells humans whether the compounds are drug-like or not. Moreover, hematoxylin, melanin, wedelolactone, β,β–dimethylacrylalkannin and cholesteryl sodium sulfate are in full compliance with the "Lipinski" principle and possess reasonable ADME/T properties, they have a greater potential of being lead compounds. The proposed five compounds are also the first to be found to have potential inhibitory effects on SARS CoV-2 Mpro. We hope that the results in this manuscript may serve as benchmarks for the above potentials. [ABSTRACT FROM AUTHOR]

New coronavirus infection causing COVID-19, which was first reported in late 2019 in China, initiated severe social and economic crisis that affected the whole world. High frequency of the errors in replication of RNA viruses, zoonotic nature of transmission, and high transmissibility allowed betacoronaviruses to cause the third pandemic in the world since the beginning of 2003: SARS-CoV in 2003, MERS-CoV in 2012, and SARS-CoV-2 in 2019. The latest pandemic united scientific community and served as a powerful impetus in the study of biology of coronaviruses: new routes of virus penetration into the human cells were identified, features of the replication cycle were studied, and new functions of coronavirus proteins were elucidated. It should be recognized that the pandemic was accompanied by the need to obtain and publish results within a short time, which led to the emergence of an array of conflicting data and low reproducibility of research results. We systematized and analyzed scientific literature, filtered the results according to reliability of the methods of analysis used, and prepared a review describing molecular mechanisms of functioning of the SARS-CoV-2 coronavirus. This review considers organization of the genome of the SARS-CoV-2 virus, mechanisms of its gene expression and entry of the virus into the cell, provides information on key mutations that characterize different variants of the virus, and their contribution to pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

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Since an outbreak started in China in 2019, coronavirus disease 2019 (COVID-19) has rapidly become a worldwide epidemic with high contagiousness and caused mass mortalities of infected cases around the world. Currently, available treatments for COVID-19, including supportive care, respiratory support and antiviral therapy, have shown limited efficacy. Thus, more effective therapeutic modalities are highly warranted. Drug repurposing, as an efficient strategy to explore a potential broader scope of the application of approved drugs beyond their original indications, accelerates the process of discovering safe and effective agents for a given disease. Since the outbreak of COVID-19 pandemic, drug repurposing strategy has been widely used to discover potential antiviral agents, and some of these drugs have advanced into clinical trials. Antitumor drugs compromise a vast variety of compounds and exhibit extensive mechanism of action, showing promising properties in drug repurposing. In this review, we revisit the potential value of antitumor drugs in the treatment of COVID-19 and systematically discuss their possible underlying mechanisms of the antiviral actions. [ABSTRACT FROM AUTHOR]

In late December 2019, the first cases of viral pneumonia caused by an unidentified pathogen were reported in China. Two years later, SARS-CoV-2 was responsible for almost 450 million cases, claiming more than 6 million lives. The COVID-19 pandemic strained the limits of healthcare systems all across the world. Identifying viral RNA through real-time reverse transcription-polymerase chain reaction remains the gold standard in diagnosing SARS-CoV-2 infection. However, equipment cost, availability, and the need for trained personnel limited testing capacity. Through an unprecedented research effort, new diagnostic techniques such as rapid diagnostic testing, isothermal amplification techniques, and next-generation sequencing were developed, enabling accurate and accessible diagnosis. Influenza viruses are responsible for seasonal outbreaks infecting up to a quarter of the human population worldwide. Influenza and SARS-CoV-2 present with flu-like symptoms, making the differential diagnosis challenging solely on clinical presentation. Healthcare systems are likely to be faced with overlapping SARS-CoV-2 and Influenza outbreaks. This review aims to present the similarities and differences of both infections while focusing on the diagnosis. We discuss the clinical presentation of Influenza and SARS-CoV-2 and techniques available for diagnosis. Furthermore, we summarize available data regarding the multiplex diagnostic assay of both viral infections. [ABSTRACT FROM AUTHOR]

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the cause of the COVID-19 pandemic that originated in China in December 2019. Although extensive research has been performed on SARS-CoV-2, the binding behavior of spike (S) protein and receptor binding domain (RBD) of SARS-CoV-2 at different environmental conditions have yet to be studied. The objective of this study is to investigate the effect of temperature, fatty acids, ions, and protein concentration on the binding behavior and rates of association and dissociation between the S protein and RBD of SARS-CoV-2 and the hydrophobic aminopropylsilane (APS) biosensors using biolayer interferometry (BLI) validated with molecular dynamics simulation. Our results suggest three conditions—high ionic concentration, presence of hydrophobic fatty acids, and low temperature—favor the attachment of S protein and RBD to hydrophobic surfaces. Increasing the temperature within an hour from 0 to 25 °C results in S protein detachment, suggesting that freezing can cause structural changes in the S protein, affecting its binding kinetics at higher temperature. At all the conditions, RBD exhibits lower dissociation capabilities than the full-length S trimer protein, indicating that the separated RBD formed stronger attachment to hydrophobic surfaces compared to when it was included in the S protein. [ABSTRACT FROM AUTHOR]

SARS-CoV-2, the agent of the COVID-19 pandemic, emerged in late 2019 in China, and rapidly spread throughout the world to reach all continents. As the virus expanded in its novel human host, viral lineages diversified through the accumulation of around two mutations a month on average. Different viral lineages have replaced each other since the start of the pandemic, with the most successful Alpha, Delta and Omicron variants of concern (VoCs) sequentially sweeping through the world to reach high global prevalence. Neither Alpha nor Delta was characterized by strong immune escape, with their success coming mainly from their higher transmissibility. Omicron is far more prone to immune evasion and spread primarily due to its increased ability to (re-)infect hosts with prior immunity. As host immunity reaches high levels globally through vaccination and prior infection, the epidemic is expected to transition from a pandemic regime to an endemic one where seasonality and waning host immunization are anticipated to become the primary forces shaping future SARS-CoV-2 lineage dynamics. In this review, we consider a body of evidence on the origins, host tropism, epidemiology, genomic and immunogenetic evolution of SARS-CoV-2 including an assessment of other coronaviruses infecting humans. Considering what is known so far, we conclude by delineating scenarios for the future dynamic of SARS-CoV-2, ranging from the good—circulation of a fifth endemic 'common cold' coronavirus of potentially low virulence, the bad—a situation roughly comparable with seasonal flu, and the ugly—extensive diversification into serotypes with long-term high-level endemicity. Lay Summary: SARS-CoV-2, the agent of the COVID-19 pandemic, emerged in late 2019 and spread globally causing the COVID-19 pandemic. When SARS-CoV-2 jumped into humans, it had essentially no genetic diversity, but as the viral population expanded, it diversified into myriad genetically distinct lineages through the acumulation of approximately two mutations a month. The majority of those lineages are now extinct. The most successful lineages so far were the Alpha, Delta and Omicron variants which all reached global prevalence and replaced each other in the process. Alpha and Delta emerged in late 2020 and spread at a time when immunization of the human population was still low and reached global prevalence primarily by being more transmissible. Omicron started expanding in late 2021, at a time when a large proportion of the human population had already been vaccinated and/or exposed to SARS-CoV-2. Omicron was so successful mainly due to its ability to (re-)infect hosts with prior immunity. In this review, we provide an overview of the evolution of SARS-CoV-2 and put it in context of what is known about other coronaviruses infecting humans. We conclude by delineating plausible scenarios for the 'endemic' future of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus, which was first identified in December 2019 in China, has resulted in a yet ongoing viral pandemic. Coronaviridae could potentially cause several disorders in a wide range of hosts such as birds and mammals. Although infections caused by this family of viruses are predominantly limited to the respiratory tract, Betacoronaviruses are potentially able to invade the central nervous system (CNS) as well as many other organs, thereby inducing neurological damage ranging from mild to lethal in both animals and humans. Over the past two decades, three novel CoVs, SARS-CoV-1, MERS-CoV, and SARS-CoV-2, emerging from animal reservoirs have exhibited neurotropic properties causing severe and even fatal neurological diseases. The pathobiology of these neuroinvasive viruses has yet to be fully known. Both clinical features of the previous CoV epidemics (SARS-CoV-1 and MERS-CoV) and lessons from animal models used in studying neurotropic CoVs, especially SARS and MERS, constitute beneficial tools in comprehending the exact mechanisms of virus implantation and in illustrating pathogenesis and virus dissemination pathways in the CNS. Here, we review the animal research which assessed CNS infections with previous more studied neurotropic CoVs to demonstrate how experimental studies with appliable animal models can provide scientists with a roadmap in the CNS impacts of SARS-CoV-2. Indeed, animal studies can finally help us discover the underlying mechanisms of damage to the nervous system in COVID-19 patients and find novel therapeutic agents in order to reduce mortality and morbidity associated with neurological complications of SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes serious disease in humans. First identified in November/December 2019 in China, it has rapidly spread worldwide. We analyzed 2790 SARS‐CoV‐2 genome sequences from 56 countries that were available on April 2, 2020, to assess the evolution of the virus during this early phase of its expansion. We aimed to assess sequence variations that had evolved in virus genomes, giving the greatest attention to the S gene. We also aimed to identify haplotypes that the variations may define and consider their geographic and chronologic distribution. Variations at 1930 positions that together cause 1203 amino acid changes were identified. The frequencies of changes normalized to the lengths of genes and encoded proteins were relatively high in ORF3a and relatively low in M. A variation that causes an Asp614Gly near the receptor‐binding domain of S were found at a high frequency, and it was considered that this may contribute to the rapid spread of viruses with this variation. Our most important findings relate to haplotypes. Sixty‐six haplotypes that constitute thirteen haplotype groups (H1–H13) were identified, and 84.6% of the 2790 sequences analyzed were associated with these haplotypes. The majority of the sequences (75.1%) were associated with haplotype groups H1–H3. The distribution pattern of the haplotype groups differed in various geographic regions. A few were country/territory specific. The location and time of emergence of some haplotypes are discussed. Importantly, nucleotide variations that define the various haplotypes and Tag/signature variations for most of the haplotypes are reported. The practical applications of these variations are discussed. Highlights: Variations at 1930 nucleotides and 1203 amino acids identified among 2790 SARS‐CoV‐2 sequences.Frequencies of changes normalized to the lengths of genes and proteins were high in ORF3a and low in M.Asp614Gly near RBD of S may have contributed to the rapid spread of viruses with this variation.84.6% of the 2790 genome sequences defined by 66 haplotypes that constitute 13 haplotype groups.75.1% of 2790 SARS‐CoV‐2 genome sequences were associated with three haplotype groups, H1–H3.The distribution of haplotypes was country/territory/region specific.Sequence variations that define the haplotypes and Tag variations for the haplotypes are reported.The Tag variations can be used as tools for epidemiologic studies. [ABSTRACT FROM AUTHOR]

Background: The spread of a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in China and other countries is of great concern worldwide with no effective vaccine. This study aimed to design a novel vaccine construct against SARS-CoV-2 from the spike S protein and orf1ab polyprotein using immunoinformatics tools. The vaccine was designed from conserved epitopes interacted against B and T lymphocytes by the combination of highly immunogenic epitopes with suitable adjuvant and linkers. Results: The proposed vaccine composed of 526 amino acids and was shown to be antigenic in Vaxigen server (0.6194) and nonallergenic in Allertop server. The physiochemical properties of the vaccine showed isoelectric point of 10.19. The instability index (II) was 31.25 classifying the vaccine as stable. Aliphatic index was 84.39 and the grand average of hydropathicity (GRAVY) was − 0.049 classifying the vaccine as hydrophilic. Vaccine tertiary structure was predicted, refined and validated to assess the stability of the vaccine via Ramachandran plot and ProSA-web servers. Moreover, solubility of the vaccine construct was greater than the average solubility provided by protein sol and SOLpro servers indicating the solubility of the vaccine construct. Disulfide engineering was performed to reduce the high mobile regions in the vaccine to enhance stability. Docking of the vaccine construct with TLR4 demonstrated efficient binding energy with attractive binding energy of − 338.68 kcal/mol and − 346.89 kcal/mol for TLR4 chain A and chain B respectively. Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells and INF-γ. Upon cloning, the vaccine protein was reverse transcribed into DNA sequence and cloned into pET28a(+) vector to ensure translational potency and microbial expression. Conclusion: A unique vaccine construct from spike S protein and orf1ab polyprotein against B and T lymphocytes was generated with potential protection against the pandemic. The present study might assist in developing a suitable therapeutics protocol to combat SARSCoV-2 infection. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking has been proven to be a risk factor in the development of many diseases. However, it remains controversial with respect to the relationship of smoking with COVID-19. The purpose of this study was to explore the role of smoking in COVID-19. Methods: A total of 622 patients with COVID-19 in China were enrolled in the study. Corresponding clinical and laboratory data were collected and analyzed. Meanwhile, Kaplan-Meier curve and Cox regression analysis were employed to analyze the association of smoking with survival in patients with COVID-19. Results: Smoking was statistically significant comparing non-survivors and survivors of patients with COVID-19 (P = 0.007). Males had higher proportion of smoking than females (91.9% vs. 8.1%, P < 0.001). Compared with the non-smoker, there was significant statistical difference in the incidence of cerebrovascular disease in smoking patients with COVID-19 (9.7% vs. 3.4%, P = 0.017). White blood cell count (6.3 vs. 5.4; P = 0.037), hemoglobin level (139.0 vs. 127.0; P < 0.001), and creatinine level (77.3 vs. 61.0; P < 0.001) were significantly increased in COVID-19 patients who smoked. Moreover, smoking patients showed a worse survival compared with non-smoking patients (Log Rank P = 0.045). After adjustment for age, gender and underlying diseases, patients with smoking still had higher risk of mortality than that of non-smoking patients (hazard ratio[HR] 1.897, 95% confidence interval [CI]1.058–3.402, P = 0.032). Conclusion: Smoking was thought to be a risk factor in predicting the prognosis of COVID-19 and smoking patients might have a higher risk of mortality than that of the non-smoking patients. [ABSTRACT FROM AUTHOR]

SARS Coronavirus 2 (SARS-CoV-2) emerged in late 2019, leading to the Coronavirus Disease 2019 (COVID-19) pandemic that continues to cause significant global mortality in human populations. Given its sequence similarity to SARS-CoV, as well as related coronaviruses circulating in bats, SARS-CoV-2 is thought to have originated in Chiroptera species in China. However, whether the virus spread directly to humans or through an intermediate host is currently unclear, as is the potential for this virus to infect companion animals, livestock, and wildlife that could act as viral reservoirs. Using a combination of surrogate entry assays and live virus, we demonstrate that, in addition to human angiotensin-converting enzyme 2 (ACE2), the Spike glycoprotein of SARS-CoV-2 has a broad host tropism for mammalian ACE2 receptors, despite divergence in the amino acids at the Spike receptor binding site on these proteins. Of the 22 different hosts we investigated, ACE2 proteins from dog, cat, and cattle were the most permissive to SARS-CoV-2, while bat and bird ACE2 proteins were the least efficiently used receptors. The absence of a significant tropism for any of the 3 genetically distinct bat ACE2 proteins we examined indicates that SARS-CoV-2 receptor usage likely shifted during zoonotic transmission from bats into people, possibly in an intermediate reservoir. Comparison of SARS-CoV-2 receptor usage to the related coronaviruses SARS-CoV and RaTG13 identified distinct tropisms, with the 2 human viruses being more closely aligned. Finally, using bioinformatics, structural data, and targeted mutagenesis, we identified amino acid residues within the Spike–ACE2 interface, which may have played a pivotal role in the emergence of SARS-CoV-2 in humans. The apparently broad tropism of SARS-CoV-2 at the point of viral entry confirms the potential risk of infection to a wide range of companion animals, livestock, and wildlife. A study using a combination of surrogate entry assays and live virus suggests that SARS-CoV-2 may have a broad host-range, revealing that the virus's spike protein can use a broad range of host ACE2 receptors to enter cells and that the sequence of this protein might have changed during the zoonotic jump into humans. [ABSTRACT FROM AUTHOR]

A novel coronavirus (SARS-CoV-2) identified in Wuhan state of China in 2019 is the causative agent of deadly disease COVID-19. It has spread across the globe (more than 210 countries) within a short period. Coronaviruses pose serious health threats to both humans and animals. A recent publication reported an experimental 3D complex structure of the S protein of SARS-CoV-2 showed that the ectodomain of the SARS-CoV-2 S protein binds to the peptidase domain (PD) of human ACE2 with a dissociation constant (Kd) of ~ 15 nM. In this study, we focused on inhibitors for ACE2: S protein complex using virtual screening and inhibition studies through molecular docking for over 200,000 natural compounds. Toxicity analysis was also performed for the best hits, and the final complex structures for four complexes were subjected to 400 ns molecular dynamics simulations for stability testing. We found two natural origin inhibitors for the S protein: human ACE2 complex (Andrographolide and Pterostilbene) which displayed better inhibition potential for ACE2 receptor and its binding with the S protein of SARS-CoV-2. Comparative studies were also performed to test and verify that these two drug candidates are also better than hydroxychloroquine which is known to inhibit this complex. However, we needed better potential drug candidates to overcome the side effects of hydroxychloroquine. Supplementary experimental studies need to be carried forward to corroborate the viability of these two new inhibitors for ACE2: S protein complex so as to curb down COVID-19. [ABSTRACT FROM AUTHOR]

The newly identified coronavirus SARS‐CoV‐2 that spread from China is causing the pandemic COVID‐19 with a fatality rate from 5‐15%. It causes fever, cough, myalgia, fatigue up to dyspnoea, responsible for hospitalization and artificial oxygenation. SARS‐CoV‐2 infects human cells using ACE2, the transmembrane protease serine 2 (TMPRSS2) and the SARS‐CoV‐2 main protease (Mpro). Once bound to ACE2 and the other two proteases in concert they allow the virus replication and spread throughout the body. Our attention has been focused on the role of ACE2 as its binding to by the virus increases bradykinin and its metabolites, which facilitate inflammation in the lung (causing cough and fever), coagulation and the complement system. These three systems are involved in angioedema, cardiovascular dysfunction and sepsis, pathologies which occur in COVID‐19 patients. Thus, we propose that blocking the kallikrein–kinin system with lanadelumab, approved for hereditary angioedema, will prevent facilitation of these 3 systems. Linked Articles: This article is part of a themed issue on The Pharmacology of COVID‐19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc [ABSTRACT FROM AUTHOR]

Occasional zoonotic viral attacks on immunologically naive populations result in massive death tolls that are capable of threatening human survival. Currently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent that causes coronavirus disease (COVID-19), has spread from its epicenter in Wuhan China to all parts of the globe. Real-time mapping of new infections across the globe has revealed that variable transmission patterns and pathogenicity are associated with differences in SARS-CoV-2 lineages, clades, and strains. Thus, we reviewed how changes in the SARS-CoV-2 genome and its structural architecture affect viral replication, immune evasion, and transmission within different human populations. We also looked at which immune dominant regions of SARS-CoV-2 and other coronaviruses are recognized by Major Histocompatibility Complex (MHC)/Human Leukocyte Antigens (HLA) genes and how this could impact on subsequent disease pathogenesis. Efforts were also placed on understanding immunological changes that occur when exposed individuals either remain asymptomatic or fail to control the virus and later develop systemic complications. Published autopsy studies that reveal alterations in the lung immune microenvironment, morphological, and pathological changes are also explored within the context of the review. Understanding the true correlates of protection and determining how constant virus evolution impacts on host-pathogen interactions could help identify which populations are at high risk and later inform future vaccine and therapeutic interventions. [ABSTRACT FROM AUTHOR]

In October 2019, a viral infectious disease appeared in the city of Wuhan in China. A new betacoronavirus, SARS-CoV-2, has been recognized as the responsible pathogen in this infection. Although coronavirus disease is principally expressed as a pulmonary infection, critical SARS-CoV-2 infection is frequently complicated with coagulopathy, and thromboembolic events are recognizable in several patients. Dehydration, acute inflammatory condition, protracted immobilization during disease, existence of multiple cardiovascular risk factors such as diabetes, obesity or hypertension, previous coronary artery disease, ischemic stroke, peripheral artery disease are frequent comorbidities in SARS-CoV-2 hospitalized subjects, which possibly augment thrombo-embolic risk. However, other causal factors can still be identified such as unrestricted angiotensin II action, the use of immunoglobulins, an increased production of adhesion molecules able to induce vascular inflammation and endothelial activation, complement stimulation, excessive production of neutrophil extracellular traps (NETs), and increased platelet count. Low-molecular-weight heparin should be chosen as early treatment because of its anti-inflammatory action and its ability to antagonize histones and so defend the endothelium. However, several therapeutic possibilities have also been proposed such as fibrinolytic treatment, drugs that target NETs, and complement inhibition. Nevertheless, although the violence of the pandemic may suggest the use of heroic treatments to reduce the frightening mortality that accompanies SARS-CoV-2 infection, we believe that experimental treatments should only be used within approved and controlled protocols, the only ones that can provide useful and specify information on the validity of the treatments. [ABSTRACT FROM AUTHOR]

Since its emergence in China in December 2019, COVID-19 has quickly spread around the globe causing a pandemic. Vaccination or the development of herd immunity seems the only way to slow down the spread of the virus; however, both are not achievable in the near future. Therefore, effective treatments to mitigate the burden of this pandemic and reduce mortality rates are urgently needed. Preclinical and clinical studies of potential antiviral and immunomodulatory compounds and molecules to identify safe and efficacious therapeutics for COVID-19 are ongoing. Two compounds, remdesivir, and dexamethasone have been so far shown to reduce COVID-19–associated death. Here, we provide a review of the potential therapeutic agents being considered for the treatment and management of COVID-19 patients. [ABSTRACT FROM AUTHOR]

The new coronavirus disease outbreak in 2019 (COVID-19) represents a dramatic challenge for healthcare systems worldwide. As to viral tropism, lungs are not the only COVID-19 target but also the heart may be involved in a not negligible percentage of the infected patients. Myocarditis-related cardiac dysfunction and potentially life-threatening arrhythmias are the main aftermaths. A few studies showed that myocardial injury in adult patients is often linked with a fatal outcome. Conversely, scientific evidence in children is sparse, although several reports were published with the description of a cardiac involvement in COVID-19 paediatric patients. In these young subjects, a background of surgically treated congenital heart disease seems to be a predisposing factor.Conclusion: This systematic review is aimed at summarizing all COVID-19 cases with a cardiac involvement published in paediatric age and trying to explain the underlying mechanisms responsible for COVID-19-related myocardial damage.What is Known:• Coronaviruses proved to be able to jump from animals to humans.• The outbreak of COVID-19 started from China (Dec 2019) and became pandemic.What is New:• Even in childhood, COVID-19 is not without the risk of cardiac involvement.• Myocarditis, heart failure, and arrhythmias are among the possible manifestations. [ABSTRACT FROM AUTHOR]

From the beginning of 2002 and 2012, severe respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV) crossed the species barriers to infect humans, causing thousands of infections and hundreds of deaths, respectively. Currently, a novel coronavirus (SARS‐CoV‐2), which has become the cause of the outbreak of Coronavirus Disease 2019 (COVID‐19), was discovered. Until 18 February 2020, there were 72 533 confirmed COVID‐19 cases (including 10 644 severe cases) and 1872 deaths in China. SARS‐CoV‐2 is spreading among the public and causing substantial burden due to its human‐to‐human transmission. However, the intermediate host of SARS‐CoV‐2 is still unclear. Finding the possible intermediate host of SARS‐CoV‐2 is imperative to prevent further spread of the epidemic. In this study, we used systematic comparison and analysis to predict the interaction between the receptor‐binding domain (RBD) of coronavirus spike protein and the host receptor, angiotensin‐converting enzyme 2 (ACE2). The interaction between the key amino acids of S protein RBD and ACE2 indicated that, other than pangolins and snakes, as previously suggested, turtles (Chrysemys picta bellii, Chelonia mydas, and Pelodiscus sinensis) may act as the potential intermediate hosts transmitting SARS‐CoV‐2 to humans. Highlights: The critical residues of S protein RBD binding with ACE2 indicated the potential intermediate hosts transmitting SARS‐CoV‐2 to humans. [ABSTRACT FROM AUTHOR]

The global spread of COVID-19 has caused a substantial societal burden and become a major global public health issue. The COVID-19 elderly population with hypertension, diabetes, cardiovascular, and cerebrovascular diseases are at risk. Mortality rates are highest in these individuals if infected with COVID-19. Although the lungs are the main organs involved in acute respiratory distress syndrome caused by COVID-19 infection, COVID-19 triggers inflammatory and immune mechanisms, inducing a "cytokine storm" that aggravates disease progression and may lead to death. Presently, effective drugs are lacking, although current studies have confirmed that drugs with therapeutic potential include redaciclovir, lopinavir/ritonavir combined with interferon-β, convalescent plasma, and monoclonal antibodies. Currently, the most reasonable and effective way to prevent COVID-19 is to control the source of infection, terminate routes of transmission, and protect susceptible populations. With the rise of COVID-19 in China and worldwide, further prevention, diagnosis, and treatment measures are a critical unmet need. Cerebrovascular disease has high incidence, disability rate, and fatality rate. COVID-19 patient outcomes may also be complicated with acute stroke. This paper summarizes the influence of COVID-19 on cerebrovascular disease and discusses possible pathophysiological mechanisms to provide new angles for the prevention and diagnosis of this disease. [ABSTRACT FROM AUTHOR]

To investigate the relationship between asthma and COVID-19. We searched the existing literature and researches to analyze the possible reasons. The possible reasons for the very low COVID-19 infection in asthma patients in China may be as follows: the expression of ACE2 in asthma patients is relatively low; the use of ICS in asthma patients may have protective effect; data bias and ethnic differences are also possible reasons, too. The relationship between asthma patients and COVID-19 has not been completely clear, which needs further study. [ABSTRACT FROM AUTHOR]

COVID-19 has swept through mainland China by human-to-human transmission. The rapid spread of SARS-CoV-2 and its variants, including the currently prevalent Omicron strain, pose a serious threat worldwide. The present review summarizes epidemiological investigation and etiological analysis of genomic, epidemiological, and pathological characteristics of the original strain and its variants, as well as progress in diagnosis and treatment. Prevention and control measures used during the current Omicron pandemic are discussed to provide further knowledge of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Simple Summary: Coronaviruses are a broad group of viruses that may infect a wide range of animals, including humans. Despite the fact that each coronavirus has a limited host range, frequent interspecies transmission of coronaviruses across diverse hosts has resulted in a complex ecology. The recently discovered SARS-CoV-2 virus is the clearest evidence of the danger of a global pandemic spreading. Natural infection with SARS-CoV-2 has been reported in a variety of domestic and wild animals, which may complicate the virus's epidemiology and influence its development. In this review, we discussed the potential determinants of SARS-CoV-2 interspecies transmission. Additionally, despite the efforts that have been made to control this pandemic and to implement the One Health policy, several problems, such as the role of animals in SARS-CoV-2 evolution and the dynamics of interspecies transmission, are still unanswered. In December 2019, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China with serious impacts on global health and economy that is still ongoing. Although interspecies transmission of coronaviruses is common and well documented, each coronavirus has a narrowly restricted host range. Coronaviruses utilize different receptors to mediate membrane fusion and replication in the cell cytoplasm. The interplay between the receptor-binding domain (RBD) of coronaviruses and their coevolution are determinants for host susceptibility. The recently emerged SARS-CoV-2 caused the coronavirus disease 2019 (COVID-19) pandemic and has also been reported in domestic and wild animals, raising the question about the responsibility of animals in virus evolution. Additionally, the COVID-19 pandemic might also substantially have an impact on animal production for a long time. In the present review, we discussed the diversity of coronaviruses in animals and thus the diversity of their receptors. Moreover, the determinants of the susceptibility of SARS-CoV-2 in several animals, with special reference to the current evidence of SARS-CoV-2 in animals, were highlighted. Finally, we shed light on the urgent demand for the implementation of the One Health concept as a collaborative global approach to mitigate the threat for both humans and animals. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19). It emerged from China in December 2019 and rapidly spread across the globe, causing a pandemic with unprecedented impacts on public health and economy. Therefore, there is an urgent need for the development of curative treatments and vaccines. In humans, COVID-19 pathogenesis shows a wide range of symptoms, from asymptomatic to severe pneumonia. Identifying animal models of SARS-CoV-2 infection that reflect the clinical symptoms of COVID-19 is of critical importance. Nonhuman primates (NHPss) correspond to relevant models to assess vaccine and antiviral effectiveness. This review discusses the use of NHPs as models for COVID-19 research, with focus on the pathogenesis of SARS-CoV-2 infection, drug discovery and pre-clinical evaluation of vaccine candidates. [ABSTRACT FROM AUTHOR]

Three major outbreaks of the coronavirus, a zoonotic virus known to cause respiratory disease, have been reported since 2002, including SARS-CoV, MERS-CoV and the most recent 2019-nCoV, or more recently known as SARS-CoV-2. Bats are known to be the primary animal reservoir for coronaviruses. However, in the past few decades, the virus has been able to mutate and adapt to infect humans, resulting in an animal-to-human species barrier jump. The emergence of a novel coronavirus poses a serious global public health threat and possibly carries the potential of causing a major pandemic outbreak in the naïve human population. The recent outbreak of COVID-19, the disease caused by SARS-CoV-2, in Wuhan, Hubei Province, China has infected over 36.5 million individuals and claimed over one million lives worldwide, as of 8 October 2020. The novel virus is rapidly spreading across China and has been transmitted to 213 other countries/territories across the globe. Researchers have reported that the virus is constantly evolving and spreading through asymptomatic carriers, further suggesting a high global health threat. To this end, current up-to-date information on the coronavirus evolution and SARS-CoV-2 modes of transmission, detection techniques and current control and prevention strategies are summarized in this review. [ABSTRACT FROM AUTHOR]

The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, was first reported in December 2019 in Wuhan, Hubei province, China. This virus has led to 61.8 million cases worldwide being reported as of December 1st, 2020. Currently, there are no definite approved therapies endorsed by the World Health Organization for COVID-19, focusing only on supportive care. Treatment centers around symptom management, including oxygen therapy or invasive mechanical ventilation. Immunotherapy has the potential to play a role in the treatment of SARS-CoV-2. Monoclonal antibodies (mAbs), in particular, is a relatively new approach in the world of infectious diseases and has the benefit of overcoming challenges with serum therapy and intravenous immunoglobulins preparations. Here, we reviewed the articles published in PubMed with the purpose of summarizing the currently available evidence for the use of neutralizing antibodies as a potential treatment for coronaviruses. Studies reporting in vivo results were summarized and analyzed. Despite promising data from some studies, none of them progressed to clinical trials. It is expected that neutralizing antibodies might offer an alternative for COVID-19 treatment. Thus, there is a need for randomized trials to understand the potential use of this treatment. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has recently emerged in China and caused a disease called coronavirus disease 2019 (COVID-19). The virus quickly spread around the world, causing a sustained global outbreak. Although SARS-CoV-2, and other coronaviruses, SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV) are highly similar genetically and at the protein production level, there are significant differences between them. Research has shown that the structural spike (S) protein plays an important role in the evolution and transmission of SARS-CoV-2. So far, studies have shown that various genes encoding primarily for elements of S protein undergo frequent mutation. We have performed an in-depth review of the literature covering the structural and mutational aspects of S protein in the context of SARS-CoV-2, and compared them with those of SARS-CoV and MERS-CoV. Our analytical approach consisted in an initial genome and transcriptome analysis, followed by primary, secondary and tertiary protein structure analysis. Additionally, we investigated the potential effects of these differences on the S protein binding and interactions to angiotensin-converting enzyme 2 (ACE2), and we established, after extensive analysis of previous research articles, that SARS-CoV-2 and SARS-CoV use different ends/regions in S protein receptor-binding motif (RBM) and different types of interactions for their chief binding with ACE2. These differences may have significant implications on pathogenesis, entry and ability to infect intermediate hosts for these coronaviruses. This review comprehensively addresses in detail the variations in S protein, its receptor-binding characteristics and detailed structural interactions, the process of cleavage involved in priming, as well as other differences between coronaviruses. [ABSTRACT FROM AUTHOR]

In December 2019, the outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a serious pandemic in China and other countries worldwide. So far, more than 460,000 confirmed cases were diagnosed in nearly 190 countries, causing globally over 20,000 deaths. Currently, the epidemic is still spreading and there is no effective means to prevent the infection. Vaccines are proved to be the most effective and economical means to prevent and control infectious diseases. Several countries, companies, and institutions announced their programs and progress on vaccine development against the virus. While most of the vaccines are under design and preparation, there are some that have entered efficacy evaluation in animals and initial clinical trials. This review mainly focused on the progress and our prospects on field of vaccine development against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

A highly pathogenic human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently recognized in Wuhan, China, as the cause of the coronavirus disease 2019 (COVID-19) outbreak which has spread rapidly from China to other countries in the world, causing a pandemic with alarming morbidity and mortality. The emerging epidemiological data about COVID-19 patients suggest an association between cardiovascular diseases (CVD) and SARS-CoV-2 infection, in term of clinical features at hospital admission and prognosis for disease severity. The aim of our review is to describe the cardiological features of COVID-19 patients at admission, the acute cardiac presentation, the clinical outcome for patients with underlying CVD and the pharmacological implications for disease management. [ABSTRACT FROM AUTHOR]

The emerging coronavirus disease (COVID-19) swept across the world, affecting more than 200 countries and territories. Genomic analysis suggests that the COVID-19 virus originated in bats and transmitted to humans through unknown intermediate hosts in the Wuhan seafood market, China, in December of 2019. This virus belongs to the Betacoronavirus group, the same group of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV), and for the similarity, it was named SARS-CoV-2. Given the lack of registered clinical therapies or vaccines, many physicians and scientists are investigating previously used clinical drugs for COVID-19 treatment. In this review, we aim to provide an overview of the CoVs origin, pathogenicity, and genomic structure, with a focus on SARS-CoV-2. Besides, we summarize the recently investigated drugs that constitute an option for COVID-19 treatment. [ABSTRACT FROM AUTHOR]

Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. The continuous evolution of coronaviruses was further highlighted with the emergence of the Middle East Respiratory Syndrome-CoV (MERS-CoV) outbreak in 2012. Currently, the world is concerned about the 2019 novel CoV (SARS-CoV-2) that was initially identified in the city of Wuhan, China in December 2019. Patients presented with severe viral pneumonia and respiratory illness. The number of cases has been mounting since then. As of late February 2020, tens of thousands of cases and several thousand deaths have been reported in China alone, in addition to thousands of cases in other countries. Although the fatality rate of SARS-CoV-2 is currently lower than SARS-CoV, the virus seems to be highly contagious based on the number of infected cases to date. In this review, we discuss structure, genome organization, entry of CoVs into target cells, and provide insights into past and present outbreaks. The future of human CoV outbreaks will not only depend on how the viruses will evolve, but will also depend on how we develop efficient prevention and treatment strategies to deal with this continuous threat. [ABSTRACT FROM AUTHOR]

The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2. [ABSTRACT FROM AUTHOR]