ABSTRACT
This article reviews the correlation between ACE2 and COVID-19 and the resulting acute respiratory distress syndrome (ARDS). ACE2 is a crucial component of the renin-angiotensin system (RAS). The classical ACE-angiotensin â ¡ (Ang II)-angiotensin type 1 receptor (AT1R) axis and the ACE2-Ang(1-7)-Mas counter-regulatory axis play an essential role in RAS system. ACE2 antagonises the activation of the classical RAS ACE-Ang II-AT1R axis and protects against lung injury. Similar to severe acute respiratory syndrome-related coronavirus, 2019 novel coronavirus (2019-nCoV) also uses ACE2 for cell entry. ARDS is a clinical high-mortality disease which is probably due to the excessive activation of RAS caused by 2019-nCoV infection, and ACE2 has a protective effect on ARDS caused by COVID-19. Because of these protective effects of ACE2 on ARDS, the development of drugs enhancing ACE2 activity may become one of the most promising approaches for the treatment of COVID-19 in the near future. In the meantime, however, the use of RAS blockers such as ACE inhibitors and angiotensin II receptor blockers that inhibit the damaging (ACE-Ang II) arm of the RAS cascade in the lung may also be promising. Trial registration number: NCT04287686.
Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/physiopathology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/physiopathology , Receptors, Virus/metabolism , Respiratory Distress Syndrome/physiopathology , Angiotensin Receptor Antagonists/pharmacology , Angiotensin-Converting Enzyme 2 , Betacoronavirus/drug effects , COVID-19 , Coronavirus Infections/drug therapy , Humans , Pandemics , Pneumonia, Viral/drug therapy , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/physiology , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/virology , SARS-CoV-2Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , RNA, Viral/isolation & purification , Viral Load , Virus Shedding , Adult , Aged , Betacoronavirus/pathogenicity , COVID-19 , China , Coronavirus Infections/virology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/virology , Pneumonia, Viral/virology , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Betacoronavirus/growth & development , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Humans , Immunity, Herd , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Pneumonia, Viral/transmission , SARS-CoV-2 , Viral Vaccines/immunologySubject(s)
Betacoronavirus , Communicable Disease Control/organization & administration , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Betacoronavirus/genetics , Betacoronavirus/physiology , COVID-19 , Communicable Disease Control/methods , Contact Tracing , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Disease Notification , Humans , Hygiene , Italy/epidemiology , Meteorological Concepts , Patient Isolation , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Population Surveillance , Protective Devices , Quarantine , SARS-CoV-2 , Seasons , Social BehaviorSubject(s)
Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Tetracyclines/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/physiology , COVID-19 , Humans , Pandemics , SARS-CoV-2 , Virus Replication/drug effects , COVID-19 Drug TreatmentABSTRACT
The SARS-CoV-2 pandemic is leading to high mortality and a global health crisis. The primary involvement is respiratory; however, the virus can also affect other organs, such as the gastrointestinal tract and liver. The most common symptoms are anorexia and diarrhea. In about half of the cases, viral RNA could be detected in the stool, which is another line of transmission and diagnosis. covid19 has a worse prognosis in patients with comorbidities, although there is not enough evidence in case of previous digestive diseases. Digestive endoscopies may give rise to aerosols, which make them techniques with a high risk of infection. Experts and scientific organizations worldwide have developed guidelines for preventive measures. The available evidence on gastrointestinal and hepatic involvement, the impact on patients with previous digestive diseases and operating guidelines for Endoscopy Units during the pandemic are reviewed.
Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/complications , Digestive System Diseases/etiology , Digestive System/virology , Pandemics , Pneumonia, Viral/complications , Aerosols , Angiotensin-Converting Enzyme 2 , Anorexia/etiology , Antiviral Agents/adverse effects , Betacoronavirus/isolation & purification , Betacoronavirus/physiology , COVID-19 , Cohort Studies , Coronavirus Infections/drug therapy , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Diarrhea/etiology , Digestive System Diseases/virology , Endoscopy, Digestive System/adverse effects , Feces/virology , Humans , Immunosuppressive Agents/adverse effects , Intestines/chemistry , Intestines/virology , Liver Diseases/etiology , Multicenter Studies as Topic , Pandemics/prevention & control , Peptidyl-Dipeptidase A/analysis , Peptidyl-Dipeptidase A/physiology , Personal Protective Equipment , Pneumonia, Viral/drug therapy , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Receptors, Virus/analysis , Receptors, Virus/physiology , Risk , SARS-CoV-2 , Universal Precautions , COVID-19 Drug TreatmentSubject(s)
Betacoronavirus , Chlorpromazine , Coronavirus Infections/drug therapy , Lung , Phenothiazines , Pneumonia, Viral/drug therapy , Psychotic Disorders/drug therapy , Antipsychotic Agents/pharmacokinetics , Antipsychotic Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/physiology , Biological Availability , Biomedical Research , COVID-19 , Chlorpromazine/pharmacokinetics , Chlorpromazine/therapeutic use , Coronavirus Infections/metabolism , Drug Repositioning/methods , Humans , Lung/drug effects , Lung/metabolism , Maximum Allowable Concentration , Needs Assessment , Pandemics , Phenothiazines/pharmacokinetics , Phenothiazines/therapeutic use , Pneumonia, Viral/metabolism , SARS-CoV-2 , Tissue DistributionABSTRACT
A male bias in mortality has emerged in the COVID-19 pandemic, which is consistent with the pathogenesis of other viral infections. Biological sex differences may manifest themselves in susceptibility to infection, early pathogenesis, innate viral control, adaptive immune responses or the balance of inflammation and tissue repair in the resolution of infection. We discuss available sex-disaggregated epidemiological data from the COVID-19 pandemic, introduce sex-differential features of immunity and highlight potential sex differences underlying COVID-19 severity. We propose that sex differences in immunopathogenesis will inform mechanisms of COVID-19, identify points for therapeutic intervention and improve vaccine design and increase vaccine efficacy.
Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Adaptive Immunity , Age Factors , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Female , Humans , Interferons/immunology , Male , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , SARS-CoV-2 , Severity of Illness Index , Sex Factors , Sociological FactorsABSTRACT
Clinical samples collected in coronavirus disease 19 (COVID-19), patients are commonly manipulated in biosafety level 2 laboratories for molecular diagnostic purposes. Here, we tested French norm NF-EN-14476+A2 derived from European standard EN-14885 to assess the risk of manipulating infectious viruses prior to RNA extraction. SARS-CoV-2 cell-culture supernatant and nasopharyngeal samples (virus-spiked samples and clinical samples collected in COVID-19 patients) were used to measure the reduction of infectivity after 10 minute contact with lysis buffer containing various detergents and chaotropic agents. A total of thirteen protocols were evaluated. Two commercially available formulations showed the ability to reduce infectivity by at least 6 log 10, whereas others proved less effective.
Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/virology , Pneumonia, Viral/virology , Virus Inactivation/drug effects , Animals , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Betacoronavirus/physiology , COVID-19 , Cell Culture Techniques/methods , Chlorocebus aethiops , Containment of Biohazards/methods , Containment of Biohazards/standards , Humans , Nasopharynx/virology , Pandemics , RNA, Viral/isolation & purification , SARS-CoV-2 , Specimen Handling/methods , Vero Cells , Viral Load/methodsABSTRACT
The COVID-19 pandemic is due to infection caused by the novel SARS-CoV-2 virus that impacts the lower respiratory tract. The spectrum of symptoms ranges from asymptomatic infections to mild respiratory symptoms to the lethal form of COVID-19 which is associated with severe pneumonia, acute respiratory distress, and fatality. To address this global crisis, up-to-date information on viral genomics and transcriptomics is crucial for understanding the origins and global dispersion of the virus, providing insights into viral pathogenicity, transmission, and epidemiology, and enabling strategies for therapeutic interventions, drug discovery, and vaccine development. Therefore, this review provides a comprehensive overview of COVID-19 epidemiology, genomic etiology, findings from recent transcriptomic map analysis, viral-human protein interactions, molecular diagnostics, and the current status of vaccine and novel therapeutic intervention development. Moreover, we provide an extensive list of resources that will help the scientific community access numerous types of databases related to SARS-CoV-2 OMICs and approaches to therapeutics related to COVID-19 treatment.
Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/drug therapy , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Genomics , Humans , Pandemics , Pneumonia, Viral/genetics , Pneumonia, Viral/immunology , SARS-CoV-2 , Viral Vaccines/immunology , COVID-19 Drug TreatmentABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first occurred in Wuhan (China) in December of 2019, causes a severe acute respiratory illness with a high mortality rate, and has spread around the world. To gain an understanding of the evolution of the newly emerging SARS-CoV-2, we herein analyzed the codon usage pattern of SARS-CoV-2. For this purpose, we compared the codon usage of SARS-CoV-2 with that of other viruses belonging to the subfamily of Orthocoronavirinae. We found that SARS-CoV-2 has a high AU content that strongly influences its codon usage, which appears to be better adapted to the human host. We also studied the evolutionary pressures that influence the codon usage of five conserved coronavirus genes encoding the viral replicase, spike, envelope, membrane and nucleocapsid proteins. We found different patterns of both mutational bias and natural selection that affect the codon usage of these genes. Moreover, we show here that the two integral membrane proteins (matrix and envelope) tend to evolve slowly by accumulating nucleotide mutations on their corresponding genes. Conversely, genes encoding nucleocapsid (N), viral replicase and spike proteins (S), although they are regarded as are important targets for the development of vaccines and antiviral drugs, tend to evolve faster in comparison to the two genes mentioned above. Overall, our results suggest that the higher divergence observed for the latter three genes could represent a significant barrier in the development of antiviral therapeutics against SARS-CoV-2.
Subject(s)
Betacoronavirus/genetics , Codon , Coronavirus/genetics , Genome, Viral , Base Composition , Betacoronavirus/chemistry , Betacoronavirus/physiology , Biological Evolution , Coronavirus/classification , Genes, Viral , Host Specificity , Mutation , Phylogeny , SARS-CoV-2ABSTRACT
Infection caused by the SARS-CoV-2 coronavirus worldwide has led the World Health Organization to declare a COVID-19 pandemic. Because there is no cure or treatment for this virus, it is emergingly urgent to find effective and validated methods to prevent and treat COVID-19 infection. In this context, alternatives related to nutritional therapy might help to control the infection. This narrative review proposes the importance and role of probiotics and diet as adjunct alternatives among the therapies available for the treatment of this new coronavirus. This review discusses the relationship between intestinal purine metabolism and the use of Lactobacillus gasseri and low-purine diets, particularly in individuals with hyperuricemia, as adjuvant nutritional therapies to improve the immune system and weaken viral replication, assisting in the treatment of COVID-19. These might be promising alternatives, in addition to many others that involve adequate intake of vitamins, minerals and bioactive compounds from food.
Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/therapy , Diet/methods , Immunomodulation/physiology , Pneumonia, Viral/therapy , Probiotics/therapeutic use , Betacoronavirus/immunology , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/microbiology , Humans , Lactobacillus gasseri/immunology , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/microbiology , Purines/immunology , Purines/metabolism , SARS-CoV-2 , Virus Replication/immunologyABSTRACT
Recently, due to the coronavirus pandemic, many guidelines and anti-contagion strategies continue to report unclear information about the persistence of coronavirus disease 2019 (COVID-19) in the environment. This certainly generates insecurity and fear in people, with an important psychological component that is not to be underestimated at this stage of the pandemic. The purpose of this article is to highlight all the sources currently present in the literature concerning the persistence of the different coronaviruses in the environment as well as in medical and dental settings. As this was a current study, there are still not many sources in the literature, and scientific strategies are moving towards therapy and diagnosis, rather than knowing the characteristics of the virus. Such an article could be an aid to summarize virus features and formulate new guidelines and anti-spread strategies.
Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Environmental Microbiology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , COVID-19 , Coronavirus Infections/transmission , Dental Offices , Humans , Medical Office Buildings , Pneumonia, Viral/transmission , Risk , SARS-CoV-2ABSTRACT
The world is currently witnessing an outbreak of a new coronavirus spreading quickly across China and affecting at least 24 other countries. With almost 65,000 infected, a worldwide death toll of at least 1370 (as of 14 February 2020), and with the potential to affect up to two-thirds of the world population, COVID-19 is considered by the World Health Organization (WHO) to be a global health emergency. The speed of spread and infectivity of COVID-19 (also known as Wuhan-2019-nCoV) are dramatically exceeding those of the Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). In fact, since September 2012, the WHO has been notified of 2494 laboratory-confirmed cases of infection with MERS-CoV, whereas the 2002-2003 epidemic of SARS affected 26 countries and resulted in more than 8000 cases. Therefore, although SARS, MERS, and COVID-19 are all the result of coronaviral infections, the causes of the coronaviruses differ dramatically in their transmissibility. It is likely that these differences in infectivity of coronaviruses can be attributed to the differences in the rigidity of their shells which can be evaluated using computational tools for predicting intrinsic disorder predisposition of the corresponding viral proteins.
Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Viral Proteins/metabolism , Animals , COVID-19 , Coronavirus Infections/epidemiology , Humans , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Viral Proteins/genetics , Virus InternalizationABSTRACT
The devastating effects of the recent global pandemic (termed COVID-19 for "coronavirus disease 2019") caused by the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) are paramount with new cases and deaths growing at an exponential rate. In order to provide a better understanding of SARS CoV-2, this article will review the proteins found in the SARS CoV-2 that caused this global pandemic.
Subject(s)
Betacoronavirus/chemistry , Betacoronavirus/physiology , Coronavirus Infections/virology , Pneumonia, Viral/virology , Viral Proteins/chemistry , Viral Proteins/metabolism , Amino Acid Sequence , Betacoronavirus/genetics , COVID-19 , Coronavirus Envelope Proteins , Coronavirus Infections/drug therapy , Coronavirus Infections/metabolism , Coronavirus Nucleocapsid Proteins , Drug Discovery/methods , Genome, Viral , Host-Pathogen Interactions/drug effects , Humans , Nucleocapsid Proteins/chemistry , Nucleocapsid Proteins/genetics , Nucleocapsid Proteins/metabolism , Pandemics , Phosphoproteins , Pneumonia, Viral/drug therapy , Pneumonia, Viral/metabolism , Polyproteins , Protein Interaction Maps/drug effects , SARS-CoV-2 , Sequence Alignment , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Viral Envelope Proteins/chemistry , Viral Envelope Proteins/genetics , Viral Envelope Proteins/metabolism , Viral Matrix Proteins/chemistry , Viral Matrix Proteins/genetics , Viral Matrix Proteins/metabolism , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/genetics , Viral Nonstructural Proteins/metabolism , Viral Proteins/genetics , Viral Regulatory and Accessory Proteins/chemistry , Viral Regulatory and Accessory Proteins/genetics , Viral Regulatory and Accessory Proteins/metabolism , Viroporin ProteinsABSTRACT
The capacity of pre-existing immunity to human common coronaviruses (HCoV) to cross-protect against de novo COVID-19is yet unknown. In this work, we studied the sera of 175 COVID-19 patients, 76 healthy donors and 3 intravenous immunoglobulins (IVIG) batches. We found that most COVID-19 patients developed anti-SARS-CoV-2 IgG antibodies before IgM. Moreover, the capacity of their IgGs to react to beta-HCoV, was present in the early sera of most patients before the appearance of anti-SARS-CoV-2 IgG. This implied that a recall-type antibody response was generated. In comparison, the patients that mounted an anti-SARS-COV2 IgM response, prior to IgG responses had lower titres of anti-beta-HCoV IgG antibodies. This indicated that pre-existing immunity to beta-HCoV was conducive to the generation of memory type responses to SARS-COV-2. Finally, we also found that pre-COVID-19-era sera and IVIG cross-reacted with SARS-CoV-2 antigens without neutralising SARS-CoV-2 infectivity in vitro. Put together, these results indicate that whilst pre-existing immunity to HCoV is responsible for recall-type IgG responses to SARS-CoV-2, it does not lead to cross-protection against COVID-19.
Subject(s)
Betacoronavirus/physiology , COVID-19/immunology , Common Cold/immunology , Immunoglobulins, Intravenous/therapeutic use , SARS-CoV-2/physiology , Aged , Aged, 80 and over , Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , Antigens, Viral/immunology , COVID-19/mortality , COVID-19/therapy , Cross Reactions , Female , Humans , Immunity, Heterologous , Immunoglobulin G/metabolism , Immunoglobulin M/metabolism , Immunologic Memory , Male , Middle Aged , Survival AnalysisABSTRACT
Viral mutations are an emerging concern in reducing SARS-CoV-2 vaccination efficacy. Second-generation vaccines will need to elicit neutralizing antibodies against sites that are evolutionarily conserved across the sarbecovirus subgenus. Here, we immunized mice containing a human antibody repertoire with diverse sarbecovirus receptor-binding domains (RBDs) to identify antibodies targeting conserved sites of vulnerability. Antibodies with broad reactivity against diverse clade B RBDs targeting the conserved class 4 epitope, with recurring IGHV/IGKV pairs, were readily elicited but were non-neutralizing. However, rare class 4 antibodies binding this conserved RBD supersite showed potent neutralization of SARS-CoV-2 and all variants of concern. Structural analysis revealed that the neutralizing ability of cross-reactive antibodies was reserved only for those with an elongated CDRH3 that extends the antiparallel beta-sheet RBD core and orients the antibody light chain to obstruct ACE2-RBD interactions. These results identify a structurally defined pathway for vaccine strategies eliciting escape-resistant SARS-CoV-2 neutralizing antibodies.