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2.
Medicina (Kaunas) ; 57(4)2021 Mar 25.
Article in English | MEDLINE | ID: covidwho-1154450

ABSTRACT

In the last two decades, three unknown pathogens have caused outbreaks, generating severe global health concerns. In 2003, after nucleic acid genotyping, a new virus was named severe acute respiratory syndrome coronavirus (SARS-CoV). After nine years, another coronavirus emerged in the middle east and was named MERS-CoV (Middle East Respiratory Syndrome-Coronavirus). Finally, in December 2019, a new unknown coronavirus was isolated from a cluster of patients and was named SARS-CoV-2 (COVID-19, coronavirus disease 2019). This review aims to propose a complete overview of autopsy in the three coronaviruses over the past two decades, showing its pivotal role in the management of unknown diseases. A total of 116 studies fulfilled the inclusion criteria: 14 studies were collected concerning SARS-CoV (87 autopsy reports, from Asian and American countries), 2 studies for MERS-CoV (2 autopsy reports, from Middle-East Asian countries), and 100 studies on SARS-CoV-2 (930 autopsy reports). Analyzing the data obtained on COVID-19, based on the country criterion, a large number of post-mortem investigation were performed in European countries (580 reports), followed by American countries (251 reports). It is interesting to note that no data were found from the Oceanic countries, maybe because of the minor involvement of the outbreak. In all cases, autopsy provided much information about each unknown coronavirus. Despite advanced technologies in the diagnostic fields, to date, autopsy remains the gold standard method to understand the biological features and the pathogenesis of unknown infections, especially when awareness of a pathogen is restricted and the impact on the healthcare system is substantial. The knowledge gained through this technique may positively influence therapeutic strategies, ultimately reducing mortality.


Subject(s)
/pathology , Severe Acute Respiratory Syndrome/pathology , Autopsy , Coronavirus Infections/pathology , Humans , Middle East Respiratory Syndrome Coronavirus , SARS Virus
3.
Virulence ; 11(1): 1006-1014, 2020 12.
Article in English | MEDLINE | ID: covidwho-684746

ABSTRACT

Novel coronavirus disease 2019 (COVID-19), caused by novel coronavirus SARS-CoV-2, has spread globally since the end of 2019. Asymptomatic carriers are of great concern as they can undermine the interventions to stop the pandemic. However, there is limited information about the characteristics and outcomes of the asymptomatic patients. Therefore, we conducted this retrospective study and retrieved data of 79 asymptomatic COVID-19 patients at admission from three designated hospitals in Wuhan, China. The asymptomatic patients could happen at any age, ranged from 9 to 96 years. These patients also had lower levels of alanine aminotransferase and C-reactive protein. Patchy shadowing was the most common manifestation in computed tomography scan. Some asymptomatic carriers developed mild or moderate symptoms during hospitalization. Age and comorbidities, especially hypertension, may be predictive factors for symptom development in the initially asymptomatic carriers at admission. Early detection and treatment for these presymptomatic patients before symptom onset can shorten the communicable period for the coronavirus and reduce the occurrence of severe cases.


Subject(s)
Asymptomatic Infections/epidemiology , Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , China/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Disease Progression , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Retrospective Studies , Risk Factors , Virus Shedding , Young Adult
4.
Int J Antimicrob Agents ; 56(4): 106129, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1121213

ABSTRACT

INTRODUCTION: The effect of anti-infective agents in COVID-19 is unclear. The impact of changes in practice on prognosis over time has not been evaluated. METHODS: Single center, retrospective study in adults hospitalized in a medicine ward for COVID-19 from March 5th to April 25th 2020. Patient characteristics were compared between two periods (before/after March 19th) considering French guidelines. The aim of the study was to evaluate how medical care impacted unfavorable outcome, namely admission to intensive care unit (ICU) and/or death. RESULTS: A total of 132 patients were admitted: mean age 59.0±16.3 years; mean C-reactive protein (CRP) level 84.0±71.1 mg/L; 46% had a lymphocyte count <1000/mm3. Prescribed anti-infective agents were lopinavir-ritonavir (n=12), azithromycin (AZI) (n=28) and AZI combined with hydroxychloroquine (HCQ) (n=52). There was a significant decrease in ICU admission, from 43% to 12%, between the two periods (P<0.0001). Delays until transfer to ICU were similar between periods (P=0.86). Pulmonary computerized tomography (CT)-scans were performed significantly more often with time (from 50% to 90%, P<0.0001), and oxygen-dependency (53% vs 80%, P=0.001) and prescription of AZI±HCQ (from 25% to 76%, P<0.0001) were also greater over time. Multivariate analyses showed a reduction of unfavorable outcome in patients receiving AZI±HCQ (hazard ratio [HR]=0.45, 95% confidence interval [CI: 0.21-0.97], P=0.04), particularly among an identified category of individuals (lymphocyte ≥1000/mm3 or CRP ≥100 mg/L). CONCLUSION: The present study showed a significant decrease in admission to ICU over time, which was probably related to multiple factors, including a better indication of pulmonary CT-scan, oxygen therapy, and a suitable prescription of anti-infective agents.


Subject(s)
Anti-Infective Agents/therapeutic use , Azithromycin/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Lopinavir/therapeutic use , Pneumonia, Viral/drug therapy , Ritonavir/therapeutic use , Adult , Aged , Betacoronavirus/pathogenicity , C-Reactive Protein/metabolism , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/mortality , Coronavirus Infections/pathology , Disease Progression , Drug Combinations , Female , Humans , Intensive Care Units , Male , Middle Aged , Multivariate Analysis , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , Prognosis , Retrospective Studies , Survival Analysis , T-Lymphocytes/pathology , T-Lymphocytes/virology , Tomography, X-Ray Computed , Treatment Outcome
5.
Ann Allergy Asthma Immunol ; 126(4): 321-337, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1111436

ABSTRACT

OBJECTIVE: To review the virology, immunology, epidemiology, clinical manifestations, and treatment of the following 3 major zoonotic coronavirus epidemics: severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19). DATA SOURCES: Published literature obtained through PubMed database searches and reports from national and international public health agencies. STUDY SELECTIONS: Studies relevant to the basic science, epidemiology, clinical characteristics, and treatment of SARS, MERS, and COVID-19, with a focus on patients with asthma, allergy, and primary immunodeficiency. RESULTS: Although SARS and MERS each caused less than a thousand deaths, COVID-19 has caused a worldwide pandemic with nearly 1 million deaths. Diagnosing COVID-19 relies on nucleic acid amplification tests, and infection has broad clinical manifestations that can affect almost every organ system. Asthma and atopy do not seem to predispose patients to COVID-19 infection, but their effects on COVID-19 clinical outcomes remain mixed and inconclusive. It is recommended that effective therapies, including inhaled corticosteroids and biologic therapy, be continued to maintain disease control. There are no reports of COVID-19 among patients with primary innate and T-cell deficiencies. The presentation of COVID-19 among patients with primary antibody deficiencies is variable, with some experiencing mild clinical courses, whereas others experiencing a fatal disease. The landscape of treatment for COVID-19 is rapidly evolving, with both antivirals and immunomodulators demonstrating efficacy. CONCLUSION: Further data are needed to better understand the role of asthma, allergy, and primary immunodeficiency on COVID-19 infection and outcomes.


Subject(s)
/epidemiology , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , /transmission , Child , Child, Preschool , Comorbidity , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Female , Humans , Infant , Male , Middle Aged , Severe Acute Respiratory Syndrome/therapy , Severe Acute Respiratory Syndrome/transmission , Young Adult
6.
J Pediatric Infect Dis Soc ; 9(3): 373-377, 2020 Jul 13.
Article in English | MEDLINE | ID: covidwho-1109260

ABSTRACT

We describe the clinical course of 57 children with coronavirus disease 2019 (COVID-19) cared for through a single hospital system. Most children were mildly symptomatic, and only a few patients with underlying medical conditions required hospitalization. Systemwide patient evaluation processes allowed for prompt identification and management of patients with COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Adolescent , Child , Child, Preschool , Coronavirus Infections/drug therapy , Coronavirus Infections/pathology , Female , Hospitalization , Hospitals, Pediatric , Humans , Infant , Infant, Newborn , Male , Pandemics , Pneumonia, Viral/pathology , Texas , Treatment Outcome , Young Adult
8.
Life Sci ; 272: 119245, 2021 May 01.
Article in English | MEDLINE | ID: covidwho-1087130

ABSTRACT

In the past 20 years, infections caused by coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2 have posed a threat to public health since they may cause severe acute respiratory syndrome (SARS) in humans. The Complement System is activated during viral infection, being a central protagonist of innate and acquired immunity. Here, we report some interactions between these three coronaviruses and the Complement System, highlighting the central role of C3 with the severity of these infections. Although it can be protective, its role during coronavirus infections seems to be contradictory. For example, during SARS-CoV-2 infection, Complement System can control the viral infection in asymptomatic or mild cases; however, it can also intensify local and systemic damage in some of severe COVID-19 patients, due to its potent proinflammatory effect. In this last condition, the activation of the Complement System also amplifies the cytokine storm and the pathogenicity of coronavirus infection. Experimental treatment with Complement inhibitors has been an enthusiastic field of intense investigation in search of a promising additional therapy in severe COVID-19 patients.


Subject(s)
/immunology , Complement System Proteins/immunology , /immunology , Animals , /drug therapy , Complement Activation/drug effects , Complement C3/immunology , Complement Inactivating Agents/pharmacology , Complement Inactivating Agents/therapeutic use , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Humans , Inflammation/complications , Inflammation/drug therapy , Inflammation/immunology , Inflammation/pathology , Middle East Respiratory Syndrome Coronavirus/immunology , SARS Virus/immunology , Severe Acute Respiratory Syndrome/complications , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/pathology
10.
Brain ; 143(10): 3089-3103, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-1066270

ABSTRACT

Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of individuals worldwide. Although the main clinical manifestations are respiratory, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected. We present cerebrovascular disease case incidence in hospitalized patients with SARS-CoV-2 infection. Patients were confirmed by microbiological/serological testing, or on chest CT semiology. Available data on co-morbidity, laboratory parameters, treatment administered, neuroimaging, neuropathological studies and clinical evolution during hospitalization, measured by the modified Rankin scale, were analysed. A bivariate study was also designed to identify differences between ischaemic and haemorrhagic subtypes. A statistical model of binary logistic regression and sensitivity analysis was designed to study the influence of independent variables over prognosis. In our centre, there were 1683 admissions of patients with COVID-19 over 50 days, of which 23 (1.4%) developed cerebrovascular disease. Within this group of patients, cerebral and chest CT scans were performed in all cases, and MRI in six (26.1%). Histological samples were obtained in 6/23 cases (two brain biopsies, and four arterial thrombi). Seventeen patients were classified as cerebral ischaemia (73.9%, with two arterial dissections), five as intracerebral haemorrhage (21.7%), and one leukoencephalopathy of posterior reversible encephalopathy type. Haemorrhagic patients had higher ferritin levels at the time of stroke (1554.3 versus 519.2, P = 0.004). Ischaemic strokes were unexpectedly frequent in the vertebrobasilar territory (6/17, 35.3%). In the haemorrhagic group, a characteristic radiological pattern was identified showing subarachnoid haemorrhage, parieto-occipital leukoencephalopathy, microbleeds and single or multiple focal haematomas. Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis. The functional prognosis during the hospital period was unfavourable in 73.9% (17/23 modified Rankin scale 4-6), and age was the main predictive variable (odds ratio = 1.5; 95% confidence interval 1.012-2.225; P = 0.043). Our series shows cerebrovascular disease incidence of 1.4% in patients with COVID-19 with high morbidity and mortality. We describe pathological and radiological data consistent with thrombotic microangiopathy caused by endotheliopathy with a haemorrhagic predisposition.


Subject(s)
Brain Ischemia/diagnostic imaging , Brain Ischemia/epidemiology , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/epidemiology , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/epidemiology , Leukoencephalopathies/epidemiology , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/epidemiology , Age Factors , Aged , Betacoronavirus , Brain/diagnostic imaging , Brain/pathology , Brain Ischemia/pathology , Cerebral Hemorrhage/blood , Cerebral Hemorrhage/pathology , Comorbidity , Coronavirus Infections/blood , Coronavirus Infections/pathology , Female , Ferritins/blood , Humans , Incidence , Leukoencephalopathies/diagnostic imaging , Leukoencephalopathies/pathology , Magnetic Resonance Imaging , Male , Neuroimaging , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , Spain/epidemiology , Tomography, X-Ray Computed
11.
mBio ; 12(1)2021 01 08.
Article in English | MEDLINE | ID: covidwho-1066816

ABSTRACT

In December 2019 a new coronavirus (CoV) emerged as a human pathogen, SARS-CoV-2. There are few data on human coronavirus infections among individuals living with HIV. In this study we probed the role of pneumococcal coinfections with seasonal CoVs among children living with and without HIV hospitalized for pneumonia. We also described the prevalence and clinical manifestations of these infections. A total of 39,836 children who participated in a randomized, double-blind, placebo-controlled clinical trial on the efficacy of a 9-valent pneumococcal conjugate vaccine (PCV9) were followed for lower respiratory tract infection hospitalizations until 2 years of age. Nasopharyngeal aspirates were collected at the time of hospitalization and were screened by PCR for four seasonal CoVs. The frequency of CoV-associated pneumonia was higher in children living with HIV (19.9%) than in those without HIV (7.6%, P < 0.001). Serial CoV infections were detected in children living with HIV. The case fatality risk among children with CoV-associated pneumonia was higher in those living with HIV (30.4%) than without HIV (2.9%, P = 0.001). C-reactive protein and procalcitonin levels were elevated in 36.8% (≥40 mg/liter) and 64.7% (≥0.5 ng/ml), respectively, of the fatal cases living with HIV. Among children without HIV, there was a 64.0% (95% CI: 22.9% to 83.2%) lower incidence of CoV-associated pneumonia hospitalizations among PCV9 recipients compared to placebo recipients. These data suggest that Streptococcus pneumoniae infections might have a role in the development of pneumonia associated with endemic CoVs, that PCV may prevent pediatric CoV-associated hospitalization, and that children living with HIV with CoV infections develop more severe outcomes.IMPORTANCE SARS-CoV-2 may cause severe hospitalization, but little is known about the role of secondary bacterial infection in these severe cases, beyond the observation of high levels of reported inflammatory markers, associated with bacterial infection, such as procalcitonin. We did a secondary analysis of a double-blind randomized trial of PCV to examine its impact on human CoV infections before the pandemic. We found that both children living with and without HIV randomized to receive PCV had evidence of less hospitalization due to seasonal CoV, suggesting that pneumococcal coinfection may play a role in severe hospitalized CoV infections.


Subject(s)
AIDS-Related Opportunistic Infections/prevention & control , Coronavirus Infections/prevention & control , Pneumococcal Vaccines/administration & dosage , Pneumonia, Viral/prevention & control , Streptococcus pneumoniae/immunology , AIDS-Related Opportunistic Infections/epidemiology , AIDS-Related Opportunistic Infections/pathology , Coinfection/epidemiology , Coinfection/microbiology , Coinfection/prevention & control , Coinfection/virology , Coronavirus/classification , Coronavirus/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Follow-Up Studies , Hospitalization/statistics & numerical data , Humans , Incidence , Infant , Pneumonia, Pneumococcal/epidemiology , Pneumonia, Pneumococcal/prevention & control , Pneumonia, Viral/epidemiology , Prevalence , Randomized Controlled Trials as Topic
12.
PLoS One ; 16(2): e0246150, 2021.
Article in English | MEDLINE | ID: covidwho-1061213

ABSTRACT

A coronavirus pandemic caused by a novel coronavirus (SARS-CoV-2) has spread rapidly worldwide since December 2019. Improved understanding and new strategies to cope with novel coronaviruses are urgently needed. Viruses (especially RNA viruses) encode a limited number and size (length of polypeptide chain) of viral proteins and must interact with the host cell components to control (hijack) the host cell machinery. To achieve this goal, the extensive mimicry of SLiMs in host proteins provides an effective strategy. However, little is known regarding SLiMs in coronavirus proteins and their potential targets in host cells. The objective of this study is to uncover SLiMs in coronavirus proteins that are present within host cells. These SLiMs have a high possibility of interacting with host intracellular proteins and hijacking the host cell machinery for virus replication and dissemination. In total, 1,479 SLiM hits were identified in the 16 proteins of 590 coronaviruses infecting humans. Overall, 106 host proteins were identified that may interact with SLiMs in 16 coronavirus proteins. These SLiM-interacting proteins are composed of many intracellular key regulators, such as receptors, transcription factors and kinases, and may have important contributions to virus replication, immune evasion and viral pathogenesis. A total of 209 pathways containing proteins that may interact with SLiMs in coronavirus proteins were identified. This study uncovers potential mechanisms by which coronaviruses hijack the host cell machinery. These results provide potential therapeutic targets for viral infections.


Subject(s)
Coronavirus Infections/pathology , Middle East Respiratory Syndrome Coronavirus/metabolism , SARS Virus/metabolism , Viral Proteins/metabolism , Amino Acid Motifs , Coronavirus Infections/virology , Databases, Protein , Humans , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Phylogeny , Protein Interaction Domains and Motifs , Proteins/chemistry , Proteins/classification , SARS Virus/isolation & purification , Signal Transduction/genetics , User-Computer Interface , Viral Proteins/chemistry , Viral Proteins/classification
13.
Monaldi Arch Chest Dis ; 90(4)2020 Sep 09.
Article in English | MEDLINE | ID: covidwho-1059326

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a lethal pandemic that has claimed millions of lives worldwide. While respiratory involvement is the most common and most virulent manifestation of COVID-19, there is enough data to suggest that myocardial injury reflected through elevated troponin levels is seen in around 7-28% of patients and is related with increased morbidity and mortality.


Subject(s)
Coronavirus Infections/physiopathology , Heart/virology , Myocarditis/physiopathology , Myocardium/pathology , Pneumonia, Viral/physiopathology , Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Humans , Myocarditis/etiology , Myocarditis/immunology , Myocarditis/pathology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology
14.
BMC Bioinformatics ; 22(1): 18, 2021 Jan 07.
Article in English | MEDLINE | ID: covidwho-1059737

ABSTRACT

BACKGROUND: The ongoing global COVID-19 pandemic is caused by SARS-CoV-2, a novel coronavirus first discovered at the end of 2019. It has led to more than 50 million confirmed cases and more than 1 million deaths across 219 countries as of 11 November 2020, according to WHO statistics. SARS-CoV-2, SARS-CoV, and MERS-CoV are similar. They are highly pathogenic and threaten public health, impair the economy, and inflict long-term impacts on society. No drug or vaccine has been approved as a treatment for these viruses. Efforts to develop antiviral measures have been hampered by the insufficient understanding of how the human body responds to viral infections at the cellular and molecular levels. RESULTS: In this study, journal articles and transcriptomic and proteomic data surveying coronavirus infections were collected. Response genes and proteins were then identified by differential analyses comparing gene/protein levels between infected and control samples. Finally, the H2V database was created to contain the human genes and proteins that respond to SARS-CoV-2, SARS-CoV, and MERS-CoV infection. CONCLUSIONS: H2V provides molecular information about the human response to infection. It can be a powerful tool to discover cellular pathways and processes relevant for viral pathogenesis to identify potential drug targets. It is expected to accelerate the process of antiviral agent development and to inform preparations for potential future coronavirus-related emergencies. The database is available at: http://www.zhounan.org/h2v .


Subject(s)
/metabolism , Coronavirus Infections/metabolism , Databases, Genetic , Databases, Protein , Severe Acute Respiratory Syndrome/metabolism , User-Computer Interface , /genetics , /virology , Coronavirus Infections/genetics , Coronavirus Infections/pathology , Coronavirus Infections/virology , Humans , Middle East Respiratory Syndrome Coronavirus/physiology , Proteomics , SARS Virus/physiology , Severe Acute Respiratory Syndrome/genetics , Severe Acute Respiratory Syndrome/pathology , Severe Acute Respiratory Syndrome/virology
15.
Int J Mol Sci ; 22(3)2021 Jan 28.
Article in English | MEDLINE | ID: covidwho-1055069

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel epidemic strain of Betacoronavirus that is responsible for the current viral pandemic, coronavirus disease 2019 (COVID-19), a global health crisis. Other epidemic Betacoronaviruses include the 2003 SARS-CoV-1 and the 2009 Middle East Respiratory Syndrome Coronavirus (MERS-CoV), the genomes of which, particularly that of SARS-CoV-1, are similar to that of the 2019 SARS-CoV-2. In this extensive review, we document the most recent information on Coronavirus proteins, with emphasis on the membrane proteins in the Coronaviridae family. We include information on their structures, functions, and participation in pathogenesis. While the shared proteins among the different coronaviruses may vary in structure and function, they all seem to be multifunctional, a common theme interconnecting these viruses. Many transmembrane proteins encoded within the SARS-CoV-2 genome play important roles in the infection cycle while others have functions yet to be understood. We compare the various structural and nonstructural proteins within the Coronaviridae family to elucidate potential overlaps and parallels in function, focusing primarily on the transmembrane proteins and their influences on host membrane arrangements, secretory pathways, cellular growth inhibition, cell death and immune responses during the viral replication cycle. We also offer bioinformatic analyses of potential viroporin activities of the membrane proteins and their sequence similarities to the Envelope (E) protein. In the last major part of the review, we discuss complement, stimulation of inflammation, and immune evasion/suppression that leads to CoV-derived severe disease and mortality. The overall pathogenesis and disease progression of CoVs is put into perspective by indicating several stages in the resulting infection process in which both host and antiviral therapies could be targeted to block the viral cycle. Lastly, we discuss the development of adaptive immunity against various structural proteins, indicating specific vulnerable regions in the proteins. We discuss current CoV vaccine development approaches with purified proteins, attenuated viruses and DNA vaccines.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/metabolism , Viral Matrix Proteins/metabolism , Animals , Betacoronavirus/genetics , Betacoronavirus/immunology , /metabolism , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Genome, Viral , Host-Pathogen Interactions , Humans , Immune Evasion , Protein Interaction Maps , /immunology , Viral Matrix Proteins/genetics , Viral Matrix Proteins/immunology , Virus Internalization , Virus Replication
17.
BMC Biol ; 19(1): 12, 2021 01 22.
Article in English | MEDLINE | ID: covidwho-1044598

ABSTRACT

BACKGROUND: Pandemics, even more than other medical problems, require swift integration of knowledge. When caused by a new virus, understanding the underlying biology may help finding solutions. In a setting where there are a large number of loosely related projects and initiatives, we need common ground, also known as a "commons." Wikidata, a public knowledge graph aligned with Wikipedia, is such a commons and uses unique identifiers to link knowledge in other knowledge bases. However, Wikidata may not always have the right schema for the urgent questions. In this paper, we address this problem by showing how a data schema required for the integration can be modeled with entity schemas represented by Shape Expressions. RESULTS: As a telling example, we describe the process of aligning resources on the genomes and proteomes of the SARS-CoV-2 virus and related viruses as well as how Shape Expressions can be defined for Wikidata to model the knowledge, helping others studying the SARS-CoV-2 pandemic. How this model can be used to make data between various resources interoperable is demonstrated by integrating data from NCBI (National Center for Biotechnology Information) Taxonomy, NCBI Genes, UniProt, and WikiPathways. Based on that model, a set of automated applications or bots were written for regular updates of these sources in Wikidata and added to a platform for automatically running these updates. CONCLUSIONS: Although this workflow is developed and applied in the context of the COVID-19 pandemic, to demonstrate its broader applicability it was also applied to other human coronaviruses (MERS, SARS, human coronavirus NL63, human coronavirus 229E, human coronavirus HKU1, human coronavirus OC4).


Subject(s)
/pathology , Genomics/methods , Knowledge Bases , Proteomics/methods , /physiology , /metabolism , Coronavirus/genetics , Coronavirus/physiology , Coronavirus Infections/metabolism , Coronavirus Infections/pathology , Coronavirus Infections/virology , Genome, Viral , Humans , Internet , Pandemics , Viral Proteins/genetics , Viral Proteins/metabolism , Workflow
18.
Jpn J Infect Dis ; 73(5): 377-380, 2020 Sep 24.
Article in English | MEDLINE | ID: covidwho-1034439

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a severe infectious disease of the respiratory tract caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2, and has a high mortality rate. The disease emerged from Wuhan, China, in late 2019, and spread to Japan, including Hokkaido, in January 2020. In February 2020, 3 children were diagnosed with COVID-19 in Furano, Hokkaido, Japan. During this period, influenza and human metapneumovirus infections were prevalent among children in the Furano region. Two of the 3 patients experienced co-infection with other respiratory viruses, including influenza virus A or human metapneumovirus. To the authors' knowledge, the cases described in the present report were the first pediatric patients with COVID-19 in Japan. In children with COVID-19, the possibility of co-infection with other respiratory pathogens should be considered.


Subject(s)
Coinfection/diagnosis , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Respiratory Tract Infections/diagnosis , Betacoronavirus/isolation & purification , Child , Child, Preschool , Coinfection/pathology , Coinfection/virology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Humans , Japan/epidemiology , Lung/diagnostic imaging , Lung/pathology , Male , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Respiratory Tract Infections/pathology , Respiratory Tract Infections/virology
20.
Nat Biotechnol ; 38(9): 1073-1078, 2020 09.
Article in English | MEDLINE | ID: covidwho-1023948

ABSTRACT

A robust serological test to detect neutralizing antibodies to SARS-CoV-2 is urgently needed to determine not only the infection rate, herd immunity and predicted humoral protection, but also vaccine efficacy during clinical trials and after large-scale vaccination. The current gold standard is the conventional virus neutralization test requiring live pathogen and a biosafety level 3 laboratory. Here, we report a SARS-CoV-2 surrogate virus neutralization test that detects total immunodominant neutralizing antibodies targeting the viral spike (S) protein receptor-binding domain in an isotype- and species-independent manner. Our simple and rapid test is based on antibody-mediated blockage of the interaction between the angiotensin-converting enzyme 2 (ACE2) receptor protein and the receptor-binding domain. The test, which has been validated with two cohorts of patients with COVID-19 in two different countries, achieves 99.93% specificity and 95-100% sensitivity, and differentiates antibody responses to several human coronaviruses. The surrogate virus neutralization test does not require biosafety level 3 containment, making it broadly accessible to the wider community for both research and clinical applications.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/genetics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Spike Glycoprotein, Coronavirus/genetics , Antibodies/immunology , Antibodies/pharmacology , Betacoronavirus/genetics , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Humans , Neutralization Tests , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Protein Interaction Domains and Motifs/genetics , Spike Glycoprotein, Coronavirus/chemistry
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