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1.
EMBO Mol Med ; 12(5): e12481, 2020 05 08.
Article in English | MEDLINE | ID: covidwho-2025763

ABSTRACT

The COVID-19 pandemic has spread to many countries around the world, but the infection and death rates vary widely. One country that appeared to have kept the infection under control despite limited societal restrictions is Japan. This commentary explores why Japan may have, up to now, been spared an escalation of the SARS-CoV-2 infections.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Angiotensin-Converting Enzyme 2 , BCG Vaccine/immunology , COVID-19 , Communicable Disease Control , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Culture , Fatty Acids, Monounsaturated , Genetic Variation , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/immunology , Humans , Japan/epidemiology , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Pneumonia, Viral/immunology , SARS-CoV-2
5.
Viruses ; 12(5)2020 05 10.
Article in English | MEDLINE | ID: covidwho-1726011

ABSTRACT

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
6.
Chin Med J (Engl) ; 133(9): 1039-1043, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-1722619

ABSTRACT

BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS: In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/genetics , Pneumonia, Viral/genetics , RNA, Viral/genetics , Adult , Aged , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/rehabilitation , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/rehabilitation , Real-Time Polymerase Chain Reaction , Retrospective Studies , SARS-CoV-2
7.
Cell Host Microbe ; 27(6): 879-882.e2, 2020 06 10.
Article in English | MEDLINE | ID: covidwho-1719463

ABSTRACT

The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis. We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for 3 to 4 weeks in all three patients. Cytokine analyses of whole blood revealed increased cytokine expression in the single most severe case. However, most inflammatory gene expression peaked after respiratory function nadir, except expression in the IL1 pathway. Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T cell activation that could exacerbate disease or prolong the infection. Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19. This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies.


Subject(s)
Coronavirus Infections/genetics , Coronavirus Infections/immunology , Pneumonia, Viral/genetics , Pneumonia, Viral/immunology , Adult , Aged , Biological Variation, Individual , COVID-19 , Cluster Analysis , Coronavirus Infections/blood , Coronavirus Infections/pathology , Cytokines/blood , Gene Expression Regulation , Humans , Male , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , Transcriptome , Up-Regulation
9.
Viruses ; 12(10)2020 10 16.
Article in English | MEDLINE | ID: covidwho-1389518

ABSTRACT

To address the expression pattern of the SARS-CoV-2 receptor ACE2 and the viral priming protease TMPRSS2 in the respiratory tract, this study investigated RNA sequencing transcriptome profiling of samples of airway and oral mucosa. As shown, ACE2 has medium levels of expression in both small airway epithelium and masticatory mucosa, and high levels of expression in nasal epithelium. The expression of ACE2 is low in mucosal-associated invariant T (MAIT) cells and cannot be detected in alveolar macrophages. TMPRSS2 is highly expressed in small airway epithelium and nasal epithelium and has lower expression in masticatory mucosa. Our results provide the molecular basis that the nasal mucosa is the most susceptible locus in the respiratory tract for SARS-CoV-2 infection and consequently for subsequent droplet transmission and should be the focus for protection against SARS-CoV-2 infection.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/genetics , Peptidyl-Dipeptidase A/biosynthesis , Pneumonia, Viral/genetics , Serine Endopeptidases/biosynthesis , Virus Internalization , Angiotensin-Converting Enzyme 2 , COVID-19 , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Epithelium/metabolism , Epithelium/virology , Gene Expression , Gene Expression Profiling , Humans , Nasal Mucosa/metabolism , Nasal Mucosa/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , Respiratory System/metabolism , Respiratory System/virology , SARS-CoV-2 , Serine Endopeptidases/genetics
12.
Fertil Steril ; 114(2): 223-232, 2020 08.
Article in English | MEDLINE | ID: covidwho-1385570

ABSTRACT

OBJECTIVE: To determine the susceptibility of the endometrium to infection by-and thereby potential damage from-SARS-CoV-2. DESIGN: Analysis of SARS-Cov-2 infection-related gene expression from endometrial transcriptomic data sets. SETTING: Infertility research department affiliated with a public hospital. PATIENT(S): Gene expression data from five studies in 112 patients with normal endometrium collected throughout the menstrual cycle. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Gene expression and correlation between viral infectivity genes and age throughout the menstrual cycle. RESULT(S): Gene expression was high for TMPRSS4, CTSL, CTSB, FURIN, MX1, and BSG; medium for TMPRSS2; and low for ACE2. ACE2, TMPRSS4, CTSB, CTSL, and MX1 expression increased toward the window of implantation. TMPRSS4 expression was positively correlated with ACE2, CTSB, CTSL, MX1, and FURIN during several cycle phases; TMPRSS2 was not statistically significantly altered across the cycle. ACE2, TMPRSS4, CTSB, CTSL, BSG, and MX1 expression increased with age, especially in early phases of the cycle. CONCLUSION(S): Endometrial tissue is likely safe from SARS-CoV-2 cell entry based on ACE2 and TMPRSS2 expression, but susceptibility increases with age. Further, TMPRSS4, along with BSG-mediated viral entry into cells, could imply a susceptible environment for SARS-CoV-2 entry via different mechanisms. Additional studies are warranted to determine the true risk of endometrial infection by SARS-CoV-2 and implications for fertility treatments.


Subject(s)
Betacoronavirus/metabolism , Coronavirus Infections/metabolism , Endometrium/metabolism , Endometrium/virology , Gene Expression Regulation, Viral , Pneumonia, Viral/metabolism , Adult , Age Factors , Angiotensin-Converting Enzyme 2 , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/genetics , Female , Humans , Menstrual Cycle , Middle Aged , Pandemics , Peptidyl-Dipeptidase A/biosynthesis , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Risk Assessment/methods , SARS-CoV-2 , Virus Internalization , Young Adult
13.
Clin Immunol ; 215: 108426, 2020 06.
Article in English | MEDLINE | ID: covidwho-1385285
14.
Cell ; 181(6): 1194-1199, 2020 06 11.
Article in English | MEDLINE | ID: covidwho-1385209

ABSTRACT

SARS-CoV-2 infection displays immense inter-individual clinical variability, ranging from silent infection to lethal disease. The role of human genetics in determining clinical response to the virus remains unclear. Studies of outliers-individuals remaining uninfected despite viral exposure and healthy young patients with life-threatening disease-present a unique opportunity to reveal human genetic determinants of infection and disease.


Subject(s)
Coronavirus Infections/genetics , Coronavirus Infections/immunology , Genetic Predisposition to Disease , Pneumonia, Viral/genetics , Pneumonia, Viral/immunology , Age Factors , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Disease Resistance , Genetic Association Studies , Genetic Diseases, Inborn/immunology , Genetic Variation , Genome, Human , Host-Pathogen Interactions , Humans , Infections/genetics , Infections/immunology , Infections/physiopathology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , SARS-CoV-2
15.
Pharmacol Res ; 157: 104820, 2020 07.
Article in English | MEDLINE | ID: covidwho-1318923

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) pandemic has become a huge threaten to global health, which raise urgent demand of developing efficient therapeutic strategy. The aim of the present study is to dissect the chemical composition and the pharmacological mechanism of Qingfei Paidu Decoction (QFPD), a clinically used Chinese medicine for treating COVID-19 patients in China. Through comprehensive analysis by liquid chromatography coupled with high resolution mass spectrometry (MS), a total of 129 compounds of QFPD were putatively identified. We also constructed molecular networking of mass spectrometry data to classify these compounds into 14 main clusters, in which exhibited specific patterns of flavonoids (45 %), glycosides (15 %), carboxylic acids (10 %), and saponins (5 %). The target network model of QFPD, established by predicting and collecting the targets of identified compounds, indicated a pivotal role of Ma Xing Shi Gan Decoction (MXSG) in the therapeutic efficacy of QFPD. Supportively, through transcriptomic analysis of gene expression after MXSG administration in rat model of LPS-induced pneumonia, the thrombin and Toll-like receptor (TLR) signaling pathway were suggested to be essential pathways for MXSG mediated anti-inflammatory effects. Besides, changes in content of major compounds in MXSG during decoction were found by the chemical analysis. We also validate that one major compound in MXSG, i.e. glycyrrhizic acid, inhibited TLR agonists induced IL-6 production in macrophage. In conclusion, the integration of in silico and experimental results indicated that the therapeutic effects of QFPD against COVID-19 may be attributed to the anti-inflammatory effects of MXSG, which supports the rationality of the compatibility of TCM.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Pneumonia, Viral/drug therapy , Animals , Anti-Inflammatory Agents/analysis , Anti-Inflammatory Agents/pharmacology , COVID-19 , Cells, Cultured , Computer Simulation , Coronavirus Infections/genetics , Gene Expression/drug effects , Glycyrrhizic Acid/pharmacology , Humans , Interleukin-6/metabolism , Lipopeptides/antagonists & inhibitors , Lipopeptides/pharmacology , Lipopolysaccharides , Male , Pandemics , Pneumonia/chemically induced , Pneumonia/metabolism , Pneumonia, Viral/genetics , Rats , SARS-CoV-2 , Signal Transduction/drug effects , Thrombin/metabolism , Toll-Like Receptors/metabolism
16.
J Med Virol ; 93(8): 5182-5187, 2021 08.
Article in English | MEDLINE | ID: covidwho-1298501

ABSTRACT

Infections due to human herpesvirus 6 (HHV-6) are frequent during early childhood. Usually, they have a favorable clinical course. Conversely, HHV-6 congenital infections occur in about 1% of neonates and may present with more severe clinical pictures. HHV-6 can be found in lung tissues and bronchoalveolar lavage (BAL) samples from patients with pneumonia and in immunocompromised patients can cause mild to severe pneumonia. In neonates, the role of HHV-6 in the genesis of severe pneumonia is poorly defined still now. We describe a healthy infant with a late-onset (15 days of life) severe interstitial pneumonia and heavy HHV-6 genome load, persistently detected in its BAL fluid. The baby underwent high-frequency oscillatory ventilation, hydroxychloroquine, steroids, and ganciclovir for 6 weeks and at 9 months she died. Next-generation sequencing of genes known to cause neonatal respiratory insufficiency revealed the presence of a "probably pathogenetic" heterozygous variant in the autosomal recessive DRC1 gene, a heterozygous variant of unknown significance (VUS) in the autosomal recessive RSPH9 gene, and a heterozygous VUS in the autosomal recessive MUC5B gene. HHV-6 infection should be considered in the differential diagnosis of late-onset severe respiratory distress in neonates and the co-occurrence of genetic predisposing factors or modifiers should be tested by specific molecular techniques. The intensity of HHV-6 genome load in BAL fluid could be an indicator of the response to antiviral therapy.


Subject(s)
Genetic Predisposition to Disease/genetics , Lung Diseases, Interstitial/genetics , Roseolovirus Infections/genetics , Cytoskeletal Proteins/genetics , Fatal Outcome , Female , Genetic Variation , Herpesvirus 6, Human/genetics , Herpesvirus 6, Human/isolation & purification , Heterozygote , Humans , Infant, Newborn , Lung Diseases, Interstitial/therapy , Lung Diseases, Interstitial/virology , Microtubule-Associated Proteins/genetics , Mucin-5B/genetics , Pneumonia, Viral/genetics , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , Roseolovirus Infections/therapy , Roseolovirus Infections/virology , Viral Load
18.
Eur J Clin Invest ; 50(7): e13259, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1084256

ABSTRACT

BACKGROUND: The clinical features of COVID-19 pneumonia range from a mild illness to patients with a very severe illness with acute hypoxemic respiratory failure requiring ventilation and Intensive Care Unit admission. AIMS: To provide a brief overview of the existing evidence for such differences in host response and outcome, and generate hypotheses for divergent patterns and avenues for future research, by highlighting similarities and differences in histopathological appearance between COVID-19 and influenza as well as previous coronavirus outbreaks, and by discussing predisposition through genetics and underlying disease. MATERIALS AND METHOD: We assessed the available early literature for histopathological patterns of COVID-19 pneumonia and underlying risk factors. RESULT: The histopathological spectrum of COVID-19 pneumonia includes variable patterns of epithelial damage, vascular complications, fibrosis and inflammation. Risk factors for a fatal disease include older age, respiratory disease, diabetes mellitus, obesity and hypertension. DISCUSSION: While some risk factors and their potential role in COVID-19 pneumonia are increasingly recognized, little is known about the mechanisms behind episodes of sudden deterioration or the infrequent idiosyncratic clinical demise in otherwise healthy and young subjects. CONCLUSION: The answer to many of the remaining questions regarding COVID-19 pneumonia pathogenesis may in time be provided by genotyping as well careful clinical, serological, radiological and histopathological phenotyping.


Subject(s)
Coronavirus Infections/pathology , Edema/pathology , Inflammation/pathology , Pneumonia, Viral/pathology , Respiratory Mucosa/pathology , Thrombosis/pathology , Age Factors , Angiotensin-Converting Enzyme 2 , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Cytokine Release Syndrome/immunology , Diabetes Mellitus/epidemiology , Fibrosis , Genetic Predisposition to Disease , HLA Antigens/genetics , Humans , Hypertension/epidemiology , Inflammation/immunology , Influenza, Human/pathology , Obesity/epidemiology , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/genetics , Pneumonia, Viral/immunology , Polymorphism, Genetic , Respiratory Mucosa/immunology , Respiratory System/pathology , Risk Factors , SARS-CoV-2 , Serine Endopeptidases/genetics , Severe Acute Respiratory Syndrome/pathology
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