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1.
PLoS One ; 16(1): e0245547, 2021.
Article in English | MEDLINE | ID: covidwho-1067419

ABSTRACT

Endemic human coronaviruses (HCoVs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are members of the family Coronaviridae. Comparing the findings of the infections caused by these viruses would help reveal the novel characteristics of SARS-CoV-2 and provide insight into the unique pathogenesis of SARS-CoV-2 infection. This study aimed to compare the clinical and radiological characteristics of SARS-CoV-2 and endemic HCoVs infection in adult hospitalized patients with community-acquired pneumonia (CAP). This study was performed at a university-affiliated tertiary hospital in the Republic of Korea, between January 1, 2015, and July 31, 2020. A total of 109 consecutive patients who were over 18 years of age with confirmed SARS-CoV-2 and endemic HCoVs were enrolled. Finally, 19 patients with SARS-CoV-2 CAP were compared to 40 patients with endemic HCoV CAP. Flu-like symptoms such as cough, sore throat, headache, myalgia, and prolonged fever were more common in SARS-CoV-2 CAP, whereas clinical findings suggestive of bacterial pneumonia such as dyspnea, leukocytosis with left shift, and increased C-reactive protein were more common in endemic HCoV CAP. Bilateral peripherally distributed ground-glass opacities (GGOs) were typical radiologic findings in SARS-CoV-2 CAP, whereas mixed patterns of GGOs, consolidations, micronodules, and pleural effusion were observed in endemic HCoV CAP. Coinfection was not observed in patients with SARS-CoV-2 CAP, but was observed in more than half of the patients with endemic HCoV CAP. There were distinctive differences in the clinical and radiologic findings between SARS-CoV-2 and endemic HCoV CAP. Further investigations are required to elucidate the mechanism underlying this difference. Follow-up observations are needed to determine if the presentation of SARS-CoV-2 CAP changes with repeated infection.


Subject(s)
/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Aged , /pathology , Cohort Studies , Coinfection/diagnostic imaging , Coinfection/epidemiology , Coinfection/pathology , Coinfection/virology , Community-Acquired Infections , Coronavirus/isolation & purification , Endemic Diseases , Female , Humans , Lung/diagnostic imaging , Male , Middle Aged , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Radiography, Thoracic/methods , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , Thorax/diagnostic imaging
2.
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
3.
Life Sci ; 253: 117723, 2020 Jul 15.
Article in English | MEDLINE | ID: covidwho-1023706

ABSTRACT

Coronavirus Disease 2019 (COVID-19) has quickly progressed to a global health emergency. Respiratory illness is the major cause of morbidity and mortality in these patients with the disease spectrum ranging from asymptomatic subclinical infection, to severe pneumonia progressing to acute respiratory distress syndrome. There is growing evidence describing pathophysiological resemblance of SARS-CoV-2 infection with other coronavirus infections such as Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Angiotensin Converting Enzyme-2 receptors play a pivotal role in the pathogenesis of the virus. Disruption of this receptor leads to cardiomyopathy, cardiac dysfunction, and heart failure. Patients with cardiovascular disease are more likely to be infected with SARS-CoV-2 and they are more likely to develop severe symptoms. Hypertension, arrhythmia, cardiomyopathy and coronary heart disease are amongst major cardiovascular disease comorbidities seen in severe cases of COVID-19. There is growing literature exploring cardiac involvement in SARS-CoV-2. Myocardial injury is one of the important pathogenic features of COVID-19. As a surrogate for myocardial injury, multiple studies have shown increased cardiac biomarkers mainly cardiac troponins I and T in the infected patients especially those with severe disease. Myocarditis is depicted as another cause of morbidity amongst COVID-19 patients. The exact mechanisms of how SARS-CoV-2 can cause myocardial injury are not clearly understood. The proposed mechanisms of myocardial injury are direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to coronary plaque destabilization, and hypoxia.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/pathology , Myocardium/pathology , Pneumonia, Viral/pathology , Coronavirus Infections/immunology , Humans , Myocarditis/virology , Myocytes, Cardiac/pathology , Myocytes, Cardiac/virology , Pandemics , Pneumonia, Viral/immunology
5.
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
6.
Nat Biotechnol ; 38(8): 970-979, 2020 08.
Article in English | MEDLINE | ID: covidwho-1023942

ABSTRACT

To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand-receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF. The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19.


Subject(s)
Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , Respiratory System/pathology , Single-Cell Analysis , Transcriptome , Adult , Aged , Bronchoalveolar Lavage Fluid/virology , Cell Communication , Cell Differentiation , Coronavirus Infections/virology , Epithelial Cells/pathology , Epithelial Cells/virology , Female , Humans , Immune System/pathology , Inflammation/immunology , Inflammation/pathology , Longitudinal Studies , Male , Middle Aged , Nasopharynx/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/virology , Respiratory System/immunology , Respiratory System/virology , Severity of Illness Index
7.
J Headache Pain ; 21(1): 38, 2020 Apr 25.
Article in English | MEDLINE | ID: covidwho-1021356

ABSTRACT

The world is currently dominated by the Corona Virus Disease 2019 (COVID-19) pandemic. Besides the obvious concerns about limitation of virus spread and providing the best possible care to infected patients, a concomitant concern has now arisen in view of a putative link between the use of certain drugs, such as Renin-Angiotensin System (RAS) inhibitors and ibuprofen, and an increased risk for COVID-19 infection. We here discuss this concern in relation to headache treatment and conclude that, based on current evidence, there is no reason to abandon treatment of headache patients with RAS inhibitors or ibuprofen.


Subject(s)
Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Coronavirus Infections/pathology , Headache/drug therapy , Ibuprofen/adverse effects , Pneumonia, Viral/pathology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Betacoronavirus , Humans , Ibuprofen/therapeutic use , Pandemics , Peptidyl-Dipeptidase A/metabolism , Renin-Angiotensin System , Risk Factors , Up-Regulation/drug effects
8.
Am J Clin Pathol ; 154(6): 748-760, 2020 11 04.
Article in English | MEDLINE | ID: covidwho-1015199

ABSTRACT

OBJECTIVES: Although diffuse alveolar damage, a subtype of acute lung injury (ALI), is the most common microscopic pattern in coronavirus disease 2019 (COVID-19), other pathologic patterns have been described. The aim of the study was to review autopsies from COVID-19 decedents to evaluate the spectrum of pathology and correlate the results with clinical, laboratory, and radiologic findings. METHODS: A comprehensive and quantitative review from 40 postmortem examinations was performed. The microscopic patterns were categorized as follows: "major" when present in more than 50% of cases and "novel" if rarely or not previously described and unexpected clinically. RESULTS: Three major pulmonary patterns were identified: ALI in 29 (73%) of 40, intravascular fibrin or platelet-rich aggregates (IFPAs) in 36 (90%) of 40, and vascular congestion and hemangiomatosis-like change (VCHL) in 20 (50%) of 40. The absence of ALI (non-ALI) was novel and seen in 11 (27%) of 40. Compared with ALI decedents, those with non-ALI had a shorter hospitalization course (P = .02), chest radiographs with no or minimal consolidation (P = .01), and no pathologically confirmed cause of death (9/11). All non-ALI had VCHL and IFPAs, and clinically most had cardiac arrest. CONCLUSIONS: Two distinct pulmonary phenotypic patterns-ALI and non-ALI-were noted. Non-ALI represents a rarely described phenotype. The cause of death in non-ALI is most likely COVID-19 related but requires additional corroboration.


Subject(s)
Coronavirus Infections/pathology , Lung/pathology , Pneumonia, Viral/pathology , Adult , Aged , Aged, 80 and over , Autopsy , Betacoronavirus , Female , Humans , Male , Middle Aged , Pandemics
9.
Am J Clin Pathol ; 154(4): 466-474, 2020 09 08.
Article in English | MEDLINE | ID: covidwho-1015195

ABSTRACT

OBJECTIVES: A subset of coronavirus disease 2019 (COVID-19) patients exhibit clinical features of cytokine storm. However, clinicopathologic features diagnostic of hemophagocytic lymphohistiocytosis (HLH) have not been reported. We studied the reticuloendothelial organs of 4 consecutive patients who died of COVID-19 and correlated with clinical and laboratory parameters to detect HLH. METHODS: Autopsies were performed on 4 patients who died of COVID-19. Routine H&E staining and immunohistochemical staining for CD163 were performed to detect hemophagocytosis. Clinical and laboratory results from premortem blood samples were used to calculate H-scores. RESULTS: All 4 cases demonstrated diffuse alveolar damage within the lungs. Three of the 4 cases had histologic evidence of hemophagocytosis within pulmonary lymph nodes. One case showed hemophagocytosis in the spleen but none showed hemophagocytosis in liver or bone marrow. Lymphophagocytosis was the predominant form of hemophagocytosis observed. One patient showed diagnostic features of HLH with an H-score of 217, while a second patient likely had HLH with a partial H-score of 145 due to a missing triglyceride level. The remaining 2 patients had H-scores of 131 and 96. CONCLUSIONS: This is the first report of severe acute respiratory syndrome coronavirus 2-associated HLH. Identification of HLH in a subset of patients with severe COVID-19 will inform clinical trials of therapeutic strategies.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Coronavirus Infections/pathology , Lymphohistiocytosis, Hemophagocytic/pathology , Lymphohistiocytosis, Hemophagocytic/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/pathology , Aged , Aged, 80 and over , Autopsy , Bone Marrow/pathology , Coronavirus Infections/complications , Fatal Outcome , Female , Humans , Liver/pathology , Lung/pathology , Lymph Nodes/pathology , Lymphohistiocytosis, Hemophagocytic/diagnosis , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Spleen/pathology
10.
Virology ; 554: 97-105, 2021 02.
Article in English | MEDLINE | ID: covidwho-1003123

ABSTRACT

We examined the pathogenicity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in cynomolgus macaques for 28 days to establish an animal model of COVID-19 for the development of vaccines and antiviral drugs. Cynomolgus macaques infected with SARS-CoV-2 showed body temperature rises and X-ray radiographic pneumonia without life-threatening clinical signs of disease. A neutralizing antibody against SARS-CoV-2 and T-lymphocytes producing interferon (IFN)-γ specifically for SARS-CoV-2 N-protein were detected on day 14 in one of three macaques with viral pneumonia. In the other two macaques, in which a neutralizing antibody was not detected, T-lymphocytes producing IFN-γ specifically for SARS-CoV-2 N protein increased on day 7 to day 14, suggesting that not only a neutralizing antibody but also cellular immunity has a role in the elimination of SARS-CoV-2. Thus, because of similar symptoms to approximately 80% of patients, cynomolgus macaques are appropriate to extrapolate the efficacy of vaccines and antiviral drugs for humans.


Subject(s)
Antibodies, Neutralizing/immunology , Disease Models, Animal , T-Lymphocytes/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibodies, Viral/immunology , /virology , Cytokines/blood , Female , Interferon-gamma/immunology , Macaca fascicularis , Male , Mouth/virology , Nasal Cavity/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , /physiology , Viral Load
11.
PLoS One ; 15(10): e0240624, 2020.
Article in English | MEDLINE | ID: covidwho-992680

ABSTRACT

BACKGROUND: There is increasing demand for post-acute care services, which is amplified by the COVID-19 pandemic. AIMS: We studied the pattern of spatial association between post-acute care services and acute care facilities and evaluated how geographic variability could influence their use. METHODS: We compiled data on CMS-certified acute care and critical access hospitals and post-acute health care services (nursing homes, home health care services, inpatient rehabilitation facilities, long-term care hospitals, and hospice facilities). We used the colocation quotient (CLQ) to measure the magnitude and direction of association (clustering or segregation) between post-acute care providers and hospitals. This metric allows pairwise comparison of categorical data; a value <1 indicates spatial segregation and a value >1 spatial clustering. Unity marks the lack of spatial dependence (random distribution). RESULTS: With the exception of nursing homes (CLQ 1.26), all other types of post-acute care providers are spatially segregated from rural critical access hospitals. Long-term care facilities ranked first (had the lowest global CLQ, 0.06), hospice facilities ranked last (had the highest global CLQ estimate, 0.54). Instead, post-acute care services either clustered with (inpatient rehabilitation 2.76, long-term care 2.10, nursing homes 1.37) or were only weakly segregated (home health care 0.86) from acute care hospitals. Home health care (1.44), hospice services (1.46), and nursing homes (1.08) spatially clustered with the same category of services. Results were robust in the sensitivity analysis and we provided illustrative examples of local variation for the states of MA and IA. CONCLUSION: Post-acute care services are isolated from critical access hospitals, and have a clustering pattern with the same category services and acute care hospitals. Such misdistribution of resources may result in both underuse and a substitution effect on the type of post-acute care between rural and urban areas and undermine public health during increasing demand, such as the COVID-19 pandemic.


Subject(s)
Coronavirus Infections/pathology , Critical Care/statistics & numerical data , Pneumonia, Viral/pathology , Spatial Analysis , Subacute Care/statistics & numerical data , Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Hospitals/statistics & numerical data , Humans , Nursing Homes/statistics & numerical data , Pandemics , Pneumonia, Viral/virology , United States
13.
Am J Physiol Lung Cell Mol Physiol ; 319(4): L585-L595, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-991951

ABSTRACT

In 2019, the United States experienced the emergence of the vaping-associated lung injury (VALI) epidemic. Vaping is now known to result in the development and progression of severe lung disease in the young and healthy. Lack of regulation on electronic cigarettes in the United States has resulted in over 2,000 patients and 68 deaths. We examine the clinical representation of VALI and the delve into the scientific evidence of how deadly exposure to electronic cigarettes can be. E-cigarette vapor is shown to affect numerous cellular processes, cellular metabolism, and cause DNA damage (which has implications for cancer). E-cigarette use is associated with a higher risk of developing crippling lung conditions such as chronic obstructive pulmonary disease (COPD), which would develop several years from now, increasing the already existent smoking-related burden. The role of vaping and virus susceptibility is yet to be determined; however, vaping can increase the virulence and inflammatory potential of several lung pathogens and is also linked to an increased risk of pneumonia. As it has emerged for cigarette smoking, great caution should also be given to vaping in relation to SARS-CoV-2 infection and the COVID-19 pandemic. Sadly, e-cigarettes are continually promoted and perceived as a safer alternative to cigarette smoking. E-cigarettes and their modifiable nature are harmful, as the lungs are not designed for the chronic inhalation of e-cigarette vapor. It is of interest that e-cigarettes have been shown to be of no help with smoking cessation. A true danger lies in vaping, which, if ignored, will lead to disastrous future costs.


Subject(s)
E-Cigarette Vapor/toxicity , Lung Diseases, Interstitial/epidemiology , Lung Injury/epidemiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Vaping/adverse effects , Adolescent , Betacoronavirus , Coronavirus Infections/pathology , Disease Susceptibility/chemically induced , Electronic Nicotine Delivery Systems/statistics & numerical data , Female , Humans , Lung Diseases, Interstitial/chemically induced , Lung Injury/chemically induced , Lung Injury/mortality , Male , Middle Aged , Pandemics , Pneumonia/epidemiology , Pneumonia, Viral/pathology , Pulmonary Disease, Chronic Obstructive/chemically induced , Pulmonary Disease, Chronic Obstructive/mortality , Smoking Cessation/methods , United States/epidemiology , Vaping/epidemiology , Vaping/mortality
14.
Biosci Rep ; 41(1)2021 01 29.
Article in English | MEDLINE | ID: covidwho-989978

ABSTRACT

Millions of people infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been diagnosed with coronavirus infectious disease 2019 (COVID-19). The prevalence and severity of COVID-19 differ between sexes. To explain these differences, we analyzed clinical features and laboratory values in male and female COVID-19 patients. The present study included a cohort of 111 people, i.e. 36 COVID-19 patients, 54 sex- and age-matched common viral community-acquired pneumonia (CAP) patients, and 21 healthy controls. Monocyte counts, lymphocyte subset counts, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels in the peripheral blood were analyzed. Higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, monocyte counts, and CRP and ALT levels were found in male COVID-19 patients. Decreased lymphocyte subset counts and proportions were observed in COVID-19 patients, except for the CD3+ and CD8+ T cell proportions. The lower CD4+ T cell proportions and higher CD8+ T cell proportions were observed in male and severe COVID-19 patients and the differences were independent of estrogen level. The CD4+ T cell proportion was negatively associated with the CD8+ T cell proportion in male COVID-19 patients; this correlation was non-significant in females. Our work demonstrates differences between sexes in circulating monocyte counts and CD4+ T cell and CD8+ T cell proportions in COVID-19 patients, independent of estrogen levels, are associated with the clinical manifestations in COVID-19 patients with high specificity.


Subject(s)
/immunology , Immunity, Innate , Lymphocytes/virology , Monocytes/virology , Pneumonia, Viral/immunology , /pathogenicity , Adult , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , C-Reactive Protein/metabolism , CD4-CD8 Ratio , /virology , Case-Control Studies , Community-Acquired Infections , Estradiol/blood , Female , Humans , Leukocyte Count , Lymphocytes/immunology , Male , Middle Aged , Monocytes/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Severity of Illness Index , Sex Factors
15.
Molecules ; 25(21)2020 Oct 22.
Article in English | MEDLINE | ID: covidwho-983187

ABSTRACT

Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , HIV Infections/drug therapy , Hepatitis C, Chronic/drug therapy , Herpes Simplex/drug therapy , Influenza, Human/drug therapy , Phytochemicals/therapeutic use , Pneumonia, Viral/drug therapy , Antiviral Agents/chemistry , Antiviral Agents/classification , Antiviral Agents/isolation & purification , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Drug Discovery , HIV/drug effects , HIV/pathogenicity , HIV/physiology , HIV Infections/pathology , HIV Infections/virology , Hepacivirus/drug effects , Hepacivirus/pathogenicity , Hepacivirus/physiology , Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/virology , Herpes Simplex/pathology , Herpes Simplex/virology , Humans , Influenza, Human/pathology , Influenza, Human/virology , Orthomyxoviridae/drug effects , Orthomyxoviridae/pathogenicity , Orthomyxoviridae/physiology , Pandemics , Phytochemicals/chemistry , Phytochemicals/classification , Phytochemicals/isolation & purification , Plants, Medicinal , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Simplexvirus/drug effects , Simplexvirus/pathogenicity , Simplexvirus/physiology , Virus Internalization/drug effects , Virus Replication/drug effects
16.
J Virol ; 94(22)2020 10 27.
Article in English | MEDLINE | ID: covidwho-982503

ABSTRACT

Animal models recapitulating human COVID-19 disease, especially severe disease, are urgently needed to understand pathogenesis and to evaluate candidate vaccines and therapeutics. Here, we develop novel severe-disease animal models for COVID-19 involving disruption of adaptive immunity in Syrian hamsters. Cyclophosphamide (CyP) immunosuppressed or RAG2 knockout (KO) hamsters were exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the respiratory route. Both the CyP-treated and RAG2 KO hamsters developed clinical signs of disease that were more severe than those in immunocompetent hamsters, notably weight loss, viral loads, and fatality (RAG2 KO only). Disease was prolonged in transiently immunosuppressed hamsters and was uniformly lethal in RAG2 KO hamsters. We evaluated the protective efficacy of a neutralizing monoclonal antibody and found that pretreatment, even in immunosuppressed animals, limited infection. Our results suggest that functional B and/or T cells are not only important for the clearance of SARS-CoV-2 but also play an early role in protection from acute disease.IMPORTANCE Syrian hamsters are in use as a model of disease caused by SARS-CoV-2. Pathology is pronounced in the upper and lower respiratory tract, and disease signs and endpoints include weight loss and viral RNA and/or infectious virus in swabs and organs (e.g., lungs). However, a high dose of virus is needed to produce disease, and the disease resolves rapidly. Here, we demonstrate that immunosuppressed hamsters are susceptible to low doses of virus and develop more severe and prolonged disease. We demonstrate the efficacy of a novel neutralizing monoclonal antibody using the cyclophosphamide transient suppression model. Furthermore, we demonstrate that RAG2 knockout hamsters develop severe/fatal disease when exposed to SARS-CoV-2. These immunosuppressed hamster models provide researchers with new tools for evaluating therapies and vaccines and understanding COVID-19 pathogenesis.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/pathology , Disease Models, Animal , Mesocricetus , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Adaptive Immunity , Animals , Animals, Genetically Modified , Betacoronavirus/physiology , Cyclophosphamide , DNA-Binding Proteins/genetics , Gene Knockout Techniques , Immunosuppressive Agents , Pandemics , Severity of Illness Index
17.
Lancet ; 396(10247): 320-332, 2020 08 01.
Article in English | MEDLINE | ID: covidwho-981695

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. We aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism. METHODS: In this case series, patients with a positive antemortem or post-mortem SARS-CoV-2 result were considered eligible for enrolment. Post-mortem examinations were done on 14 people who died with COVID-19 at the King County Medical Examiner's Office (Seattle, WA, USA) and Snohomish County Medical Examiner's Office (Everett, WA, USA) in negative-pressure isolation suites during February and March, 2020. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry, electron microscopy, and quantitative RT-PCR. FINDINGS: The median age of our cohort was 73·5 years (range 42-84; IQR 67·5-77·25). All patients had clinically significant comorbidities, the most common being hypertension, chronic kidney disease, obstructive sleep apnoea, and metabolic disease including diabetes and obesity. The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi. Coronavirus-like particles were detected in the respiratory system, kidney, and gastrointestinal tract. Lymphocytic myocarditis was observed in one patient with viral RNA detected in the tissue. INTERPRETATION: The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium. Microthrombi, where observed, were scarce and endotheliitis was not identified. Although other non-pulmonary organs showed susceptibility to infection, their contribution to the pathogenesis of SARS-CoV-2 infection requires further examination. FUNDING: None.


Subject(s)
Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Adult , Aged , Aged, 80 and over , Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/ultrastructure , Alveolar Epithelial Cells/virology , Autopsy , Betacoronavirus , Coronavirus Infections/epidemiology , Female , Gastrointestinal Tract/pathology , Gastrointestinal Tract/ultrastructure , Gastrointestinal Tract/virology , Heart/virology , Humans , Kidney/pathology , Kidney/ultrastructure , Kidney/virology , Liver/pathology , Liver/ultrastructure , Liver/virology , Male , Middle Aged , Myocardium/pathology , Myocardium/ultrastructure , Pandemics , Pneumonia, Viral/epidemiology , Pulmonary Alveoli/pathology , Pulmonary Alveoli/ultrastructure , Respiratory Mucosa/pathology , Respiratory Mucosa/ultrastructure , Respiratory Mucosa/virology , Spleen/pathology , Spleen/ultrastructure , Spleen/virology , Thrombosis/pathology , Trachea/pathology , Trachea/ultrastructure , Trachea/virology , Washington/epidemiology
18.
BMC Infect Dis ; 20(1): 961, 2020 Dec 17.
Article in English | MEDLINE | ID: covidwho-979851

ABSTRACT

BACKGROUND: The clinical characteristics of patients with confirmed 2019 novel coronavirus disease (COVID-19) in Jilin Province, China were investigated. METHODS: Clinical, laboratory, radiology, and treatment data of 41 hospitalized patients with confirmed COVID-19 were retrospectively collected. The population was stratified by disease severity as mild, moderate, or severe, based on guidelines of the National Health and Medical Commission of China. RESULTS: The 41 hospitalized patients with COVID-19 were studied, and the median age was 45 years (interquartile range [IQR], 31-53; range, 10-87 years) and 18 patients (43.9%) were female. All of the patients had recently visited Wuhan or other places (ie, Beijing, Thailand) or had Wuhan-related exposure. Common symptoms included fever (32[78%]) and cough (29[70.7%]). All patients were without hepatitis B/C virus hepatitis. CRP (C-reactive protein, 11.3 mg/L [interquartile range {IQR}, 2.45-35.2]) was elevated in 22 patients (53.7%), and cardiac troponin I (1.5 ng/mL [IQR, 0.8-5.0]) was elevated in 41 patients (100%). Chest computed tomographic scans showed bilateral ground glass opacity (GGO) or GGO with consolidation in the lungs of 27(65.9%) patients. 31(75.6%) patients had an abnormal electrocardiograph (ECG). Comparing the three groups, the levels of CRP and cardiac troponin I, GGO distribution in bilateral lungs, and electrocardiogram changes were statistically significant (p < 0.05). Cardiac troponin I had a strong positive correlation with CRP (r = 0.704, p = 0.042) and LDH (r = 0.738, p = 0.037). CONCLUSION: Significant differences among the groups suggest that several clinical parameters may serve as biomarkers of COVID-19 severity at hospital admission. Elevated cTnI could be considered as a predictor of severe COVID-19, reflecting the prognosis of patients with severe COVID-19. The results warrant further inspection and confirmation.


Subject(s)
/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , /pathology , Child , China/epidemiology , Female , Heart/physiopathology , Hospitalization , Humans , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , Prognosis , Retrospective Studies , Young Adult
19.
IEEE Trans Ultrason Ferroelectr Freq Control ; 67(11): 2230-2240, 2020 11.
Article in English | MEDLINE | ID: covidwho-978669

ABSTRACT

Since the emergence of the COVID-19 pandemic in December of 2019, clinicians and scientists all over the world have faced overwhelming new challenges that not only threaten their own communities and countries but also the world at large. These challenges have been enormous and debilitating, as the infrastructure of many countries, including developing ones, had little or no resources to deal with the crisis. Even in developed countries, such as Italy, health systems have been so inundated by cases that health care facilities became oversaturated and could not accommodate the unexpected influx of patients to be tested. Initially, resources were focused on testing to identify those who were infected. When it became clear that the virus mainly attacks the lungs by causing parenchymal changes in the form of multifocal pneumonia of different levels of severity, imaging became paramount in the assessment of disease severity, progression, and even response to treatment. As a result, there was a need to establish protocols for imaging of the lungs in these patients. In North America, the focus was on chest X-ray and computed tomography (CT) as these are widely available and accessible at most health facilities. However, in Europe and China, this was not the case, and a cost-effective and relatively fast imaging modality was needed to scan a large number of sick patients promptly. Hence, ultrasound (US) found its way into the hands of Chinese and European physicians and has since become an important imaging modality in those locations. US is a highly versatile, portable, and inexpensive imaging modality that has application across a broad spectrum of conditions and, in this way, is ideally suited to assess the lungs of COVID-19 patients in the intensive care unit (ICU). This bedside test can be done with little to no movement of the patients from the unit that keeps them in their isolated rooms, thereby limiting further exposure to other health personnel. This article presents a basic introduction to COVID-19 and the use of the US for lung imaging. It further provides a high-level overview of the existing US technologies that are driving development in current and potential future US imaging systems for lung, with a specific emphasis on portable and 3-D systems.


Subject(s)
Coronavirus Infections/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Ultrasonography/methods , Betacoronavirus , Comorbidity , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Humans , Imaging, Three-Dimensional , Lung/diagnostic imaging , Lung/pathology , Lung/physiopathology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology
20.
Emerg Microbes Infect ; 9(1): 2465-2473, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-975181

ABSTRACT

We previously described a mathematical model to simulate the course of the COVID-19 pandemic and try to predict how this outbreak might evolve in the following two months when the pandemic cases will drop significantly. Our original paper prepared in March 2020 analyzed the outbreaks of COVID-19 in the US and its selected states to identify the rise, peak, and decrease of cases within a given geographic population, as well as a rough calculation of accumulated total cases in this population from the beginning to the end of June 2020. The current report will describe how well the later actual trend from March to June fit our model and prediction. Similar analyses are also conducted to include countries other than the US. From such a wide global data analysis, our results demonstrated that different US states and countries showed dramatically different patterns of pandemic trend. The values and limitations of our modelling are discussed.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Models, Theoretical , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Betacoronavirus , Geography , Humans , Pandemics , Seasons
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