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1.
Bone Marrow Transplant ; 56(9): 2212-2220, 2021 09.
Article in English | MEDLINE | ID: covidwho-1387241

ABSTRACT

The SARS-COV-2 pandemic has led to strict and generalized transmission prevention measures that may have changed the epidemiological landscape of common seasonal respiratory virus (CSRV). Through a prospective CSRV survey program conducted from 2016 onwards in allogeneic stem cell transplant (allo-HSCT) recipients with respiratory symptoms, we aimed to analyze and compare the epidemiology and characteristics of CSRV over three consecutive periods [from February 1 to September 30 of 2018 (P1), 2019 (P2), and 2020 (P3)]. CSRV screening was performed through multiplex PCR assays during the study period. We identified 188 consecutive allo-HSCT recipients with 406 episodes screened for CSRV during the study period, of which 147 developed 300 CSRV. In P1 and P2 we diagnosed 115 (38.3%) and 145 (48.3%) CSRV episodes, respectively, whereas in P3 only 40 (13.3%) episodes were detected (p < 0.001). During P3, we observed a reduction of 80.2% in Ev/Rh, 93.3% in RSV, 80% in hIV, 96.3% HPIV, 68.4% in hMPV, 77.7% in ADV, 100% in HBoV, and 53.6% in HCoV as compared to P1 and P2. Consequently, we also observed a decline in absolute numbers of lower respiratory tract disease (68.1%), co-infections (91.7%), and hospitalizations (72.6%) during P3. We diagnosed SARS-COV-2 in nine allo-HSCT recipients, representing 23% of all CSRV detections in that period. In conclusion, we provide evidence of a significant drop in CSRV circulation during the SARS-COV-2 pandemic in our allo-HSCT recipients, indicating that prevention measures in the general population are highly effective in reducing CSRV prevalence and its complications in immunocompromised patients.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Respiratory Tract Infections , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Pandemics , Prospective Studies , Respiratory Tract Infections/epidemiology , SARS-CoV-2 , Seasons , Transplant Recipients
2.
J Infect Dis ; 224(1): 31-38, 2021 07 02.
Article in English | MEDLINE | ID: covidwho-1294729

ABSTRACT

Virus-virus interactions influence the epidemiology of respiratory infections. However, the impact of viruses causing upper respiratory infections on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication and transmission is currently unknown. Human rhinoviruses cause the common cold and are the most prevalent respiratory viruses of humans. Interactions between rhinoviruses and cocirculating respiratory viruses have been shown to shape virus epidemiology at the individual host and population level. Here, we examined the replication kinetics of SARS-CoV-2 in the human respiratory epithelium in the presence or absence of rhinovirus. We show that human rhinovirus triggers an interferon response that blocks SARS-CoV-2 replication. Mathematical simulations show that this virus-virus interaction is likely to have a population-wide effect as an increasing prevalence of rhinovirus will reduce the number of new coronavirus disease 2019 cases.


Subject(s)
Antibiosis , COVID-19/virology , Coinfection , Picornaviridae Infections/virology , Rhinovirus/physiology , SARS-CoV-2/physiology , Virus Replication , COVID-19/epidemiology , Cell Line , Cells, Cultured , Fluorescent Antibody Technique , Humans , Respiratory Mucosa/virology
3.
J Paediatr Child Health ; 57(12): 1886-1892, 2021 12.
Article in English | MEDLINE | ID: covidwho-1255446

ABSTRACT

AIM: To describe the epidemiology of respiratory viruses in children before and during the 2020 SARS-CoV-2 pandemic and the relationship to public health measures instituted by the Victorian government. METHODS: Retrospective audit of respiratory viruses at a tertiary paediatric hospital in Melbourne from January 2015 up to week 47, 2020 in children under 18 years of age. The proportion of positive cases in weeks 1-47 in 2015-2019 (period 1) were compared to weeks 1-47, 2020 (period 2), and reviewed in the context of public health restrictions in Victoria. RESULTS: An annual average of 4636 tests were performed in period 1 compared to 3659 tests in period 2. Proportions of positive influenza A virus, influenza B virus, respiratory syncytial virus (RSV) and human parainfluenza virus were significantly reduced in period 2 compared to period 1: 77.3, 89.4, 68.6 and 66.9% reductions, respectively (all P < 0.001). From week 12-47, 2020, 28 893 SARS-CoV-2 tests were performed with a 0.64% positivity rate. Influenza viruses were not detected after week 17, RSV was not detected after week 35. CONCLUSIONS: Strict public health measures and border closures were successful in eliminating community transmission of SARS-CoV-2 in Melbourne. This was associated with a significant reduction in other respiratory virus infections in children. Identifying sustainable and effective ongoing public health interventions to reduce transmission of RSV and influenza could result in reduced morbidity and mortality in children and requires further research.


Subject(s)
COVID-19 , Influenza A virus , Influenza, Human , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Adolescent , Child , Humans , Infant , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Public Health , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/prevention & control , Retrospective Studies , SARS-CoV-2
4.
Pediatr Infect Dis J ; 40(5): 385-388, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1236269

ABSTRACT

BACKGROUND: Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is the reference laboratory method to diagnose SARS-CoV-2 infection then requires equipment and is time-consuming. There is a crucial demand for rapid techniques such as antigen detection test. Considering the different diagnostic accuracy of tests with other respiratory viruses in adults and children, SARS-CoV-2 antigen test must be evaluated specifically in children. METHODS: The purpose of this study was to evaluate the performance of Panbio COVID-19 Ag Rapid Test Device (Abbott) as a point-of-care test for diagnosis of SARS-CoV-2 in comparison to RT-qPCR in a pediatric population. RESULTS: Four hundred forty nasopharyngeal swabs were tested. Amongst the 18 positive RT-qPCR samples, 14 were detected by the rapid antigen test, given an overall sensitivity of 77.7%. All the samples detected positive with the antigen rapid test were also positive with RT-qPCR. CONCLUSION: The sensitivity of Panbio COVID-19 Ag Rapid Test Device is lower in children than in adults. Nevertheless, considering the good values of specificity, negative and positive predictive values this test could be used as a frontline test to obtain quick results, although the negative values with COVID-19 high clinical suspicion should be confirmed using RT-qPCR.


Subject(s)
Antigens, Viral/isolation & purification , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Point-of-Care Testing , Real-Time Polymerase Chain Reaction/methods , Sensitivity and Specificity
5.
Zhonghua Yan Ke Za Zhi ; 57(4): 305-310, 2021 Apr 11.
Article in Chinese | MEDLINE | ID: covidwho-1173000

ABSTRACT

Coronaviruses are a common class of respiratory viruses that can cause human infections. 2019 novel coronavirus(2019-nCoV), a new coronavirus that has recently caused a pandemic, has affected millions of people and put tremendous pressure on the health systems of almost every country in the world. Coronaviruses are known to spread from person to person through droplets or contact. The 2019-nCoV has also been found in the conjunctival secretions and tears of some clinically diagnosed patients. To assess whether the eye is one of the transmission routes of the virus, we review literature, and summarize the anatomy of the eye-nose pathway, the expression of the virus receptor in the eye, the preclinical animal studies, and the clinical data. We analyze the possibility of eyes as a means of transmission and propose some suggestions of ocular protection. (Chin J Ophthalmol, 2021, 57: 305-310).


Subject(s)
COVID-19 , Coronavirus Infections , Coronavirus , Animals , Humans , Pandemics , SARS-CoV-2
6.
PLoS Biol ; 19(3): e3001158, 2021 03.
Article in English | MEDLINE | ID: covidwho-1156073

ABSTRACT

Since its emergence in December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread globally and become a major public health burden. Despite its close phylogenetic relationship to SARS-CoV, SARS-CoV-2 exhibits increased human-to-human transmission dynamics, likely due to efficient early replication in the upper respiratory epithelium of infected individuals. Since different temperatures encountered in the human upper and lower respiratory tract (33°C and 37°C, respectively) have been shown to affect the replication kinetics of several respiratory viruses, as well as host innate immune response dynamics, we investigated the impact of temperature on SARS-CoV-2 and SARS-CoV infection using the primary human airway epithelial cell culture model. SARS-CoV-2, in contrast to SARS-CoV, replicated to higher titers when infections were performed at 33°C rather than 37°C. Although both viruses were highly sensitive to type I and type III interferon pretreatment, a detailed time-resolved transcriptome analysis revealed temperature-dependent interferon and pro-inflammatory responses induced by SARS-CoV-2 that were inversely proportional to its replication efficiency at 33°C or 37°C. These data provide crucial insight on pivotal virus-host interaction dynamics and are in line with characteristic clinical features of SARS-CoV-2 and SARS-CoV, as well as their respective transmission efficiencies.


Subject(s)
Gene Expression Profiling/methods , Gene Expression Regulation, Viral/genetics , SARS Virus/genetics , SARS-CoV-2/genetics , Animals , Antiviral Agents/pharmacology , Cells, Cultured , Chlorocebus aethiops , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/virology , Gene Expression Regulation, Viral/drug effects , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/genetics , Humans , Interferons/pharmacology , SARS Virus/drug effects , SARS Virus/physiology , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Species Specificity , Temperature , Vero Cells , Virus Replication/drug effects , Virus Replication/genetics
7.
J Infect Dis ; 224(1): 31-38, 2021 07 02.
Article in English | MEDLINE | ID: covidwho-1146657

ABSTRACT

Virus-virus interactions influence the epidemiology of respiratory infections. However, the impact of viruses causing upper respiratory infections on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication and transmission is currently unknown. Human rhinoviruses cause the common cold and are the most prevalent respiratory viruses of humans. Interactions between rhinoviruses and cocirculating respiratory viruses have been shown to shape virus epidemiology at the individual host and population level. Here, we examined the replication kinetics of SARS-CoV-2 in the human respiratory epithelium in the presence or absence of rhinovirus. We show that human rhinovirus triggers an interferon response that blocks SARS-CoV-2 replication. Mathematical simulations show that this virus-virus interaction is likely to have a population-wide effect as an increasing prevalence of rhinovirus will reduce the number of new coronavirus disease 2019 cases.


Subject(s)
Antibiosis , COVID-19/virology , Coinfection , Picornaviridae Infections/virology , Rhinovirus/physiology , SARS-CoV-2/physiology , Virus Replication , COVID-19/epidemiology , Cell Line , Cells, Cultured , Fluorescent Antibody Technique , Humans , Respiratory Mucosa/virology
8.
Carbohydr Polym ; 260: 117797, 2021 May 15.
Article in English | MEDLINE | ID: covidwho-1084646

ABSTRACT

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has resulted in a pandemic and continues to spread at an unprecedented rate around the world. Although a vaccine has recently been approved, there are currently few effective therapeutics to fight its associated disease in humans, COVID-19. SARS-CoV-2 and the related severe acute respiratory syndrome (SARS-CoV-1), and Middle East respiratory syndrome (MERS-CoV) result from zoonotic respiratory viruses that have bats as the primary host and an as yet unknown secondary host. While each of these viruses has different protein-based cell-surface receptors, each rely on the glycosaminoglycan, heparan sulfate as a co-receptor. In this study we compare, for the first time, differences and similarities in the structure of heparan sulfate in human and bat lungs. Furthermore, we show that the spike glycoprotein of COVID-19 binds 3.5 times stronger to human lung heparan sulfate than bat lung heparan sulfate.


Subject(s)
Heparitin Sulfate/metabolism , Lung/chemistry , Receptors, Virus/metabolism , SARS-CoV-2/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Animals , Chiroptera , Female , Heparitin Sulfate/chemistry , Heparitin Sulfate/isolation & purification , Humans , Male , Molecular Structure , Molecular Weight , Protein Binding , Receptors, Virus/chemistry , Receptors, Virus/isolation & purification
9.
Nat Commun ; 12(1): 6, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1007633

ABSTRACT

The current practice for diagnosis of COVID-19, based on SARS-CoV-2 PCR testing of pharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk, likely underestimates the true prevalence of infection. Serologic methods can more accurately estimate the disease burden by detecting infections missed by the limited testing performed to date. Here, we describe the validation of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A comparison of antibody profiles detected on the array from control sera collected prior to the SARS-CoV-2 pandemic versus convalescent blood specimens from virologically confirmed COVID-19 cases demonstrates near complete discrimination of these two groups, with improved performance from use of antigen combinations that include both spike protein and nucleoprotein. This array can be used as a diagnostic tool, as an epidemiologic tool to more accurately estimate the disease burden of COVID-19, and as a research tool to correlate antibody responses with clinical outcomes.


Subject(s)
Antibodies, Viral/blood , Antigens, Viral/blood , COVID-19/immunology , SARS-CoV-2/immunology , Antibodies, Viral/immunology , Antigens, Viral/immunology , COVID-19/blood , COVID-19/diagnosis , COVID-19 Testing , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Microarray Analysis/methods , Middle East Respiratory Syndrome Coronavirus/immunology , Neutralization Tests , SARS Virus/immunology , Spike Glycoprotein, Coronavirus/immunology
11.
Arch Dis Child ; 2020 Dec 01.
Article in English | MEDLINE | ID: covidwho-952912

ABSTRACT

In contrast to other respiratory viruses, children have less severe symptoms when infected with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we discuss proposed hypotheses for the age-related difference in severity of coronavirus disease 2019 (COVID-19).Factors proposed to explain the difference in severity of COVID-19 in children and adults include those that put adults at higher risk and those that protect children. The former include: (1) age-related increase in endothelial damage and changes in clotting function; (2) higher density, increased affinity and different distribution of angiotensin converting enzyme 2 receptors and transmembrane serine protease 2; (3) pre-existing coronavirus antibodies (including antibody-dependent enhancement) and T cells; (4) immunosenescence and inflammaging, including the effects of chronic cytomegalovirus infection; (5) a higher prevalence of comorbidities associated with severe COVID-19 and (6) lower levels of vitamin D. Factors that might protect children include: (1) differences in innate and adaptive immunity; (2) more frequent recurrent and concurrent infections; (3) pre-existing immunity to coronaviruses; (4) differences in microbiota; (5) higher levels of melatonin; (6) protective off-target effects of live vaccines and (7) lower intensity of exposure to SARS-CoV-2.

12.
J Infect ; 81(6): 966-972, 2020 12.
Article in English | MEDLINE | ID: covidwho-922066

ABSTRACT

OBJECTIVES: The effect of SARS-CoV-2 on existing respiratory viruses in circulation and the overall burden of viral respiratory disease remains uncertain. Traditionally, severe viral respiratory disease disproportionally affects those with underlying chronic lung diseases. This study aimed to assess the impact of SARS-CoV-2 on the prevalence and clinical characteristics of respiratory virus disease in hospitalised adults. METHODS: Data for this cohort study were from hospitalised adults who had multiplex PCR testing for respiratory viruses over several seasons in Hampshire, UK. Respiratory virus detection during the first epidemic peak of SARS-CoV-2 was compared to detection during the same time period across previous years. RESULTS: 856 patients had multiplex PCR for respiratory viruses between March and May over 5 years. Before 2020, a non-SARS-CoV-2 virus was detected in 54% patients (202/371) compared to 4.1% (20/485) in 2020 (p < 0.0001). SARS-CoV-2 was associated with asthma or COPD exacerbations in a smaller proportion of infected patients compared to other viruses (1.0% vs 37%, p < 0.0001). CONCLUSIONS: The emergence of SARS-CoV-2 was associated with substantial reductions in the circulation of seasonal respiratory viruses and large differences in the characteristics of viral-associated disease, including illness in a greater proportion of patients without underlying lung disease.


Subject(s)
COVID-19/epidemiology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , SARS-CoV-2/isolation & purification , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , Cohort Studies , Female , Hospitalization , Humans , Influenza A virus/isolation & purification , Influenza B virus/isolation & purification , Male , Middle Aged , Multiplex Polymerase Chain Reaction , Prospective Studies , Respiratory Syncytial Virus, Human/isolation & purification , Respiratory Tract Infections/diagnosis , Seasons , United Kingdom/epidemiology , Virus Diseases/epidemiology
13.
BMC Infect Dis ; 20(1): 688, 2020 Sep 21.
Article in English | MEDLINE | ID: covidwho-781448

ABSTRACT

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the peak season of common respiratory viral infections. However, the clinical symptoms of most SARS-CoV-2 infected patients are not significantly different from those of common respiratory viral infections. Therefore, knowing the epidemiological patterns of common respiratory viruses may be valuable to improve the diagnostic and therapeutic efficacy of patients with suspected COVID-19, especially in Southwest China (a mild epidemic area). METHODS: A total of 2188 patients with clinically suspected of COVID-19 in Southwest China were recruited from January 21 to February 29, 2020. Nasopharyngeal swabs, throat swabs and sputum specimens were collected to detect SARS-CoV-2 by using real-time reverse transcription-polymerase chain reaction (RT-PCR) and other 12 viruses via PCR fragment analysis combined with capillary electrophoresis. Clinical characteristics and laboratory test findings were acquired from electronic medical records. All data were analyzed to unravel the epidemiological patterns. RESULTS: Only 1.1% (24/2188) patients with suspected COVID-19 were eventually confirmed to have SARS-CoV-2 infection, and the most frequently observed symptoms were fever (75.0%, 18/24) and cough (20.8%, 5/24). The overall detection rate of other respiratory pathogens was 10.3% (226/2188). Among them, human rhinovirus (3.2%, 71/2188), human parainfluenza viruses (1.6%, 35/2188), influenza B virus (1.2%, 26/2188) and mycoplasma pneumonia (1.2%, 26/2188) were the predominantly detected pathogens in this study. Moreover, the co-infection was observed in 22 specimens. Notably, one COVID-19 case had a coexisting infection with human parainfluenza virus (4.2%, 1/24) and bocavirus was the most common virus tending to occur in co-infection with other respiratory pathogens. CONCLUSIONS: This study reveals the epidemiological features of common respiratory viruses and their clinical impact during the ongoing outbreak of COVID-19 in a mild epidemic area. The findings highlight the importance of understanding the transmission patterns of the common respiratory virus in COVID-19 regions, which can provide information support for the development of appropriate treatment plans and health policies, while eliminating unnecessary fear and tension.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Respiratory System/virology , Respiratory Tract Infections/virology , Adult , COVID-19 , China/epidemiology , Coinfection/epidemiology , Cough/virology , Female , Humans , Male , Middle Aged , Pandemics , Real-Time Polymerase Chain Reaction , Retrospective Studies , SARS-CoV-2 , Young Adult
14.
Blood ; 136(18): 2080-2089, 2020 10 29.
Article in English | MEDLINE | ID: covidwho-740364

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious respiratory virus that can lead to venous/arterial thrombosis, stroke, renal failure, myocardial infarction, thrombocytopenia, and other end-organ damage. Animal models demonstrating end-organ protection in C3-deficient mice and evidence of complement activation in humans have led to the hypothesis that SARS-CoV-2 triggers complement-mediated endothelial damage, but the mechanism is unclear. Here, we demonstrate that the SARS-CoV-2 spike protein (subunit 1 and 2), but not the N protein, directly activates the alternative pathway of complement (APC). Complement-dependent killing using the modified Ham test is blocked by either C5 or factor D inhibition. C3 fragments and C5b-9 are deposited on TF1PIGAnull target cells, and complement factor Bb is increased in the supernatant from spike protein-treated cells. C5 inhibition prevents the accumulation of C5b-9 on cells, but not C3c; however, factor D inhibition prevents both C3c and C5b-9 accumulation. Addition of factor H mitigates the complement attack. In conclusion, SARS-CoV-2 spike proteins convert nonactivator surfaces to activator surfaces by preventing the inactivation of the cell-surface APC convertase. APC activation may explain many of the clinical manifestations (microangiopathy, thrombocytopenia, renal injury, and thrombophilia) of COVID-19 that are also observed in other complement-driven diseases such as atypical hemolytic uremic syndrome and catastrophic antiphospholipid antibody syndrome. C5 inhibition prevents accumulation of C5b-9 in vitro but does not prevent upstream complement activation in response to SARS-CoV-2 spike proteins.


Subject(s)
Betacoronavirus , Complement Factor D/antagonists & inhibitors , Complement Inactivating Agents/pharmacology , Complement Pathway, Alternative/drug effects , Spike Glycoprotein, Coronavirus/pharmacology , Cell Line , Complement Activation/drug effects , Complement C3/metabolism , Complement C5/antagonists & inhibitors , Complement Factor H/metabolism , Complement Membrane Attack Complex/metabolism , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/physiology
15.
mSphere ; 5(4)2020 08 26.
Article in English | MEDLINE | ID: covidwho-730989

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak urgently necessitates sensitive and convenient COVID-19 diagnostics for the containment and timely treatment of patients. We aimed to develop and validate a novel reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay to detect SARS-CoV-2. Patients with suspected COVID-19 and close contacts were recruited from two hospitals between 26 January and 8 April 2020. Respiratory samples were collected and tested using RT-LAMP, and the results were compared with those obtained by reverse transcription-quantitative PCR (RT-qPCR). Samples yielding inconsistent results between these two methods were subjected to next-generation sequencing for confirmation. RT-LAMP was also applied to an asymptomatic COVID-19 carrier and patients with other respiratory viral infections. Samples were collected from a cohort of 129 cases (329 nasopharyngeal swabs) and an independent cohort of 76 patients (152 nasopharyngeal swabs and sputum samples). The RT-LAMP assay was validated to be accurate (overall sensitivity and specificity of 88.89% and 99.00%, respectively) and diagnostically useful (positive and negative likelihood ratios of 88.89 and 0.11, respectively). RT-LAMP showed increased sensitivity (88.89% versus 81.48%) and high consistency (kappa, 0.92) compared to those of RT-qPCR for SARS-CoV-2 screening while requiring only constant-temperature heating and visual inspection. The time required for RT-LAMP was less than 1 h from sample preparation to the result. In addition, RT-LAMP was feasible for use with asymptomatic patients and did not cross-react with other respiratory pathogens. The developed RT-LAMP assay offers rapid, sensitive, and straightforward detection of SARS-CoV-2 infection and may aid the expansion of COVID-19 testing in the public domain and hospitals.IMPORTANCE We developed a visual and rapid reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay targeting the S gene for SARS-CoV-2 infection. The strength of our study was that we validated the RT-LAMP assay using 481 clinical respiratory samples from two prospective cohorts of suspected COVID-19 patients and on the serial samples from an asymptomatic carrier. The developed RT-LAMP approach showed an increased sensitivity (88.89%) and high consistency (kappa, 0.92) compared with those of reverse transcription-quantitative PCR (RT-qPCR) for SARS-CoV-2 screening while requiring only constant-temperature heating and visual inspection, facilitating SARS-CoV-2 screening in well-equipped labs as well as in the field. The time required for RT-LAMP was less than 1 h from sample preparation to the result (more than 2 h for RT-qPCR). This study showed that the RT-LAMP assay was a simple, rapid, and sensitive approach for SARS-CoV-2 infection and can facilitate COVID-19 diagnosis, especially in resource-poor settings.


Subject(s)
Betacoronavirus/genetics , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , Pneumonia, Viral/diagnosis , Adult , Asymptomatic Diseases , COVID-19 , COVID-19 Testing , Female , Humans , Male , Middle Aged , Pandemics , Prospective Studies , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2 , Sensitivity and Specificity
16.
Int J Obes (Lond) ; 44(9): 1810-1817, 2020 09.
Article in English | MEDLINE | ID: covidwho-639794

ABSTRACT

Overweight and obesity are major risk factors for diabetes, cardiovascular disease, and lung disease. These diseases are the most commonly reported health conditions that predispose individuals with SARS-CoV-2 infection to require hospitalization including intensive care unit admissions. The innate immune response is the host's first line of defense against a human coronavirus infection. However, most coronaviruses are armed with one strategy or another to overcome host antiviral defense, and the pathogenicity of the virus is related to its capacity to suppress host immunity. The multifaceted nature of obesity including its effects on immunity can fundamentally alter the pathogenesis of acute respiratory distress syndrome and pneumonia, which are the major causes of death due to SARS-CoV-2 infection. Elevated circulating leptin concentrations are a hallmark of obesity, which is associated with a leptin-resistant state. Leptin is secreted by adipocytes in proportion to body fat and regulates appetite and metabolism through signaling in the hypothalamus. However, leptin also signals through the Jak/STAT and Akt pathways, among others, to modulate T cell number and function. Thus, leptin connects metabolism with the immune response. Therefore, it seems appropriate that its dysregulation would have serious consequences during an infection. We propose that leptin may be the link between obesity and its high prevalence as a comorbidity of the SARS-CoV-2 infection. In this article, we present a synthesis of the mechanisms underpinning susceptibility to respiratory viral infections and the contribution of the immunomodulatory effects of obesity to the outcome.


Subject(s)
Coronavirus Infections , Leptin , Obesity , Pandemics , Pneumonia, Viral , Betacoronavirus , COVID-19 , Comorbidity , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/metabolism , Host-Pathogen Interactions/immunology , Humans , Leptin/blood , Leptin/immunology , Leptin/metabolism , Obesity/epidemiology , Obesity/immunology , Obesity/metabolism , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/metabolism , SARS-CoV-2 , Signal Transduction/immunology
17.
Lancet Child Adolesc Health ; 4(9): 662-668, 2020 09.
Article in English | MEDLINE | ID: covidwho-624286

ABSTRACT

BACKGROUND: Kawasaki disease is an acute febrile systemic childhood vasculitis, which is suspected to be triggered by respiratory viral infections. We aimed to examine whether the ongoing COVID-19 epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with an increase in the incidence of Kawasaki disease. METHODS: We did a quasi-experimental interrupted time series analysis over the past 15 years in a tertiary paediatric centre in the Paris region, a French epicentre of the COVID-19 outbreak. The main outcome was the number of Kawasaki disease cases over time, estimated by quasi-Poisson regression. In the same centre, we recorded the number of hospital admissions from the emergency department (2005-2020) and the results of nasopharyngeal multiplex PCR to identify respiratory pathogens (2017-2020). These data were compared with daily hospital admissions due to confirmed COVID-19 in the same region, recorded by Public Health France. FINDINGS: Between Dec 1, 2005, and May 20, 2020, we included 230 patients with Kawasaki disease. The median number of Kawasaki disease hospitalisations estimated by the quasi-Poisson model was 1·2 per month (IQR 1·1-1·3). In April, 2020, we identified a rapid increase of Kawasaki disease that was related to SARS-CoV-2 (six cases per month; 497% increase [95% CI 72-1082]; p=0·0011), starting 2 weeks after the peak of the COVID-19 epidemic. SARS-CoV-2 was the only virus circulating intensely during this period, and was found in eight (80%) of ten patients with Kawasaki disease since April 15 (SARS-CoV-2-positive PCR or serology). A second peak of hospital admissions due to Kawasaki disease was observed in December, 2009 (six cases per month; 365% increase ([31-719]; p=0.0053), concomitant with the influenza A H1N1 pandemic. INTERPRETATION: Our study further suggests that viral respiratory infections, including SAR-CoV-2, could be triggers for Kawasaki disease and indicates the potential timing of an increase in incidence of the disease in COVID-19 epidemics. Health-care providers should be prepared to manage an influx of patients with severe Kawasaki disease, particularly in countries where the peak of COVID-19 has recently been reached. FUNDING: French National Research Agency.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Forecasting , Mucocutaneous Lymph Node Syndrome/epidemiology , Pandemics , Pneumonia, Viral/complications , Adolescent , COVID-19 , Child , Child, Preschool , Coronavirus Infections/epidemiology , Female , Follow-Up Studies , France/epidemiology , Humans , Incidence , Infant , Infant, Newborn , Male , Mucocutaneous Lymph Node Syndrome/etiology , Pneumonia, Viral/epidemiology , Retrospective Studies , SARS-CoV-2
18.
Small ; 16(32): e2002169, 2020 08.
Article in English | MEDLINE | ID: covidwho-612774

ABSTRACT

The ongoing global novel coronavirus pneumonia COVID-19 outbreak has engendered numerous cases of infection and death. COVID-19 diagnosis relies upon nucleic acid detection; however, currently recommended methods exhibit high false-negative rates and are unable to identify other respiratory virus infections, thereby resulting in patient misdiagnosis and impeding epidemic containment. Combining the advantages of targeted amplification and long-read, real-time nanopore sequencing, herein, nanopore targeted sequencing (NTS) is developed to detect SARS-CoV-2 and other respiratory viruses simultaneously within 6-10 h, with a limit of detection of ten standard plasmid copies per reaction. Compared with its specificity for five common respiratory viruses, the specificity of NTS for SARS-CoV-2 reaches 100%. Parallel testing with approved real-time reverse transcription-polymerase chain reaction kits for SARS-CoV-2 and NTS using 61 nucleic acid samples from suspected COVID-19 cases show that NTS identifies more infected patients (22/61) as positive, while also effectively monitoring for mutated nucleic acid sequences, categorizing types of SARS-CoV-2, and detecting other respiratory viruses in the test sample. NTS is thus suitable for COVID-19 diagnosis; moreover, this platform can be further extended for diagnosing other viruses and pathogens.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Nanopores , Nucleic Acid Amplification Techniques/methods , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Betacoronavirus/classification , COVID-19 , Coronavirus Infections/epidemiology , DNA, Viral/genetics , DNA, Viral/isolation & purification , Genes, Viral , Humans , Limit of Detection , Mutation , Nanotechnology , Nucleic Acid Amplification Techniques/statistics & numerical data , Pandemics , Pneumonia, Viral/epidemiology , RNA, Viral/genetics , RNA, Viral/isolation & purification , Real-Time Polymerase Chain Reaction , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/virology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Sensitivity and Specificity
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