The outbreak of COVID-19 started in mid-December2019 in Wuhan, China. Up to 29 February 2020,SARS-CoV-2(HCoV-19/2019-nCoV) had infected more than 85 000 people in the world. In this study,we used 93 complete genomes o...The outbreak of COVID-19 started in mid-December2019 in Wuhan, China. Up to 29 February 2020,SARS-CoV-2(HCoV-19/2019-nCoV) had infected more than 85 000 people in the world. In this study,we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu TM database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak.We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau(τ)using the formula t=τ/2 u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes.Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes(31 found in samples from China and 31 from outside China)were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome(bat-RaTG13-CoV)as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes,and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore,phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.展开更多
Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillan...Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.展开更多
Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute resp...Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome,multiple organ failure,and death.Despite extensive studies on the pathogenicity of SARS-CoV-2,its impact on the hepatobiliary system remains unclear.While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels,the exact source of this damage is not fully understood.Proposed mechanisms for injury include direct cytotoxicity,collateral damage from inflammation,drug-induced liver injury,and ischemia/hypoxia.However,evidence often relies on blood tests with liver enzyme abnormalities.In this comprehensive review,we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients,drawing from liver biopsies,complete autopsies,and in vitro liver analyses.We present evidence of the direct impact of SARS-CoV-2 on the liver,substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes,including mitochondrial swelling,endoplasmic reticulum dilatation,and hepatocyte apoptosis.Additional ly,we describe the diverse liver pathology observed during COVID-19 infection,encompassing necrosis,steatosis,cholestasis,and lobular inflammation.We also discuss the emergence of long-term complications,notably COVID-19-related secondary sclerosing cholangitis.Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.展开更多
In coronavirus disease 2019(COVID-19),severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)primarily targets the respiratory system,but evidence suggests extrapulmonary organ involvement,notably in the liver.Vir...In coronavirus disease 2019(COVID-19),severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)primarily targets the respiratory system,but evidence suggests extrapulmonary organ involvement,notably in the liver.Viral RNA has been detected in hepatic tissues,and in situ hybridization revealed virions in blood vessels and endothelial cells.Electron microscopy confirmed viral particles in hepatocytes,emphasizing the need for understanding hepatotropism and direct cytopathic effects in COVID-19-related liver injury.Various factors contribute to liver injury,including direct cytotoxicity,vascular changes,inflammatory responses,immune reactions from COVID-19 and vaccinations,and druginduced liver injury.Although a typical hepatitis presentation is not widely documented,elevated liver biochemical markers are common in hospitalized COVID-19 patients,primarily showing a hepatocellular pattern of elevation.Long-term studies suggest progressive cholestasis may affect 20%of patients with chronic liver disease post-SARS-CoV-2 infection.The molecular mechanisms underlying SARS-CoV-2 infection in the liver and the resulting liver damage are complex.This“Editorial”highlights the expression of the Angiotensin-converting enzyme-2 receptor in liver cells,the role of inflammatory responses,the impact of hypoxia,the involvement of the liver's vascular system,the infection of bile duct epithelial cells,the activation of hepatic stellate cells,and the contribution of monocyte-derived macrophages.It also mentions that pre-existing liver conditions can worsen the outcomes of COVID-19.Understanding the interaction of SARS-CoV-2 with the liver is still evolving,and further research is required.展开更多
In Zanzibar, from the start of the pandemic in March 2020 to the time of sampling in December 2020, SARS-CoV-2 seroprevalence data was limited. We conducted a seroprevalence study to evaluate the magnitude of SARS-CoV...In Zanzibar, from the start of the pandemic in March 2020 to the time of sampling in December 2020, SARS-CoV-2 seroprevalence data was limited. We conducted a seroprevalence study to evaluate the magnitude of SARS-CoV-2 exposure among healthcare workers, school children, and people who attended general markets in Zanzibar. The objectives of the study were to analyse the total antibodies from selected higher-risk population groups in order to determine magnitude in SARS CoV-2 exposure. Blood samples were collected from eligible and consented participants (adults and children), and their serum was analyzed for total antibodies against SARS-CoV-2 using ELISA. A questionnaire was used to collect participants’ demographic and clinical data. The overall SARS-CoV-2 seroprevalence across all age groups was 33%, and a higher seroprevalence was observed in the 40 - 49 years’ age group relative to other ages as well as in those who attended markets. A runny nose (18.8% of participants) was the most frequently reported SARS-CoV-2 infection-related symptom. Multivariable analysis showed significantly higher odds of infection in people living in urban districts. The findings provide insight into SARS-CoV-2 infection among school children, health workers, and people who attended markets in Zanzibar in the early stages of the pandemic. Exposure in these groups might have been influenced by infection and prevention strategies taken by the government, as well as shopping behavior, school overcrowding, and population density in urban settings. The study had methodological limitations, including cross-sectional design. Further, well-designed, longitudinal studies are recommended to understand exposure and transmission at a population level.展开更多
BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To determine the effects of SARS-CoV-2 infe...BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with CLD.METHODS A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong.Patients with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,2022.Primary outcome was incidence of HCC.Secondary outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 infection.Incidence rate ratios(IRRs)were estimated by Poisson regression models.RESULTS Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching.Upon 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to COVID-19-CLD.In both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to COVID-19-CLD.CONCLUSION Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they were more likely to receive palliative treatment than those without.The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase.展开更多
The discovery of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) in Wuhan, Hubei province, China, in December 2019 raised global health warnings. Quickly, in 2020, the virus crossed borders and infected i...The discovery of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) in Wuhan, Hubei province, China, in December 2019 raised global health warnings. Quickly, in 2020, the virus crossed borders and infected individuals across the world, evolving into the COVID-19 pandemic. Notably, early signs of the virus’s existence were observed in various countries before the initial outbreak in Wuhan. As of 12<sup>th</sup> of April, the respiratory disease had infected over 762 million people worldwide, with over 6.8 million deaths recorded. This has led scientists to focus their efforts on understanding the virus to develop effective means to diagnose, treat, prevent, and control this pandemic. One of the areas of focus is the isolation of this virus, which plays a crucial role in understanding the viral dynamics in the laboratory. In this study, we report the isolation and detection of locally circulating SARS-CoV-2 in Kenya. The isolates were cultured on Vero Cercopithecus cell line (CCL-81) cells, RNA extraction was conducted from the supernatants, and reverse transcriptase-polymerase chain reaction (RT-PCR). Genome sequencing was done to profile the strains phylogenetically and identify novel and previously reported mutations. Vero CCL-81 cells were able to support the growth of SARS-CoV-2 in vitro, and mutations were detected from the two isolates sequenced (001 and 002). Genome sequencing revealed the circulation of two isolates that share a close relationship with the Benin isolate with the D614G common mutation identified along the S protein. These virus isolates will be expanded and made available to the Kenya Ministry of Health and other research institutions to advance SARS-CoV-2 research in Kenya and the region.展开更多
Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the produc...Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies(DSAs)or increase in mean fluorescence intensity(MFI)of pre-existing DSAs in kidney transplant recipients(KTRs).This study involved a detailed literature search through December 2nd,2023 using PubMed as the primary database.The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords:"COVID-19","SARS-CoV-2 Vaccination","Kidney,Renal Transplant",and"Donor specific antibodies".The results from related studies were collated and analyzed.A total of 6 studies were identified,encompassing 460 KTRs vaccinated against COVID-19.Immunological responses were detected in 8 KTRs of which 5 had increased MFIs,1 had de novo DSA,and 2 were categorized as either having de novo DSA or increased MFI.There were 48 KTRs with pre-existing DSAs prior to vaccination,but one study(Massa et al)did not report whether pre-existing DSAs were associated with post vaccination outcomes.Of the remaining 5 studies,35 KTRs with pre-existing DSAs were identified of which 7 KTRs(20%)developed de novo DSAs or increased MFIs.Overall,no immunological response was detected in 452(98.3%)KTRs.Our study affirms prior reports that COVID-19 vaccination is safe for KTRs,especially if there are no pre-existing DSAs.However,if KTRs have pre-existing DSAs,then an increased immunological risk may be present.These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the pathogen of the ongoing coronavirus disease 2019(COVID-19)global pandemic.Here,by centralizing published cell-based experiments,clinical trials,and vir...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the pathogen of the ongoing coronavirus disease 2019(COVID-19)global pandemic.Here,by centralizing published cell-based experiments,clinical trials,and virtual drug screening data from the NCBI PubMed database,we developed a database of SARS-CoV-2 inhibitors for COVID-19,dbSCI,which includes 234 SARS-CoV-2 inhibitors collected from publications based on cell-based experiments,81 drugs of COVID-19 in clinical trials and 1305 potential SARS-CoV-2 inhibitors from bioinformatics analyses.dbSCI provides four major functions:(1)search the drug target or its inhibitor for SARS-CoV-2,(2)browse target/inhibitor information collected from cell experiments,clinical trials,and virtual drug screenings,(3)download,and(4)submit data.Each entry in dbSCI contains 18 types of information,including inhibitor/drug name,targeting protein,mechanism of inhibition,experimental technique,experimental sample type,and reference information.In summary,dbSCI provides a relatively comprehensive,credible repository for inhibitors/drugs against SARS-CoV-2 and their potential targeting mechanisms and it will be valuable for further studies to control COVID-19.展开更多
Liver is unlikely the key organ driving mortality in coronavirus disease 2019(COVID-19)however,liver function tests(LFTs)abnormalities are widely observed mostly in moderate and severe cases.According to this review,t...Liver is unlikely the key organ driving mortality in coronavirus disease 2019(COVID-19)however,liver function tests(LFTs)abnormalities are widely observed mostly in moderate and severe cases.According to this review,the overall prevalence of abnormal LFTs in COVID-19 patients ranges from 2.5%to 96.8%worldwide.The geographical variability in the prevalence of underlying diseases is the determinant for the observed discrepancies between East and West.Multifactorial mechanisms are implicated in COVID-19-induced liver injury.Among them,hypercytokinemia with“bystander hepatitis”,cytokine storm syndrome with subsequent oxidative stress and endotheliopathy,hypercoagulable state and immuno-thromboinflammation are the most determinant mechanisms leading to tissue injury.Liver hypoxia may also contribute under specific conditions,while direct hepatocyte injury is an emerging mechanism.Except for initially observed severe acute respiratory distress syndrome corona virus-2(SARS-CoV-2)tropism for cholangiocytes,more recent cumulative data show SARS-CoV-2 virions within hepatocytes and sinusoidal endothelial cells using electron microscopy(EM).The best evidence for hepatocellular invasion by the virus is the identification of replicating SARS-CoV-2 RNA,S protein RNA and viral nucleocapsid protein within hepatocytes using in-situ hybridization and immunostaining with observed intrahepatic presence of SARS-CoV-2 by EM and by in-situ hybridization.New data mostly derived from imaging findings indicate possible long-term sequelae for the liver months after recovery,suggesting a post-COVID-19 persistent live injury.展开更多
The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodi...The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies(mAbs)in the treatment of coronavirus infectious disease 2019(COVID-19).The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied.Immunoglobulin M(IgM)appeared earlier and lasted for a short time,while immunoglobulin G(IgG)appeared later and lasted longer.IgM tests can be used for early diagnosis of COVID-19,and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons.The combination of antibody testing and nucleic acid testing,which complement each other,can improve the diagnosis rate of COVID-19.Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients.COVID-19 convalescent plasma,highly concentrated immunoglobulin,and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products.Due to the continuous emergence of mutated strains of the novel coronavirus,especially omicron,its immune escape ability and infectivity are enhanced,making the effects of authorized products reduced or invalid.Therefore,the optimal application of anti-SARS-CoV-2 antibody products(especially anti-SARS-CoV-2 specific mAbs)is more effective in the treatment of COVID-19 and more conducive to patient recovery.展开更多
BACKGROUND While stroke and lower extremity venous thromboemboli have been commonly reported following acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),spinal cord infarction or ischemi...BACKGROUND While stroke and lower extremity venous thromboemboli have been commonly reported following acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),spinal cord infarction or ischemia has been extremely rare.Findings of long coronavirus disease(COVID)in this select population have not been studied.CASE SUMMARY We present the case of a 70-year-old female with sudden onset of trunk and lower extremity sensorimotor loss due to spinal cord infarction,attributed to acute infection with SARS-CoV-2.Diagnostic work up confirmed a T3 complete(ASIA impairment Scale A)paraplegia resulting from a thrombotic infarct.Her reported myalgias,neuropathic pain,spasticity,bladder spasms,and urinary tract infections exceeded the frequency and severity of many spinal cord injury(SCI)individuals of similar age and degree of neurologic impairment.In her first year after contracting COVID-19,she underwent 2 separate inpatient rehabilitation courses,but also required acute hospitalization 6 additional times for subsequent infections or uncontrolled pain.Yet other complications of complete non-traumatic SCI(NTSCI),including neurogenic bowel and temperature hypersens-itivity,were mild,and pressure injuries were absent.She has now transitioned from the acute to chronic phase of spinal cord injury care,with subsequent development of post-acute sequelae of SARS-CoV-2 infection(PASC).CONCLUSION This individual experienced significant challenges with the combined effects of acute T3 NTSCI and acute COVID-19,with subsequent progression to PASC.Core Tip:Although stroke and venous thromboembolism have been frequently observed with acute coronavirus disease 2019(COVID-19),spinal cord infarction leading to paraplegia has rarely been seen.We report a case of spinal cord infarction shortly following infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Consequently,this individual has experienced severe neurologic disability,with subsequent development of long COVID.Symptoms such as myalgias,neuropathic pain,muscle spasms,and frequent bacterial infections are present in post-acute sequelae of SARS-CoV-2 infection(PASC),independent of spinal cord injury(SCI).Over the past 3 years,the dual presence of PASC and recent SCI may have led to increased severity of symptoms shared by both conditions.INTRODUCTION Among vascular events,spinal cord infarction is relatively rare,accounting for only 0.3%-1%of all strokes[1]and 5%-8%of acute myelopathies[2].One cause of spinal cord infarction arises from a thrombotic event in vulnerable areas of the thoracic cord,particularly between T8-12,which is supplied by the artery of Adamkiewicz.While deep vein thrombosis,pulmonary embolism,and stroke are commonly observed complications of coronavirus disease 2019(COVID-19),spinal cord infarction is comparatively infrequent[3-6].The cytokine release following acute infection,which peaks 7 d after contracting the virus,may be responsible for the increase in thrombotic events associated with acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[7,8].This case discussed in this report differs from other published accounts describing spinal cord infarcts attributed to acute SARS-CoV-2,because we have followed this individual for nearly 3 years after contracting COVID-19,covering her difficulties with“long COVID,”which has now officially named post-acute sequelae of SARS-CoV-2 infection(PASC)by the World Health Organization[9].The term PASC may be assigned to“individuals with a history of probable or confirmed SARS-CoV-2 infection,usually 3 mo from the onset of COVID-19 with symptoms that last for at least 2 mo and cannot be explained by an alternative diagnosis”.The definition further states that PASC generally impacts everyday functioning and that symptoms may be of new onset,follow initial recovery from an acute COVID-19 episode,or persist from the initial illness.Moreover,symptoms may also fluctuate or relapse over time[9].Common complaints of PASC include fatigue,cough shortness of breath,cognitive deficits or“brain fog”.Reported features of PASC may also involve headache,heart palpitations,exercise intolerance,joint pain or swelling,myalgias,vertigo,peripheral neuropathy,altered taste or smell,disordered sleep,anxiety,depression,and thromboembolic events[10-13].While a number of the above symptoms may occur subsequent to SCI,many would be unusual,such as persistent cough,fatigue months after SCI,changes in taste or smell,continued exercise intolerance,new onset cognitive deficits or“brain fog”,unrelated to any sedating medications or concomitant brain injury.Our patient became symptomatic prior to COVID-19 vaccine availability and has given written consent to share her story for educational publication.This project was approved by the Institutional Review Board of the MetroHealth System.展开更多
Background: The persistence of the rapid spread of the COVID-19 pandemic is linked to the appearance of several variants of SARS-CoV2 with an impact on biological diagnosis, treatment and vaccination. The United State...Background: The persistence of the rapid spread of the COVID-19 pandemic is linked to the appearance of several variants of SARS-CoV2 with an impact on biological diagnosis, treatment and vaccination. The United States Food and Drug Administration (FDA) has granted several SARS-CoV-2 detection tests Emergency Use Authorization (EUA) for diagnosis and better epidemiological surveillance. Thus, multiple RT-PCR tests have been developed and brought to market in order to meet the urgent need for the diagnosis of COVID-19. However, comparative data between these tests in clinical laboratories are scarcely available to assess their performance. Objective: To compare two molecular methods for detecting SARS-CoV-2: the RT-PCR, Allplex™2019-nCoV tests on CFX96 Bio-Rad and the Abbott m2000sp/rt RealTime SARS-CoV-2. Materials and Methods: Nasopharyngeal and oropharyngeal swabs were taken from patients to diagnose SARS-CoV-2 infection. For each sample, we searched for the virus with two different RT-PCR tests: 1) first on Abbott m2000 SARS-CoV-2 targeting the N and RdRp genes, 2) then on Allplex™2019-nCoV Assay looking for the E, N and RdRp genes. Results: Percentages of the agreement were calculated. A total of 100 samples that tested negative and 90 positives on Abbott m2000 SARS-CoV-2 were retested on Allplex™2019-nCoV. Overall agreement was 74.74% on all samples. The specific agreement was 84% and 64.4% respectively for negative and positive samples with the RealTime SARS-CoV-2 test. A positive correlation (r<sup>2</sup> = 0.63;p Conclusion: Our results showed good overall agreement between RT-PCR, Allplex™2019-nCoV and Abbott RealTime SARS-CoV-2 tests in the diagnosis of COVID-19. As the concordance is low for small viremias, the RT-PCR Allplex™2019-nCoV Assay would be better indicated during the acute and symptomatic phase of the disease.展开更多
Otitis media with effusion is a common disease in otolaryngology. Bacteria are the most common pathogen of otitis media with effusion, and other factors such as viruses have also been reported. The present study is ai...Otitis media with effusion is a common disease in otolaryngology. Bacteria are the most common pathogen of otitis media with effusion, and other factors such as viruses have also been reported. The present study is aimed to investigate whether the increasing otitis media cases recently is correlated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the COVID-19-related otitis media is commonly existed. Thirty-two patients with otitis media were enrolled Blood cell analysis, C-reactive protein, interleukin-6 test bacterial and fungal cultures were tested. Nine patients were identified with positive SARS-CoV-2 RNA in middle ear discharge. All the subjects had the common symptoms of stuffy ear, hearing loss, and echoacousia. No positive results were found in cultures for bacterial and fungus of middle ear discharge. The levels of C-reactive protein (CRP) were significantly up-regulated in positive cases (P = 0.0335). The levels of proinflammatory cytokine interleukin-6 (IL-6) were higher in positive cases. There were no significant differences of age, gender and prothrombin time (PT) between positive and negative cases. Nasal sprays, ciliary stimulants, and prophylactic antibiotics or low-dose steroid treatments were sequentially used in the otitis media patients caused by SARS-CoV-2 infection. All the patients had improvements of typical symptoms within two to four weeks during the following-up. Thus, SARS-CoV-2 infection caused COVID-19 related otitis media is commonly existed, and the prognosis is good after treatments.展开更多
Objective:Since the opportunity of widespread administration of the fourth mRNA-based coronavirus disease 2019(COVID-19)vaccine dose remains controversial,this article provides a pooled analysis of the efficacy of the...Objective:Since the opportunity of widespread administration of the fourth mRNA-based coronavirus disease 2019(COVID-19)vaccine dose remains controversial,this article provides a pooled analysis of the efficacy of the second COVID-19 mRNA-based homologous vaccine booster in eliciting anti-SARS-CoV-2 serum antibody response in general immunocompetent populations.Methods:We conducted a digital search in Medline using the keywords"fourth dose"or"second booster"and"antibodies"and"COVID-19"or"SARS-CoV-2"and"BNT162b2"or"mRNA-1273",to identify all clinical studies which evaluated the anti-SARS-CoV-2 serum antibody response after the fourth mRNA-based COVID-19 homologous vaccine dose administration in general immunocompetent populations compared to the response seen before its administration and after the first booster.Results:Four studies totaling 571 recipients of the second mRNA-based COVID-19 vaccine booster were finally included in our analysis.The weighted mean difference(WMD)ratio of anti-SARS-CoV-2 serum antibodies levels measured after and before administration of the fourth vaccine dose was 9.7(95%CI,6.5-12.9)in those receiving BNT162b2 and 12.0(95%CI,5.8-18.2)in those receiving mRNA-1273,respectively.The WMD ratio of anti-SARS-CoV-2 serum antibodies levels measured at the peak of the fourth and third vaccine doses was 1.4(95%CI,1.2-1.7)in those receiving BNT162b2 and 1.9(95%CI,1.5-2.4)in those receiving mRNA-1273,respectively.Conclusion:Our data confirm the efficacy of the fourth mRNA-based COVID-19 vaccine dose in restoring a satisfactory level of anti-SARS-CoV-2 serum antibodies,though such effectiveness seems only marginally superior to that of the first booster.展开更多
The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19/SARS-CoV-2/2019-nCoV), is a global threat to the human population. Here, we briefly summarize the a...The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19/SARS-CoV-2/2019-nCoV), is a global threat to the human population. Here, we briefly summarize the available data for the zoonotic origins of HCoV-19, with reference to the other two epidemics of highly virulent coronaviruses, SARSCoV and MERS-CoV, which cause severe pneumonia in humans. We propose to intensify future efforts for tracing the origins of HCoV-19, which is a very important scientific question for the control and prevention of the pandemic.展开更多
Thecoronavirusdisease2019(COVID-19)pandemic continues to pose a global threat to the human population. Identifying animal species susceptible to infection with the SARS-CoV-2/HCoV-19 pathogen is essential for controll...Thecoronavirusdisease2019(COVID-19)pandemic continues to pose a global threat to the human population. Identifying animal species susceptible to infection with the SARS-CoV-2/HCoV-19 pathogen is essential for controlling the outbreak and for testing valid prophylactics or therapeutics based on animal model studies. Here,different aged Chinese tree shrews(adult group, 1 year old;old group, 5–6 years old), which are close relatives to primates, were infected with SARS-CoV-2. X-ray, viral shedding, laboratory, and histological analyses were performed on different days postinoculation(dpi). Results showed that Chinese tree shrews could be infected by SARS-CoV-2. Lung infiltrates were visible in X-ray radiographs in most infected animals. Viral RNA was consistently detected in lung tissues from infected animals at 3,5, and 7 dpi, along with alterations in related parameters from routine blood tests and serum biochemistry, including increased levels of aspartate aminotransferase(AST) and blood urea nitrogen(BUN). Histological analysis of lung tissues from animals at 3 dpi(adult group) and 7 dpi(old group) showed thickened alveolar septa and interstitial hemorrhage. Several differences were found between the two different aged groups in regard to viral shedding peak. Our results indicate that Chinese tree shrews have the potential to be used as animal models for SARS-CoV-2 infection.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),causing coronavirus disease 2019(COVID-19),can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and mo...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),causing coronavirus disease 2019(COVID-19),can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and molecular mimicry.Here we summarise the current knowledge about autoimmune liver diseases(AILDs)and SARS-CoV-2,focusing on:(1)The risk of SARS-CoV-2 infection and the course of COVID-19 in patients affected by AILDs;(2)the role of SARS-CoV-2 in inducing liver damage and triggering AILDs;and(3)the ability of vaccines against SARS-CoV-2 to induce autoimmune responses in the liver.Data derived from the literature suggest that patients with AILDs do not carry an increased risk of SARS-Cov-2 infection but may develop a more severe course of COVID-19 if on treatment with steroids or thiopurine.Although SARSCoV-2 infection can lead to the development of several autoimmune diseases,few reports correlate it to the appearance of de novo manifestation of immunemediated liver diseases such as autoimmune hepatitis(AIH),primary biliary cholangitis(PBC)or AIH/PBC overlap syndrome.Different case series of an AIHlike syndrome with a good prognosis after SARS-CoV-2 vaccination have been described.Although the causal link between SARS-CoV-2 vaccines and AIH cannot be definitively established,these reports suggest that this association could be more than coincidental.展开更多
基金Ten Thousand Talents Program of Yunnan for Top-notch Young Talentsthe open research project of“Cross-Cooperative Team”of the Germplasm Bank of Wild Species,Kunming Institute of Botany,Chinese Academy of Sciences.
文摘The outbreak of COVID-19 started in mid-December2019 in Wuhan, China. Up to 29 February 2020,SARS-CoV-2(HCoV-19/2019-nCoV) had infected more than 85 000 people in the world. In this study,we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu TM database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak.We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau(τ)using the formula t=τ/2 u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes.Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes(31 found in samples from China and 31 from outside China)were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome(bat-RaTG13-CoV)as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes,and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore,phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.
文摘Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.
文摘Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome,multiple organ failure,and death.Despite extensive studies on the pathogenicity of SARS-CoV-2,its impact on the hepatobiliary system remains unclear.While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels,the exact source of this damage is not fully understood.Proposed mechanisms for injury include direct cytotoxicity,collateral damage from inflammation,drug-induced liver injury,and ischemia/hypoxia.However,evidence often relies on blood tests with liver enzyme abnormalities.In this comprehensive review,we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients,drawing from liver biopsies,complete autopsies,and in vitro liver analyses.We present evidence of the direct impact of SARS-CoV-2 on the liver,substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes,including mitochondrial swelling,endoplasmic reticulum dilatation,and hepatocyte apoptosis.Additional ly,we describe the diverse liver pathology observed during COVID-19 infection,encompassing necrosis,steatosis,cholestasis,and lobular inflammation.We also discuss the emergence of long-term complications,notably COVID-19-related secondary sclerosing cholangitis.Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.
基金Supported by Agencia Nacional de Promoción Científica y Tecnológica(PICTO-2021-COVID secuelas-00005 to JQ).
文摘In coronavirus disease 2019(COVID-19),severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)primarily targets the respiratory system,but evidence suggests extrapulmonary organ involvement,notably in the liver.Viral RNA has been detected in hepatic tissues,and in situ hybridization revealed virions in blood vessels and endothelial cells.Electron microscopy confirmed viral particles in hepatocytes,emphasizing the need for understanding hepatotropism and direct cytopathic effects in COVID-19-related liver injury.Various factors contribute to liver injury,including direct cytotoxicity,vascular changes,inflammatory responses,immune reactions from COVID-19 and vaccinations,and druginduced liver injury.Although a typical hepatitis presentation is not widely documented,elevated liver biochemical markers are common in hospitalized COVID-19 patients,primarily showing a hepatocellular pattern of elevation.Long-term studies suggest progressive cholestasis may affect 20%of patients with chronic liver disease post-SARS-CoV-2 infection.The molecular mechanisms underlying SARS-CoV-2 infection in the liver and the resulting liver damage are complex.This“Editorial”highlights the expression of the Angiotensin-converting enzyme-2 receptor in liver cells,the role of inflammatory responses,the impact of hypoxia,the involvement of the liver's vascular system,the infection of bile duct epithelial cells,the activation of hepatic stellate cells,and the contribution of monocyte-derived macrophages.It also mentions that pre-existing liver conditions can worsen the outcomes of COVID-19.Understanding the interaction of SARS-CoV-2 with the liver is still evolving,and further research is required.
文摘In Zanzibar, from the start of the pandemic in March 2020 to the time of sampling in December 2020, SARS-CoV-2 seroprevalence data was limited. We conducted a seroprevalence study to evaluate the magnitude of SARS-CoV-2 exposure among healthcare workers, school children, and people who attended general markets in Zanzibar. The objectives of the study were to analyse the total antibodies from selected higher-risk population groups in order to determine magnitude in SARS CoV-2 exposure. Blood samples were collected from eligible and consented participants (adults and children), and their serum was analyzed for total antibodies against SARS-CoV-2 using ELISA. A questionnaire was used to collect participants’ demographic and clinical data. The overall SARS-CoV-2 seroprevalence across all age groups was 33%, and a higher seroprevalence was observed in the 40 - 49 years’ age group relative to other ages as well as in those who attended markets. A runny nose (18.8% of participants) was the most frequently reported SARS-CoV-2 infection-related symptom. Multivariable analysis showed significantly higher odds of infection in people living in urban districts. The findings provide insight into SARS-CoV-2 infection among school children, health workers, and people who attended markets in Zanzibar in the early stages of the pandemic. Exposure in these groups might have been influenced by infection and prevention strategies taken by the government, as well as shopping behavior, school overcrowding, and population density in urban settings. The study had methodological limitations, including cross-sectional design. Further, well-designed, longitudinal studies are recommended to understand exposure and transmission at a population level.
基金Supported by Collaborative Research Fund Scheme,University Grants Committee,No.C7154-20GFData Discovery for Health(D24H)Innovation and Technology Commission,AIR@InnoHK.
文摘BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with CLD.METHODS A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong.Patients with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,2022.Primary outcome was incidence of HCC.Secondary outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 infection.Incidence rate ratios(IRRs)were estimated by Poisson regression models.RESULTS Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching.Upon 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to COVID-19-CLD.In both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to COVID-19-CLD.CONCLUSION Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they were more likely to receive palliative treatment than those without.The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase.
文摘The discovery of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) in Wuhan, Hubei province, China, in December 2019 raised global health warnings. Quickly, in 2020, the virus crossed borders and infected individuals across the world, evolving into the COVID-19 pandemic. Notably, early signs of the virus’s existence were observed in various countries before the initial outbreak in Wuhan. As of 12<sup>th</sup> of April, the respiratory disease had infected over 762 million people worldwide, with over 6.8 million deaths recorded. This has led scientists to focus their efforts on understanding the virus to develop effective means to diagnose, treat, prevent, and control this pandemic. One of the areas of focus is the isolation of this virus, which plays a crucial role in understanding the viral dynamics in the laboratory. In this study, we report the isolation and detection of locally circulating SARS-CoV-2 in Kenya. The isolates were cultured on Vero Cercopithecus cell line (CCL-81) cells, RNA extraction was conducted from the supernatants, and reverse transcriptase-polymerase chain reaction (RT-PCR). Genome sequencing was done to profile the strains phylogenetically and identify novel and previously reported mutations. Vero CCL-81 cells were able to support the growth of SARS-CoV-2 in vitro, and mutations were detected from the two isolates sequenced (001 and 002). Genome sequencing revealed the circulation of two isolates that share a close relationship with the Benin isolate with the D614G common mutation identified along the S protein. These virus isolates will be expanded and made available to the Kenya Ministry of Health and other research institutions to advance SARS-CoV-2 research in Kenya and the region.
文摘Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies(DSAs)or increase in mean fluorescence intensity(MFI)of pre-existing DSAs in kidney transplant recipients(KTRs).This study involved a detailed literature search through December 2nd,2023 using PubMed as the primary database.The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords:"COVID-19","SARS-CoV-2 Vaccination","Kidney,Renal Transplant",and"Donor specific antibodies".The results from related studies were collated and analyzed.A total of 6 studies were identified,encompassing 460 KTRs vaccinated against COVID-19.Immunological responses were detected in 8 KTRs of which 5 had increased MFIs,1 had de novo DSA,and 2 were categorized as either having de novo DSA or increased MFI.There were 48 KTRs with pre-existing DSAs prior to vaccination,but one study(Massa et al)did not report whether pre-existing DSAs were associated with post vaccination outcomes.Of the remaining 5 studies,35 KTRs with pre-existing DSAs were identified of which 7 KTRs(20%)developed de novo DSAs or increased MFIs.Overall,no immunological response was detected in 452(98.3%)KTRs.Our study affirms prior reports that COVID-19 vaccination is safe for KTRs,especially if there are no pre-existing DSAs.However,if KTRs have pre-existing DSAs,then an increased immunological risk may be present.These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.
基金supported by the Innovation and Entrepreneurship Training Program for College Students in Henan University(20221022009)the Key Scientific Research Project of Henan Province(22A310012)+1 种基金supporting program for Central Plain Young Top Talents(ZYQR201912176)the program from Academy for Advanced Interdisciplinary Studies of Henan University(Y21008L).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the pathogen of the ongoing coronavirus disease 2019(COVID-19)global pandemic.Here,by centralizing published cell-based experiments,clinical trials,and virtual drug screening data from the NCBI PubMed database,we developed a database of SARS-CoV-2 inhibitors for COVID-19,dbSCI,which includes 234 SARS-CoV-2 inhibitors collected from publications based on cell-based experiments,81 drugs of COVID-19 in clinical trials and 1305 potential SARS-CoV-2 inhibitors from bioinformatics analyses.dbSCI provides four major functions:(1)search the drug target or its inhibitor for SARS-CoV-2,(2)browse target/inhibitor information collected from cell experiments,clinical trials,and virtual drug screenings,(3)download,and(4)submit data.Each entry in dbSCI contains 18 types of information,including inhibitor/drug name,targeting protein,mechanism of inhibition,experimental technique,experimental sample type,and reference information.In summary,dbSCI provides a relatively comprehensive,credible repository for inhibitors/drugs against SARS-CoV-2 and their potential targeting mechanisms and it will be valuable for further studies to control COVID-19.
文摘Liver is unlikely the key organ driving mortality in coronavirus disease 2019(COVID-19)however,liver function tests(LFTs)abnormalities are widely observed mostly in moderate and severe cases.According to this review,the overall prevalence of abnormal LFTs in COVID-19 patients ranges from 2.5%to 96.8%worldwide.The geographical variability in the prevalence of underlying diseases is the determinant for the observed discrepancies between East and West.Multifactorial mechanisms are implicated in COVID-19-induced liver injury.Among them,hypercytokinemia with“bystander hepatitis”,cytokine storm syndrome with subsequent oxidative stress and endotheliopathy,hypercoagulable state and immuno-thromboinflammation are the most determinant mechanisms leading to tissue injury.Liver hypoxia may also contribute under specific conditions,while direct hepatocyte injury is an emerging mechanism.Except for initially observed severe acute respiratory distress syndrome corona virus-2(SARS-CoV-2)tropism for cholangiocytes,more recent cumulative data show SARS-CoV-2 virions within hepatocytes and sinusoidal endothelial cells using electron microscopy(EM).The best evidence for hepatocellular invasion by the virus is the identification of replicating SARS-CoV-2 RNA,S protein RNA and viral nucleocapsid protein within hepatocytes using in-situ hybridization and immunostaining with observed intrahepatic presence of SARS-CoV-2 by EM and by in-situ hybridization.New data mostly derived from imaging findings indicate possible long-term sequelae for the liver months after recovery,suggesting a post-COVID-19 persistent live injury.
文摘The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies(mAbs)in the treatment of coronavirus infectious disease 2019(COVID-19).The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied.Immunoglobulin M(IgM)appeared earlier and lasted for a short time,while immunoglobulin G(IgG)appeared later and lasted longer.IgM tests can be used for early diagnosis of COVID-19,and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons.The combination of antibody testing and nucleic acid testing,which complement each other,can improve the diagnosis rate of COVID-19.Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients.COVID-19 convalescent plasma,highly concentrated immunoglobulin,and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products.Due to the continuous emergence of mutated strains of the novel coronavirus,especially omicron,its immune escape ability and infectivity are enhanced,making the effects of authorized products reduced or invalid.Therefore,the optimal application of anti-SARS-CoV-2 antibody products(especially anti-SARS-CoV-2 specific mAbs)is more effective in the treatment of COVID-19 and more conducive to patient recovery.
文摘BACKGROUND While stroke and lower extremity venous thromboemboli have been commonly reported following acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),spinal cord infarction or ischemia has been extremely rare.Findings of long coronavirus disease(COVID)in this select population have not been studied.CASE SUMMARY We present the case of a 70-year-old female with sudden onset of trunk and lower extremity sensorimotor loss due to spinal cord infarction,attributed to acute infection with SARS-CoV-2.Diagnostic work up confirmed a T3 complete(ASIA impairment Scale A)paraplegia resulting from a thrombotic infarct.Her reported myalgias,neuropathic pain,spasticity,bladder spasms,and urinary tract infections exceeded the frequency and severity of many spinal cord injury(SCI)individuals of similar age and degree of neurologic impairment.In her first year after contracting COVID-19,she underwent 2 separate inpatient rehabilitation courses,but also required acute hospitalization 6 additional times for subsequent infections or uncontrolled pain.Yet other complications of complete non-traumatic SCI(NTSCI),including neurogenic bowel and temperature hypersens-itivity,were mild,and pressure injuries were absent.She has now transitioned from the acute to chronic phase of spinal cord injury care,with subsequent development of post-acute sequelae of SARS-CoV-2 infection(PASC).CONCLUSION This individual experienced significant challenges with the combined effects of acute T3 NTSCI and acute COVID-19,with subsequent progression to PASC.Core Tip:Although stroke and venous thromboembolism have been frequently observed with acute coronavirus disease 2019(COVID-19),spinal cord infarction leading to paraplegia has rarely been seen.We report a case of spinal cord infarction shortly following infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Consequently,this individual has experienced severe neurologic disability,with subsequent development of long COVID.Symptoms such as myalgias,neuropathic pain,muscle spasms,and frequent bacterial infections are present in post-acute sequelae of SARS-CoV-2 infection(PASC),independent of spinal cord injury(SCI).Over the past 3 years,the dual presence of PASC and recent SCI may have led to increased severity of symptoms shared by both conditions.INTRODUCTION Among vascular events,spinal cord infarction is relatively rare,accounting for only 0.3%-1%of all strokes[1]and 5%-8%of acute myelopathies[2].One cause of spinal cord infarction arises from a thrombotic event in vulnerable areas of the thoracic cord,particularly between T8-12,which is supplied by the artery of Adamkiewicz.While deep vein thrombosis,pulmonary embolism,and stroke are commonly observed complications of coronavirus disease 2019(COVID-19),spinal cord infarction is comparatively infrequent[3-6].The cytokine release following acute infection,which peaks 7 d after contracting the virus,may be responsible for the increase in thrombotic events associated with acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[7,8].This case discussed in this report differs from other published accounts describing spinal cord infarcts attributed to acute SARS-CoV-2,because we have followed this individual for nearly 3 years after contracting COVID-19,covering her difficulties with“long COVID,”which has now officially named post-acute sequelae of SARS-CoV-2 infection(PASC)by the World Health Organization[9].The term PASC may be assigned to“individuals with a history of probable or confirmed SARS-CoV-2 infection,usually 3 mo from the onset of COVID-19 with symptoms that last for at least 2 mo and cannot be explained by an alternative diagnosis”.The definition further states that PASC generally impacts everyday functioning and that symptoms may be of new onset,follow initial recovery from an acute COVID-19 episode,or persist from the initial illness.Moreover,symptoms may also fluctuate or relapse over time[9].Common complaints of PASC include fatigue,cough shortness of breath,cognitive deficits or“brain fog”.Reported features of PASC may also involve headache,heart palpitations,exercise intolerance,joint pain or swelling,myalgias,vertigo,peripheral neuropathy,altered taste or smell,disordered sleep,anxiety,depression,and thromboembolic events[10-13].While a number of the above symptoms may occur subsequent to SCI,many would be unusual,such as persistent cough,fatigue months after SCI,changes in taste or smell,continued exercise intolerance,new onset cognitive deficits or“brain fog”,unrelated to any sedating medications or concomitant brain injury.Our patient became symptomatic prior to COVID-19 vaccine availability and has given written consent to share her story for educational publication.This project was approved by the Institutional Review Board of the MetroHealth System.
文摘Background: The persistence of the rapid spread of the COVID-19 pandemic is linked to the appearance of several variants of SARS-CoV2 with an impact on biological diagnosis, treatment and vaccination. The United States Food and Drug Administration (FDA) has granted several SARS-CoV-2 detection tests Emergency Use Authorization (EUA) for diagnosis and better epidemiological surveillance. Thus, multiple RT-PCR tests have been developed and brought to market in order to meet the urgent need for the diagnosis of COVID-19. However, comparative data between these tests in clinical laboratories are scarcely available to assess their performance. Objective: To compare two molecular methods for detecting SARS-CoV-2: the RT-PCR, Allplex™2019-nCoV tests on CFX96 Bio-Rad and the Abbott m2000sp/rt RealTime SARS-CoV-2. Materials and Methods: Nasopharyngeal and oropharyngeal swabs were taken from patients to diagnose SARS-CoV-2 infection. For each sample, we searched for the virus with two different RT-PCR tests: 1) first on Abbott m2000 SARS-CoV-2 targeting the N and RdRp genes, 2) then on Allplex™2019-nCoV Assay looking for the E, N and RdRp genes. Results: Percentages of the agreement were calculated. A total of 100 samples that tested negative and 90 positives on Abbott m2000 SARS-CoV-2 were retested on Allplex™2019-nCoV. Overall agreement was 74.74% on all samples. The specific agreement was 84% and 64.4% respectively for negative and positive samples with the RealTime SARS-CoV-2 test. A positive correlation (r<sup>2</sup> = 0.63;p Conclusion: Our results showed good overall agreement between RT-PCR, Allplex™2019-nCoV and Abbott RealTime SARS-CoV-2 tests in the diagnosis of COVID-19. As the concordance is low for small viremias, the RT-PCR Allplex™2019-nCoV Assay would be better indicated during the acute and symptomatic phase of the disease.
文摘Otitis media with effusion is a common disease in otolaryngology. Bacteria are the most common pathogen of otitis media with effusion, and other factors such as viruses have also been reported. The present study is aimed to investigate whether the increasing otitis media cases recently is correlated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the COVID-19-related otitis media is commonly existed. Thirty-two patients with otitis media were enrolled Blood cell analysis, C-reactive protein, interleukin-6 test bacterial and fungal cultures were tested. Nine patients were identified with positive SARS-CoV-2 RNA in middle ear discharge. All the subjects had the common symptoms of stuffy ear, hearing loss, and echoacousia. No positive results were found in cultures for bacterial and fungus of middle ear discharge. The levels of C-reactive protein (CRP) were significantly up-regulated in positive cases (P = 0.0335). The levels of proinflammatory cytokine interleukin-6 (IL-6) were higher in positive cases. There were no significant differences of age, gender and prothrombin time (PT) between positive and negative cases. Nasal sprays, ciliary stimulants, and prophylactic antibiotics or low-dose steroid treatments were sequentially used in the otitis media patients caused by SARS-CoV-2 infection. All the patients had improvements of typical symptoms within two to four weeks during the following-up. Thus, SARS-CoV-2 infection caused COVID-19 related otitis media is commonly existed, and the prognosis is good after treatments.
文摘Objective:Since the opportunity of widespread administration of the fourth mRNA-based coronavirus disease 2019(COVID-19)vaccine dose remains controversial,this article provides a pooled analysis of the efficacy of the second COVID-19 mRNA-based homologous vaccine booster in eliciting anti-SARS-CoV-2 serum antibody response in general immunocompetent populations.Methods:We conducted a digital search in Medline using the keywords"fourth dose"or"second booster"and"antibodies"and"COVID-19"or"SARS-CoV-2"and"BNT162b2"or"mRNA-1273",to identify all clinical studies which evaluated the anti-SARS-CoV-2 serum antibody response after the fourth mRNA-based COVID-19 homologous vaccine dose administration in general immunocompetent populations compared to the response seen before its administration and after the first booster.Results:Four studies totaling 571 recipients of the second mRNA-based COVID-19 vaccine booster were finally included in our analysis.The weighted mean difference(WMD)ratio of anti-SARS-CoV-2 serum antibodies levels measured after and before administration of the fourth vaccine dose was 9.7(95%CI,6.5-12.9)in those receiving BNT162b2 and 12.0(95%CI,5.8-18.2)in those receiving mRNA-1273,respectively.The WMD ratio of anti-SARS-CoV-2 serum antibodies levels measured at the peak of the fourth and third vaccine doses was 1.4(95%CI,1.2-1.7)in those receiving BNT162b2 and 1.9(95%CI,1.5-2.4)in those receiving mRNA-1273,respectively.Conclusion:Our data confirm the efficacy of the fourth mRNA-based COVID-19 vaccine dose in restoring a satisfactory level of anti-SARS-CoV-2 serum antibodies,though such effectiveness seems only marginally superior to that of the first booster.
文摘The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19/SARS-CoV-2/2019-nCoV), is a global threat to the human population. Here, we briefly summarize the available data for the zoonotic origins of HCoV-19, with reference to the other two epidemics of highly virulent coronaviruses, SARSCoV and MERS-CoV, which cause severe pneumonia in humans. We propose to intensify future efforts for tracing the origins of HCoV-19, which is a very important scientific question for the control and prevention of the pandemic.
基金partly supported by the National Key R&D Program of China(2020YFC0842000 to Y.T.Z.)National Natural Science Foundation of China(U1902215 to Y.G.Y.)+2 种基金National Science and Technology Major Projects of Infectious Disease Funds(2017ZX10304402 to Y.T.Z.)Yunnan Province(2018FB046 to D.D.Y.)CAS“Light of West China”Program(xbzg-zdsys-201909to Y.G.Y.and Y.T.Z.)。
文摘Thecoronavirusdisease2019(COVID-19)pandemic continues to pose a global threat to the human population. Identifying animal species susceptible to infection with the SARS-CoV-2/HCoV-19 pathogen is essential for controlling the outbreak and for testing valid prophylactics or therapeutics based on animal model studies. Here,different aged Chinese tree shrews(adult group, 1 year old;old group, 5–6 years old), which are close relatives to primates, were infected with SARS-CoV-2. X-ray, viral shedding, laboratory, and histological analyses were performed on different days postinoculation(dpi). Results showed that Chinese tree shrews could be infected by SARS-CoV-2. Lung infiltrates were visible in X-ray radiographs in most infected animals. Viral RNA was consistently detected in lung tissues from infected animals at 3,5, and 7 dpi, along with alterations in related parameters from routine blood tests and serum biochemistry, including increased levels of aspartate aminotransferase(AST) and blood urea nitrogen(BUN). Histological analysis of lung tissues from animals at 3 dpi(adult group) and 7 dpi(old group) showed thickened alveolar septa and interstitial hemorrhage. Several differences were found between the two different aged groups in regard to viral shedding peak. Our results indicate that Chinese tree shrews have the potential to be used as animal models for SARS-CoV-2 infection.
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),causing coronavirus disease 2019(COVID-19),can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and molecular mimicry.Here we summarise the current knowledge about autoimmune liver diseases(AILDs)and SARS-CoV-2,focusing on:(1)The risk of SARS-CoV-2 infection and the course of COVID-19 in patients affected by AILDs;(2)the role of SARS-CoV-2 in inducing liver damage and triggering AILDs;and(3)the ability of vaccines against SARS-CoV-2 to induce autoimmune responses in the liver.Data derived from the literature suggest that patients with AILDs do not carry an increased risk of SARS-Cov-2 infection but may develop a more severe course of COVID-19 if on treatment with steroids or thiopurine.Although SARSCoV-2 infection can lead to the development of several autoimmune diseases,few reports correlate it to the appearance of de novo manifestation of immunemediated liver diseases such as autoimmune hepatitis(AIH),primary biliary cholangitis(PBC)or AIH/PBC overlap syndrome.Different case series of an AIHlike syndrome with a good prognosis after SARS-CoV-2 vaccination have been described.Although the causal link between SARS-CoV-2 vaccines and AIH cannot be definitively established,these reports suggest that this association could be more than coincidental.