Dear Editor,The Coronavirus disease 2019 COVID-19 pandemic has caused over 670 million cases and million deaths worldwide, many of which are attributed to cardiovascular complications. Virus-induced endothelial damage, endothelial barrier dysfunction, thrombosis, and cytokine storm are implicated in heart and multi-organ failure. The prognosis is worsened by comorbidities, including diabetes and arterial hypertension, characterized by an inflammatory and pro-thrombotic milieu and upregulation of total and glycosylated Angiotensin-Converting Enzyme 2 ACE2 in pericytes represent a preferential target of SARS-CoV-2 These perivascular cells preserve vascular integrity through physical and paracrine crosstalk with capillary endothelial cells. Pericyte dysfunction and detachment favor the SARS-CoV-2 to spread from the bloodstream and damage the infection starts with the engagement of the Spike S-protein with its cellular ACE-2 and CD147 receptors. Due to the homology with human proteins, the S-protein also acts as a natural ligand activating the ERK1/2 MAPK signaling pathway in cardiac Some evidence suggests that the S-protein, CD147, cyclophilin, and MAPK axis are essential in triggering the cytokine However, an in vivo demonstration of the S-proteinâs direct damaging effect on cardiac pericytes is present study investigated the acute effects of intravenously injected S-protein on the heart microvasculature of otherwise healthy mice. Moreover, we analyzed the expressional changes caused by the S-protein in primary cultures of human cardiac pericytes using bulk RNA-Sequencing. Finally, the RNA-Sequencing data were cross-referenced with single-nuclei sn-RNA-Sequencing datasets of COVID-19 patientsâ hearts to determine how expressional changes after SARS-CoV-2 infection overlap with those caused by the S-protein healthy CD1 mice 6 male, 6 female were randomized to receive either 10 ”g endotoxin-free S-protein resuspended in 100 ”L sterile PBS or PBS only, intravenously. They were culled three days later for molecular and histological analyses Fig. 1a. S-protein immunoreactive levels in the circulation were like those reported in COVID-19 patients early after infection and before seroconversion ± ng/mL.7 Immunohistochemistry of the hearts demonstrated that the S-protein, although not altering the capillary density, increased the fraction that expresses ICAM-1, an adhesion molecule implicated in leucocyte-endothelial interactions Fig. 1b and remarkably reduced the pericyte density, coverage, and viability Fig. 1câe. SARS-CoV-2 can trigger direct or indirect activation of all three complement Here, we show that the in vivo administration of S-protein increased complement-activated C5a protein levels in peripheral blood and the heart Fig. 1f, g. Moreover, the S-protein increased the heartâs abundance of CD45+ immune cells ± cells/mm2 vs. ± cell/mm2 in PBS-treated mice, specifically Ly6G/6C+ neutrophils/monocytes Fig. 1h and F4/80+ macrophages Fig. 1i. Leucocytes can crawl along pericyte processes to enlarged gaps between adjacent pericytes in an ICAM-1-dependent manner during inflammation. Controls for immunohistochemistry stainings are provided in Supplementary Fig. 1aâi Injection of S-protein in vivo in mice. a Experimental design of the in vivo study in mice. b Representative immunofluorescence images of mice hearts showing capillaries IB4, green and activated endothelium ICAM-1, red. Bar graphs summarize the quantitative analysis of capillaries positive for ICAM-1, expressed as a percentage of total vessels. c Representative immunofluorescence images showing capillaries IB4, green and pericytes PDGFRÎČ, red. Bar graphs summarize the quantitative analysis of pericyte density. d Representative immunofluorescence images showing longitudinal capillaries IB4, green covered by pericytes PDGFRÎČ, red. Bar graphs report the quantitative analysis of pericyte coverage. e Representative immunofluorescence images of mice hearts showing endothelial cells IB4, green, pericytes PDGFRÎČ, red, and TUNEL-positive nuclei apoptotic nuclei, magenta. Bar graphs report the quantification of TUNEL+ pericytes. f Measurement of C5a in mice plasma using ELISA. g Immunohistochemistry/DAB staining and a bar graph showing the accumulation of the activated complement factor C5a in the mice hearts. Nuclei are shown in blue Haematoxylin. The graph reports the integrated optical density IOD values. Representative immunofluorescence images of mice hearts showing the presence of neutrophils/monocytes hâLy6G/6 C, green and macrophages iâF4/80, green. Cardiomyocytes are labeled with α-Sarcomeric Actin red. Bar graphs report the density of Ly6G/6 C+ neutrophils/monocytes and F4/80+ macrophages. In all immunofluorescence images, DAPI labels nuclei in blue. For all images, the scale bar is 50 ÎŒm. For all analyses, n = 6 per group. All data are presented as individual values and means ± SEM. Statistical tests after a normality test, an unpaired t-Test was applied. jâl RNA-Sequencing analysis of human cardiac pericytes challenged with the S-protein in vitro. n = 3 patients. j Experimental design and volcano plot showing transcripts differentially expressed in S-protein-treated nM human cardiac pericytes vs. PBS vehicle-treated pericytes. The terms of the most relevant genes were reported. k Bar graph indicating all differentially expressed KEGG pathways. l Bar graphs indicating the most relevant differentially expressed Reactome pathways. FDR = false discovery rate. Genes were considered differentially expressed for FDR †mâp Sn-RNA-Sequencing analysis of pericytes from COVID-19 patientsâ hearts. n = 22 COVID patients, n = 25 controls. m Plots show the ordering of pericytes in pseudo-time. The starting point of pseudo-time is from the pericytes of healthy donors. n A heatmap summarizing the mean expression of normalized unique molecular identifiers UMIs of genes in the modules resulting from the pseudo-time analysis. o A volcano plot showing fold-change of module expression COVID-19 compared to healthy donors and enrichment significance of each module and differentially expressed genes from bulk RNA-Sequencing comparing PBS-vehicle and Spike. p A plot summarising overlapped/similar Reactome and Gene Ontology terms overrepresented in each module and differentially expressed genes in bulk RNA-Sequencing. q Schematic summarizing major findings and candidate mechanisms underpinning the S-protein damaging action. Left panel We provide novel evidence that S-protein alone can damage the heart microvasculature of otherwise healthy mice. On one side, the S-protein acts as a ligand activating intracellular pericyte signaling, which results in pericyte detachment, death, and decreased vascular coverage, thus disrupting the coronary microcirculation. On the other, the S-protein triggers endothelial activation ICAM-1+ endothelial cells, resulting in increased homing of leukocytes to the heart and accumulation of activated complement protein C5a. Right panel A comparison between the expressional changes induced by the S-protein in primary human cardiac pericytes in vitro and single-nuclei sn-RNA-Sequencing pseudo-time trajectories analysis in pericytes extracted from the heart of deceased COVID-19 patients revealed overlapping expressional responses as indicated. These findings suggest that at least some of the in vivo effects of SARS-CoV-2 on human cardiac pericytes may be due to the modulation of inflammatory and epigenetic pathways triggered by the S-protein interaction with its cell surface receptors. The drawing was created with size imageTo further validate the theory of the S-protein acting as a direct transcriptomic influencer, we added it or the PBS vehicle to human primary cardiac pericytes in vitro for 48 h. RNA-Sequencing analysis indicated the differential modulation of 309 RNA transcripts, with 201 genes being up-regulated and 108 genes down-regulated by the S-protein at FDR < Fig. 1j. KEGG pathway analysis showed an overrepresentation of inflammatory pathways, for example, TNF, IL-17, and NF-kappa B signaling pathways, cytokine-cytokine receptor interaction, and cell adhesion molecules CAMs. Moreover, there was an enrichment for pathways associated with infectious diseases, including Legionellosis, Pertussis, Malaria, Herpes virus, and Epstein-Barr virus infection Fig. 1k. An overview of the pathway analysis based on the Reactome database further pinpointed the transcriptional induction of cytokine signaling pathways, such as IL-10, IL-4, and IL-13 signaling and Toll-like receptor cascade Fig. 1l and Supplementary Fig. S2, and the downregulation of pathways implicated in histone deacetylation and methylation and chromatin modification, and RNA polymerase-related mechanisms controlling promoter opening and clearance, transcription, and chain elongation Fig. 1l and Supplementary Fig. S2. The analysis of modulated biological processes confirmed the upregulation of cellular responses to stress and the downregulation of homeostatic responses associated with healing and angiogenesis processes Supplementary Fig. S3. A comprehensive list of regulated pathways is provided in Supplementary Dataset to dissect clinically relevant targets further, we cross-interrogated the transcriptional landscape of pericytes exposed in vitro to the recombinant S-protein and pericytes from the hearts of COVID-19 patients. Additionally, we employed a pseudo-time inference approach to probe individual genesâ expression dynamics along with the progression of the disease. To this aim, we extracted pericytes from the integrated Seurat, R object downloaded from Delorey et al., 20219 using marker genes followed by a pseudo-time analysis of pericytes collected from the heart of COVID-19 patients Fig. 1m. The pseudo-time analysis allowed the identification of pericyte genes that are differential and co-expressed along the trajectory. This resulted in the recognition of 37 gene clusters Fig. 1n. Next, to identify common signals between ex vivo and in vivo datasets, we tested for the overrepresentation of expressional changes in pericytes exposed to S-protein and gene clusters in the human heart. We observed that seven gene clusters 1, 2, 6, 13, 15, 20, and 27, FDR < significantly overlapped with the expressional changes observed in pericytes exposed to the S-protein experiment Fig. 1o. Cluster 15 was enriched for cytokine-related pathways, metallothioneins, and regulation of histone acetylation, while clusters 1, 6 and 27 were overrepresented for extracellular matrix organization, elastic fibre formation, and integrin cell surface interactions Fig. 1p and Supplementary Dataset 2. Studies have reported that COVID-19 can cause cardiovascular complications due to impaired extracellular matrix organisation and reduced elastic fibre levels, potentially leading to blood These findings suggest a convergence of signals that proteins of the virion envelope mediate at least part of the transcriptional changes induced by the virus in the hearts of infected people. Therefore, some of the in vivo effects of SARS-CoV-2 on human cardiac pericytes may be attributable to the interaction between the S-protein and the hostâs transcriptomic program modulating inflammatory and epigenetic we performed drug target enrichment analysis using the LINCS L1000CDS and DrugBank databases. This analysis allowed us to identify drugs that reverse the expressional changes induced by the S-protein in pericytes Supplementary Dataset 3 and 4. Among the top fifty compounds, we found a prevalence of anti-tumoral, pro-apoptotic, anti-viral, anti-inflammatory and anti-thrombotic drugs, some of which have already been trialed in COVID-19 patients. Although more research is needed to determine if pharmacological interference with the signaling emanating from the S-protein can alleviate COVID-19 outcomes, these data suggest a competitive effect of anti-inflammatory and anti-tumoral drugs. In addition, several compounds like Quercetin or ubiquitin-conjugating enzyme inhibitors may help moderate inflammation by eliminating S-Protein-induced senescent summarized in Fig. 1q provide novel evidence of the SARS-CoV-2 S-proteinâs direct pathogenic action on cardiac pericytes and the heartâs microvasculature. It is plausible that the harmful effects observed in healthy mice three days after a single systemic injection of the S-protein might be intensified in the presence of cardiovascular risk factors and prolonged exposure. These possibilities merit further investigation. Moreover, we showed that the S-protein modifies the transcriptional program of human cells to the virusâ advantage. This new information could have significant implications for the treatment of COVID-19, for instance, using anti-S-protein engineering approaches to protect vascular cells. Data availabilityThe articleâs data can be obtained as reasonably required from the corresponding author. The main datasets underlying transcriptomic analyses are provided as supplementary datasets Dataset 1â4. The bulk RNA-Seq raw data have been deposited in NCBIâs Gene Expression Omnibus and are accessible through GEO Series accession number N. et al. Glycated ACE2 receptor in diabetes open door for SARS-COV-2 entry in cardiomyocyte. Cardiovasc. Diabetol. 20, 99 2021.Article PubMed PubMed Central Google Scholar Sardu, C. et al. Could Anti-Hypertensive Drug Therapy Affect the Clinical Prognosis of Hypertensive Patients With COVID-19 Infection? Data From Centers of Southern Italy. J. Am. Heart Assoc. 9, e016948 2020.Article PubMed PubMed Central Google Scholar Tucker, N. R. et al. Myocyte-Specific Upregulation of ACE2 in Cardiovascular Disease Implications for SARS-CoV-2-Mediated Myocarditis. Circulation 142, 708â710 2020.CAS PubMed PubMed Central Google Scholar Muus, C. et al. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics. Nat. Med. 27, 546â559 2021.Article CAS PubMed PubMed Central Google Scholar Daems, M. et al. SARS-CoV-2 infection causes prolonged cardiomyocyte swelling and inhibition of HIF1alpha translocation in an animal model COVID-19. Front. Cardiovasc. Med. 9, 964512 2022.Article CAS PubMed PubMed Central Google Scholar Khan, A. O. et al. Preferential uptake of SARS-CoV-2 by pericytes potentiates vascular damage and permeability in an organoid model of the microvasculature. Cardiovasc. Res. 118, 3085â3096 2022.Article CAS PubMed PubMed Central Google Scholar Avolio, E. et al. The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling a potential non-infective mechanism of COVID-19 microvascular disease. Clin. Sci. 135, 2667â2689 2021.Article CAS Google Scholar Afzali, B., Noris, M., Lambrecht, B. N. & Kemper, C. The state of complement in COVID-19. Nat. Rev. Immunol. 22, 77â84 2022.Article CAS PubMed Google Scholar Delorey, T. M. et al. COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets. Nature 595, 107â113 2021.Article CAS PubMed PubMed Central Google Scholar Shi, S. et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. 5, 802â810 2020.Article PubMed PubMed Central Google Scholar Download referencesAcknowledgementsThe authors wish to acknowledge the members of the University of Bristol COVID-19 Emergency Research Group UNCOVER for their scientific support. Drawings were generated with work was supported by the British Heart Foundation BHF project grant âTargeting the SARS-CoV-2 S-protein binding to the ACE2 receptor to preserve human cardiac pericytes function in COVID-19â PG/20/10285 to and European Commission H2020 CORDIS project COVIRNA project/id/101016072 to and and BHF Chair award CH/15/1/31199 to In addition, it was supported by a grant from the National Institute for Health Research NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. is a postdoctoral researcher supported by the Heart Research UK translational project grant âTargeting pericytes for halting pulmonary hypertension in infants with congenital heart diseaseâ RG2697/21/23 to and is an investigator of the Wellcome Trust 106115/Z/14/Z.Author informationAuthor notesThese authors contributed equally Elisa Avolio, Prashant K SrivastavaAuthors and AffiliationsBristol Medical School, Translational Health Sciences, University of Bristol, Bristol, UKElisa Avolio, Michele Carrabba, Christopher T. W. Tsang, Yue Gu, Anita C. Thomas & Paolo MadedduNational Heart & Lung Institute, Imperial College, London, UKPrashant K. Srivastava, Jiahui Ji & Costanza EmanueliSchool of Biochemistry, University of Bristol, Bristol, UKKapil Gupta & Imre BergerAuthorsElisa AvolioYou can also search for this author in PubMed Google ScholarPrashant K. SrivastavaYou can also search for this author in PubMed Google ScholarJiahui JiYou can also search for this author in PubMed Google ScholarMichele CarrabbaYou can also search for this author in PubMed Google ScholarChristopher T. W. TsangYou can also search for this author in PubMed Google ScholarYue GuYou can also search for this author in PubMed Google ScholarAnita C. ThomasYou can also search for this author in PubMed Google ScholarKapil GuptaYou can also search for this author in PubMed Google ScholarImre BergerYou can also search for this author in PubMed Google ScholarCostanza EmanueliYou can also search for this author in PubMed Google ScholarPaolo MadedduYou can also search for this author in PubMed Google research conception and design. manuscript writing. histological analyses of mice hearts. cellular and molecular biology experiments. transcriptomic analyses in pericytes. in vivo procedures with mice. production and provision of Spike protein. funding, supervision of transcriptomic studies, and manuscript editing. funding provision. study supervision. All authors data interpretation and manuscript revision. All authors approved the authorship and the final version of the manuscript for authorCorrespondence to Paolo declarations Competing interests The authors declare no competing interests. Ethics declarations The animal study was covered by a license from the British Home Office PPL 1377882 and complied with EU Directive 2010/63/EU. Procedures were carried out according to the principles in the Guide for the Care and Use of Laboratory Animals The Institute of Laboratory Animal Resources, 1996. Termination was conducted according to humane methods outlined in the Guidance on the Operation of the Animals Scientific Procedures Act 1986 Home Office 2014. The collection of human patientsâ cardiac waste tissue was covered by the ethical approval number 15/LO/1064 from the North Somerset and South Bristol Research Ethics Committee. Patients gave informed written consent. Supplementary informationRights and permissions Open Access This article is licensed under a Creative Commons Attribution International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original authors and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the articleâs Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the articleâs Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit Reprints and PermissionsAbout this articleCite this articleAvolio, E., Srivastava, Ji, J. et al. Murine studies and expressional analyses of human cardiac pericytes reveal novel trajectories of SARS-CoV-2 Spike protein-induced microvascular damage. Sig Transduct Target Ther 8, 232 2023. citationReceived 11 January 2023Revised 28 April 2023Accepted 08 May 2023Published 02 June 2023DOIPrinsippemeriksaan kuantitatif antibodi spesifik SARS COV 2 ini menggunakan pemeriksaan laboratorium imunoserologi pada sebuah alat automatik (autoanalyzer) untuk mendeteksi antibodi terhadap SARS-CoV-2 atau pemeriksaan ini biasa disebut dengan ECLIA (ELECTRO CHEMILUMINESCENCE IMMUNOASSAY). Ao longo da pandemia de Covid-19, muitos nomes que nĂŁo costumavam fazer parte da nossa vida se tornaram comuns. Boa parte dessas palavras novas sĂŁo semelhantes e atĂ© parecem sinĂŽnimos, mas se referem a conceitos diferentes. Entender exatamente o que quer dizer cada novo termo da pandemia Ă© importante para evitar a propagação de informaçÔes falsas ou incompletas. A diretora do LaboratĂłrio de Biotecnologia Viral do Instituto Butantan, Soraia Attie Calil Jorge, explica alguns desses conceitos e mostra por que Ă© tĂŁo importante entendĂȘ-los. VĂrus x BactĂ©rias VĂrus seres que dependem de outros para se reproduzir, ou seja, que precisam infectar cĂ©lulas humanas, de plantas e atĂ© de bactĂ©rias para dar origem a seus descendentes. NĂŁo possuem cĂ©lulas por isso se discute se sĂŁo seres vivos ou nĂŁo, apenas material genĂ©tico e proteĂna. Ăs vezes, levam consigo parte da membrana da cĂ©lula que infectaram; por isso, existem vĂrus envelopados e vĂrus nĂŁo-envelopados, sendo que o envelopado Ă© aquele que passou a ter em sua formação parte da membrana da cĂ©lula invadida. Quando entram em nosso corpo, rompendo a membrana para se multiplicar, geralmente estouram nossas cĂ©lulas, causando sua lise dissolução. BactĂ©ria organismos mais independentes do que os vĂrus. SĂŁo cĂ©lulas que possuem material genĂ©tico e diversos mecanismos para se desenvolver e multiplicar, sem precisar de outra cĂ©lula. Por mais que algumas sejam prejudiciais ao nosso corpo, existem certas bactĂ©rias em nosso organismo que sĂŁo benĂ©ficas e nĂŁo causam doença alguma, geralmente fornecem substĂąncias importantes ou regulam parte do nosso metabolismo. CoronavĂrus X SARS-CoV-2 X Covid-19 CoronavĂrus nome dado a uma extensa famĂlia de vĂrus que se assemelham. Muitos deles jĂĄ nos infectaram diversas vezes ao longo da histĂłria da humanidade. Dentro dessa famĂlia hĂĄ vĂĄrios tipos de coronavĂrus, inclusive os chamados SARS-CoVs a sĂndrome respiratĂłria aguda grave, conhecida pela sigla SARS, que hĂĄ alguns anos começou na China e se espalhou para paĂses da Ăsia, tambĂ©m Ă© causada por um coronavĂrus. SARS-CoV-2 vĂrus da famĂlia dos coronavĂrus que, ao infectar humanos, causa uma doença chamada Covid-19. Por ser um microrganismo que atĂ© pouco tempo nĂŁo era transmitido entre humanos, ele ficou conhecido, no inĂcio da pandemia, como ânovo coronavĂrusâ. Covid-19 doença que se manifesta em nĂłs, seres humanos, apĂłs a infecção causada pelo vĂrus SARS-CoV-2. PrevalĂȘncia x IncidĂȘncia PrevalĂȘncia visĂŁo geral de uma doença, ou seja, quantos casos ou mortes aquela doença provocou em sua totalidade. No Brasil, jĂĄ temos mais de 21 milhĂ”es de casos e mais de 588 mil mortes por Covid-19, entĂŁo esse nĂșmero equivale Ă prevalĂȘncia da doença. IncidĂȘncia Ă© um indicador mais fechado, que nĂŁo olha em Ăąmbito geral para uma doença, mas traça um recorte em determinado perĂodo de tempo. Em agosto, o Brasil registrou a menor incidĂȘncia mensal de mortes por Covid-19 em 2021, com pouco mais de 24 mil Ăłbitos. Mortalidade x Letalidade Mortalidade Ă o tanto de pessoas que adoeceram e morreram em relação a toda a população de uma regiĂŁo. Tem relação com um cenĂĄrio geral, como a totalidade de mortos por determinada doença em uma população inteira durante uma pandemia, epidemia ou surto. Letalidade estĂĄ ligada ao patĂłgeno o vĂrus SARS-CoV-2, no caso e avalia o nĂșmero de mortes em relação Ă s pessoas que apresentam a doença ativa, e nĂŁo em relação Ă população toda. Em outras palavras, mede a porcentagem de pessoas infectadas que evoluem para Ăłbito. O SARS-CoV-2 nĂŁo tem uma alta letalidade 2,9%, pois muitas pessoas que contraem o vĂrus ficam assintomĂĄticas, Ă s vezes sem nem mesmo saber que estĂŁo infectadas. Penyakitkoronavirus 2019 (bahasa Inggris: corona virus disease 2019, disingkat Covid-19) adalah penyakit menular yang disebabkan oleh SARS-CoV-2, salah satu jenis koronavirus. Penyakit ini mengakibatkan pandemi. Penderita Covid-19 dapat mengalami demam, batuk kering, dan kesulitan bernapas. Sakit tenggorokan, pilek, atau bersin-bersin lebih jarang ditemukan.
. 2021 Oct;2710 doi Epub 2021 Jun 7. Sheila F Lumley 2 , Jia Wei 3 , Stuart Cox 4 , Tim James 4 , Anita Justice 4 , Gerald Jesuthasan 4 , Denise O'Donnell 3 , Alison Howarth 3 , Stephanie B Hatch 3 , Brian D Marsden 5 , E Yvonne Jones 3 , David I Stuart 3 , Daniel Ebner 6 , Sarah Hoosdally 7 , Derrick W Crook 2 , Tim E A Peto 2 , Timothy M Walker 8 , Nicole E Stoesser 2 , Philippa C Matthews 2 , Koen B Pouwels 9 , A Sarah Walker 7 , Katie Jeffery 4 Affiliations PMID 34111577 PMCID PMC8180449 DOI Free PMC article Quantitative SARS-CoV-2 anti-spike responses to Pfizer-BioNTech and Oxford-AstraZeneca vaccines by previous infection status David W Eyre et al. Clin Microbiol Infect. 2021 Oct. Free PMC article Abstract Objectives We investigated determinants of severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 anti-spike IgG responses in healthcare workers HCWs following one or two doses of Pfizer-BioNTech or Oxford-AstraZeneca vaccines. Methods HCWs participating in regular SARS-CoV-2 PCR and antibody testing were invited for serological testing prior to first and second vaccination, and 4 weeks post-vaccination if receiving a 12-week dosing interval. Quantitative post-vaccination anti-spike antibody responses were measured using the Abbott SARS-CoV-2 IgG II Quant assay detection threshold â„50 AU/mL. We used multivariable logistic regression to identify predictors of seropositivity and generalized additive models to track antibody responses over time. Results 3570/3610 HCWs were seropositive >14 days post first vaccination and prior to second vaccination 2706/2720 were seropositive after the Pfizer-BioNTech and 864/890 following the Oxford-AstraZeneca vaccines. Previously infected and younger HCWs were more likely to test seropositive post first vaccination, with no evidence of differences by sex or ethnicity. All 470 HCWs tested >14 days after the second vaccination were seropositive. Quantitative antibody responses were higher after previous infection median IQR >21 days post first Pfizer-BioNTech 14 604 7644-22 291 AU/mL versus 1028 564-1985 AU/mL without prior infection p 21 days post second Pfizer vaccination in those not previously infected, 10 058 6408-15 582 AU/mL, were similar to those after prior infection followed by one vaccine dose. Conclusions SARS-CoV-2 vaccination leads to detectable anti-spike antibodies in nearly all adult HCWs. Whether differences in response impact vaccine efficacy needs further study. Keywords Antibody; Quantitative anti-spike antibody; SARS-CoV-2; Serology; Vaccine. Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved. Figures Fig. 1 Anti-spike IgG-positive results by days since first vaccination, by prior infection status and vaccine received. Tests performed after a second dose of vaccine are not included. The number of tests performed and positive and the resulting percentage is shown under each bar. Fig. 2 The relationship between vaccine, age and probability of testing anti-spike IgG seropositive >14 days post first vaccination. Model predictions are shown using reference categories for sex and ethnicity white, female, respectively and in those without prior evidence of infection. Fig. 3 Modelled quantitative anti-spike IgG responses following first vaccination by vaccine and previous infection status. Panels A and B show responses in previously infected healthcare workers HCWs and panels C and D HCWs without evidence of previous infection. Panels A and C show data for those receiving PfizerâBioNTech vaccine and panels B and D OxfordâAstraZeneca vaccine. Model predictions are shown at three example ages 30, 45, and 60 years. The shaded ribbon shows the 95% confidence interval. Values are plotted from 7 days prior to vaccination to illustrate baseline values models are fitted using data from 28 days prior to vaccination onwards. Fig. 4 Modelled quantitative anti-spike IgG titres following second PfizerâBioNTech vaccination by previous infection status. Panel A shows those who were previous infected including those previously infected at baseline or testing PCR-positive between vaccines and panel B those who had no evidence of previous infection. Model predictions are shown at three example ages 30, 45, and 60 years. The shaded ribbon shows the 95% confidence interval. Data were included in each model from 7 days before the second vaccination to allow pre-vaccination levels to be fitted correctly. Similar articles Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients. Rabinowich L, Grupper A, Baruch R, Ben-Yehoyada M, Halperin T, Turner D, Katchman E, Levi S, Houri I, Lubezky N, Shibolet O, Katchman H. Rabinowich L, et al. J Hepatol. 2021 Aug;752435-438. doi Epub 2021 Apr 21. J Hepatol. 2021. PMID 33892006 Free PMC article. 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COVID-19 vaccines comparison of biological, pharmacological characteristics and adverse effects of Pfizer/BioNTech and Moderna Vaccines. Meo SA, Bukhari IA, Akram J, Meo AS, Klonoff DC. Meo SA, et al. Eur Rev Med Pharmacol Sci. 2021 Feb;2531663-1669. doi Eur Rev Med Pharmacol Sci. 2021. PMID 33629336 Review. SARS-CoV-2 Proteins Are They Useful as Targets for COVID-19 Drugs and Vaccines? Mohammed MEA. Mohammed MEA. Curr Mol Med. 2022;22150-66. doi Curr Mol Med. 2022. PMID 33622224 Review. Cited by Tracking Changes in Mobility Before and After the First SARS-CoV-2 Vaccination Using Global Positioning System Data in England and Wales Virus Watch Prospective Observational Community Cohort Study. Nguyen V, Liu Y, Mumford R, Flanagan B, Patel P, Braithwaite I, Shrotri M, Byrne T, Beale S, Aryee A, Fong WLE, Fragaszy E, Geismar C, Navaratnam AMD, Hardelid P, Kovar J, Pope A, Cheng T, Hayward A, Aldridge R; Virus Watch Collaborative. Nguyen V, et al. JMIR Public Health Surveill. 2023 Mar 8;9e38072. doi JMIR Public Health Surveill. 2023. PMID 36884272 Free PMC article. Impact of BNT162b2 Booster Dose on SARS-CoV-2 Anti-Trimeric Spike Antibody Dynamics in a Large Cohort of Italian Health Care Workers. Renna LV, Bertani F, Podio A, Boveri S, Carrara M, Pinton A, Milani V, Spuria G, Nizza AF, Basilico S, Dubini C, Cerri A, Menicanti L, Corsi-Romanelli MM, Malavazos AE, Cardani R. Renna LV, et al. Vaccines Basel. 2023 Feb 17;112463. doi Vaccines Basel. 2023. PMID 36851340 Free PMC article. Robust specific RBD responses and neutralizing antibodies after ChAdOx1 nCoV-19 and CoronaVac vaccination in SARS-CoV-2- seropositive individuals. Fernandes ER, Taminato M, de Souza Apostolico J, Gabrielonni MC, Lunardelli VAS, Maricato JT, Andersen ML, Tufik S, Rosa DS. Fernandes ER, et al. J Allergy Clin Immunol Glob. 2023 May;22100083. doi Epub 2023 Feb 21. J Allergy Clin Immunol Glob. 2023. PMID 36845213 Free PMC article. Durability of ChAdOx1 nCoV-19 Covishield Vaccine Induced Antibody Response in Health Care Workers. Verma A, Goel A, Katiyar H, Tiwari P, Mayank, Sana A, Khetan D, Bhadauria DS, Raja A, Khokher N, Shalimar, Singh RK, Aggarwal A. Verma A, et al. Vaccines Basel. 2022 Dec 30;11184. doi Vaccines Basel. 2022. PMID 36679930 Free PMC article. The Influence of Two Priming Doses of Different Anti-COVID-19 Vaccines on the Production of Anti-SARS-CoV-2 Antibodies After the Administration of the Pfizer/BioNTech Booster. Wolszczak Biedrzycka B, BieĆkowska A, SmoliĆska-FijoĆek E, Biedrzycki G, Dorf J. Wolszczak Biedrzycka B, et al. Infect Drug Resist. 2022 Dec 29;157811-7821. doi eCollection 2022. Infect Drug Resist. 2022. PMID 36600955 Free PMC article. References Folegatti Ewer Aley Angus B., Becker S., Belij-Rammerstorfer S. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020;396467â478. - PMC - PubMed Wajnberg A., Amanat F., Firpo A., Altman Bailey Mansour M. Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science. 2020;3701227â1230. - PMC - PubMed GeurtsvanKessel Okba Igloi Z., Bogers S., Embregts Laksono An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment. Nat Commun. 2020;113436. - PMC - PubMed Medicines and Healthcare products Regulatory Agency . 2020. MHRA guidance on coronavirus COVID-19 Walsh Frenck Falsey Kitchin N., Absalon J., Gurtman A. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med. 2020;3832439â2450. - PMC - PubMed MeSH terms Substances LinkOut - more resources Full Text Sources Elsevier Science Europe PubMed Central PubMed Central Medical Genetic Alliance MedlinePlus Health Information Miscellaneous NCI CPTAC Assay Portal
Infectionand deaths cases by SARS-CoV-2 still increase and have not decreased significantly. Main protease (Mpro) is playing an important role in the replication of SARS-CoV-2 life cycle and causes of rapid transmission. Natural compounds are potential to be antiviral candidates with high bioavailability and low cytotoxicity. Orchids of Dendrobium genus have
IntroductionIt has been more than one year since the first reported case of the novel coronavirus disease 2019 COVID-19, which has already cost more than 2 million lives Fortunately, vaccines against severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 have been developed with record-breaking speed and vaccine programs are ongoing worldwide to take the pandemic under During this expansion of research focus from treatment to prevention of COVID-19, the immune evasion mechanism and immunopathogenic nature of SARS-CoV-2 adds uncertainty to the efficacy of this global vaccination During natural infection, SARS-CoV-2 could avoid the innate antiviral response mediated by interferons IFNs via an array of possible strategies,4,5 which not only leads to viral replication and spreading but also could delay or impair the adaptive immune response including T cell and antibody The significant prevalence of SARS-CoV-2 RNA re-positive cases among discharged patients further raises the concern about the effectiveness and persistency of immune responses after natural Recent long-term follow-up surveys report significant decrease of SARS-CoV-2 antibody titers 5 to 8 months after infection,10,11,12 but its correlation with reduced capacity of SARS-CoV-2 neutralization and immune memory is still vaccination, equally important is the recovery and rehabilitation of COVID-19 Mild cases usually do not require hospitalization but may share similar long-lasting symptoms or discomforts with severe cases, which may reduce life quality after recovery from Also, cardiac magnet resonance imaging cMRI screening revealed surprisingly high prevalence of subclinical myocardial inflammation and fibrosis in recently recovered Due to the overloading of medical systems and the fear of in-hospital transmission, long-term follow-up studies of the structural and functional recovery of COVID-19-involved organs are still this prospective cohort study of recovered COVID-19 patients from Xiangyang, China, we aimed to assess long-term antibody response at 12 months after infection and comprehensively evaluate the structural and functional recovery of the lung and cardiovascular systems. We also attempted to identify potential risk factors associated with those long-term January 15 through 31 March 2020, a total of 307 patients were diagnosed with COVID-19 at Xiangyang Central Hospital, which represented of 549 cases in the downtown and of 1175 cases city-wide. During hospitalization, 12 patients succumbed to COVID-19-induced respiratory distress or lethal infection, which translated to a mortality rate of in line with the citywide mortality rate of 40/1175. All 295 survivors were invited to participate in this study and the final cohort consisted of 121 survivors including 19 recovered from severe COVID-19 Supplementary Fig. 1. Clinical procedures were performed at Xiangyang Central Hospital between 25 December 2020 and 29 January and clinical features of participantsDemographic-wise, this cohort consisted of middle-aged Chinese population with an overall comorbidity prevalence of including hypertension and diabetes as the most common preexisting conditions, which was typical for the local agricultural and industrial population with a preference of high-salt diets Table 1. The participants of this study were among the earliest confirmed COVID-19 patients with virological confirmation dates as early as January 19, 2020. Standard of care consisted of antivirals, antibiotics, immunomodulants and supplemental oxygen was given to participants following CDC guidelines Supplementary Table 1. Only 1 in this cohort received invasive ventilation Supplementary Table 1, which reflected the dismal mortality rate among critically ill patients relying on respiratory Of note, the basic characteristics of this cohort were comparable with the entire population of COVID-19 survivors treated at this hospital Supplementary Table 2.Table 1 Characteristics of participants by COVID-19 severityFull size tableAfter stratifying the cohort by severity graded according to the guideline,21 severe groups had higher ages, less females, and more comorbidities Table 1. Severe group also presented more symptoms at admission, and received more aggressive immunomodulatory therapies, supplemental oxygen, and ICU care during hospitalization Supplementary Table 1. Both severe and non-severe groups share similar lengths since symptom onset, while the severe group had shorter periods since recovery because of longer hospitalization Table 1.Long-lasting SARS-CoV-2 antibody response 1-year after infectionFirst, blood samples were screened by colloidal gold-based immunochromatographic assays GICA separately detecting IgM and IgG against At a median of 11 months post- infection, only 4% 95% CI, 2â10% participants returned positive IgM results, which included both positive and weakly positive results, while 62% 95% CI, 54â71% were IgG positive Table 1, comparing to prevalence of IgM among pre-discharge samples from the same Severe group showed higher prevalence of IgG, while the prevalence of IgM was equally low in both groups Table 1.Next, the concentration of total antibodies against the receptor-binding domain of SARS-CoV-2 spike protein RBD was quantitatively measured by chemiluminescence microparticle immunoassays CMIA.24 Although signal/cutoff S/CO ratios were lower in non-severe group, all but 1 of the results were above the positive diagnostic threshold of S/CO = when all 100 samples of unexposed individuals, which were randomly chosen from sera of in-hospital patients who had negative results from multiple PCR and serological tests for SARS-CoV-2 before and after the date of serum collection, had S/CO values participants were exposed to SARS-CoV-2 and diagnosed with COVID-19 during January to March 2020. During their COVID-19 disease courses, they have received combinations of therapies including antivirals, immunomodulatory agents, antibiotics, supplemental oxygen, and ICU outcomes of this study were immunity against SARS-CoV-2 and functional recovery of the lung and other involved organs. Immunity against SARS-CoV-2 was assessed by multiple antibody assays. The colloidal gold-based test kit gave positive, weak positive, and negative readout of anti-SARS-CoV-2 IgM and IgG separately. The quantitative chemiluminescence microparticle immunoassay for antibodies against SARS-CoV-2 RBD was performed according to manufacturerâs protocol and previous publication,24 and the results were deemed positive if the signal/cutoff S/CO ratio â„1. For ELISA tests, results were recorded and analyzed as continuous variables and the limit of sensitivity was calculated as mean + 2 Ă SD of 20 serum samples negative for SARS-CoV-2 antibodies in chemiluminescence assays. Functional recovery of the lung was assessed based on 1 current CT images comparing to images taken before discharge and during earlier follow-ups, 2 pulmonary function test results, and 3 six-minute walk test results. Recovery of the heart was assessed based on ECG, echocardiogram, and cardiac MRI scans. Recovery of other potentially involved organs were assessed by laboratory tests Roche Diagnostics.Sample sizeAn initial target sample size of 108 was determined based on the assumption of a 15 ratio of severe and non-severe COVID-19 patient enrollment and α = This sample size was calculated to have 90% power to detect a 10% difference of antibody concentrations. The final sample size exceeded the target in both analysisQuantitative data were presented in violin plots with all data points shown. Patient characteristics and clinical data were summarized as incidence with prevalence or median with IQR and were assessed with Fisherâs exact test dichotomous variables or Ï2 test variables with more than two categories for categorical variables and MannâWhitney U test for continuous variables. Antibody concentrations were log-transformed before being analyzed as continuous variables. The difference of antibody concentrations between groups were assessed by the MannâWhitney U test two groups or KruskalâWallis test with post hoc comparisons more than two groups. Special tests were mentioned in figure legends. Correlation was assessed by Spearmanâs Ï test. Linearity between two factors was assessed by simple linear regression. Generalized linear models were used to assess factors associated with antibody titers. Analyses were performed using SPSS 26 IBM or Prism 9 GraphPad. Missing data were excluded pairwise from analyses. Significance was evaluated at α = .05 and all tests were 2-sided. *p < **p < ***p < Data availabilityReasonable requests for original dataset and clinical documents would be fulfilled by Dr. Peng Hong P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270â273 2020.Article CAS PubMed PubMed Central Google Scholar Parker, E. P. K., Shrotri, M. & Kampmann, B. Keeping track of the SARS-CoV-2 vaccine pipeline. Nat. Rev. Immunol. 20, 650 2020.Article CAS PubMed Google Scholar Sette, A. & Crotty, S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell 184, 861â880 2021.Article CAS PubMed PubMed Central Google Scholar Blanco-Melo, D. et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell 181, 1036â 2020.Article CAS PubMed PubMed Central Google Scholar Lei, X. et al. Activation and evasion of type I interferon responses by SARS-CoV-2. Nat. Commun. 11, 3810 2020.Article CAS PubMed PubMed Central Google Scholar Oved, K. et al. Multi-center nationwide comparison of seven serology assays reveals a SARS-CoV-2 non-responding seronegative subpopulation. EClinicalMedicine 29, 100651 2020.Article PubMed Google Scholar Anna, F. et al. High seroprevalence but short-lived immune response to SARS-CoV-2 infection in Paris. Eur. J. Immunol. 51, 180â190 2021.Article CAS PubMed Google Scholar Lu, J. et al. Clinical, immunological and virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR. EBioMedicine 59, 102960 2020.Article PubMed PubMed Central Google Scholar Yang, C. et al. Viral RNA level, serum antibody responses, and transmission risk in recovered COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results a population-based observational cohort study. Emerg. Microbes Infect. 9, 2368â2378 2020.Article CAS PubMed PubMed Central Google Scholar Choe, P. G. et al. Waning antibody responses in asymptomatic and symptomatic SARS-CoV-2 infection. Emerg. Infect. Dis. 27, 327â329 2021.Article CAS PubMed Central Google Scholar Huang, C. et al. 6-month consequences of COVID-19 in patients discharged from hospital a cohort study. Lancet 397, 220â232 2021.Article CAS PubMed PubMed Central Google Scholar Self, W. H. et al. Decline in SARS-CoV-2 antibodies after mild infection among frontline health care personnel in a multistate hospital network - 12 states, April-August 2020. Morb. Mortal. Wkly. Rep. 69, 1762â1766 2020.Article CAS Google Scholar Wajnberg, A. et al. Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science 370, 1227â1230 2020.Article CAS PubMed PubMed Central Google Scholar Dan, J. M. et al. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science 371, eabf4063 2021.Article CAS PubMed Google Scholar Yelin, D. et al. Long-term consequences of COVID-19 research needs. Lancet Infect. Dis. 20, 1115â1117 2020.Article CAS PubMed PubMed Central Google Scholar Gandhi, R. T., Lynch, J. B. & Del Rio, C. Mild or moderate Covid-19. N. Engl. J. Med. 383, 1757â1766 2020.Article CAS PubMed Google Scholar Carfi, A., Bernabei, R. & Landi, F., Gemelli Against, Persistent symptoms in patients after acute COVID-19. JAMA 324, 603â605 2020.Article CAS PubMed PubMed Central Google Scholar Puntmann, V. O. et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 COVID-19. JAMA Cardiol. 5, 1265â1273 2020.Article PubMed PubMed Central Google Scholar Cortinovis, M., Perico, N. & Remuzzi, G. Long-term follow-up of recovered patients with COVID-19. Lancet 397, 173â175 2021.Article CAS PubMed PubMed Central Google Scholar Dupuis, C. et al. Association between early invasive mechanical ventilation and day-60 mortality in acute hypoxemic respiratory failure related to coronavirus disease-2019 pneumonia. Crit. Care Explor 3, e0329 2021.Article PubMed PubMed Central Google Scholar NHCPRC. National Health Commission of the Peopleâs Republic of China. Chinese management guideline for COVID-19 version 7 [in Chinese]. 2020.Pan, Y. et al. Serological immunochromatographic approach in diagnosis with SARS-CoV-2 infected COVID-19 patients. J. Infect. 81, e28âe32 2020.Article CAS PubMed PubMed Central Google Scholar Shen, L. et al. Delayed specific IgM antibody responses observed among COVID-19 patients with severe progression. Emerg. Microbes Infect. 9, 1096â1101 2020.Article CAS PubMed PubMed Central Google Scholar Liu, W. et al. Clinical application of chemiluminescence microparticle immunoassay for SARS-CoV-2 infection diagnosis. J. Clin. Virol. 130, 104576 2020.Article CAS PubMed PubMed Central Google Scholar Atyeo, C. et al. Distinct early serological signatures track with SARS-CoV-2 survival. Immunity 53, 524â 2020.Article CAS PubMed PubMed Central Google Scholar Long, Q. X. et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat. Med. 26, 845â848 2020.Article CAS PubMed Google Scholar Schmidt, F. et al. Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses. J. Exp. Med. 217, 11 e20201181 2020.Article PubMed CAS Google Scholar Khoury, D. S. et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat. Med. 27, 1205â1211 2021.Article CAS PubMed Google Scholar Wang, P. et al. Antibody resistance of SARS-CoV-2 variants and Nature 593, 130â135 2021.Article CAS PubMed Google Scholar McCrohon, J. A. et al. Differentiation of heart failure related to dilated cardiomyopathy and coronary artery disease using gadolinium-enhanced cardiovascular magnetic resonance. Circulation 108, 54â59 2003.Article CAS PubMed Google Scholar Chaowu, Y. & Li, L. Histopathological basis of myocardial late gadolinium enhancement in patients with systemic hypertension. Circulation 130, 2210â2212 2014.Article PubMed Google Scholar Wadhera, R. K. et al. Variation in COVID-19 hospitalizations and deaths across New York City boroughs. JAMA 323, 2192â2195 2020.Article CAS PubMed PubMed Central Google Scholar Paremoer, L., Nandi, S., Serag, H. & Baum, F. Covid-19 pandemic and the social determinants of health. BMJ 372, n129 2021.Article PubMed PubMed Central Google Scholar Wu, Z. & McGoogan, J. M. Characteristics of and important lessons from the coronavirus disease 2019 COVID-19 outbreak in China summary of a report of 72314 cases from the Chinese center for disease control and prevention. JAMA 323, 1239â1242 2020.Article CAS PubMed Google Scholar Ji, Y., Ma, Z., Peppelenbosch, M. P. & Pan, Q. Potential association between COVID-19 mortality and health-care resource availability. Lancet Glob. Health 8, e480 2020.Article PubMed PubMed Central Google Scholar Li, Q. et al. The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity. Cell 182, 1284â 2020.Article CAS PubMed PubMed Central Google Scholar Trump, S. et al. Hypertension delays viral clearance and exacerbates airway hyperinflammation in patients with COVID-19. Nat. Biotechnol. 39, 705â716 2021.Article CAS PubMed Google Scholar Hu, F. et al. A compromised specific humoral immune response against the SARS-CoV-2 receptor-binding domain is related to viral persistence and periodic shedding in the gastrointestinal tract. Cell Mol. Immunol. 17, 1119â1125 2020.Article CAS PubMed Google Scholar Naidu, S. B. et al. The high mental health burden of "Long COVID" and its association with on-going physical and respiratory symptoms in all adults discharged from hospital. Eur. Respir. J. 57, 2004364 2021.Article CAS PubMed PubMed Central Google Scholar Sudre, C. H. et al. Attributes and predictors of long COVID. Nat. Med. 27, 626â631 2021.Article CAS PubMed PubMed Central Google Scholar Augustin, M. et al. Post-COVID syndrome in non-hospitalised patients with COVID-19 a longitudinal prospective cohort study. Lancet Reg. Health Eur. 6, 100122 2021.Article PubMed PubMed Central Google Scholar Peghin, M. et al. Post-COVID-19 symptoms 6 months after acute infection among hospitalized and non-hospitalized patients. Clin. Microbiol. Infect. 27, 1507â1513 2021.Article CAS PubMed PubMed Central Google Scholar Rogers, J. P. et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry 7, 611â627 2020.Article PubMed PubMed Central Google Scholar Reichard, R. R. et al. Neuropathology of COVID-19 a spectrum of vascular and acute disseminated encephalomyelitis ADEM-like pathology. Acta Neuropathol. 140, 1â6 2020.Article CAS PubMed PubMed Central Google Scholar Varatharaj, A. et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients a UK-wide surveillance study. Lancet Psychiatry 7, 875â882 2020.Article PubMed PubMed Central Google Scholar Francone, M. et al. Chest CT score in COVID-19 patients correlation with disease severity and short-term prognosis. Eur. Radiol. 30, 6808â6817 2020.Article CAS PubMed PubMed Central Google Scholar Holland, A. E. et al. An official European Respiratory Society/American Thoracic Society technical standard field walking tests in chronic respiratory disease. Eur. Respir. J. 44, 1428â1446 2014.Article PubMed Google Scholar Hajiro, T. et al. Analysis of clinical methods used to evaluate dyspnea in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 158, 1185â1189 1998.Article CAS PubMed Google Scholar Graham, B. L. et al. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am. J. Respir. Crit. Care Med. 200, e70âe88 2019.Article PubMed PubMed Central Google Scholar Milanese, M. et al. Suggestions for lung function testing in the context of COVID-19. Respir. Med. 177, 106292 2020.Article PubMed PubMed Central Google Scholar Download referencesAcknowledgementsWe thank Chun Mao Xiangyang Central Hospital and Juan Xiao Hubei University of Arts and Science for organization and administrative support of patient recruitments and clinical examinations. We also thank Rongjie Zhao, Zhangli Li Thermo Fisher Scientific China, Shanghai, China, and GenScript Nanjing, China for technical support and protocol optimization. This work was supported by Xiangyang Science and Technology Bureau 2020YL10, 2020YL14, 2020YL17, and 2020YL39, National Natural Science Foundation of China 31501116, Shenzhen Science and Technology Innovation Commission JCYJ20190809100005672, Shenzhen Sanming Project of Medicine SZSM201911013, and US Department of Veterans Affairs 5I01BX001353.Author informationAuthor notesThese authors contributed equally Yan Zhan, Yufang Zhu, Shanshan Wang, Shijun Jia, Yunling Gao, Yingying LuAuthors and AffiliationsDepartment of Rehabilitation Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, ChinaYan Zhan, Shanshan Wang, Peng Du, Hao Yu, Chang Liu & Peijun LiuDepartment of Laboratory Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, ChinaYufang Zhu, Caili Zhou & Ran LiangDepartment of Radiology and Medical Imaging, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, ChinaShijun Jia & Feng WuDepartment of Research Affairs, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, ChinaYunling Gao & Jin ChengDepartment of Nephrology, Center of Nephrology and Urology, Sun Yat-sen University Seventh Hospital, Shenzhen, Guangdong, 518107, ChinaYingying Lu, Zhihua Zheng & Peng HongDepartment of Biomedical Science, Shenzhen Research Institute, City University of Hong Kong, Kowloon Tong, Hong Kong, ChinaYingying LuDepartment of Rehabilitation Medicine, Xiangzhou District Peopleâs Hospital, Xiangyang, Hubei, 441000, ChinaDingwen SunDepartment of Rehabilitation Medicine, Gucheng Peopleâs Hospital, Affiliated Gucheng Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441700, ChinaXiaobo WangDivision of Quality Control, Xiangyang Central Blood Station, Xiangyang, Hubei, 441000, ChinaZhibing HouDepartment of Respiratory and Critical Care Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, ChinaQiaoqiao Hu & Yulan ZhengDepartment of Pathology, Mount Sinai St. Lukeâs Roosevelt Hospital Center, New York, NY, 10025, USAMiao CuiDepartment of Oncology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, ChinaGangling TongDepartment of Dermatology, Sun Yat-sen University Seventh Hospital, Shenzhen, Guangdong, 518107, ChinaYunsheng Xu & Linyu ZhuDivision of Research and Development, US Department of Veterans Affairs New York Harbor Healthcare System, Brooklyn, NY, 11209, USAPeng HongDepartment of Cell Biology, State University of New York Downstate Health Sciences University, Brooklyn, NY, 11203, USAPeng HongAuthorsYan ZhanYou can also search for this author in PubMed Google ScholarYufang ZhuYou can also search for this author in PubMed Google ScholarShanshan WangYou can also search for this author in PubMed Google ScholarShijun JiaYou can also search for this author in PubMed Google ScholarYunling GaoYou can also search for this author in PubMed Google ScholarYingying LuYou can also search for this author in PubMed Google ScholarCaili ZhouYou can also search for this author in PubMed Google ScholarRan LiangYou can also search for this author in PubMed Google ScholarDingwen SunYou can also search for this author in PubMed Google ScholarXiaobo WangYou can also search for this author in PubMed Google ScholarZhibing HouYou can also search for this author in PubMed Google ScholarQiaoqiao HuYou can also search for this author in PubMed Google ScholarPeng DuYou can also search for this author in PubMed Google ScholarHao YuYou can also search for this author in PubMed Google ScholarChang LiuYou can also search for this author in PubMed Google ScholarMiao CuiYou can also search for this author in PubMed Google ScholarGangling TongYou can also search for this author in PubMed Google ScholarZhihua ZhengYou can also search for this author in PubMed Google ScholarYunsheng XuYou can also search for this author in PubMed Google ScholarLinyu ZhuYou can also search for this author in PubMed Google ScholarJin ChengYou can also search for this author in PubMed Google ScholarFeng WuYou can also search for this author in PubMed Google ScholarYulan ZhengYou can also search for this author in PubMed Google ScholarPeijun LiuYou can also search for this author in PubMed Google ScholarPeng HongYou can also search for this author in PubMed Google ScholarContributionsY. Zhan and conceptualized the study; Y. Zhan, and recruited patients, performed physical examinations, and abstracted historic data; Y. Zhu, and performed laboratory tests and interpreted results; and conducted sonographic and radiological examinations and interpreted results; and Y. Zheng conducted PFT and interpreted results; Y. Zhan, and conducted functional tests, assessed rehabilitation status and interpreted data; and interpreted metabolic and immunological findings; Y. Zhan, and conducted data quality checks and performed statistical analyses; Y. Zhan and wrote the manuscript. All authors read and approved the final authorsCorrespondence to Feng Wu, Yulan Zheng, Peijun Liu or Peng declarations Competing interests The authors declare no competing interests. Supplementary informationRights and permissions Open Access This article is licensed under a Creative Commons Attribution International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original authors and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the articleâs Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the articleâs Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit Reprints and PermissionsAbout this articleCite this articleZhan, Y., Zhu, Y., Wang, S. et al. SARS-CoV-2 immunity and functional recovery of COVID-19 patients 1-year after infection. Sig Transduct Target Ther 6, 368 2021. citationReceived 06 March 2021Revised 16 September 2021Accepted 20 September 2021Published 13 October 2021DOI
Sementarametode yang digunakan dalam pemeriksaan ini adalah Electro Chemiluminescence Immunoassay (ECLIA) yang menggunakan protein rekombinan mewakili Receptor binding domain (RBD) antigen Spike (S), dengan mengukur antibodi spesifik dengan afinitas tinggi terhadap SARS-CoV-2 secara kuantitatif dalam serum pasien dengan satuanEvaluation of Three Quantitative Anti-SARS-CoV-2 Antibody Immunoassays Sabine Chapuy-Regaud et al. Microbiol Spectr. 2021. Free PMC article Abstract The severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 emerged in December 2019 and caused a dramatic pandemic. Serological assays are used to check for immunization and assess herd immunity. We evaluated commercially available assays designed to quantify antibodies directed to the SARS-CoV-2 Spike S antigen, either total WantaĂŻ SARS-CoV-2 Ab ELISA or IgG SARS-CoV-2 IgG II Quant on Alinity, Abbott, and Liaison SARS-CoV-2 TrimericS IgG, Diasorin. The specificities of the WantaĂŻ, Alinity, and Liaison assays were evaluated using 100 prepandemic sera and were 98, 99, and 97%, respectively. The sensitivities of all three were around 100% when tested on 35 samples taken 15 to 35 days postinfection. They were less sensitive for 150 sera from late infections >180 days. Using the first WHO international standard NIBSC, we showed that the Wantai results were concordant with the NIBSC values, while Liaison and Alinity showed a proportional bias of and 7, respectively. The results of the 3 immunoassays were significantly globally pairwise correlated and for late infection sera P < They were correlated for recent infection sera measured with Alinity and Liaison P < However, the Wantai results of recent infections were not correlated with those from Alinity or Liaison. All the immunoassay results were significantly correlated with the neutralizing antibody titers obtained using a live virus neutralization assay with the SARS-CoV-2 strain. These assays will be useful once the protective anti-SARS-CoV-2 antibody titer has been determined. IMPORTANCE Standardization and correlation with virus neutralization assays are critical points to compare the performance of serological assays designed to quantify anti-SARS-CoV-2 antibodies in order to identify their optimal use. We have evaluated three serological immunoassays based on the virus spike antigen that detect anti-SARS-CoV-2 antibodies a microplate assay and two chemiluminescent assays performed with Alinity Abbott and Liaison Diasorin analysers. We used an in-house live virus neutralization assay and the first WHO international standard to assess the comparison. This study could be useful to determine guidelines on the use of serological results to manage vaccination and treatment with convalescent plasma or monoclonal antibodies. Keywords COVID; SARS-CoV-2; binding antibodies; immunoassay; neutralizing antibodies. Conflict of interest statement The authors declare no conflict of interest. Figures FIG 1 Distribution of the results. A WantaĂŻ, B Liaison, and C Alinity assays according to patient groups. Black lines = median of each group. Red lines = manufacturerâs negative/positive threshold. Zero 0 values in the Liaison negative group n = 92, the Liaison late infection group n = 15, the Alinity negative group n = 14, and the Alinity late infection group n = 7 are not shown. FIG 2 ROC curves for WantaĂŻ black line, Liaison green line and Alinity red line. Gray line y = x. The AUROCs were WantaĂŻ 95% CI to Liaison 95% CI to and Alinity 95% CI to indicating their capacity to accurately detect anti-SARS-CoV-2 antibodies. FIG 3 Quantification of anti-SARS-CoV-2 antibodies relative to the NIBSC international standard. Serial dilutions of the NIBSC 20/136 standard were assayed with the A WantaĂŻ, B Liaison, and C Alinity assay. Neutralizing antibodies NAb were also determined with a live method D. The black line represents the regression line and the dashed lines its 95% CI. The dashed red line represents the y = x line. AU arbitrary units. BAU binding antibody unit. The equations were y = x â slope 95% CI to y-intercept 95% CI â to for WantaĂŻ; y = x â slope 95% CI to y-intercept 95% CI â to for Liaison; y = x - slope 95% CI to y-intercept 95% CI â to for Alinity and y = x + slope 95% CI to y-intercept 95% CI â to for NAb titers. FIG 4 Correlation between the immunoassay results. Pairwise distribution of the WantaĂŻ, Liaison, and Alinity assays values for all positive results A to C, recent infections D to F, and late infections G to I. When the Spearman rank coefficient r indicated a significant correlation, the regression line was drawn. Dashed lines 95% CI limits. FIG 5 Immunoassays results and neutralizing antibody titers. Distribution of the WantaĂŻ, Liaison, and Alinity assay values and the NAb titers for all positive results A to C The NAb titers were determined in a live virus neutralization assay using the B strain. Spearmanâs rank coefficients r and their P value are indicated. The box extends from the 25th to 75th percentiles and whiskers from minimal to maximal values. Similar articles Performance evaluation of three automated quantitative immunoassays and their correlation with a surrogate virus neutralization test in coronavirus disease 19 patients and pre-pandemic controls. Jung K, Shin S, Nam M, Hong YJ, Roh EY, Park KU, Song EY. Jung K, et al. J Clin Lab Anal. 2021 Sep;359e23921. doi Epub 2021 Aug 8. J Clin Lab Anal. 2021. PMID 34369009 Free PMC article. Inference of SARS-CoV-2 spike-binding neutralizing antibody titers in sera from hospitalized COVID-19 patients by using commercial enzyme and chemiluminescent immunoassays. Valdivia A, Torres I, Latorre V, FrancĂ©s-GĂłmez C, Albert E, Gozalbo-Rovira R, Alcaraz MJ, Buesa J, RodrĂguez-DĂaz J, Geller R, Navarro D. Valdivia A, et al. Eur J Clin Microbiol Infect Dis. 2021 Mar;403485-494. doi Epub 2021 Jan 6. Eur J Clin Microbiol Infect Dis. 2021. PMID 33404891 Free PMC article. Serological Assays for Assessing Postvaccination SARS-CoV-2 Antibody Response. Mahmoud SA, Ganesan S, Naik S, Bissar S, Zamel IA, Warren KN, Zaher WA, Khan G. Mahmoud SA, et al. Microbiol Spectr. 2021 Oct 31;92e0073321. doi Epub 2021 Sep 29. Microbiol Spectr. 2021. PMID 34585943 Free PMC article. Overview of Neutralization Assays and International Standard for Detecting SARS-CoV-2 Neutralizing Antibody. Liu KT, Han YJ, Wu GH, Huang KA, Huang PN. Liu KT, et al. Viruses. 2022 Jul 18;1471560. doi Viruses. 2022. PMID 35891540 Free PMC article. Review. Recent Developments in SARS-CoV-2 Neutralizing Antibody Detection Methods. Banga Ndzouboukou JL, Zhang YD, Fan XL. 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Viruses. 2022 Aug 24;1491860. doi Viruses. 2022. PMID 36146666 Free PMC article. Review. References Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, Si H-R, Zhu Y, Li B, Huang C-L, Chen H-D, Chen J, Luo Y, Guo H, Jiang R-D, Liu M-Q, Chen Y, Shen X-R, Wang X, Zheng X-S, Zhao K, Chen Q-J, Deng F, Liu L-L, Yan B, Zhan F-X, Wang Y-Y, Xiao G-F, Shi Z-L. 2020. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579270â273. doi - DOI - PMC - PubMed Olbrich L, Castelletti N, SchĂ€lte Y, GarĂ M, PĂŒtz P, Bakuli A, Pritsch M, Kroidl I, Saathoff E, Guggenbuehl Noller JM, Fingerle V, Le Gleut R, Gilberg L, Brand I, Falk P, Markgraf A, DeĂĄk F, Riess F, Diefenbach M, Eser T, Weinauer F, Martin S, Quenzel E-M, Becker M, Durner J, Girl P, MĂŒller K, Radon K, Fuchs C, Wölfel R, Hasenauer J, Hoelscher M, Wieser A, On Behalf Of The KoCo-Study Group null. 2021. Head-to-head evaluation of seven different seroassays including direct viral neutralisation in a representative cohort for SARS-CoV-2. J Gen Virol 102. doi - DOI - PMC - PubMed Montesinos I, Dahma H, Wolff F, Dauby N, Delaunoy S, Wuyts M, Detemmerman C, Duterme C, Vandenberg O, Martin C, Hallin M. 2021. Neutralizing antibody responses following natural SARS-CoV-2 infection Dynamics and correlation with commercial serologic tests. J Clin Virol 144104988. doi - DOI - PMC - PubMed Favresse J, Cadrobbi J, Eucher C, Elsen M, Laffineur K, DognĂ© J-M, Douxfils J. 2021. Clinical performance of three fully automated anti-SARS-CoV-2 immunoassays targeting the nucleocapsid or spike proteins. J Med Virol 932262â2269. doi - DOI - PMC - PubMed Liu W, Liu L, Kou G, Zheng Y, Ding Y, Ni W, Wang Q, Tan L, Wu W, Tang S, Xiong Z, Zheng S. 2020. Evaluation of nucleocapsid and spike protein-based enzyme-linked immunosorbent assays for detecting antibodies against SARS-CoV-2. J Clin Microbiol 58e00461-20. doi - DOI - PMC - PubMed Publication types MeSH terms Substances LinkOut - more resources Full Text Sources Atypon Europe PubMed Central PubMed Central Medical Genetic Alliance MedlinePlus Health Information Miscellaneous NCI CPTAC Assay Portal Metodeyang digunakan dalam pemeriksaan Anti SARS-CoV-2 Kuantitatif adalah Electro Chemiluminescence Immunoassay (ECLIA) yang menggunakan protein rekombinan mewakili RBD antigen S, mengukur antibodi spesifik dengan afinitas tinggi terhadap SARS-CoV-2 secara kuantitatif dalam serum pasien dengan satuan U/ml (1 U/ml setara dengan 0.972
INTENDED USEă SARS-CoV-2 Neutralizing Antibody Detection Kit is a Competitive Enzyme-Linked Immunosorbent Assay (ELISA) intended for qualitative and semi-quantitative detection of total neutralizing antibodies to SARS-CoV-2 in human serum and plasma. The SARS- CoV-2 Neutralizing Antibody DeteMulaitanggal 25 Januari 2021 Prodia menyediakan pemeriksaan Anti SARS-CoV-2 Kuantitatif untuk mengkuantifikasi antibodi terhadap protein Spike-RBS dalam satuan U/mL (setara dengan 0.972 BAU/mL, International Standard WHO).. Perbedaan dengan pemeriksaan Anti SARS-CoV-2 (kualitatif) terletak pada target protein yang digunakan. V7ePh8O.
anti sars cov 2 kuantitatif
