SementaraPaket 2 terdiri dari Hematologi Lengkap, Anti SARS-CoV-2 S Kuantitatif, CRP Kuantitatif, Vitamin D-25-OH, dan D-Dimer. Untuk harga yang yang dipasang, Mesha mengaku sesuai dengan harga yang ditetapkan oleh pemerintah. "Kalau untuk harga kita sesuaikan dengan regulasi yang ditetapkan oleh Pemerintah," jelasnya. Thetiters of SARS-CoV-2 neutralizing antibody and SARS-CoV-2 spike-protein binding IgG antibodies, determined by ELISA assay of patient plasma, were compared against vaccine efficacy over a 13What is the main idea of the passage A The descendant on the family tree of from ECONOMICS MANAGERIAL at Jenderal Soedirman University cash. 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-protein’s 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 patients’ 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 µg endotoxin-free S-protein resuspended in 100 µL 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. 1c–e. 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 heart’s 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. 1a–i 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 PDGFRβ, red. Bar graphs summarize the quantitative analysis of pericyte density. d Representative immunofluorescence images showing longitudinal capillaries IB4, green covered by pericytes PDGFRβ, red. Bar graphs report the quantitative analysis of pericyte coverage. e Representative immunofluorescence images of mice hearts showing endothelial cells IB4, green, pericytes PDGFRβ, 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 h—Ly6G/6 C, green and macrophages i—F4/80, 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 μm. 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. j–l 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 ≤ m–p Sn-RNA-Sequencing analysis of pericytes from COVID-19 patients’ 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 genes’ 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 host’s 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-protein’s direct pathogenic action on cardiac pericytes and the heart’s 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 virus’ 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 article’s data can be obtained as reasonably required from the corresponding author. The main datasets underlying transcriptomic analyses are provided as supplementary datasets Dataset 1–4. The bulk RNA-Seq raw data have been deposited in NCBI’s 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? 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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, 2667–2689 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, 77–84 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, 107–113 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, 802–810 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 “Targeting the SARS-CoV-2 S-protein binding to the ACE2 receptor to preserve human cardiac pericytes function in COVID-19” 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 “Targeting pericytes for halting pulmonary hypertension in infants with congenital heart disease” 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 patients’ 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 article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s 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 2023DOI - Seperti diketahui, orang yang sudah pernah terinfeksi Covid-19 akan memiliki kekebalan tubuh atau antibodi terhadap serangan virus SARS-CoV-2 penyebab Covid-19 di masa depan. Namun, seberapa besar kekebalan tubuh orang yang pernah terpapar Covid-19?Mengenai persoalan ini, Dokter Spesialis Patologi Klinik Primaya Hospital Bekasi Barat dan Bekasi Timur, dr Muhammad Irhamsyah SpPK MKes angkat bicara. Irhamsyah menjelaskan bahwa terdapat metode pemeriksaan kekebalan tubuh manusia terhadap Covid-19 melalui pemeriksaan Antibodi SARS-CoV-2 kuantitatif. Baca juga Daftar 5 Kelompok Prioritas Vaksinasi Covid-19 Tahap Kedua, dari Guru hingga Pedagang Pemeriksaan Antibodi SARS-CoV-2 suatu pemeriksaan untuk mendeteksi suatu protein yang disebut antibodi, khususnya antibodi spesifik terhadap SARS-CoV-2 ini."Pemeriksaan ini dapat dilakukan pada orang-orang yang sudah pernah terinfeksi Covid-19, orang yang sudah mendapatkan vaksinasi, serta dapat digunakan untuk mengukur antibodi pada donor plasma konvalesen yang akan ditransfusikan,” kata Irhamsyah. Cara kerja pemeriksaan kuantitatif antibodi ECLIA Dijelaskan dr Irhamsyah, prinsip pemeriksaan kuantitatif antibodi spesifik SARS-CoV-2 ini menggunakan pemeriksaan laboratorium imunoserologi pada sebuah alat automatik autoanalyzer. Alat automatik ini dipergunakan untuk mendeteksi antibodi terhadap SAR-CoV-2. Pemeriksaan ini biasa disebut dengan Electro Chemiluminescence Immunoasssay ECLIA. ECLIA akan mendeteksi, mengikat, serta mengukur antibodi netralisasi. Sebagai informasi, antibodi netralisasi adalah antibodi yang dapat berikatan spesifik pada bagian struktur protein spike SARS-CoV-2. Protein spike adalah protein berbentuk paku yang tersebar di permukaan virus Covid-19, sebelum virus Covid-19 memasuki sel-sel pada tubuh kita dengan menggunakan label-label yang berikatan spesifik dengan antibodi netralisasi tersebut. Adapun, jenis sampel yang dapat digunakan dalam pemeriksaan ini yaitu sampel serum dan plasma dengan cara diambil darah vena. 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, 2–10% participants returned positive IgM results, which included both positive and weakly positive results, while 62% 95% CI, 54–71% 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 manufacturer’s protocol and previous publication,24 and the results were deemed positive if the signal/cutoff S/CO ratio ≥1. For ELISA tests, results were recorded and analyzed as continuous variables and the limit of sensitivity was calculated as mean + 2 × 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 Fisher’s exact test dichotomous variables or χ2 test variables with more than two categories for categorical variables and Mann–Whitney 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 Mann–Whitney U test two groups or Kruskal–Wallis test with post hoc comparisons more than two groups. Special tests were mentioned in figure legends. Correlation was assessed by Spearman’s ρ 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. 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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 People’s Hospital, Xiangyang, Hubei, 441000, ChinaDingwen SunDepartment of Rehabilitation Medicine, Gucheng People’s 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. Luke’s 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 article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s 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

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