Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
1.
Cell Rep ; 38(3): 110271, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1588135

ABSTRACT

The utility of the urinary proteome in infectious diseases remains unclear. Here, we analyzed the proteome and metabolome of urine and serum samples from patients with COVID-19 and healthy controls. Our data show that urinary proteins effectively classify COVID-19 by severity. We detect 197 cytokines and their receptors in urine, but only 124 in serum using TMT-based proteomics. The decrease in urinary ESCRT complex proteins correlates with active SARS-CoV-2 replication. The downregulation of urinary CXCL14 in severe COVID-19 cases positively correlates with blood lymphocyte counts. Integrative multiomics analysis suggests that innate immune activation and inflammation triggered renal injuries in patients with COVID-19. COVID-19-associated modulation of the urinary proteome offers unique insights into the pathogenesis of this disease. This study demonstrates the added value of including the urinary proteome in a suite of multiomics analytes in evaluating the immune pathobiology and clinical course of COVID-19 and, potentially, other infectious diseases.


Subject(s)
COVID-19/urine , Immunity , Metabolome , Proteome/analysis , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/immunology , COVID-19/pathology , Case-Control Studies , Child , Child, Preschool , China , Cohort Studies , Female , Humans , Immunity/physiology , Male , Metabolome/immunology , Metabolomics , Middle Aged , Patient Acuity , Proteome/immunology , Proteome/metabolism , Proteomics , Urinalysis/methods , Young Adult
2.
Front Immunol ; 12: 705772, 2021.
Article in English | MEDLINE | ID: covidwho-1376700

ABSTRACT

Autoimmune diseases (ADs) could occur due to infectious diseases and vaccination programs. Since millions of people are expected to be infected with SARS-CoV-2 and vaccinated against it, autoimmune consequences seem inevitable. Therefore, we have investigated the whole proteome of the SARS-CoV-2 for its ability to trigger ADs. In this regard, the entire proteome of the SARS-CoV-2 was chopped into more than 48000 peptides. The produced peptides were searched against the entire human proteome to find shared peptides with similar experimentally confirmed T-cell and B-cell epitopes. The obtained peptides were checked for their ability to bind to HLA molecules. The possible population coverage was calculated for the most potent peptides. The obtained results indicated that the SARS-CoV-2 and human proteomes share 23 peptides originated from ORF1ab polyprotein, nonstructural protein NS7a, Surface glycoprotein, and Envelope protein of SARS-CoV-2. Among these peptides, 21 peptides had experimentally confirmed equivalent epitopes. Amongst, only nine peptides were predicted to bind to HLAs with known global allele frequency data, and three peptides were able to bind to experimentally confirmed HLAs of equivalent epitopes. Given the HLAs which have already been reported to be associated with ADs, the ESGLKTIL, RYPANSIV, NVAITRAK, and RRARSVAS were determined to be the most harmful peptides of the SARS-CoV-2 proteome. It would be expected that the COVID-19 pandemic and the vaccination against this pathogen could significantly increase the ADs incidences, especially in populations harboring HLA-B*08:01, HLA-A*024:02, HLA-A*11:01 and HLA-B*27:05. The Southeast Asia, East Asia, and Oceania are at higher risk of AD development.


Subject(s)
Autoimmunity , COVID-19 Vaccines/immunology , COVID-19/immunology , Proteome/immunology , SARS-CoV-2/immunology , Viral Proteins/immunology , Autoimmune Diseases/etiology , Autoimmune Diseases/immunology , COVID-19/complications , COVID-19 Vaccines/adverse effects , Computer Simulation , Epitopes, B-Lymphocyte/immunology , HLA Antigens/immunology , Humans , Peptide Fragments/immunology , Peptide Library
3.
Front Immunol ; 12: 669357, 2021.
Article in English | MEDLINE | ID: covidwho-1344263

ABSTRACT

Development of adaptive immunity after COVID-19 and after vaccination against SARS-CoV-2 is predicated on recognition of viral peptides, presented on HLA class II molecules, by CD4+ T-cells. We capitalised on extensive high-resolution HLA data on twenty five human race/ethnic populations to investigate the role of HLA polymorphism on SARS-CoV-2 immunogenicity at the population and individual level. Within populations, we identify wide inter-individual variability in predicted peptide presentation from structural, non-structural and accessory SARS-CoV-2 proteins, according to individual HLA genotype. However, we find similar potential for anti-SARS-CoV-2 cellular immunity at the population level suggesting that HLA polymorphism is unlikely to account for observed disparities in clinical outcomes after COVID-19 among different race/ethnic groups. Our findings provide important insight on the potential role of HLA polymorphism on development of protective immunity after SARS-CoV-2 infection and after vaccination and a firm basis for further experimental studies in this field.


Subject(s)
COVID-19/immunology , Histocompatibility Antigens Class II/genetics , Immunity, Cellular , SARS-CoV-2/immunology , Antigen Presentation , CD4-Positive T-Lymphocytes/immunology , COVID-19/genetics , Genotype , Histocompatibility Antigens Class II/immunology , Humans , Peptides/immunology , Polymorphism, Genetic , Proteome/immunology , Viral Proteins/immunology
4.
PLoS Biol ; 19(6): e3001265, 2021 06.
Article in English | MEDLINE | ID: covidwho-1278162

ABSTRACT

The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here, we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which 1 epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the 6 other known human CoVs. We also confirm reactivity against 4 of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to 9 SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Viral Proteins/immunology , Antibodies, Viral/blood , COVID-19/pathology , Coronavirus/immunology , Cross Reactions , Epitopes, B-Lymphocyte , Humans , Immunodominant Epitopes , Immunoglobulin G/blood , Immunoglobulin G/immunology , Proteome/immunology , Severity of Illness Index
5.
Cell ; 184(15): 3962-3980.e17, 2021 07 22.
Article in English | MEDLINE | ID: covidwho-1252549

ABSTRACT

T cell-mediated immunity plays an important role in controlling SARS-CoV-2 infection, but the repertoire of naturally processed and presented viral epitopes on class I human leukocyte antigen (HLA-I) remains uncharacterized. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two cell lines at different times post infection using mass spectrometry. We found HLA-I peptides derived not only from canonical open reading frames (ORFs) but also from internal out-of-frame ORFs in spike and nucleocapsid not captured by current vaccines. Some peptides from out-of-frame ORFs elicited T cell responses in a humanized mouse model and individuals with COVID-19 that exceeded responses to canonical peptides, including some of the strongest epitopes reported to date. Whole-proteome analysis of infected cells revealed that early expressed viral proteins contribute more to HLA-I presentation and immunogenicity. These biological insights, as well as the discovery of out-of-frame ORF epitopes, will facilitate selection of peptides for immune monitoring and vaccine development.


Subject(s)
Epitopes, T-Lymphocyte/immunology , Histocompatibility Antigens Class I/immunology , Open Reading Frames/genetics , Peptides/immunology , Proteome/immunology , SARS-CoV-2/immunology , A549 Cells , Alleles , Amino Acid Sequence , Animals , Antigen Presentation/immunology , COVID-19/immunology , COVID-19/virology , Female , HEK293 Cells , Humans , Kinetics , Male , Mice , Peptides/chemistry , T-Lymphocytes/immunology
6.
Nature ; 595(7866): 283-288, 2021 07.
Article in English | MEDLINE | ID: covidwho-1233713

ABSTRACT

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1-6. Although pathological innate immune activation is well-documented in severe disease1, the effect of autoantibodies on disease progression is less well-defined. Here we use a high-throughput autoantibody discovery technique known as rapid extracellular antigen profiling7 to screen a cohort of 194 individuals infected with SARS-CoV-2, comprising 172 patients with COVID-19 and 22 healthcare workers with mild disease or asymptomatic infection, for autoantibodies against 2,770 extracellular and secreted proteins (members of the exoproteome). We found that patients with COVID-19 exhibit marked increases in autoantibody reactivities as compared to uninfected individuals, and show a high prevalence of autoantibodies against immunomodulatory proteins (including cytokines, chemokines, complement components and cell-surface proteins). We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signalling and by altering peripheral immune cell composition, and found that mouse surrogates of these autoantibodies increase disease severity in a mouse model of SARS-CoV-2 infection. Our analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics. Our findings suggest a pathological role for exoproteome-directed autoantibodies in COVID-19, with diverse effects on immune functionality and associations with clinical outcomes.


Subject(s)
Autoantibodies/analysis , Autoantibodies/immunology , COVID-19/immunology , COVID-19/metabolism , Proteome/immunology , Proteome/metabolism , Animals , Antigens, Surface/immunology , COVID-19/pathology , COVID-19/physiopathology , Case-Control Studies , Complement System Proteins/immunology , Cytokines/immunology , Disease Models, Animal , Disease Progression , Female , Humans , Male , Mice , Organ Specificity/immunology
7.
Viruses ; 13(5)2021 04 24.
Article in English | MEDLINE | ID: covidwho-1201582

ABSTRACT

The emerging SARS-CoV-2 pandemic entails an urgent need for specific and sensitive high-throughput serological assays to assess SARS-CoV-2 epidemiology. We, therefore, aimed at developing a fluorescent-bead based SARS-CoV-2 multiplex serology assay for detection of antibody responses to the SARS-CoV-2 proteome. Proteins of the SARS-CoV-2 proteome and protein N of SARS-CoV-1 and common cold Coronaviruses (ccCoVs) were recombinantly expressed in E. coli or HEK293 cells. Assay performance was assessed in a COVID-19 case cohort (n = 48 hospitalized patients from Heidelberg) as well as n = 85 age- and sex-matched pre-pandemic controls from the ESTHER study. Assay validation included comparison with home-made immunofluorescence and commercial enzyme-linked immunosorbent (ELISA) assays. A sensitivity of 100% (95% CI: 86-100%) was achieved in COVID-19 patients 14 days post symptom onset with dual sero-positivity to SARS-CoV-2 N and the receptor-binding domain of the spike protein. The specificity obtained with this algorithm was 100% (95% CI: 96-100%). Antibody responses to ccCoVs N were abundantly high and did not correlate with those to SARS-CoV-2 N. Inclusion of additional SARS-CoV-2 proteins as well as separate assessment of immunoglobulin (Ig) classes M, A, and G allowed for explorative analyses regarding disease progression and course of antibody response. This newly developed SARS-CoV-2 multiplex serology assay achieved high sensitivity and specificity to determine SARS-CoV-2 sero-positivity. Its high throughput ability allows epidemiologic SARS-CoV-2 research in large population-based studies. Inclusion of additional pathogens into the panel as well as separate assessment of Ig isotypes will furthermore allow addressing research questions beyond SARS-CoV-2 sero-prevalence.


Subject(s)
Antibodies, Viral/immunology , Antigens, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibody Formation , COVID-19/blood , COVID-19/virology , Cohort Studies , Coronavirus Nucleocapsid Proteins/genetics , Coronavirus Nucleocapsid Proteins/immunology , Enzyme-Linked Immunosorbent Assay , Escherichia coli , Female , HEK293 Cells , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Open Reading Frames , Pandemics , Phosphoproteins , Proteome/immunology , SARS-CoV-2/genetics , Young Adult
8.
Front Immunol ; 12: 636222, 2021.
Article in English | MEDLINE | ID: covidwho-1177977

ABSTRACT

Dendritic cell (DC)-derived exosomes (DC EXO), natural nanoparticles of endosomal origin, are under intense scrutiny in clinical trials for various inflammatory diseases. DC EXO are eobiotic, meaning they are well-tolerated by the host; moreover, they can be custom-tailored for immune-regulatory or -stimulatory functions, thus presenting attractive opportunities for immune therapy. Previously we documented the efficacy of immunoregulatory DCs EXO (regDCs EXO) as immunotherapy for inflammatory bone disease, in an in-vivo model. We showed a key role for encapsulated TGFß1 in promoting a bone sparing immune response. However, the on- and off-target effects of these therapeutic regDC EXO and how target signaling in acceptor cells is activated is unclear. In the present report, therapeutic regDC EXO were analyzed by high throughput proteomics, with non-therapeutic EXO from immature DCs and mature DCs as controls, to identify shared and distinct proteins and potential off-target proteins, as corroborated by immunoblot. The predominant expression in regDC EXO of immunoregulatory proteins as well as proteins involved in trafficking from the circulation to peripheral tissues, cell surface binding, and transmigration, prompted us to investigate how these DC EXO are biodistributed to major organs after intravenous injection. Live animal imaging showed preferential accumulation of regDCs EXO in the lungs, followed by spleen and liver tissue. In addition, TGFß1 in regDCs EXO sustained downstream signaling in acceptor DCs. Blocking experiments suggested that sustaining TGFß1 signaling require initial interaction of regDCs EXO with TGFß1R followed by internalization of regDCs EXO with TGFß1-TGFß1R complex. Finally, these regDCs EXO that contain immunoregulatory cargo and showed biodistribution to lungs could downregulate the main severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) target receptor, ACE2 on recipient lung parenchymal cells via TGFß1 in-vitro. In conclusion, these results in mice may have important immunotherapeutic implications for lung inflammatory disorders.


Subject(s)
COVID-19/immunology , Dendritic Cells/immunology , Exosomes/immunology , Proteome/immunology , SARS-CoV-2/immunology , Animals , Mice , Proteomics , Receptor, Transforming Growth Factor-beta Type I/immunology , Transforming Growth Factor beta1/immunology
9.
Front Immunol ; 12: 629185, 2021.
Article in English | MEDLINE | ID: covidwho-1175541

ABSTRACT

The WHO declared the COVID-19 outbreak a public health emergency of international concern. The causative agent of this acute respiratory disease is a newly emerged coronavirus, named SARS-CoV-2, which originated in China in late 2019. Exposure to SARS-CoV-2 leads to multifaceted disease outcomes from asymptomatic infection to severe pneumonia, acute respiratory distress and potentially death. Understanding the host immune response is crucial for the development of interventional strategies. Humoral responses play an important role in defending viral infections and are therefore of particular interest. With the aim to resolve SARS-CoV-2-specific humoral immune responses at the epitope level, we screened clinically well-characterized sera from COVID-19 patients with mild and severe disease outcome using high-density peptide microarrays covering the entire proteome of SARS-CoV-2. Moreover, we determined the longevity of epitope-specific antibody responses in a longitudinal approach. Here we present IgG and IgA-specific epitope signatures from COVID-19 patients, which may serve as discriminating prognostic or predictive markers for disease outcome and/or could be relevant for intervention strategies.


Subject(s)
COVID-19/immunology , Epitopes/immunology , Proteome/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Viral/immunology , Female , Humans , Immunity, Humoral , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Male
10.
Eur J Immunol ; 51(7): 1839-1849, 2021 07.
Article in English | MEDLINE | ID: covidwho-1151897

ABSTRACT

Humoral immunity to the Severe Adult Respiratory Syndrome (SARS) Coronavirus (CoV)-2 is not fully understood yet but is a crucial factor of immune protection. The possibility of antibody cross-reactivity between SARS-CoV-2 and other human coronaviruses (HCoVs) would have important implications for immune protection but also for the development of specific diagnostic ELISA tests. Using peptide microarrays, n = 24 patient samples and n = 12 control samples were screened for antibodies against the entire SARS-CoV-2 proteome as well as the Spike (S), Nucleocapsid (N), VME1 (V), R1ab, and Protein 3a (AP3A) of the HCoV strains SARS, MERS, OC43, and 229E. While widespread cross-reactivity was revealed across several immunodominant regions of S and N, IgG binding to several SARS-CoV-2-derived peptides provided statistically significant discrimination between COVID-19 patients and controls. Selected target peptides may serve as capture antigens for future, highly COVID-19-specific diagnostic antibody tests.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , Protein Array Analysis/methods , SARS-CoV-2/immunology , Viral Proteins/immunology , Adult , Aged , Amino Acid Sequence/genetics , Antibodies, Viral/immunology , Coronavirus 229E, Human/immunology , Coronavirus Nucleocapsid Proteins/immunology , Coronavirus OC43, Human/immunology , Cross Reactions/immunology , Diagnostic Tests, Routine , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Middle East Respiratory Syndrome Coronavirus/immunology , Phosphoproteins/immunology , Proteome/immunology , SARS Virus/immunology , Spike Glycoprotein, Coronavirus/immunology , Young Adult
11.
Cell Rep ; 34(11): 108852, 2021 03 16.
Article in English | MEDLINE | ID: covidwho-1135278

ABSTRACT

As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Adaptive Immunity/immunology , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , COVID-19/virology , Child , Humans , Immunity, Humoral/immunology , Proteome/immunology , SARS-CoV-2/immunology , Signal Transduction/immunology , Viral Load/immunology
12.
J Proteome Res ; 19(11): 4649-4654, 2020 11 06.
Article in English | MEDLINE | ID: covidwho-974860

ABSTRACT

The Bacillus Calmette-Guerin vaccine is still widely used in the developing world. The vaccination prevents infant death not only from tuberculosis but also from unrelated infectious agents, especially respiratory tract infections and neonatal sepsis. It is proposed that these off-target protective effects of the BCG vaccine are mediated by the general long-term boosting of innate immune mechanisms, also termed "trained innate immunity". Recent studies indicate that both COVID-19 incidence and total deaths are strongly associated with the presence or absence of national mandatory BCG vaccination programs and encourage the initiation of several clinical studies with the expectation that revaccination with BCG could reduce the incidence and severity of COVID-19. Here, presented results from the bioinformatics analysis of the Mycobacterium bovis (strain BCG/Pasteur 1173P2) proteome suggests four immunodominant antigens that could induce an immune response against SARS-CoV-2.


Subject(s)
BCG Vaccine , Bacterial Proteins , Betacoronavirus , Coronavirus Infections , Drug Repositioning , Pandemics , Pneumonia, Viral , BCG Vaccine/chemistry , BCG Vaccine/immunology , Bacterial Proteins/chemistry , Bacterial Proteins/immunology , Betacoronavirus/chemistry , Betacoronavirus/immunology , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Humans , Mycobacterium bovis/chemistry , Mycobacterium bovis/immunology , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Proteome/chemistry , Proteome/immunology , SARS-CoV-2 , Viral Vaccines/chemistry , Viral Vaccines/immunology
13.
PLoS One ; 15(12): e0243285, 2020.
Article in English | MEDLINE | ID: covidwho-963818

ABSTRACT

More than twenty years ago the reverse vaccinology paradigm came to light trying to design new vaccines based on the analysis of genomic information in order to select those pathogen peptides able to trigger an immune response. In this context, focusing on the proteome of Trypanosoma cruzi, we investigated the link between the probabilities for pathogen peptides to be presented on a cell surface and their distance from human self. We found a reasonable but, as far as we know, undiscovered property: the farther the distance between a peptide and the human-self the higher the probability for that peptide to be presented on a cell surface. We also found that the most distant peptides from human self bind, on average, a broader collection of HLAs than expected, implying a potential immunological role in a large portion of individuals. Finally, introducing a novel quantitative indicator for a peptide to measure its potential immunological role, we proposed a pool of peptides that could be potential epitopes and that can be suitable for experimental testing. The software to compute peptide classes according to the distance from human self is free available at http://www.iasi.cnr.it/~dsantoni/nullomers.


Subject(s)
Chagas Disease/immunology , Histocompatibility Antigens Class I/immunology , Peptides/immunology , Protozoan Proteins/immunology , Trypanosoma cruzi/immunology , Amino Acid Sequence , Epitopes/chemistry , Epitopes/immunology , Humans , Peptides/chemistry , Proteome/chemistry , Proteome/immunology , Protozoan Proteins/chemistry , Trypanosoma cruzi/chemistry
15.
Cell Rep Med ; 1(7): 100123, 2020 10 20.
Article in English | MEDLINE | ID: covidwho-793949

ABSTRACT

Comprehensive understanding of the serological response to SARS-CoV-2 infection is important for both pathophysiologic insight and diagnostic development. Here, we generate a pan-human coronavirus programmable phage display assay to perform proteome-wide profiling of coronavirus antigens enriched by 98 COVID-19 patient sera. Next, we use ReScan, a method to efficiently sequester phage expressing the most immunogenic peptides and print them onto paper-based microarrays using acoustic liquid handling, which isolates and identifies nine candidate antigens, eight of which are derived from the two proteins used for SARS-CoV-2 serologic assays: spike and nucleocapsid proteins. After deployment in a high-throughput assay amenable to clinical lab settings, these antigens show improved specificity over a whole protein panel. This proof-of-concept study demonstrates that ReScan will have broad applicability for other emerging infectious diseases or autoimmune diseases that lack a valid biomarker, enabling a seamless pipeline from antigen discovery to diagnostic using one recombinant protein source.


Subject(s)
Antigens, Viral/immunology , COVID-19 Serological Testing/methods , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Antibodies, Viral/blood , COVID-19/blood , Female , Humans , Male , Middle Aged , Peptide Library , Protein Array Analysis , Proteome/immunology , Reproducibility of Results , SARS-CoV-2/immunology , Sensitivity and Specificity , Viral Proteins/immunology
17.
Mol Cell Proteomics ; 19(11): 1749-1759, 2020 11.
Article in English | MEDLINE | ID: covidwho-713514

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n = 15) and influenza (n = 13) patients. We identified a large set of differentially expressed proteins (n = 132) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.


Subject(s)
Blood Proteins/immunology , Coronavirus Infections/immunology , Cough/immunology , Cytokine Release Syndrome/immunology , Fever/immunology , Headache/immunology , Influenza, Human/immunology , Myalgia/immunology , Pneumonia, Viral/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus/pathogenicity , Blood Proteins/genetics , COVID-19 , Child , Coronavirus Infections/genetics , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Cough/genetics , Cough/physiopathology , Cough/virology , Cytokine Release Syndrome/genetics , Cytokine Release Syndrome/physiopathology , Cytokine Release Syndrome/virology , Cytokines/genetics , Cytokines/immunology , Female , Fever/genetics , Fever/physiopathology , Fever/virology , Gene Expression Profiling , Gene Expression Regulation , Headache/genetics , Headache/physiopathology , Headache/virology , Humans , Influenza, Human/genetics , Influenza, Human/physiopathology , Influenza, Human/virology , Male , Middle Aged , Myalgia/genetics , Myalgia/physiopathology , Myalgia/virology , Orthomyxoviridae/pathogenicity , Pandemics , Pneumonia, Viral/genetics , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Protein Array Analysis , Proteome/genetics , Proteome/immunology , Receptors, Cytokine/genetics , Receptors, Cytokine/immunology , SARS-CoV-2 , Signal Transduction/immunology
SELECTION OF CITATIONS
SEARCH DETAIL