Serum Proteomics in COVID-19 Patients: Altered Coagulation and Complement Status as a Function of IL-6 Level.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32786691", "kind": "science-record", "revision": 5, "content_hash": "sha256:c949405f9fd0514b359f4678d1e137869dd9fb62db93927bd204c94973c05048", "created_at": "2026-11-01T17:33:57Z", "updated_at": "2026-11-01T22:45:11Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Serum Proteomics in COVID-19 Patients: Altered Coagulation and Complement Status as a Function of IL-6 Level.", "doi": "10.1021/acs.jproteome.0c00365", "pmid": "32786691", "authors": ["Angelo D'Alessandro", "Tiffany Thomas", "Monika Dzieciatkowska", "Ryan C Hill", "Richard O Francis", "Krystalyn E Hudson", "James C Zimring", "Eldad A Hod", "Steven L Spitalnik", "Kirk C Hansen"], "journal": "Journal of proteome research", "year": 2020, "abstract": "Over 5 million people around the world have tested positive for the beta coronavirus SARS-CoV-2 as of May 29, 2020, a third of which are in the United States alone. These infections are associated with the development of a disease known as COVID-19, which is characterized by several symptoms, including persistent dry cough, shortness of breath, chills, muscle pain, headache, loss of taste or smell, and gastrointestinal distress. COVID-19 has been characterized by elevated mortality (over 100 thousand people have already died in the US alone), mostly due to thromboinflammatory complications that impair lung perfusion and systemic oxygenation in the most severe cases. While the levels of pro-inflammatory cytokines such as interleukin-6 (IL-6) have been associated with the severity of the disease, little is known about the impact of IL-6 levels on the proteome of COVID-19 patients. The present study provides the first proteomics analysis of sera from COVID-19 patients, stratified by circulating levels of IL-6, and correlated to markers of inflammation and renal function. As a function of IL-6 levels, we identified significant dysregulation in serum levels of various coagulation factors, accompanied by increased levels of antifibrinolytic components, including several serine protease inhibitors (SERPINs). These were accompanied by up-regulation of the complement cascade and antimicrobial enzymes, especially in subjects with the highest levels of IL-6, which is consistent with an exacerbation of the acute phase response in these subjects. Although our results are observational, they highlight a clear increase in the levels of inhibitory components of the fibrinolytic cascade in severe COVID-19 disease, providing potential clues related to the etiology of coagulopathic complications in COVID-19 and paving the way for potential therapeutic interventions, such as the use of pro-fibrinolytic agents. Raw data for this study are available through ProteomeXchange with identifier PXD020601.", "claims": [{"id": "claim-method", "statement": "Of note, both PLS-DA (Figure 1.C) and hierarchical clustering analyses (Figure 1.E) revealed a signature associated with SARS-CoV-2 positivity in the serum proteome (separated across Principal Component 1 (PC1), which explained 15.5% of the total variance; Figure 1.C). The components that increased or decreased significantly across all groups in this dataset (ANOVA) were annotated in red or blue, respectively, against KEGG pathway hsa04610 (Figure 2, center panel; a larger version of this panel is provided in Supplementary Figure 3).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32786691", "locator": "sections[8] \"Serum proteomics as a function of IL-6 levels\" paragraph 2", "quote": "Of note, both PLS-DA (Figure 1.C) and hierarchical clustering analyses (Figure 1.E) revealed a signature associated with SARS-CoV-2 positivity in the serum proteome (separated across Principal Component 1 (PC1), which explained 15.5% of the total variance; Figure 1.C)."}, {"asset": "source:pmid:32786691", "locator": "sections[9] \"Complement and coagulation cascades\" paragraph 2", "quote": "The components that increased or decreased significantly across all groups in this dataset (ANOVA) were annotated in red or blue, respectively, against KEGG pathway hsa04610 (Figure 2, center panel; a larger version of this panel is provided in Supplementary Figure 3)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Raw data for this study are available through ProteomeXchange with identifier PXD020601.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32786691", "locator": "sections[16] \"fn-group\" paragraph 1", "quote": "Raw data for this study are available through ProteomeXchange with identifier PXD020601."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Sera of COVID-19 patients, especially those with IL-6 levels >10 pg/ml, contained increased levels of multiple proteins in the acute phase response that is initiated by IL-6 – specifically components of the coagulation and complement cascades (top enriched pathway – p-value: 1.6 e-31 – Figure 2).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:32786691", "locator": "sections[9] \"Complement and coagulation cascades\" paragraph 2", "quote": "Sera of COVID-19 patients, especially those with IL-6 levels >10 pg/ml, contained increased levels of multiple proteins in the acute phase response that is initiated by IL-6 – specifically components of the coagulation and complement cascades (top enriched pathway – p-value: 1.6 e-31 – Figure 2)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Sera of COVID-19 patients, especially those with IL-6 levels >10 pg/ml, contained increased levels of multiple proteins in the acute phase response that is initiated by IL-6 – specifically components of the coagulation and complement cascades (top enriched pathway – p-value: 1.6 e-31 – Figure 2).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:32786691"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD020601"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD020601"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32786691", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1021/acs.jproteome.0c00365", "sha256": "sha256:2905eb034e3e61ff131d21afc2f8d79472978ffadf8cae98f3bd1a3ae7fb6a35", "bytes": 30564, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1021/acs.jproteome.0c00365", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7640953", "source": "ncbi_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD020601", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD020601", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD020601", "version": null, "note": "Raw data for this study are available through ProteomeXchange with identifier PXD020601.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Raw data for this study are available through ProteomeXchange with identifier PXD020601.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Serum proteomics in COVID-19 patients: Altered coagulation and complement status as a function of IL-6 level", "resolution_checked_at": "2026-11-01T17:30:50Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:PXD020601 not downloaded", "asset:data:geo:PXD020601 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "reordered", "quote": "Of note, both PLS-DA (Figure 1.C) and hierarchical clustering analyses (Figure 1.E) revealed a signature associated with SARS-CoV-2 positivity in the serum proteome (separated across Principal Component 1 (PC1), which explained 15.5% of the total variance; Figure 1.C). The components that increased or decreased significantly across all groups in this dataset (ANOVA) were annotated in red or blue, respectively, against KEGG pathway hsa04610 (Figure 2, center panel; a larger version of this panel is provided in Supplementary Figure 3)."}}, {"id": "method-2", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "hierarchical clustering"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["PXD020601"], "resolved_accessions": ["PXD020601"], "statements": ["Raw data for this study are available through ProteomeXchange with identifier PXD020601."], "basis": "The paper names PXD020601 in ProteomeXchange and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:32786691", "data:geo:PXD020601"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:PXD020601"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:00:41Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 8612, "completion_tokens": 1771, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:32786691", "type": "paper", "label": "pmid:32786691"}, {"id": "source:pmid:32786691", "type": "manuscript", "label": "PMID 32786691 full text"}, {"id": "data:geo:PXD020601", "type": "dataset", "label": "GEO PXD020601"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:32786691", "type": "paper", "label": "pmid:32786691"}, {"id": "source:pmid:32786691", "type": "manuscript", "label": "PMID 32786691 full text"}, {"id": "data:geo:PXD020601", "type": "dataset", "label": "GEO PXD020601"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-32786691", "type": "extraction", "used": ["source:pmid:32786691"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-PXD020601", "type": "accession_resolution", "used": ["data:geo:PXD020601"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:32786691", "parent_hash": "sha256:09893738a1d6704c4452e3140f05a309acd8dda7d0de041b26a90ef9b4c6dc41", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:PXD020601 licence not read", "asset:data:geo:PXD020601 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Of note, both PLS-DA (Figure 1.C) and hierarchical clustering analyses (Figure 1.E) revealed a signature associated with SARS-CoV-2 positivity in the serum proteome (separated across Principal Component 1 (PC1), which explained 15.5% of the total variance; Figure 1.C). The components that increased or decreased significantly across all groups in this dataset (ANOVA) were annotated in red or blue, respectively, against KEGG pathway hsa04610 (Figure 2, center panel; a larger version of this panel is provided in Supplementary Figure 3)."], "order_basis": "analysis_only", "id": "assay:1"}]}