{"doi":"10.3389/fimmu.2022.945021","title":"Antibodies against Spike protein correlate with broad autoantigen recognition 8 months post SARS-CoV-2 exposure, and anti-calprotectin autoantibodies associated with better clinical outcomes","abstract":"<jats:p>Autoantibodies to multiple targets are found during acute COVID-19. Whether all, or some, persist after 6 months, and their correlation with sustained anti-SARS-CoV-2 immunity, is still controversial. Herein, we measured antibodies to multiple SARS-CoV-2 antigens (Wuhan-Hu-1 nucleoprotein (NP), whole spike (S), spike subunits (S1, S2 and receptor binding domain (RBD)) and Omicron spike) and 102 human proteins with known autoimmune associations, in plasma from healthcare workers 8 months post-exposure to SARS-CoV-2 (n=31 with confirmed COVID-19 disease and n=21 uninfected controls (PCR and anti-SARS-CoV-2 negative) at baseline). IgG antibody responses to SARS-CoV-2 antigens were significantly higher in the convalescent cohort than the healthy cohort, highlighting lasting antibody responses up to 8 months post-infection. These were also shown to be cross-reactive to the Omicron variant spike protein at a similar level to lasting anti-RBD antibodies (correlation r=0.89). Individuals post COVID-19 infection recognised a common set of autoantigens, specific to this group in comparison to the healthy controls. Moreover, the long-term level of anti-Spike IgG was associated with the breadth of autoreactivity post-COVID-19. There were further moderate positive correlations between anti-SARS-CoV-2 responses and 11 specific autoantigens. The most commonly recognised autoantigens were found in the COVID-19 convalescent cohort. Although there was no overall correlation in self-reported symptom severity and anti-SARS-CoV-2 antibody levels, anti-calprotectin antibodies were associated with return to healthy normal life 8 months post infection. Calprotectin was also the most common target for autoantibodies, recognized by 22.6% of the overall convalescent cohort. Future studies may address whether, counter-intuitively, such autoantibodies may play a protective role in the pathology of long-COVID-19.</jats:p>","journal":"Frontiers in Immunology","year":2022,"id":634186,"datarank":0.4887144807032224,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.0,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1644666,"name":"Sabrina Sonda","orcid":null,"position":1,"is_corresponding":false},{"id":1644667,"name":"Fay H. Johnston","orcid":null,"position":2,"is_corresponding":false},{"id":1306540,"name":"Kylie J. Smith","orcid":"0000-0003-2793-3460","position":3,"is_corresponding":false},{"id":596312,"name":"Nicola Stephens","orcid":"0000-0002-7952-4581","position":4,"is_corresponding":false},{"id":1644668,"name":"Michelle McPherson","orcid":null,"position":5,"is_corresponding":false},{"id":259523,"name":"Katie L. 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Herein, we measured antibodies to multiple SARS-CoV-2 antigens (Wuhan-Hu-1 nucleoprotein (NP), whole spike (S), spike subunits (S1, S2 and receptor binding domain (RBD)) and Omicron spike) and 102 human proteins with known autoimmune associations, in plasma from healthcare workers 8 months post-exposure to SARS-CoV-2 (n=31 with confirmed COVID-19 disease and n=21 uninfected controls (PCR and anti-SARS-CoV-2 negative) at baseline). IgG antibody responses to SARS-CoV-2 antigens were significantly higher in the convalescent cohort than the healthy cohort, highlighting lasting antibody responses up to 8 months post-infection. These were also shown to be cross-reactive to the Omicron variant spike protein at a similar level to lasting anti-RBD antibodies (correlation r=0.89). Individuals post COVID-19 infection recognised a common set of autoantigens, specific to this group in comparison to the healthy controls. Moreover, the long-term level of anti-Spike IgG was associated with the breadth of autoreactivity post-COVID-19. There were further moderate positive correlations between anti-SARS-CoV-2 responses and 11 specific autoantigens. The most commonly recognised autoantigens were found in the COVID-19 convalescent cohort. Although there was no overall correlation in self-reported symptom severity and anti-SARS-CoV-2 antibody levels, anti-calprotectin antibodies were associated with return to healthy normal life 8 months post infection. Calprotectin was also the most common target for autoantibodies, recognized by 22.6% of the overall convalescent cohort. Future studies may address whether, counter-intuitively, such autoantibodies may play a protective role in the pathology of long-COVID-19.</jats:p>","is_dataset_classified":null,"base_score":3.258096538021482,"endowment":3.258096538021482,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36032086","pmcid":"PMC9403331","openalex_id":"https://openalex.org/W4291008482","authors":[],"funders":[],"total_grants":0,"fwci":2.3173,"citation_percentile":0.9045276,"influential_citations":0,"citation_trend":[{"year":2023,"count":13},{"year":2024,"count":9},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.frontiersin.org/articles/10.3389/fimmu.2022.945021/pdf","host_type":"journal"},{"url":"https://www.frontiersin.org/articles/10.3389/fimmu.2022.945021/pdf","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fimmu.2022.945021/full","host_type":"publisher"},{"url":"https://doi.org/10.3389/fimmu.2022.945021","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36032086","host_type":"repository"},{"url":"https://doaj.org/article/b5b6a5911d2f4e4cb038f98d112bf382","host_type":"repository"},{"url":"https://figshare.com/articles/journal_contribution/Antibodies_against_Spike_protein_correlate_with_broad_autoantigen_recognition_8_months_post_SARS-CoV-2_exposure_and_anti-calprotectin_autoantibodies_associated_with_better_clinical_outcomes/27562098","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9403331","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9403331","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9403331?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["SARS-CoV-2 and COVID-19 Research","Long-Term Effects of COVID-19","COVID-19 Clinical Research Studies"],"mesh_terms":["COVID-19","SARS-CoV-2","Post-Acute COVID-19 Syndrome","Antibodies, Viral","Autoantibodies","Autoantigens","Humans","Immunoglobulin G","Leukocyte L1 Antigen Complex","Spike Glycoprotein, Coronavirus"],"keywords":["Autoantibody","Immunology","Antibody","Medicine","Cohort","Antigen","Serology","Disease","Virology","Internal medicine","Antibodies","Autoantibodies","Autoimmunity","Covid-19","Sars-cov-2"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T13:17:36.168560Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}