{"doi":"10.1101/2021.01.07.21249116","title":"Multi-organ complement deposition in COVID-19 patients","abstract":"BACKGROUND: Increased levels of circulating complement activation products have been reported in COVID-19 patients, but only limited information is available on complement involvement at tissue level. The mechanisms and pathways of local complement activation remain unclear. METHODS: We performed immunofluorescence analyses of autopsy specimens of lungs, kidney and liver from nine COVID-19 patients who died of acute respiratory failure. Snap-frozen samples embedded in OCT were stained with antibodies against complement components and activation products, IgG and spike protein of SARS-CoV-2. FINDINGS: Lung deposits of C1q, C4, C3 and C5b-9 were localized in the capillaries of the interalveolar septa and on alveolar cells. IgG displayed a similar even distribution, suggesting classical pathway activation. The spike protein is a potential target of IgG, but its uneven distribution suggests that other viral and tissue molecules may be targeted by IgG. Factor B deposits were also seen in COVID-19 lungs and are consistent with activation of the alternative pathway, whereas MBL and MASP-2 were hardly detectable. Analysis of kidney and liver specimens mirrored findings observed in the lung. Complement deposits were seen on tubules and vessels of the kidney with only mild C5b-9 staining in glomeruli, and on hepatic artery and portal vein of the liver. INTERPRETATION: Complement deposits in different organs of deceased COVID-19 patients caused by activation of the classical and alternative pathways support the multi-organ nature of the disease. FUNDING: Grants from the Italian Ministry of Health (COVID-2020-12371808) to PLM and National Institutes of Health HL150146 to NP are gratefully acknowledged.","journal":"medRxiv","year":2021,"id":213218,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9366,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":500638,"name":"Paolo Durigutto","orcid":"0000-0003-3862-4970","position":1,"is_corresponding":false},{"id":650917,"name":"Alessandro Mangogna","orcid":"0000-0001-7910-1274","position":2,"is_corresponding":false},{"id":650918,"name":"Rossana Bussani","orcid":"0000-0001-8241-9726","position":3,"is_corresponding":false},{"id":650919,"name":"Stefano D’Errico","orcid":"0000-0003-3689-0001","position":4,"is_corresponding":false},{"id":652294,"name":"Martina Zanon","orcid":null,"position":5,"is_corresponding":false},{"id":251398,"name":"Nicola Pozzi","orcid":"0000-0003-2309-7100","position":6,"is_corresponding":false},{"id":78001,"name":"Pier Luigi Meroni","orcid":"0000-0002-3394-1451","position":7,"is_corresponding":false},{"id":251397,"name":"Francesco Tedesco","orcid":"0000-0003-2462-0493","position":8,"is_corresponding":false},{"id":467802,"name":"Paolo Macor","orcid":"0000-0003-3079-4019","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-18T23:52:31.378994Z","pmid":"33442701","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":[]}