{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T18:35:35Z","timestamp":1768674935891,"version":"3.49.0"},"posted":{"date-parts":[[2021,1,8]]},"group-title":"Allergy and Immunology","reference-count":33,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>Grants from the Italian Ministry of Health (COVID-2020-12371808) to PLM and National Institutes of Health HL150146 to NP are gratefully acknowledged.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2021.01.07.21249116","type":"posted-content","created":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T18:13:13Z","timestamp":1610215993000},"source":"Crossref","is-referenced-by-count":24,"title":["Multi-organ complement deposition in COVID-19 patients"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3079-4019","authenticated-orcid":false,"given":"Paolo","family":"Macor","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3862-4970","authenticated-orcid":false,"given":"Paolo","family":"Durigutto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7910-1274","authenticated-orcid":false,"given":"Alessandro","family":"Mangogna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8241-9726","authenticated-orcid":false,"given":"Rossana","family":"Bussani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3689-0001","authenticated-orcid":false,"given":"Stefano","family":"D\u2019Errico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Zanon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2309-7100","authenticated-orcid":false,"given":"Nicola","family":"Pozzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3394-1451","authenticated-orcid":false,"given":"PierLuigi","family":"Meroni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2462-0493","authenticated-orcid":false,"given":"Francesco","family":"Tedesco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2021011009400511000_2021.01.07.21249116v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30627-9."},{"key":"2021011009400511000_2021.01.07.21249116v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2020.03.041"},{"key":"2021011009400511000_2021.01.07.21249116v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-0595-z"},{"key":"2021011009400511000_2021.01.07.21249116v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2020.03.053"},{"key":"2021011009400511000_2021.01.07.21249116v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/path.1570"},{"issue":"7","key":"2021011009400511000_2021.01.07.21249116v1.6","doi-asserted-by":"crossref","first-page":"e9610","DOI":"10.15252\/msb.20209610","article-title":"The protein expression profile of ACE2 in human tissues","volume":"16","year":"2020","journal-title":"Mol Syst Biol"},{"issue":"5","key":"2021011009400511000_2021.01.07.21249116v1.7","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S2213-2600(20)30079-5","article-title":"Clinical course and outcomes of critically ill patients with SARS- CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study","volume":"8","year":"2020","journal-title":"Lancet Respir Med"},{"key":"2021011009400511000_2021.01.07.21249116v1.8","doi-asserted-by":"crossref","unstructured":"Vardhana SA , Wolchok JD . 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