Multi-organ complement deposition in COVID-19 patients.

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.