Most patients who became
critically ill following
infection with
COVID-19 develop
severe acute respiratory syndrome (SARS) attributed to a maladaptive or inadequate immune response. The
complement system is an important component of the innate immune system that is involved in the opsonization of viruses but also in triggering further immune cell responses. Complement activation was seen in plasma adsorber material that clogged during the treatment of
critically ill patients with
COVID-19. Apart from the lung, the kidney is the second most common organ affected by
COVID-19. Using immunohistochemistry for
complement factors C1q, MASP-2, C3c, C3d, C4d, and
C5b-9 we investigated the involvement of the
complement system in six kidney biopsies with
acute kidney failure in different clinical settings and three kidneys from autopsy material of patients with
COVID-19. Renal tissue was analyzed for signs of renal injury by detection of
thrombus formation using CD61, endothelial cell rarefaction using the marker E-26 transformation specific-related gene (ERG-) and proliferation using
proliferating cell nuclear antigen (
PCNA)-staining. SARS-CoV-2 was detected by in situ hybridization and immunohistochemistry. Biopsies from patients with
hemolytic uremic syndrome (HUS, n = 5), severe acute tubular injury (ATI, n = 7), zero biopsies with
disseminated intravascular coagulation (
DIC, n = 7) and 1 year protocol biopsies from renal transplants (Ctrl, n = 7) served as controls. In the material clogging plasma adsorbers used for extracorporeal
therapy of patients with
COVID-19 C3 was the dominant
protein but
collectin 11 and MASP-2 were also identified. SARS-CoV-2 was sporadically present in varying numbers in some biopsies from patients with
COVID-19. The highest frequency of CD61-positive platelets was found in peritubular capillaries and arteries of
COVID-19 infected renal specimens as compared to all controls. Apart from
COVID-19 specimens, MASP-2 was detected in glomeruli with
DIC and ATI. In contrast, the classical pathway (i.e. C1q) was hardly seen in
COVID-19 biopsies. Both C3 cleavage products C3c and C3d were strongly detected in renal arteries but also occurs in glomerular capillaries of
COVID-19 biopsies, while tubular C3d was stronger than C3c in biopsies from
COVID-19 patients. The
membrane attack complex C5b-9, demonstrating terminal pathway activation, was predominantly deposited in
COVID-19 biopsies in peritubular capillaries, renal arterioles, and tubular basement membrane with similar or even higher frequency compared to controls. In conclusion, various
complement pathways were activated in
COVID-19 kidneys, the
lectin pathway mainly in peritubular capillaries and in part the classical pathway in renal arteries whereas the alternative pathway seem to be crucial for tubular complement activation. Therefore, activation of the
complement system might be involved in the worsening of renal injury.
Complement inhibition might thus be a promising treatment option to prevent deregulated activation and subsequent collateral tissue injury.