- Based on pulmonary and cutaneous biopsy and autopsy samples, some critically ill patients present a generalized thrombotic microvascular injury.
- Cutaneous manifestation consistent with a thrombotic microvascular injury included retiform purpura or livedo racemose.
- Histological findings suggest that some of the severe cases of COVID-19 would have thrombotic injuries mediated by a systemic activation of the alternative and lectin-based complement pathways.
- Important deposits of terminal complement complex C5b-9, C4d, and MASP2 in the microvasculature of lungs, normal-appearing skin and retiform cutaneous lesions.
- Paucicellular terminal lung parenchymal injury with septal capillary damage.
- These histological findings could be associated with an increase in dead space fraction, resulting in respiratory failure with high lung compliance and less lung consolidation than typical ARDS. This supports the fact that COVID-19 gives a different respiratory outcome than typical ARDS.
- Inhibitors of the alternative or lectin complement pathways (e.g. narsoplimab, eculizumab) may be useful in some severe cases of COVID-19 with suspected generalized thrombotic microvascular
- Skin biopsy, if easily accessible, might be a interesting tool to include with other laboratory testing (D-dimers, factor VIII, fibrinogen, other coagulation factors, antiphospholipid antibodies, CRP, pro-inflammatory cytokines (IL-1, IL-6), complement proteins (C3, C4, C5b-9, Bb)) for establishing criteria for specific anticomplement or anticoagulation therapy in critically ill patient.
Magro C. et al. studied skin and lung tissues from 5 critically ill patients with COVID-19 defined by respiratory failure and purpuric skin rash.
- Magro C., Mulvey J.J., Berlin D. et al (April 9, 2020). Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Translational Research. https://doi.org/10.1016/j.trsl.2020.04.007