Immune signaling sequence explains some severe COVID-19 cases

A 3-D rendering of the lungs is shown behind floating images of SARS-COV-2

A study in Blood confirms how an immune pathway, complement, is activated and can be inhibited in response to the novel coronavirus, COVID-19.

Researchers confirm spiked S proteins that extend from the surface of SARS-COV-2, the pathogen that causes COVID-19, activate an alternative pathway, known as complement, as the spikes touch cell surfaces. Complement sends out a cascading response. The scientists suspect genetic mutations or variations within the complement pathway may explain why some people have severe reactions to COVID-19. An inability for the immune system to switch “off” and transition to an anti-inflammatory response can lead to internal bleeding, blood clots, organ damage, or problems breathing.

The team recommends researchers follow genetic clues and patterns within the complement pathway as the pandemic progresses. Genomic insights could confirm underpinnings of severe SARS-COV-2 infections and expand knowledge about complement-related conditions, including a few rare blood disorders and age-related macular degeneration (AMD). AMD is a risk factor for intubation and dying from COVID-19.

The researchers also found inhibiting factor D, a complement protein, could prevent activating the alternative pathway of complement following SARS-COV-2 infection. These findings provide insight for future research, such as testing therapies that inhibit factor D or H, a regulatory arm of the alternative complement pathway. The authors suggest inhibiting factor H may be more effective, but the precise mechanisms are unknown.
This research was supported by the National Heart, Lung, and Blood Institute.