2020 Winner

Aniara is happy to announce the winner of the 2020 Aniara grant
in the amount of $10,000 - Saravanan Subramaniam, Ph.D

Saravanan Subramaniam, Ph.D
Saravanan Subramaniam, Ph.D

We are proud to announce the winner of our 2020 Coagulation Research Grant

Saravanan Subramaniam, Ph.D

He now has $10,000 to use towards his project
Complement -mediated inflammation and coagulation in SARS-CoV-2 infection.


Abstract:
Complement -mediated inflammation and coagulation in SARS-CoV-2 infection

Sepsis remains the leading cause of death in ICU patients. A recent statistic showed that global sepsis incident cases increased to ~50 million and ~11 million deaths per year. The local manifestations of severe COVID-19 in the lung are viral pneumonia, lung injury, and acute respiratory distress syndrome (ARDS). The distant complications include sepsis, acute cardiac injury, heart failure, disseminated intravascular coagulopathy (DIC), deep vein thrombosis and pulmonary embolism. In a case series of 12 consecutive COVID-19 autopsies, 58% of patients showed unsuspected venous thromboembolism. The clinical evidence for excessive coagulation activation, i.e., D-dimer levels and platelet consumption, skyrocket in lethal disease and predict prognosis at the time of hospital admission. Accumulating data indicate that complement and neutrophils contribute to the maladaptive immune response that fuels hyperinflammation and thrombotic microangiopathy, thereby increasing COVID-19 mortality.

Synthesis of complement proteins in epithelial cells that line the alveolar wall may provide a local source of these proteins for inflammatory responses in the lung. Complement fragments (C3a, C4a, and C5a) trigger inflammation as anaphylatoxins and chemotactic factors, and unusual complement activation results in various inflammatory diseases. We suspect that activation of the complement system during SARS-CoV-2 infection leads to the uncontrolled production of C3a and C5a anaphylatoxins, enhancing inflammation and blood clots leading to organ failure. Targeting C3a-C3aR and/or C5a-C5aR axis has the potential to largely control not only ARDS but also the systemic inflammation/coagulation affecting the microvascular beds of the lung, kidney, brain, and other vital organs, which seems to be a complication in severely infected patients. To test this, we will infect transgenic mice (k18-hACE2) with SARS-CoV-2 for 2, 4, and 7 days post-infection (dpi) and characterize complement activation and coagulation. We will use various complement inhibitors to study the complement activation-mediated infection severity and blood coagulation activation in vivo.

Congrats Saravanan!