Ravulizumab and COVID-19
Ravulizumab and COVID-19
Ultomiris (Ravulizumab), is a monoclonal antibody that specifically targets terminal
 complement products and is proposed for the treatment of COVID-19 induced microvasculature
 injury and endothelial damage leading to thrombotic microangiopathy (TMA) causing acute
 kidney injury (AKI). Ravulizumab is to be used for participants with a confirmed diagnosis of
 COVID-19 who clinically or diagnostically present with deteriorating renal function.
 Ravulizumab causes immediate and sustained inhibition of the terminal complement cascade. The
 use of ravulizumab could ameliorate COVID-19 induced kidney injury due to TMA, shorten
 hospital stay, and improve the overall survival.
The novel coronavirus (COVID 19) is responsible for the current pandemic with the numbers of
 diagnoses and fatalities rising daily. It is reported that of those requiring medical
 intensive care almost 49% will expire prior hospital discharge. The initial peak of
 hospitalized patients in Boston, MA occurred on April 15, 2020 however new presentations
 continue to manifest at a local and national level.

 The exact pathophysiology is still not clear. There are various theories that explain the
 pathophysiology which includes but is not limited to direct viral damage via the
 angiotensin-converting enzyme 2 receptor, systemic inflammatory response with cytokine storm,
 and aggravated hypoxia.

 Recently, it has been observed that signs and symptoms of severe COVID 19 describe
 complement-mediated TMA rather than the sepsis induced coagulopathy. This strengthens the
 hypothesis that complement inhibition by C5a inhibitor, Ultomiris (ravulizumab) could
 ameliorate COVID 19 induced TMA, improve renal function, shorten the hospital stay and reduce
 the overall mortality.

 In those affected with severe or fatal COVID-19, there is evidence of end-organ damage with
 acute kidney injury which has heightened the interest in studying the excessive cytokine
 release and its overall effect in the form of multi-organ failure.

 Ultomiris (Ravulizumab) is a long acting second generation monoclonal antibody against a
 terminal complement product C5a and is FDA approved for the treatment of Paroxysmal Nocturnal
 Hemoglobinuria (PNH) and atypical hemolytic uremic syndrome.The benefit of Ultomiris has not
 been clinically evaluated in COVID 19 induced TMA.

 Recently, ravulizumab has been utilized in the setting of a phase 3 clinical trial for the
 treatment of COVID 19 induced pneumonia, acute lung injury and acute respiratory distress. As
 it binds to C5 and impedes the cleavage of C5 by C5 convertase to generate C5a and membrane
 attack complex, ravulizumab could possibly improve the renal function in COVID 19 induced TMA
 and potentially improve overall survival, due to similar pathophysiology in the
 microvasculature of the kidney. More so, studies are being conducted to determine renal and
 cardiovascular sequelae of COVID-19 infection, which further enhances the interest to closely
 examine and evaluate those patients presenting 30-60 days after COVID-19 infection with signs
 of renal failure. There remains an unmet clinical need to investigate this approach with a
 randomized controlled trial to determine if complement cascade inhibition can improve the
 clinical outcome for COVID 19 induced acute kidney injury as measured by improvement of renal
 function and decline in the overall morbidity and mortality.
Inclusion Criteria:

 1. Males or Females 18 years of age or above and weighing 40kg or above at the time of
 providing informed consent.

 2. A clinical diagnosis of thrombotic microangiopathy will then be applied to include the
 following criteria: i) D-dimer > 100% the upper limit of the reference range and ii)
 serum creatinine >25% of the normal range or iii) >25% increase from patient's
 baseline serum creatinine.

 3. Diagnosis of SARS-CoV-2 infection within 90 days prior to enrollment

 Exclusion Criteria:

 1. Participant is not expected to survive more than 24 hours.

 2. Participant has an unresolved Neisseria Meningitides infection.

 3. Hypersensitivity to murine proteins or to one of the excipients of ravulizumab.