COVID-19
The Hayek Lab continues to study COVID-19 closely. Here are some of our findings:
A Randomized, Placebo-Controlled Phase 2/3 Study to Determine the Safety and Effectiveness of Azeliragon in the Treatment of Patients Hospitalized for COVID-19
High suPAR levels predispose patients to AKI (acute kidney injury) in various conditions, including critical illness. In hospitalized patients, suPAR levels were found to be 3-10x fold in those with COVID-19 than other respiratory diseases, and strongly predictive of AKI, including the need for dialysis. suPAR levels were also strongly associated with poor outcomes in patients hospitalized for COVID-19, including respiratory failure and death.
suPAR is involved in the pathogenesis of kidney disease, with a recent study showing the Receptor for Advanced Glycation Endproducts (RAGE) as an essential co-receptor for suPAR signalling in kidney cells.
Azeliragon is an orally administered small molecule, owned by the clinical stage pharmaceutical company, Cantex Pharmaceuticals, that inhibits interactions between RAGE and its natural ligands.
Together with Cantex Pharmaceuticals, we have designed a quadruple masked (participant, provider, investigator, outcomes assessor), placebo-controlled, study of Azeliragon to determine the safety and preliminary results regarding effectiveness of Azeliragon in decreasing the incidence of AKI, need for mechanical ventilation, and death in patients hospitalized for COVID-19 or Pneumonia.
Please see information regarding our study on ClinicalTrials.gov
More information about the study and enrollment can be found here.
M2C2
Michigan Medicine COVID-19 Cohort
Our lab has compiled data from over 3000 adult (over 18) patients hospitalized primarily for COVID-19 treatment in the Michigan Medicine COVID-19 Cohort (M2C2).
This study seeks to better understand the progression of illness and outcomes among COVID-19 patients through the inflammatory response initiated by the virus. Inflammation is a normal response to infection, and in the case of the SARS-CoV-2 virus, it can also cause damage to the organs.
The M2C2 dataset covers demographics and comorbidities, clinical presentation, past medical and familial history. Medications at presentation, historically, and upon discharge; all aspects of patient care and treatment during hospitalization, including lab work, vital signs, oxygenation and ventilation requirements, and imaging findings are also recorded.
To analyze the specific role of inflammation in viral pathogenesis, patients are subject to a diagnostic blood test to measure levels of inflammatory biomarkers including soluble urokinase plasminogen activator receptor (suPAR), high sensitive C reactive protein (hs-CRP), brain natriuretic protein (BNP), high sensitive troponin T (hsTnT), interleukin 6 (IL-6), osteopontin, a2-antiplasmin. Characterized outcomes such as the need for mechanical ventilation or dialysis, length of hospitalization, and death continue to be followed, updated, and assessed.
Data is collected and stored on a REDCap database.
Interested in collaborating with the M2C2 ? Contact Salim Hayek.
See our study on Clinicaltrials.gov
University of Michigan has created a fantastic COVID-19 resource from multiple basic science perspectives.
See REDCap for more information about the database software.
Inflammatory Biomarkers and Outcomes
With the worldwide COVID-19 pandemic, and health systems exceeding capacity even in developed countries, with continued spread and increased case numbers expected to continue rising through the year, adequate triage of patients is essential. Given the non-specific nature and variable progression of symptoms of the novel coronavirus, identifying patients who will require a higher level of care is challenging. Knowing COVID-19 infections are characterized by hyperinflammatory syndrome, we are determining whether biomarkers can be used to help triage patients presenting with suspected COVID-19 symptoms, using the M2C2 dataset, differentiating those who should be seen by specialists earlier in hopes of decreasing mortality.
We have identified several biomarkers of interest that are upregulated during infection, and are currently collecting data from multiple centers on confirmed COVID-19 cases to develop cutoff levels of biomarkers separately or in combination, including the very promising biomarker, suPAR.
This project represents a low-risk, high-reward approach to address the challenge of COVID-19 mortality rates.
Find more information about the novel coronavirus from the CDC.
See the Johns Hopkins COVID-19 tracker.
COVID-19 at Michigan Medicine.
Patient-specific guidance for COVID-19 infections.
Information on COVID-19 research at the University of Michigan.
General University of Michigan COVID-19 updates.
ISIC
International Study of Inflammation in COVID-19
The International Study of Inflammation in COVID-19, ISIC, is actively collecting and assaying blood samples from medical centers around the world, specifically looking at the inflammatory marker suPAR to determine the usage in triaging patients presenting to hospitals with COVID-19.
Preliminary studies showed suPAR as a risk factor for respiratory failure in COVID-19 patients, prompting larger studies.
In our first publication on suPAR's association with Acute Kidney Disease in COVID-19, 352 patients with suPAR measured within 48 hours of hospital admission showed a strong association with incident AKI, independent of such clinical characteristics as kidney function and inflammatory biomarkers. This association was predictive of the need for dialysis.
We and collaborators at Copenhagen University, Denmark; University of Athens, Greece; University Hospital Duesseldorf, Germany; University of Berlin, Germany; University of Thessaly, Greece; and Rush University, Chicago IL are continuing to collect patient data for larger and more definitive studies as the most recent COVID surge threatens health systems worldwide.
ISIC is an ancillary project to M2C2 - see ISIC on Clinicaltrials.gov
STOP-COVID
Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19
The COVID-19 pandemic has had a devastating impact around the world, and combating this pandemic will require a multidisciplinary approach from the medical research community, including translational studies to understand the pathogenesis of disease, randomized controlled trials of novel and repurposed pharmacotherapies, and rigorously conducted epidemiologic studies that include granular patient-level data.
We are working with Drs. David E Leaf and Shruti Gupta at Harvard Medical School and Brigham and Women's Hospital on a multicenter observational study of the clinical features and outcomes of critically ill patients with COVID-19 admitted to intensive care units across the U.S, entitled STOP-COVID.
Our goals are to determine the independent risk factors for hospital mortality and acute organ injury, and to identify treatment strategies associated with improved survival.
Harvard's Leaf lab website.
STOP-COVID on Clinicaltrials.gov
Coronavirus updates from Harvard.
More information on observational studies.