The Hayek Lab continues to study COVID-19 closely. Here are some of our findings:
Michigan Medicine COVID-19 Cohort
Over the past year and a half, our lab has compiled data from over 1,500 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.
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.
suPAR Extraction in COVID19
Extracorporeal suPAR Extraction to Prevent COVID-19 Associated Acute Kidney Injury
COVID19 related Acute Kidney Injury is strongly associated with in-hospital mortality, and 40% of survivors have no recovered kidney function by discharge. AKI is a complex and heterogeneous process with dependence on both host factors (such as age, diabetes, and hypertension), and extrinsic factors (such as certain nephrotoxic drugs or infections). Inflammation is a crucial link between these host and extrinsic factors, and recent evidence separately suggests that suPAR is a mediator of both kidney injury and COVID19 outcomes. The M2C2 cohort found that suPAR levels at admission in patients who subsequently developed AKI was 60% higher than those without AKI, and these findings were in contrast with other biomarkers of inflammation, including hs-CRP, d-Dimer, and ferritin.
Miltenyi Biotec has developed a Therasorb suPAR apheresis platform that uses the Life21 Apheresis system for blood withdraw and separation of blood cells from plasma, processing the plasma through a suPAR adsorber for specific extraction of the suPAR protein.
This clinical trial will use Miltenyi's Life21 Apheresis and Therasorb platform to treat hospitalized COVID19 patients with high levels of suPAR and without pre-existing kidney injury to determine if the extraction of suPAR prevents COVID19-association AKI.
The KIDCOV study: Assessment of Kidney Injury and Associated Risk Factors for SARS-CoV-2.
The human kidney is a target for the SARS-CoV-2 virus as it avidly binds to various proteases (TMPRSS2, CTSL) and the ACE2 receptor, the latter expressed on the brush border apical membrane of the proximal tubule and in the glomerulus in podocytes. Acute Kidney Injury (AKI) incidence in patients with symptomatic, systemic COVID19 ranges from 23%-60% in COVID19 infected patients, most of these patients being hospitalized during the early course of their illness.
There is an unmet need to evaluate the impact of sub-clinical/mild COVID19 disease in the outpatient setting on prevalent and incident renal injury over time, as this data is currently unavailable. The KIDCOV study will evaluate the impact of pre-existing kidney disease or renal disease risk factors (such as diabetes, hypertension) in this population, to assess if a kidney under stress due to SARS-CoV-2 infection is more susceptible to renal injury. We will also evaluate various baseline and demographic variables on the impact of COVID19 kidney injury. KIDCOV will enroll patients from 3 different states, California , Michigan, and Illinois, with no requirement for these individuals to leave their homes for blood sampling or doctor visits.
Improving early detection of new or worsening kidney damage is urgently needed in order to implement preventative measures and target therapeutics that can minimize post-COVID19 kidney damage.
Donate to the KIDCOV study here -
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.
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.