Summary. Five common blood biomarkers were investigated in the report: 

  1. IL-6 (interleukin 6). IL-6 is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. In layman’s terms: IL-6 one of several cytokines (proteins) that stimulate immune response and often are an indicator of inflammation.
  2. D-dimers (degraded proteins). D-dimer is a fibrin degradation product, a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two D fragments of the fibrin protein joined by a cross-link. D-dimer concentration may be determined by a blood test to help diagnose thrombosis. In layman’s terms: D-dimers are generated from breakdown of clots, and can be an indicator of blood vessel damage and the potentially deadly condition of thrombosis.
  3. CRP (C-reactive protein) C-reactive protein is an annular, pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin-6 secretion by macrophages and T cells.  In layman’s terms: CRP is released by the liver in response to inflammation.
  4. LDH (Lactate Dehydrogenase) Lactate dehydrogenase is an enzyme found in nearly all living cells. LDH catalyzes the conversion of lactate to pyruvate and back, as it converts NAD⁺ to NADH and back. A dehydrogenase is an enzyme that transfers a hydride from one molecule to another. LDH exists in four distinct enzyme classes. In layman’s terms:LSH  an enzyme in lactic acid that stimulates tissue regeneration.
  5. Ferritin (a protein for iron storage). Ferritin is a universal intracellular protein that stores iron and releases it in a controlled biochemical mechanism. Ferritin is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. In humans, Ferritin acts as a buffer against iron deficiency and iron overload in red blood cells. In layman’s terms: Iron is critical for healthy red blood cells to transport oxygen throughout the body. High or low levels of Ferritin can signal anemia or infection which can affect normal blood cell function.

SARS-CoV-2 which causes the COVID-19 disease is known to bind to ACE2 receptor which is found widely throughout the body, including lung, heart, kidney, and endothelium (blood vessels) which is a single layer of squamous endothelial cells that line the interior surface of blood vessels, and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall.


Reprinted for educational purposes and social benefit, not for profit.

Shant Ayanian, Juan Reyes, Lei Lynn, Karolyn Teufel.

Biomarkers in Medicine, 2020; DOI: 10.2217/bmm-2020-0309

Aim: To describe the association between D-dimer, CRP, IL-6, ferritin, LDH and the clinical outcomes in a cohort of 299 novel coronavirus disease (COVID-19) patients treated on the inpatient medical service at a university hospital in the District of Columbia (DC, USA).

Methodology/results: In this retrospective study, we included all laboratory confirmed COVID-19 adults admitted to the inpatient medicine service at the George Washington University Hospital between March 12, 2020 and May 9, 2020. We analyzed the association of biomarkers on intensive care unit transfer, intubation and mortality. Threshold values for all biomarkers were found to be statistically significant and independently associated with higher odds of clinical deterioration and death.

Conclusion: Laboratory markers of inflammation and coagulopathy can help clinicians identify patients who are at high risk for clinical deterioration in COVID-19.

Summary points

Background

  • The global pandemic caused by novel coronavirus disease (COVID-19) remains poorly understood by clinicians.
  • Identifying biologic markers associated with prognosis can help clinicians recognize disease severity.
  • The clinical impact of these biological markers on outcomes in the US population remains unclear.

Materials & methods

  • A retrospective cohort of COVID-19 patients were identified, their admission and peak biomarkers were extracted and the odds of adverse clinical outcomes were calculated.

Results

  • A total of 299 patients were identified with a mortality of 24% and 200 patients had a full biomarker panel check.
  • IL-6, CRP, ferritin, lactate dehydrogenase and D-dimer threshold levels all had an independent increased odds of intensive care unit transfer, intubation requirement and death.
  • Lactate dehydrogenase had the highest odds associated with patient mortality, followed by D-dimer.
  • CRP and D-dimer had the highest odds associated with intensive care unit transfer and intubation, respectively.

Conclusion

  • Biomarkers of inflammation and coagulopathy can aid in identifying hospitalized COVID-19 patients at risk for clinical deterioration.

Learn More:

  • Blood test may point to patients at higher risk for COVID-19 deterioration, death – ScienceDaily
  • George Washington University (GW) researchers found five biomarkers, medical indicators found in the blood, associated with higher odds of clinical deterioration and death in COVID-19 patients. Published in Future Medicine, these findings will help physicians better predict outcomes for COVID-19 patients in the U.S.
  • “When we first started treating COVID-19 patients, we watched them get better or get worse, but we didn’t know why,” said Juan Reyes, MD, co-author of the study and assistant professor of medicine at the GW School of Medicine and Health Sciences. “Some initial studies had come out of China showing certain biomarkers were associated with bad outcomes. There was a desire to see if that was true for our patients here in the U.S.”
  • The research team evaluated 299 patients diagnosed with COVID-19 admitted to GW Hospital between March 12 and May 9, 2020. Of these patients, 200 had all five biomarkers being evaluated — IL-6, D-dimer, CRP, LDH and ferritin. Elevated levels of these biomarkers were associated with inflammation and bleeding disorder, showing an independent increased risk for ICU admission, invasive ventilatory support, and death. The highest odds of death occurred when the LDH level was greater than 1200 units/l and a D-dimer level was greater than 3 ?g/ml.
  • “We hope these biomarkers help physicians determine how aggressively they need to treat patients, whether a patient should be discharged, and how to monitor patients who are going home, among other clinical decisions,” said Shant Ayanian, MD, first author of the study and assistant professor of medicine at the GW School of Medicine and Health Sciences.
  • Currently, physicians determine risk for COVID-19 deterioration and death based on age and certain underlying medical conditions, like having an immunocompromised state, obesity, and heart disease. Performing a simple blood test for patients admitted to the emergency department, then also making decisions based on biomarkers present, may further aid point-of-care clinical decision making. Reyes, Ayanian, and the GW research team will continue to analyze this data to help physicians make more informed decisions for patients, as well as help hospitals that may need to stratify resources.
  • “The association between biomarkers and clinical outcomes in novel coronavirus pneumonia in a US cohort” was published in Future Medicine.