October 15, 2020
Some people respond to COVID-19 by releasing high amounts of immune proteins called cytokines, which form when the body detects a foreign invader. But release of excessive amounts of cytokines leads to a large immune response that can cause organ damage. With grant support from the Lupus Research Alliance, Dr. Roberto Caricchio of Temple University and his team tracked immune responses of COVID-19 patients to develop criteria that may predict this large cytokine response. Being able to predict whether a patient will release too many cytokines in response to COVID-19 would help doctors choose more effective treatments and use these treatments before organ damage occurs. Study results were published September, 2020 in the highly prestigious medical journal, Annals of the Rheumatic Diseases.
Dr.Caricchio’s team used a wide range of tests to track the immune responses of over 500 COVID-19 patients over the their hospital stay. Some of these tests measured the levels of cytokines. Some COVID-19 patients released extremely high amounts of cytokines, called a ‘cytokine storm,’ which can lead to lung, kidney, heart, or muscle damage. To see if a patient had a cytokine storm, researchers used a combined score looking at the need for supplemental oxygen and the levels of proteins that cause inflammation. Using this score, of 513 patients, 64 developed a cytokine storm, and more male patients had a cytokine storm than female patients. The criteria could be applied to COVID-19 patients at any hospital or level of hospitalization anywhere in the world because the markers used to define the criteria are common laboratory tests, making the criteria very valuable for guiding decisions about how to treat COVID-19 patients worldwide.
Since there are different types of cytokine storms, doctors have developed scores that help determine which type of cytokine storm a patient is having. Researchers wanted to see if they could use these scores to detect a specific type of cytokine storm among COVID-19 patients. However, the use of existing cytokine storm scores did not correctly identify COVID-19 patients who were experiencing a cytokine storm. This suggested that the COVID-19 cytokine storm may be different from that seen in some patients with other diseases, such as cancer, juvenile idiopathic arthritis and SLE.
Once Dr. Caricchio’s group had the data from COVID-19 patients, they found which test results were most strongly linked to patients experiencing a cytokine storm and created a scoring system to find cytokine storms in COVID-19 patients. Of the 62 test results, 12 were linked to COVID-19 patients with cytokine storm. By scoring each of these 12 tests, a final score was determined that would identify patients undergoing a cytokine storm. Results from two additional tests were added as signs of inflammation.
To figure out whether the identified tests could predict COVID-19 cytokine storm, researchers compared the scoring system results with COVID-19 patients who had already been diagnosed as having cytokine storm in the clinic. According to the new criteria, 84% of these patients were correctly diagnosed with cytokine storm, showing that the scoring system matched the clinical decision well. Of the patients with COVID-19-related cytokine storm, 43 percent met the new criteria on the first day, which led researchers to propose that this test can be used to quickly predict COVID-19 cytokine storm. The researchers also used their criteria on a new group of patients called a cohort to show that it could predict cytokine storm in many COVID-19 patients.
This innovative scoring system could allow doctors to assess whether a patient has the type of cytokine storm unique to COVID-19. Dr. Caricchio and his team suggest that using these criteria to predict cytokine storms early, COVID-19 patients could receive appropriate treatment earlier and thus limit organ damage and other complications. Some lupus patients can also develop cytokine storms, but this study suggests that the cytokine storm that develops in COVID-19 patients is different from that seen in other types of patients, including some lupus patients. However, the specific similarities and differences between cytokine storm development in some lupus patients and in some COVID-19 patients need further study.
In April 2020 Temple University shut down due to the mandatory lockdown. Dr. Caricchio had to pause his LRA-funded research as well. While he was reassuring lupus patients in the Philadelphia area regarding the shortage of hydroxychloroquine, he was also involved in the care of hospitalized patients with COVID-19 when they developed the cytokine storm. The LRA funds gave him the opportunity to collaborate with frontline clinicians and researchers and realize the project. Although he is still involved in COVID-19 research, he is now back in the Lupus Clinic and his laboratory is actively investigating lupus again.
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