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October 28, 2020
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Predictive criteria identifies patients at risk for cytokine storm in COVID-19

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New criteria comprising inflammation, cell death and tissue damage, and prerenal electrolyte imbalance may predict cytokine storm in COVID-19 at an early stage, according to findings published in the Annals of the Rheumatic Diseases.

“A significant number of patients hospitalized with COVID-19 infection develop an hyperinflammatory response called cytokine storm,” Roberto Caricchio, MD, FACR, of the Temple University School of Medicine, in Philadelphia, told Healio Rheumatology. “These patients tend to have longer length of hospital stay and importantly are at greater risk of complications and death. There are no criteria to identify these patients.”

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“The ability to predict early on during the hospitalization which patient develops the cytokine storm could help initiate early treatment, shorten hospitalization and improve clinical outcome,” Roberto Caricchio, MD, FACR, told Healio Rheumatology. Source: Adobe Stock

To develop criteria to predict cytokine storm associated with COVID-19, Caricchio studied 513 patients with a confirmed diagnosis of COVID-19 admitted to Temple University Hospital from March 10 to April 17. All included patients had been hospitalized for up to 1 week prior to enrollment and demonstrated ground-glass opacity by high-resolution computerized tomography of the chest as per radiology reading, as well as a reverse transcriptase PCR for COVID-19 RNA.

The researchers analyzed laboratory results for the first 7 days of hospitalization for each patient and used logistic regression and principal component analysis to determine the predictive criteria. They then used a “genetic algorithm” to find the cutoffs for each laboratory result. The researchers validated the criteria with a second cohort of 258 patients.

Roberto Caricchio, MD, FACR
Roberto Caricchio

According to the researchers, the criteria for macrophage activation syndrome, hemophagocytic lymphohistiocytosis and the HScore failed to identify cytokine storm associated with COVID-19. Instead, Caricchio and colleagues used new criteria that included three clusters of laboratory results. These involved inflammation, cell death and tissue damage, and prerenal electrolyte imbalance. These criteria demonstrated a sensitivity of 0.85 and a specificity of 0.8. In addition, they were able to identify patients with longer hospitalization and increased mortality.

The results underscore the importance of hyperinflammation and tissue damage in cytokine storm associated with COVID-19, the researchers wrote.

“Interestingly the criteria could be grouped in three major pathological aspect of COVID-19 disease: inflammation, cell death and tissue damage and prerenal electrolyte imbalance,” Caricchio said. “The patients who met the criteria had three times longer length of hospitalization and six times higher mortality. Importantly the vast majority of patients who met the criteria, did so within the first 7 days and half of them at the time of admission. Therefore, the criteria are able to identify the cytokine storm very early during hospitalization.”

“The ability to predict early on during the hospitalization which patient develops the cytokine storm could help initiate early treatment, shorten hospitalization and improve clinical outcome,” he added. “Importantly these criteria are based on available routine laboratory tests accessible to most hospitals and could be readily used in clinical practice.”