These Two Tests May Determine COVID-19 Severity

A proportion of patients with COVID-19 are more prone to developing COVID-19-associated hyperinflammation regardless of age and comorbidity status, finds an observational study published on Friday in The Lancet Rheumatology.

In this study, physicians described an association between elevated inflammatory markers C-reactive protein and ferritin, and the likelihood that elevated levels in a patient with COVID-19 may escalate in severity.

Although the study included only 269 patients, it provides additional insight in terms of why some patients who contract COVID-19, advance to a more severe stage of the disease driven by the hyperinflammatory process known as the cytokine storm.

In patients who required oxygen, non-invasive ventilation or intubation, "we found an independent association between patients meeting the COVID-19-associated hyperinflammation (COV-HI) criteria and the need for ventilatory support or death, after accounting for age, sex, and comorbidity. Furthermore, 33% of the entire cohort met the COV-HI criteria upon presentation, and 74% of those who went on to need ventilatory support met the COV-HI criteria before escalation was required. Our work builds on, and contributes to, the evidence enabling risk prediction models for people with COVID-19," wrote the authors who were led by Jessica J. Manson, a rheumatologist with the University College London Hospitals NHS Trust.

THE STUDY

This was a retrospective cohort study of 269 adults with COVID-19 who were treated at hospitals in the United Kingdom from March 1-31.

For the purposes of this study, the hyperinflammatory phenotype, or COVID-19-associated hyperinflammation (COV-HI), was defined as a patient who had a C-reactive protein (CRP) concentration greater than 150 mg/L (compared to normal concentrations of 0.8 mg/L to 3.0 mg/L) or doubling within 24 hours from than 50 mg/L. Or, the patients had a ferritin concentration greater than 1,500 µg/L (which compares to normal ranges of 12 to 300 ng/mL for males and 12 to 150 ng/mL for females).

The study cohort was narrowed down to 178 patients who required respiratory support. But of the 269 adults, 90 met the criteria for COVID-19-associated hyperinflammation criteria at admission and of these patients, 40 percent of these patients died during follow-up despite being among the younger patients and having fewer comorbidities. Of 176 patients who required full respiratory support, 65 also had COVID-19-associated hyperinflammation at admission, and 67 of the 90 patients who received escalated respiratory care also met the criteria for COVID-19-associated hyperinflammation.

Just having COVID-19-associated hyperinflammation increase the risk of needing respiratory support within 24 hours or even death (hazard ratio 2·24 [95% CI 1·62–2·87]).

COMMENTARY

In a commentary that was published with study, physicians Kiran Reddy, Angela J. Rogers, and Daniel F. McAuley, wrote that this study suggests a predictive value of inflammatory markers.

"These important new data provide evidence that there is heterogeneity in the host response to severe acute respiratory syndrome coronavirus 2 infection that is associated with highly disparate clinical outcomes for patients. It is vital that this work prompts further investigations to understand the mechanisms underlying this heterogeneity and to inform appropriate therapeutic interventions. The rapid development of a precision medicine approach in COVID-19 could also inform clinical trials in acute respiratory distress syndrome (ARDS) and sepsis, and thus affect the care of critically ill patients in years to come," they wrote.

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REFERENCES

Jessica J Manson, PhD, Colin Crooks, PhD, Meena Naja, MBBS, et al. "COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study," The Lancet Rheumatology. Published: August 21, 2020 DOI:https://doi.org/10.1016/S2665-9913(20)30275-7

Kiran Reddy, Angela J Rogers, Daniel F McAuley. "Delving beneath the surface of hyperinflammation in COVID-19," The Lancet Rheumatology. Published: August 21, 2020 DOI:https://doi.org/10.1016/S2665-9913(20)30304-0