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Published on: September 20, 2024
Temporal Dynamics of Host Immune Response Associated With Disease Severity and Time to Recovery in Patients
Anthony Sophonsri1, Diana Le1,2, Mimi Lou1
1Department of Clinical Pharmacy, University of Southern California, School of Pharmacy, Los Angeles, CA.
Objectives:
The objective of this study was to compare the temporal dynamics of two viral-induced inflammatory proteins interferon gamma inducible protein-10 (IP-10) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as well as C-reactive protein (CRP) among patients hospitalized for COVID-19 and examine their prognostic significance.
Design:
Prospective observational cohort study.
Setting:
Multicenter, inpatient.
Patients:
Adult patients infected with severe acute respiratory syndrome coronavirus 2 between March 2021 and October 2021.
Interventions:
Patient sera were collected on days 1, 3, 5, and 7 of hospitalization. Levels of IP-10, TRAIL, and CRP were measured using a point-of-need diagnostic immunoassay platform (MeMed BV, MeMed, Haifa, Israel) and compared between patients grouped by disease severity (severe vs nonsevere).
Measurements And Main Results:
Baseline characteristics were similar regardless of severity except for a higher prevalence of diabetes and heart failure among severe patients. The immune profile at admission was similar between groups; IP-10 and CRP levels generally decreased while TRAIL levels increased over time in all patients. However, the severe group had higher IP-10 (median 713 vs 328 pg/mL; p = 0.045) and lower TRAIL levels (median 21 vs 30 pg/mL; p = 0.003) on day 3 compared with nonsevere patients. A breakpoint IP-10 level of greater than or equal to 570 pg/mL and TRAIL level of less than 25 pg/mL on day 3 were associated with COVID-19 severity. Patients with elevated day 3 IP-10 levels (≥ 570 pg/mL) were more likely to experience prolonged recovery time (median 12 vs 3 d; p < 0.001). The severe group had prolonged use of corticosteroids (12 vs 5 d; p < 0.001) and had a higher rate of secondary infections (20% vs 6%; p = 0.04) and in-hospital mortality (20% vs 0%; p < 0.001) as compared with nonsevere patients.
Conclusions:
The observed patterns in host immune response revealed a turning point in COVID-19 disease on hospital day 3 and the potential utility of IP-10 and TRAIL as sensitive markers associated with disease severity and time to recovery.
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