Serial blood serum measurements of calprotectin and deoxyribonuclease in COVID-19 patients during hospitalization and recovery until one year: a prospective, multicenter, observational study

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Abstract Objectives To examine circulating calprotectin and deoxyribonuclease (DNase) serum levels during hospitalization in COVID-19 patients, their continuity post-discharge and dynamics in relation to disease severity. Methods Serum levels were measured in samples collected from 252 COVID-19 patients during hospitalization (admission, days 3–5 and 7–10), at 3 months and after 1 year, and related to admission to intensive care unit (ICU) or high dependency unit (HDU), and 60-day total mortality. Results During hospitalization, calprotectin and DNase levels were significantly elevated compared to healthy controls (HC). Calprotectin was increased in ICU/HDU patients compared to those at wards during hospitalization and in non-survivors compared to survivors during prolonged hospitalization. High calprotectin levels at admission were associated with male sex, PaO2/FiO2 ratio and national COVID-19 wave 2 and 3 compared to wave 1. High admission levels of both calprotectin and ferritin were associated with an approximately twofold higher odds ratio for ICU/HDU admission than either marker alone. DNase was lower at admission in non-survivors compared to survivors. Post-discharge, DNase but not calprotectin levels remained elevated extending to 1-year follow-up compared to HC. Conclusions COVID‑19 non‑survivors showed persistently higher calprotectin levels during prolonged hospitalization, and elevated admission calprotectin was associated with later pandemic waves and poorer oxygenation. Incorporating calprotectin with ferritin improved prediction of ICU/HDU admission. DNase levels were lower at admission in non‑survivors, while overall DNase remained elevated from hospitalization through 1‑year follow‑up compared with HC, suggesting a possible role in long‑term COVID‑19–related immune alterations.

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