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

BMC Infect Dis. 2026 Mar 2;26(1):723. doi: 10.1186/s12879-026-12939-x.

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.

Keywords: COVID-19; Calprotectin; DNase; Deoxyribonuclease; Myeloid-related protein 8/14; S100A8/A9; SARS-CoV-2.

Publication types

  • Observational Study
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • COVID-19* / blood
  • COVID-19* / mortality
  • Deoxyribonucleases* / blood
  • Female
  • Hospitalization
  • Humans
  • Intensive Care Units
  • Leukocyte L1 Antigen Complex* / blood
  • Male
  • Middle Aged
  • Prospective Studies
  • SARS-CoV-2
  • Severity of Illness Index

Substances

  • Leukocyte L1 Antigen Complex
  • Deoxyribonucleases
  • Biomarkers