key: cord-0980994-3olr7j4y
authors: Mao, Qin; Wang, Chunyi; Wen, Wen; Zhou, Mengyun; Tang, Jiake; Chen, Chen; Cheng, Yongran; Wu, Qi; Zhang, Xingwei; Feng, Zhanhui; Wang, Mingwei
title: A meta-analysis of the association between calprotectin and the severity of COVID-19
date: 2022-01-21
journal: J Infect
DOI: 10.1016/j.jinf.2022.01.022
sha: 0a7a59de6832e34c62b3bae47336f6532194c808
doc_id: 980994
cord_uid: 3olr7j4y

nan

care unit treatment, invasive mechanical ventilation, multiple organ failure or death) and a non-severe group according to their disease condition. Our analysis of these eight cohort studies generated consistent results; calprotectin plasma levels in the severe group were significantly higher than the non -severe group. A meta-analysis forest plot showed the overall pooled estimate was 1.18 (95% confidence interval (CI): 0.74, 1.62) ( Figure 1) . Also, the heterogeneity (I 2 ) was 82.3% and the Egger value was 0.469, indicating no publication bias.

Thus, plasma calprotectin levels were related to COVID -19 patient severity; the index was significantly higher in the severe group than the non -severe group. This observation was also consistent with a previous meta -analysis. 3 Typically, calprotectin is released upon initial inflammatory stimulus, and is triggered by the toll-like receptor-4 (TLR-4) on granulocytes, and is involved in neutrophil -related inflammation processes. Calprotectin exerts antibacterial effects toward some bacteria, including Escherichia coli and Staphylococcus aureus. 1 ,4 Therefore, calprotectin is an effective antibacterial protein.

Calprotectin concentrations greater than 24.1 mg/L are associated with a significant increase of approximately 25% in the risk of death, 5 thus the higher the calprotectin level, the more severe the inflammation, the more severe the patient's condition, and the worse the prognosis. Christensen et al. reported that patients with severe Novel Coronavirus Pneumonia had higher plasma B cell activity and calprotectin levels, while transcripts related to immune function were mostly reduced, affecting B cells in particular. 6 Therefore, these data suggest a new exploratory direction for COVID-19 patient treatments in the future.

Calprotectin is found not only in the blood (serum or plasma), but also in the feces. Several studies reported that SARS -CoV-2 bound to intestinal epithelial cells via specific receptors and promoted acute inflammation characterized by neutrophil and macrophage infiltration. 7 Therefore, fecal calprotectin levels may also be used to study patients with Novel Coronavirus Pneumonia. Similarly, fecal calprotectin levels in a COVID-19 plus diarrhea group were significantly higher than in controls. 8 Shokri-Afra et al. also identified higher plasma and fecal calprotectin levels in COVID-19 patients when compared with healthy subjects, but no differences in patients with or without gastrointestina l symptoms. 9 Ojetti et al. Table 1 The main results of studies that reported Calprotectin.

*Severe group (intensive care unit (ICU) treatment, invasive mechanical ventilation, multiple organ failure or death **Plasma calprotectin level is displayed at the level of mean ± SD or median (IQR)

Serum calprotectin is not an independent predictor of severe COVID-19 in ambulatory adult patients

Assessment of antiphospholipid antibodies and calprotectin as biomarkers for discriminating mild from severe COVID-19

Calprotectin, an Emerging Biomarker of Interest in COVID-19: A Systematic Review and Meta-Analysis

Circulating calprotectin as a supporting inflammatory marker in discriminating SARS-CoV-2 infection: an observational study

Oxidative Stress and Inflammatory Biomarkers for the Prediction of Severity and ICU Admission in Unselected Patients Hospitalized with COVID-19

Critical COVID-19 is associated with distinct leukocyte phenotypes and transcriptome patterns

Calprotectin and SARS-CoV-2: A Brief-Report of the Current Literature. Healthcare (Basel)

Faecal calprotectin indicates intestinal inflammation in COVID-19

The work was supported by the Key medical disciplines of Hangzhou.