Neutrophil calprotectin identifies severe pulmonary disease in COVID-19

Authors: Shi, Hui et al.

Link to paper: https://www.medrxiv.org/content/10.1101/2020.05.06.20093070v1

Journal/ Pre-Print:Medrxiv

Tags: Immunology/Immunity, Clinical/ Diagnostics, Therapeutics

Research Highlights

1. Higher levels of calprotectin in the sera of COVID-19 patients (n=96) compared to healthy controls (n=47)

2. Positive correlation between calprotectin and other acute phase reactants including CRP, D-dimer, ferritin and absolute neutrophil count

3. Calprotectin levels seem indicative of impaired oxygenation and the requirement for mechanical ventilation

Summary 

In this study, the authors link the neutrophil activation marker calprotectin to respiratory disease in hospitalised COVID-19 patients. Serum calprotectin levels were elevated in COVID-19 patients (n=96) and levels associated with oxygenation status in longitudinal samples (5 worsening, 3 improving). Calprotectin levels positively associated with CRP, absolute neutrophil count, D-dimer, ferritin, lactate dehydrogenase, neutrophil-to-lymphocyte-ratio, platelet count and negatively correlated with haemoglobin levels. Calprotectin, neutrophil count, neutrophil-lymphocyte ratio and CRP levels tracked closely with oxygenation status (higher in patients on mechanical ventilation vs room air). The authors suggest a relationship between neutrophil activation and severe respiratory disease in COVID-19. 

Impact for SARS-CoV2/COVID19 research efforts

Develop diagnostic tools for SARS-CoV2/COVID19

Calprotectin in blood serum as an indicator of patients with COVID-19 likely to progress to respiratory failure

Treat of SARS-CoV2/COVID19 positive individuals

Neutrophil-targeting therapies as a possible strategy to reduce the clinical severity of COVID-19

Study Type

· Patient Case study

Strengths and limitations of the paper

Novelty: Serum calprotectin levels track closely with respiratory severity

Standing in the field: Supports previous studies on the role of neutrophils in moderate-to-severe cases of COVID-1

Appropriate statistics: Yes, statistical tests clearly stated

Viral model used: Patients confirmed positive for SARS-CoV2 by RNA testing

Translatability: Authors suggest that neutrophil targeting therapies may be a possible strategy for COVID-19 patients at risk of respiratory failure.

Serum calprotectin might be used as a biomarker of COVID-19 severity.

Main limitations:

· Demographics of healthy control not reported – unknown if matched for age, gender and co-morbidities

· Small number of longitudinal samples (n=8) showing changes in calprotectin levels relating to oxygenation status

· Weak-moderate association between calprotectin and clinical tests with correlation coefficient values r<0.51

· Calpro is a non-specific marker of inflammation. Patients might have already have elevated levels pre-infection from underlying pathologies