Elevated Levels of Neutrophil Activated Proteins, Alpha-Defensins (DEFA1), Calprotectin (S100A8/A9) and Myeloperoxidase (MPO) Are Associated With Disease Severity in COVID-19 Patients.

Shubham Shrivastava,Prashant Jedge,Akhilesh Chandra Mishra,Purwa Doke,Sonali Palkar,Shweta Chelluboina,Vidya A. Arankalle

doi:10.3389/fcimb.2021.751232

Abstract

Understanding of the basis for severity and fatal outcome of SARS-CoV-2 infection is of paramount importance for developing therapeutic options and identification of prognostic markers. So far, accumulation of neutrophils and increased levels of pro-inflammatory cytokines are associated with disease severity in COVID-19 patients. In this study, we aimed to compare circulatory levels of neutrophil secretory proteins, alpha-defensins (DEFA1), calprotectin (S100A8/A9), and myeloperoxidase (MPO) in COVID-19 patients with different clinical presentations. We studied 19 healthy subjects, 63 COVID-19 patients with mild (n=32) and severe (n=31) disease, 23 asymptomatic individuals identified through contact tracing programme and 23 recovering patients (1-4 months post-disease). At the time of disease presentation, serum levels of DEFA1 were significantly higher in patients with mild (mean230 ± 17, p<0.0001) and severe (mean452 ± 46, p<0.0001) disease respectively in comparison to healthy subjects (mean113 ± 11). S100A8/A9 proteins were significantly higher in COVID-19 patients (p<0.0001) irrespective of disease severity. The levels of DEFA1, S100A8/A9 and MPO reduced to normal in recovering patients and comparable to healthy subjects. Surprisingly, DEFA1 levels were higher in severe than mild patients in first week of onset of disease (p=0.004). Odds-ratio analysis showed that DEFA1 could act as potential biomarker in predicting disease severity (OR=11.34). In addition, levels of DEFA1 and S100A8/A9 were significantly higher in patients with fatal outcome (p=0.004 and p=0.03) respectively. The rise in DEFA1 levels was independent of secondary infections. In conclusion, our data suggest that induction of elevated levels of alpha-defensins and S100A8/A9 is associated with poor disease outcome in COVID-19 patients.

Highlights

COVID-19 is a recently emerged viral disease caused by a betacoronavirus, SARS-CoV-2
These were further classified as mild (n=32) or severe (n=31) infections based on disease severity (WHO 2020) (3) 23 asymptomatic individuals identified among contacts of COVID-19 patients and (4) 23 COVID-19 patients during convalescence (1-4 months post disease onset)
This study provides comparative, circulatory expression profiles of DEFA1, S100A8/A9 and MPO in COVID-19 patients with different clinical presentations

Summary

Introduction

COVID-19 is a recently emerged viral disease caused by a betacoronavirus, SARS-CoV-2. The viral infection has spread globally in a short span of time affecting 196 million people and causing approximately 4.2 million deaths as of 29th July 2021 (John Hopkins University Coronavirus tracker). Majority of the infected individuals exhibit either no or mild symptoms and about 15% develop severe pneumonia with approximately 6% progressing to acute respiratory distress syndrome (ARDS) and multiorgan failure (Guan et al, 2020). Inflammatory cytokines, IL-6, IL-10 and TNF-alpha have been identified as independent predictors of disease severity and clinical outcome (Del Valle et al, 2020; Dhar et al, 2021). Spike protein of SARS-CoV-2 is reported to induce inflammatory cytokines in macrophages (Khan et al, 2021). One of the hypotheses for progression to serious disease complications is imbalanced host immune response with ineffective early innate immunity followed by impaired adaptive immune responses and hyper-inflammation (BlancoMelo et al, 2020; Tay et al, 2020)

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