Analysis of differential expression of matrix metalloproteins and defensins in the nasopharyngeal milieu of mild and severe COVID-19 cases

Khekashan Imtiaz, Nida Farooqui, Khalid Ahmed, Alnara Zhamalbekova, Muhammad Faraz Anwar, Khitab Gul, Azhar R Hussain, Antonio Sarría‐Santamera, Syed Hani Abidi

2024

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DOI 10.1101/2024.05.12.593784
Data confidence 70 medium
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Abstract

Abstract Introduction A subset of COVID-19 disease patients suffers a severe form of the illness, however, underlying early pathophysiological mechanisms associated with the severe form of COVID-19 disease remain to be fully understood. Several studies showed the association of COVID-19 disease severity with the changes in the expression profile of various matrix metalloproteinases (MMPs) and defensins. However, the link between the changes in the expression of matrix metalloproteinase (MMPs) and defensins (DA) in the nasopharyngeal milieu, during early phases of infection, and disease severity remains poorly understood. Therefore, we performed differential gene expression analysis of matrix metalloproteinases (MMPs) and defensins in the nasopharyngeal swab samples collected from mild and severe COVID-19 cases within three days of infection and examined the association between MMP and DA expression and disease severity. Material and Method A total of 118 previously collected nasopharyngeal samples from mild and severe COVID-19 patients (as per the WHO criteria) were used in this study. To determine the viral loads and assess the mRNA expression of matrix metalloproteinase (MMPs) and defensins, a real-time qPCR assay was used. To assess statistically significant differences in the mean expression of viral loads and the cytokines in between the severe and mild groups, an unpaired T-test was applied. The Pearson correlation test was used to assess the correlation between cytokine expressions. In addition, a multivariable logistic regression analysis was carried out with all the variables from the data set using ‘severity’ as the outcome variable. Results Our results showed that the expression of DA3 and MMP2 to be considerably lower in the severe group than in the mild group. Furthermore, there was a significant association between MMP1 and DA4 and DA6 (r=0.5, p=0.0001); as well as between MMP7 and DA1 and DA6 (r=0.5, p=0.00). Additionally, the regression analysis shows a significant correlation (p 0.05) between MMP2 and the severity of COVID-19 disease. Conclusion The early detection of changes in the expression of MMPs and defensins may act as a useful biomarker/predictor for possible severe COVID-19 disease, which may be useful in the clinical management of patients to reduce COVID-19-associated morbidity and mortality.