Correlations of Myeloperoxidase (MPO), Adenosine deaminase (ADA), C-C motif chemokine 22 (CCL22), Tumour necrosis factor alpha (TNFα) and Interleukin-6 (IL-6) mRNA expression in the nasopharyngeal specimens with the diagnosis and severity of SARS-CoV-2 infections

Abstract

Cytokine dynamics in patients with coronavirus disease 2019 (COVID-19) have been studied in blood but seldomly in respiratory specimens. We studied different cell markers and cytokines in fresh nasopharyngeal swab specimens for the diagnosis and for stratifying the severity of COVID-19. This was a retrospective case-control study comparing Myeloperoxidase (MPO), Adenosine deaminase (ADA), C-C motif chemokine ligand 22 (CCL22), Tumour necrosis factor alpha (TNFα) and Interleukin-6 (IL-6) mRNA expression in 490 (327 patients and 163 control) nasopharyngeal specimens from 317 (154 COVID-19 and 163 control) hospitalized patients. Of the 154 COVID-19 cases, 46 died. Both total and normalized MPO, ADA, CCL22, TNFα, and IL-6 mRNA expression levels were significantly higher in the nasopharyngeal specimens of infected patients when compared with controls, with ADA showing better performance (OR 5.703, 95% CI 3.424-9.500, p < 0.001). Receiver operating characteristics (ROC) curve showed that the cut-off value of normalized ADA mRNA level at 2.37 × 10^-3 had a sensitivity of 81.8% and specificity of 83.4%. While patients with severe COVID-19 had more respiratory symptoms, and elevated lactate dehydrogenase, multivariate analysis showed that severe COVID-19 patients had lower CCL22 mRNA (OR 0.211, 95% CI 0.060-0.746, p = 0.016) in nasopharyngeal specimens, while lymphocyte count, C-reactive protein, and viral load in nasopharyngeal specimens did not correlate with disease severity. In summary, ADA appears to be a better biomarker to differentiate between infected and uninfected patients, while CCL22 has the potential in stratifying the severity of COVID-19.

Keywords: CCL22; COVID-19 severity; Nasopharyngeal specimen; adenosine deaminase; myeloperoxidase.

Figure 1.

Flowchart of patient inclusion in this study. Severe disease is defined as the need for supplemental oxygen on admission, admission to the intensive care unit (ICU) due to COVID-19, or death. Abbreviations: NPS, Nasopharyngeal specimens.

Figure 2.

Comparison of normalized and total MPO, ADA, CCL22, TNFα, and IL-6 mRNA expression in nasopharyngeal specimens between COVID-19 infected and uninfected individuals. The bar represents the median of the samples, the hinges mark the interquartile range. *p < 0.05, **p < 0.005, ***p < 0.001.

Figure 3.

Receiver operating characteristics (ROC) curve of normalized MPO, ADA, CCL22, TNFα, and IL-6 mRNA expression in identification of COVID-19 infected patients. The dotted line represents the line of identity.

Figure 4.

Comparison of normalized MPO, ADA, CCL22, TNFα, and IL-6 mRNA expression in nasopharyngeal swabs between different specimens in COVID-19 patients. The central point represents the median of the samples, the hinges mark the interquartile range. *p < 0.05, **p < 0.005, ***p < 0.001.

Figure 5.

Comparison of normalized MPO, ADA, CCL22, TNFα, and IL-6 mRNA expression in nasopharyngeal swabs between different specimens in patients with mild and severe COVID-19. The central point represents the median of the samples, the hinges mark the interquartile range. *p < 0.05, **p < 0.005, ***p < 0.001.