key: cord-0797781-h5h5txew
authors: Shi, Shengjie; Su, Min; Shen, Ge; Hu, Yan; Yi, Fan; Zeng, Ziyan; Zhu, Pan; Yang, Gang; Zhou, Hui; Li, Qiong; Xie, Xiaobing
title: Matrix metalloproteinase 3 as a valuable marker for patients with COVID‐19
date: 2020-07-11
journal: J Med Virol
DOI: 10.1002/jmv.26235
sha: b81c3c03b5750438cb60df31418ac7d58abf20ca
doc_id: 797781
cord_uid: h5h5txew

The situation of the coronavirus disease 2019 (COVID‐19) continues to evolve, our study explored the significance of serum levels of matrix metalloproteinase 3 (MMP3) as a marker for patients with COVID‐19. Sixty‐two COVID‐19 patients in the First Hospital of Hunan University of Chinese Medicine and Loudi Center for Diseases Prevention and Control, from January to March 2020, were sampled as the novel coronavirus pneumonia infected group. One hundred and thirty‐one cases from the First Hospital of Hunan University of Chinese Medicine, including 67 healthy individuals and 64 non‐COVID‐19 inpatients, served as the noninfected group. Approximately every 5 days, sera from 20 cases were collected and analyzed three times, using an automatic biochemical analyzer, to detect serum MMP3 concentrations. Correlation was analyzed between MMP3 and other proinflammatory cytokines. Following normality tests, differences in serum MMP3 levels between the infected and noninfected group were analyzed via SPSS (version 25.0) software, using the Wilcoxon rank sum test. The MMP3 concentration was 44.44 (23.46 ~ 72.12) ng/mL in the infected group and 32.42 (28.16 ~ 41.21) ng/mL in the noninfected group. The difference between the two groups was statistically significant (Z = −2.799, P = .005 < .05). A positive correlation was found between MMP3 and interleukin 1β (IL‐1β; r = .681, P = .000 < .05), and IL‐6 (r = .529, P = .002 < .05). Serum MMP3 concentration, measured over three separate time points, were 55.98 (30.80 ~ 75.97) ng/mL, 34.84 (0.00 ~ 51.84) ng/mL, and 5.71 (0.00 ~ 40.46) ng/mL, respectively. Detection of serum MMP3 levels may play an important role in the development of therapeutic approaches for COVID‐19 and may indicate the severity of disease.

group. Approximately every 5 days, sera from 20 cases were collected and analyzed three times, using an automatic biochemical analyzer, to detect serum MMP3 concentrations. Correlation was analyzed between MMP3 and other proinflammatory cytokines. Following normality tests, differences in serum MMP3 levels between the infected and noninfected group were analyzed via SPSS (version 25.0) software, using the Wilcoxon rank sum test. The MMP3 concentration was 44.44 (23.46~72.12) ng/mL in the infected group and 32.42 (28.16~41.21) ng/mL in the noninfected group. The difference between the two groups was statistically significant (Z = −2.799, P = .005 < .05). A positive correlation was found between MMP3 and interleukin 1β (IL-1β; r = .681, P = .000 < .05), and IL-6 (r = .529, P = .002 < .05). Serum MMP3 concentration, measured over three separate time points, were 55.98 (30.80~75.97) ng/mL, 34.84 (0.00~51.84) ng/mL, and 5.71 symptoms include dry cough, fever, and fatigue. 1,2 Since its emergence, SARS-CoV-2 has spread rapidly all over the world, arousing widespread concern. To date, the viral nucleic acid test remains the main diagnostic tool used to detect COVID-19, whereas serum immunoglobulin G (IgG) and IgM antibodies can be used to detect the SARS-CoV-2 infection. 3 Laboratory examination plays a vital role in the diagnosis and treatment of COVID-19, wherein relevant test indicators may provide evidence-based support for clinicians. Our previous study 4 has found that MMP3 has good clinical value in the differential diagnosis of benign and malignant hydrothorax and ascites. In this study, we attempt to show a possible connection between matrix metalloproteinase 3 (MMP3) and COVID-19.

MMP3 is an important member of a large family of MMPs containing zinc-dependent endopeptidases. Matrix degradation and remodeling have been recognized as the main function of MMPs.

However, subsequent studies reveal that MMPs may participate in diverse pathophysiological processes, such as the regulation of inflammatory and immune responses as well as cell-cell communication, among others. Reportedly, 5, 6 in addition to the above functions, MMP3 also activates other MMPs in the family. In particular, it participates in many physiological and pathological processes that are associated with the inflammatory process. For example, studies have confirmed that MMP3 levels may be used to monitor the activity of rheumatoid arthritis and to predict its severity. 7, 8 Recent studies have investigated the effects of MMP3 on respiratory disorders, including acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pulmonary fibrosis, and lung cancer. 5, 9 Therefore, this study makes a major contribution to research on COVID-19 by demonstrating the significance of MMP3 and providing ideas for future scientific research. Interleukin 1β (IL-1β) and IL-6 test kits were purchased from Human Diagnostic Products Co, Ltd (Beijing). All tests were conducted by authorized, skilled laboratory personnel in accordance with the manufacturer's specifications and instructions.

Data were analyzed using SPSS (version 25.0) software. Normality tests were conducted for measurement data, where normal data were expressed as the mean and standard deviation, while t test was used for comparison between two groups. Data that did not conform to normality were expressed as the median and interquartile, and the Wilcoxon rank sum test was used to compare the differences in serum MMP3 levels between the two groups. Spearman's correlation analysis was used to explore the correlation between MMP3 and IL-1β, and IL-6. Statistical significance was set at P < .05.

Normality tests indicated that data from both the novel coronavirus pneumonia infected group and the noninfected group were not normal. Therefore, the Wilcoxon rank sum test was used to compare the two groups. The MMP3 serum levels in the infected and noninfected groups are shown (Table 1) And a positive correlation was found between healthy people and hospitalized patients (Z = −4.644, P = .000 < .05). The distribution of MMP-3 and the statistical significance were plotted using a quartile box (Figure 2A,B) . And the MMP3 serum levels in healthy people and hospitalized patients are shown in Table 1 .

Of the 62 patients with COVID-19 infection, 31 were tested for MMP3, IL-1β, and IL-6 at the same time and their correlation was analyzed. Spearman's correlation analysis showed correlations between MMP-3 and IL-1β (r = .681, P = .000 < .05; Figure 3A ), and IL-6 (r = .529, P = .002 < .05; Figure 3B ).

To detect serum MMP3 concentrations, sera from 20 patients were 

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The authors declare that there are no conflict of interests.

SS and MS contributed to the article drafting, revising, and data analysis. GS, FY, and XX contributed to the conception and design.YH, ZZ, PZ, GY, HZ, and QL contributed to data collection and technical analysis. XX is the guarantor for this study.

Hospital of Hunan University of Chinese Medicine.

http://orcid.org/0000-0003-4413-3983