Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 1 2023 02 20 91 98 Behrooz Ghezelbash Department of Immunology, Faculty of Medicine, Isfahan University of Medical Science, Isfahan, Iran Mehdi Rostami Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Mohammad Heidarvand Department of Immunology, Faculty of Medicine, Isfahan University of Medical Science, Isfahan, Iran Alireza Mafi Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Hamid Chegni Department of Medical Laboratory Science, School of Allied Medical Sciences, Shahid Beheshti University of Medical Science, Tehran, Iran Nahid Eskandari Department of Immunology, Faculty of Medicine, Isfahan University of Medical Science, Isfahan, Iran 2022 08 13 2022 12 17 Some risk causes may be associated with the severity of COVID-19. The central host-pathogen factors might affect infection are human receptor angiotensin-converting enzyme 2 (ACE2), trans-membrane protease serine 2 (TMPRSS2), and SARS-CoV-2 surface spike (S)-protein. The main purpose of this study was to determine the differences in the expression the metalloproteinases-2  (MMP-2), MMP-9, ACE2, and TMPRSS2 genes and their correlation with lymphopenia in the mild and severe types of the COVID-19 patients. Eighty-eight patients, aged 36 to 60 years old with the mild (n=44) and severe (n=44) types of COVID-19 were enrolled. Total RNA was isolated from the peripheral blood mononuclear cells (PBMCs). The changes of MMP-2, MMP-9, ACE2 and TMPRSS2 gene expression in PBMCs from mild and severe COVID-19 patients were examined by the real time-quantitative polymerase chain reaction (RT-qPCR) assay and, compared between the groups. Data were collected from May 2021 to March 2022. The mean age of the patients in both groups was 48 (interquartile range, 36–60), and there were no appreciable differences in age or gender distribution between the two groups. The present study showed that a significant increase in the expression of ACE2, TMPRSS2, MMP-2, and MMP-9 genes in the severe type of the COVID-19 patients compared, to the mild type of the COVID-19 patients. Overall, it suggests the expression levels of these genes on the PBMC surface in the immune system are susceptible to infection by SARS-COV-2 and therefore could potentially predict the patients’ outcome. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3626 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3626/1925