Research Article Differentially Expressed Genes Study Shown Potential for BCG Stimulation in Reducing the Severity of COVID-19 Irandi Putra Pratomo , 1,2,3 Aryo Tedjo , 4,5,6 Dimas R Noor, 7 and Wisnu Ananta Kusuma 8,9 1 Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia 2 COVID-19 Task Force-Pulmonology and Respiratory Medicine Unit, Universitas Indonesia University Hospital, Universitas Indonesia, Depok, Indonesia 3 Bioinformatics Core Facilities, Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia 4 Drug Development Research Cluster, Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia 5 Department of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia 6 Master’s Programme Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, DKI Jakarta, Indonesia 7 Human Cancer Research Center, Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia 8 Department of Computer Science, Faculty of Mathematics and Natural Science, IPB University, Bogor, Indonesia 9 Tropical Biopharmaca Research Center, IPB University, Bogor, Indonesia Correspondence should be addressed to Wisnu Ananta Kusuma; ananta@apps.ipb.ac.id Received 29 March 2022; Revised 29 July 2022; Accepted 16 August 2022; Published 10 September 2022 Academic Editor: Sachchida Nand Rai Copyright © 2022 Irandi Putra Pratomo et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. e incidence of COVID-19 infection and death is known to be lower in tuberculosis (TB) endemic countries than in nonendemic countries. e Bacillus Calmette-Guerin (BCG) vaccination, which is commonly administered in TB endemic countries, was previously reported to have a nonspecific protective effect against several infections, including COVID-19. In this study, we used a differentially expressed genes (DEG) approach to analyze the genes modulated by BCG vaccination and COVID-19 infection. e Gene Expression Omnibus (GEO) database was used to select a COVID-19 gene expression data set with GSE164805, GSE14408, and GSE58636, and DEG in each data set were identified using the GEO2R online tools and selected using the adjusted p value (padj) 0.05 criteria. e protein-protein interaction (PPI) network was constructed from DEGs with the same trend of expression (upregulation or downregulation) using STRING version 11. e PPI network was performed by using the highest confidence number (0.9). DEGs that have a high-trust network were collected and functional cluster analysis of biological processes from Gene Ontology (GO), pathway analysis from the Human KEGG pathway, and COVID-19-related gene analysis was carried out using the Enrichr database. We found that either BCG or tuberculin increased the expression of several genes related to hyperinflammation, such as CCL3, CCL4, CSF2, IL1B, and LTA. In severe COVID-19, these genes were downregulated. is leads to the hypothesis that revaccination may have a protective effect against the severity of COVID-19 by reducing the hyperinflammatory status. 1. Introduction COVID-19 is a respiratory disease caused by SARS-CoV2 infection that has killed over 200,000 people worldwide [1]. At the beginning of pandemic times, developing countries were once predicted to face the highest number of deaths due to COVID-19. However, the mortality rate was found to be higher in developed countries such as the United States and Europe [2]. Madan et al. (2020) showed that COVID-19 incidence was lower in TB endemic areas compared to non- Hindawi International Journal of Inflammation Volume 2022, Article ID 1490408, 7 pages https://doi.org/10.1155/2022/1490408