The Coronavirus 2019 (COVID-19) quickly became a pandemic, configuring an international public state of emergency. The virus that causes the disease, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggers clinical manifestations ranging from asymptomatic infection to severe acute respiratory syndrome and death. In addition to respiratory symptoms, patients with COVID-19 may experience cardiac complications, including viral myocarditis and arrhythmias. Although the ischemic and inflammatory responses caused by COVID-19 can negatively affect cardiac function, the direct impact of the infection on human cardiomyocytes is still not well understood. Many researchers are exploring molecular changes at the transcriptional level, but little is known about the factors that post-transcriptionally regulate gene expression during SARS-CoV-2 infection. MicroRNAs (miRs) are a class of small non- coding RNAs that post-transcriptionally regulate gene expression and have therapeutic potential in several pathologies. We employed a systems and integrative immunology approach by analyzing transcriptomic data, aiming to identify the molecular networks regulated by miRs. We used the NetworkAnalyst 3.0 tool for differential expression analysis of RNA sequencing (RNAseq) data from four public datasets. Read counts were used to identify differentially expressed genes (DEGs) through the DESeq2 pipeline. The enriched biological processes identified using the WebGestalt and EnrichR tools. While up-regulated DEGs across these studies enriched BPs related to the immune response (e.g., T cell activation, cytokine production and regulation of hematopoiesis), the down-regulated DEGs enriched BPs related to metabolic dysregulation (e.g., complex assembly NADPH dehydrogenase; generation of precursor metabolites and energy; small molecule catabolic process) and the muscular system. A total of 601 common DEGs across all datasets were identified. For the interactome analysis of mRis and these common DEGs, we focused on those associated with the immune response, cardiac muscle contraction, extracellular matrix remodeling and thrombosis, using the QUICKgo platform to select BPs while avoiding overlapping category terms Using the MiRTarBase tool, we identified 331 potential regulatory miRs of SARS-CoV-2 infected cardiomyocytes Of these, 19 miRs are potential regulators of immune response genes, 4 miRs associated with cardiac muscle contraction, 21 associated with extracellular matrix and 6 target regulators associated with coagulation. Of note, there are miRs that potentially regulate genes involved in the inflammatory response and interferon type I signaling pathway, such as miR-155-5p and those involved in the cardiac muscle cell contraction process, such as miR-29a-3p, miR-29b -3p and miR-146b-3p. Our systems and integrative immunology approach of identified possible miRs- mRNA regulatory molecular networks and pathways potentially associated with immune response-related molecules of cardiomyocytes infected with SARS-CoV-2. In the last phase of this project, we will carry out an experimental approach to evaluate the expression of these miRs and proteins by SARS-CoV-2 infected cardiomyocytes through the analysis of their microRNAoma and proteome.