In silico immune infiltration profiling reveals the role of naïve B cells in lung tissues of COVID-19 patients

Abstract COVID-19 caused by SARS-CoV-2 has rapidly spread to more than 160 countries worldwide since 2020. Despite the tremendous efforts and resources spent around the world trying to explore antiviral drugs, there is still no effective clinical treatment for COVID-19. Approximately 15% of COVID-19 cases progress to pneumonia, patients with severe pneumonia may die from acute respiratory distress syndrome (ARDS). In addition, further pulmonary fibrosis from SARS-CoV-2 infection causes ARDS that often leads to irreversible impairment of lung function. If the mechanisms by which SARS-CoV-2 infection primarily cause immune responses or immune cell infiltration can be identified, it is possible to alleviate or prevent severe lung damage by modulating the infiltration and activation of specific immune cells to mitigate excessive immunity response.The extent to which subsets of immune cells are significantly altered in the lung tissue of COVID-19 patients remains unclear. This study applied the CIBERSORT method to comprehensively evaluate the immune infiltration landscape in lung tissues of COVID-19 patients, and further compared with the one from lung tissue of patients with idiopathic pulmonary fibrosis (IPF). We found several immune cell subtypes; particularly naïve B cells are highly infiltrated in COVID-19 group. A comparison of functional gene set analysis revealed that non-differentiated naïve B cells may be the main cause of the overactive humoral immune response. We further compared several specific COVID-19 cases receiving therapies targeting B cells and found that appropriate suppression of naïve B cells might be a new strategy to alleviate severe symptoms of COVID-19.