Myeloid-Derived Suppressor Cells as a Potential Biomarker and Therapeutic Target in COVID-19.

Clinical presentations of COVID-19 are highly variable, yet the precise mechanisms that govern the pathophysiology of different disease courses remain poorly defined. Across the spectrum of disease severity, COVID-19 impairs both innate and adaptive host immune responses by activating innate immune cell recruitment, while resulting in low lymphocyte counts. Recently, several reports have shown that patients with severe COVID-19 exhibit a dysregulated myeloid cell compartment, with increased myeloid-derived suppressor cells (MDSCs) correlating with disease severity. MDSCs, in turn, promote virus survival by suppressing T-cell responses and driving a highly pro-inflammatory state through the secretion of various mediators of immune activation. Here, we summarize the evidence on MDSCs and myeloid cell dysregulation in COVID-19 infection and discuss the potential of MDSCs as biomarkers and therapeutic targets in COVID-19 pneumonia and associated disease.

Learning from HIV-1 to predict the immunogenicity of T cell epitopes in SARS-CoV-2.

We describe a physics-based learning model for predicting the immunogenicity of cytotoxic T lymphocyte (CTL) epitopes derived from diverse pathogens including SARS-CoV-2. The model was trained and optimized on the relative immunodominance of CTL epitopes in human immunodeficiency virus infection. Its accuracy was tested against experimental data from patients with COVID-19. Our model predicts that only some SARS-CoV-2 epitopes predicted to bind to HLA molecules are immunogenic. The immunogenic CTL epitopes across all SARS-CoV-2 proteins are predicted to provide broad population coverage, but those from the SARS-CoV-2 spike protein alone are unlikely to do so. Our model also predicts that several immunogenic SARS-CoV-2 CTL epitopes are identical to seasonal coronaviruses circulating in the population and such cross-reactive CD8+ T cells can indeed be detected in prepandemic blood donors, suggesting that some level of CTL immunity against COVID-19 may be present in some individuals before SARS-CoV-2 infection.