A single-cell atlas reveals shared and distinct immune responses and metabolic profiles in SARS-CoV-2 and HIV-1 infections

Abstract

Introduction: Within the inflammatory immune response to viral infection, the distribution and cell type-specific profiles of immune cell populations and the immune-mediated viral clearance pathways vary according to the specific virus. Uncovering the immunological similarities and differences between viral infections is critical to understanding disease progression and developing effective vaccines and therapies. Insight into COVID-19 disease progression has been bolstered by the integration of single-cell (sc)RNA-seq data from COVID-19 patients with data from related viruses to compare immune responses. Expanding this concept, we propose that a high-resolution, systematic comparison between immune cells from SARS-CoV-2 infection and an inflammatory infectious disease with a different pathophysiology will provide a more comprehensive picture of the viral clearance pathways that underscore immunological and clinical differences between infections.Methods: Using a novel consensus single-cell annotation method, we integrate previously published scRNA-seq data from 111,566 single PBMCs from 7 COVID-19, 10 HIV-1+, and 3 healthy patients into a unified cellular atlas. We compare in detail the phenotypic features and regulatory pathways in the major immune cell clusters.Results: While immune cells in both COVID-19 and HIV-1+ cohorts show shared inflammation and disrupted mitochondrial function, COVID-19 patients exhibit stronger humoral immunity, broader IFN-I signaling, elevated Rho GTPase and mTOR pathway activity, and downregulated mitophagy.Discussion: Our results indicate that differential IFN-I signaling regulates the distinct immune responses in the two diseases, revealing insight into fundamental disease biology and potential therapeutic candidates.

SARS-CoV-2 and COVID-19: From Crisis to Solution

“…In terms of pathology, other comparable diseases with potential for chronic persistent infection and organ damage include HCV / Hepatitis C with damage and increased cancer risk to the liver, group A Streptococcus / Scarlet fever, damaging the heart valves, kidneys, joints and brain, HIV/AIDS particularly damaging the immune system allowing opportunistic infections and cancers 144 , and, H. pylori causing ongoing stomach damage and increasing stomach cancer risk 145 . Damage to the immune system by SARS-CoV-2 has both differences and striking similarities to long-term outcomes of HIV infection 146,50,144,147 and both are recognized as main causes of lymphocytopenia 148 . Importantly, these other debilitating chronic diseases also tend to have an influenza-like acute disease onset, but we differentiate the flu-like symptoms of initial HIV and HCV infection from the chronic conditions of AIDS and Hepatitis C, and recognize their causal connection.…”

COVID-19-Omics Report: From Individual Omics Approaches to Precision Medicine

“…For example, low expression of interferon-gamma and interferon-response genes pathways were identified as baseline risk factors for subsequent cytokine release syndrome during COVID-19 [15,111,112]. The significantly reduced expression of the inflammation suppressor IFN I-and IFN III-type genes and the overexpression of monocyteand granulocyte-derived hyper-inflammatory cytokine transcripts (e.g., GMCSF) at the first symptoms of the disease were proposed to predict COVID-19 mortality [113][114][115]. Transcripts that encode the main effectors of the IFN I type-mediated antiviral response and interferon-stimulated genes (ISGs) (e.g., IFI44L, IFI27, RSAD2, SIGLEC1, IFIT1, ISG15) were downregulated in patients who became critically ill compared to the patients with mild and moderate diseases [116].…”