SARS-CoV-2 pseudovirus dysregulates hematopoiesis and induces inflammaging of hematopoietic stem and progenitor cells

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primarily affects the respiratory system but may induce hematological alterations such as anemia, lymphopenia and thrombocytopenia. Previous studies have reported that SARS-CoV-2 efficiently infects hematopoietic stem and progenitor cells (HSPCs); however, the subsequent effects on hematopoiesis and immune reconstitution have not yet been described. Here we evaluated the pathological effects of infection of umbilical-cord-blood-derived HSPCs with the SARS-CoV-2 Omicron variant pseudovirus (PsV). Transcriptomic analysis of Omicron PsV-infected HSPCs revealed the upregulation of genes involved in inflammation, aging and the NLRP3 inflammasome, suggesting a potential trigger of inflammaging. Omicron PsV-infected HSPCs presented decreased numbers of multipotential progenitors (granulocyte‒erythrocyte‒macrophage‒megakaryocyte colony-forming units) ex vivo and repopulated primitive hematopoietic stem cells (Ki-67−hCD34+ cells) in an HSPC transplantation NOD-scid IL2rγnull mouse model (Omicron mouse). Furthermore, Omicron PsV infection induced myeloid-biased differentiation of HSPCs. Treatment with nanographene oxide, an antiviral agent, partially mitigated the myeloid bias and inflammaging phenotype both in vitro and in vivo. These findings provide insights into the abnormal hematopoietic and immune effects of SARS-CoV-2 infection and highlight potential therapeutic interventions. The coronavirus disease 2019 (COVID-19) pandemic highlights systemic effects of SARS-CoV-2 beyond respiratory symptoms. Researchers investigated its impact on hematopoietic stem and progenitor cells (HSPCs), which produce blood cells, using a pseudovirus mimicking the Omicron variant. Infection caused inflammation and skewed blood production toward myeloid cells (e.g., macrophages), reducing lymphoid cells (e.g., T and B cells). This imbalance mirrors immune disruptions in COVID-19, such as lymphopenia and excessive inflammation. To address these effects, researchers tested nanographene oxide (NGO), a material with antiviral and anti-inflammatory properties. NGO reduced inflammation and partially restored normal blood production without harming HSPCs. Treated cells showed improved immune balance and reduced myeloid bias. These findings reveal how SARS-CoV-2 disrupts blood cell production and suggest NGO’s potential as a therapeutic tool to manage immune imbalances in COVID-19 and other viral infections. Further studies could explore its broader clinical applications. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.