A Shift Towards an Immature Myeloid Profile in Peripheral Blood of Critically Ill COVID-19 Patients

Abstract

Background SARS-CoV-2 , the etiological agent causing COVID-19, has infected more than 27 million people with over 894000 deaths worldwide since its emergence in December 2019. Factors for severe diseases, such as diabetes, hypertension, and obesity have been identified however, the precise pathogenesis is poorly understood. To understand its pathophysiology and to develop effective therapeutic strategies, it is essential to define the prevailing immune cellular subsets. Methods We performed whole circulating immune cells scRNAseq from five critically ill COVID-19 patients, trajectory and gene ontology analysis. Results Immature myeloid populations, such as promyelocytes-myelocytes, metamyelocytes, band neutrophils, monocytoid precursors, and activated monocytes predominated. The trajectory with pseudotime analysis supported the finding of immature cell states. While the gene ontology showed myeloid cell activation in immune response, DNA and RNA processing, defense response to the virus, and response to type 1 interferon. Lymphoid lineage was scarce. Expression of genes such as C/EBPβ, IRF1and FOSL2 potentially suggests the induction of trained immunity. Conclusions Our results uncover transcriptomic profiles related to immature myeloid lineages and suggest the potential induction of trained immunity.

Oxidative Stress and Hyper-Inflammation as Major Drivers of Severe COVID-19 and Long COVID: Implications for the Benefit of High-Dose Intravenous Vitamin C

“…Elevated HIF-1 α levels seem to play an important role in promoting SARS-CoV-2 infection by inducing pro-inflammatory responses to the virus, suppressing IFN, stimulating NET-formation due to increased glycolysis (Duan et al, 2021;Peng et al, 2021;Borella et al, 2022;Tian et al, 2021) and increasing the cardiovascular risk after SARS-Cov-2 infection (Zhang L. et al, 2021). Therefore, the increased expression of HIF 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients might be an important therapeutic target (Vadillo et al, 2021), in this context one group also investigated the potential use of HIF prolyl hydroxylase inhibitors (Wing et al, 2021). Furthermore, the transcription factor HIF is important for erythropoiesis, and COVID-19 is often associated with anemia (Taneri et al, 2020), but also lymphopenia, neutrophilia, thrombocytopenia, and stress erythropoiesis (Elahi, 2022).…”

Natural resources to control COVID-19: could lactoferrin amend SARS-CoV-2 infectivity?

“…The MDSCs populations are significantly predominant in the critically ill COVID-19 patients, such as band neutrophils, metamyelocytes, promyelocytes-myelocytes, monocytoid precursor, and immature monocytes. These clusters were defined by many up-regulated gene expression such as (LFT, LPR-1, LPR-2, ADAM8, CD58, CR1, FCER1G, MGAM, MMP8, MMP9, S100A8/9) linked to the SARS-CoV-2 infection consequences (Vadillo et al, 2020). On the other side of LF regulatory potential, LF could bind the low-density lipoprotein receptor protein 2 (LPR-2), which is expressed on many myeloid and leukocyte cells.…”

Platelet‐derived immuno‐inflammatory indices show best performance in early prediction of COVID‐19 progression

“…Predominating immature myeloid cell populations have been observed in critically ill COVID‐19 patients. In this regard, higher RDW and PDW levels at admission were observed among severe COVID‐19 patients and those who passed away compared to survivors 6,27–36 …”

“…In this regard, higher RDW and PDW levels at admission were observed among severe COVID‐19 patients and those who passed away compared to survivors. 6 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 …”