Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients

Since its emergence, in December 2019, COVID-19 has resulted in more than 12 million people infected and has killed more than 570000. Hypoxemia has been identified as one of the main clinical manifestations of this disease, especially in severe cases. We have previously reported that in critically ill COVID-19 patients there is a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, which, together with mature monocytes and segmented neutrophils, comprise the vast majority of blood cells in these patients. Such an immature myeloid profile may be the result of a physiological response known as emergency myelopoiesis. In the present study, we performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α (HIF1α) mRNA and its transcriptionally regulated genes. HIF1α is a master transcription factor involved in the cellular response to hypoxia. We herein report that these cellular subsets express high levels of HIF1α mRNA and several of their transcriptional targets, including those related to inflammation, such as CXCL8, CXCR1, CXCR2, and CXCR4; those potentially involved in virus sensing, such as TLR2 and TLR4; and those related to metabolism, such as SLC2A3, PFKFB3, PGK1, GAPDH and SOD2. The up-regulation and participation of HIF1α in relevant events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy.