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Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients.
Taniguchi-Ponciano, Keiko; Vadillo, Eduardo; Mayani, Héctor; Gonzalez-Bonilla, César Raúl; Torres, Javier; Majluf, Abraham; Flores-Padilla, Guillermo; Wacher-Rodarte, Niels; Galan, Juan Carlos; Ferat-Osorio, Eduardo; Blanco-Favela, Francisco; Lopez-Macias, Constantino; Ferreira-Hermosillo, Aldo; Ramirez-Renteria, Claudia; Peña-Martínez, Eduardo; Silva-Román, Gloria; Vela-Patiño, Sandra; Mata-Lozano, Carlos; Carvente-Garcia, Roberto; Basurto-Acevedo, Lourdes; Saucedo, Renata; Piña-Sanchez, Patricia; Chavez-Gonzalez, Antonieta; Marrero-Rodríguez, Daniel; Mercado, Moisés.
  • Taniguchi-Ponciano K; Unidad de Investigación Médica en Enfermedades Endocrinas, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Vadillo E; Unidad de Investigación Médica en Enfermedades Oncológicas, UMAE Hospital de Oncología, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Mayani H; Unidad de Investigación Médica en Enfermedades Oncológicas, UMAE Hospital de Oncología, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Gonzalez-Bonilla CR; Titular, Coordinación de Investigación en Salud, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Torres J; Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, UMAE Hospital de Pediatría, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Majluf A; Unidad de Investigación Médica en trombosis, hemostasia y aterogénesis, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Flores-Padilla G; Servicio de Medicina Interna, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Wacher-Rodarte N; Unidad de Investigación Médica en Epidemiología Clínica, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Galan JC; Servicio de Medicina Interna, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Ferat-Osorio E; División de Investigación en Salud, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Blanco-Favela F; Unidad de Investigación Médica en Inmunología, UMAE Hospital de Pediatría, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Lopez-Macias C; Unidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Ferreira-Hermosillo A; Unidad de Investigación Médica en Enfermedades Endocrinas, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Ramirez-Renteria C; Unidad de Investigación Médica en Enfermedades Endocrinas, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Peña-Martínez E; Unidad de Investigación Médica en Enfermedades Endocrinas, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Silva-Román G; Unidad de Investigación Médica en Enfermedades Endocrinas, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Vela-Patiño S; Unidad de Investigación Médica en Enfermedades Endocrinas, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Mata-Lozano C; Unidad de Investigación Médica en Enfermedades Endocrinas, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Carvente-Garcia R; Analitek S.A. de C.V., CDMX, México.
  • Basurto-Acevedo L; Unidad de Investigación Médica en Enfermedades Endocrinas, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Saucedo R; Analitek S.A. de C.V., CDMX, México.
  • Piña-Sanchez P; Unidad de Investigación Médica en Enfermedades Endocrinas, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Chavez-Gonzalez A; Unidad de Investigación Médica en Enfermedades Endocrinas, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Marrero-Rodríguez D; Unidad de Investigación Médica en Enfermedades Oncológicas, UMAE Hospital de Oncología, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
  • Mercado M; Unidad de Investigación Médica en Enfermedades Oncológicas, UMAE Hospital de Oncología, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.
Ann Med ; 53(1): 197-207, 2021 12.
Article in English | MEDLINE | ID: covidwho-990290
ABSTRACT

BACKGROUND:

COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood.

METHODS:

We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells.

RESULTS:

Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2).

CONCLUSIONS:

The up-regulation and participation of HIF1α in 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. Key messages Critically ill COVID-19 patients show emergency myelopoiesis. HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets. HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Critical Illness / Sequence Analysis, RNA / Myeloid Cells / Hypoxia-Inducible Factor 1, alpha Subunit / COVID-19 Type of study: Prognostic study / Reviews Limits: Female / Humans / Male Language: English Journal: Ann Med Journal subject: Medicine Year: 2021 Document Type: Article Affiliation country: 07853890.2020.1858234

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Critical Illness / Sequence Analysis, RNA / Myeloid Cells / Hypoxia-Inducible Factor 1, alpha Subunit / COVID-19 Type of study: Prognostic study / Reviews Limits: Female / Humans / Male Language: English Journal: Ann Med Journal subject: Medicine Year: 2021 Document Type: Article Affiliation country: 07853890.2020.1858234