Type 2 diabetes mellitus impaired nasal immunity and increased the risk of hyposmia in COVID-19 mild pneumonia patients

Int Immunopharmacol. 2021 Apr:93:107406. doi: 10.1016/j.intimp.2021.107406. Epub 2021 Jan 22.

Abstract

In patients with COVID-19,type 2 diabetes mellitus (T2DM) can impair the function of nasal-associated lymphoid tissue (NALT) and result in olfactory dysfunction. Exploring the causative alterations of T2DM within the nasal mucosa and NALT could provide insight into the pathogenic mechanisms and bridge the gap between innate immunity and adaptive immunity for virus clearance. Here, we designed a case-control study to compare the olfactory function (OF) among the groups of normal control (NC), COVID-19 mild pneumonia (MP), and MP patients with T2DM (MPT) after a 6-8 months' recovery, in which MPT had a higher risk of hyposmia than MP and NC. No significant difference was found between the MP and NC. This elevated risk of hyposmia indicated that T2DM increased COVID-19 susceptibility in the nasal cavity with unknown causations. Therefore, we used the T2DM animal model (db/db mice) to evaluate how T2DM increased COVID-19 associated susceptibilities in the nasal mucosa and lymphoid tissues. Db/db mice demonstratedupregulated microvasculature ACE2 expression and significant alterations in lymphocytes component of NALT. Specifically, db/db mice NALT had increased immune-suppressive TCRγδ+ CD4-CD8- T and decreased immune-effective CD4+/CD8+ TCRβ+ T cells and decreased mucosa-protective CD19+ B cells. These results indicated that T2DM could dampen the first-line defense of nasal immunity, and further mechanic studies of metabolic damage and NALT restoration should be one of the highest importance for COVID-19 healing.

Keywords: COVID-19; Hyposmia; Nasal-associated lymphoid tissue; Olfactory dysfunction; Type 2 diabetes mellitus.

MeSH terms

  • Adult
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • Anosmia / immunology*
  • Anosmia / metabolism
  • Anosmia / virology*
  • B-Lymphocytes / immunology
  • COVID-19 / immunology*
  • COVID-19 / metabolism
  • COVID-19 / physiopathology
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / immunology*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / virology*
  • Female
  • Humans
  • Immunity, Mucosal / immunology
  • Lymphoid Tissue / immunology
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Models, Animal
  • Nasal Mucosa / immunology
  • Olfactory Mucosa / metabolism
  • Risk Factors
  • SARS-CoV-2 / isolation & purification
  • Serine Endopeptidases / metabolism
  • T-Lymphocytes / immunology

Substances

  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases