The Presence of Circulating Nucleated Red Blood Cells Is Associated With Disease Severity in Patients of Hemorrhagic Fever With Renal Syndrome

Jingang Zhang; Kang Tang; Yun Zhang; Ying Ma; Chunmei Zhang; Haifeng Hu; Xiaozhou Jia; Ran Zhuang; Boquan Jin; Meng Wang; Xiyue Zhang; Dalu Liu; Yusi Zhang

doi:10.3389/fmed.2021.665410

The Presence of Circulating Nucleated Red Blood Cells Is Associated With Disease Severity in Patients of Hemorrhagic Fever With Renal Syndrome

Front Med (Lausanne). 2021 May 25:8:665410. doi: 10.3389/fmed.2021.665410. eCollection 2021.

Authors

Jingang Zhang^{1

2}, Kang Tang¹, Yun Zhang¹, Ying Ma¹, Chunmei Zhang¹, Haifeng Hu³, Xiaozhou Jia⁴, Ran Zhuang¹, Boquan Jin¹, Meng Wang¹, Xiyue Zhang¹, Dalu Liu⁵, Yusi Zhang¹

Affiliations

¹ Department of Immunology, Basic Medicine School, Air Force Medical University, Xi'an, China.
² Brigade of Cadet, Air Force Medical University, Xi'an, China.
³ Center for Infectious Diseases, Second Affiliated Hospital of Air Force Medical University, Xi'an, China.
⁴ Department of Infectious Disease, Xi'an Eighth Hospital, Xi'an, China.
⁵ Department of Radiation Medicine and Protection, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Medical University, Xi'an, China.

Abstract

Hemorrhagic fever with renal syndrome (HFRS) is a regional infectious disease of epidemic potential caused by the Hantaan virus (HTNV). Red blood cells (RBCs) are the major components of peripheral blood. However, pathological changes in RBCs and the underlying mechanisms during HTNV infection remain largely unclear. Therefore, this study sought to explore changes in RBCs in the peripheral blood of HFRS patients. We isolated PBMCs from HFRS patients and performed single-cell RNA sequencing. The results showed that clusters of RBCs in the peripheral blood of HFRS could be classified as nucleated red blood cells (NRBC) based on their cellular components, gene expression profiles and cell surface markers. In addition, it was shown that the higher the count of NRBC in peripheral blood, the more severe the disease status was. Moreover, hematological indices related to RBCs were analyzed and the results showed that impairment in the folate pathway might be the possible reason behind the presence of NRBCs. This study, for the first time showed that the presence of NRBCs in the peripheral blood of HFRS patients was associated with disease severity. This was also the first study to show that infection with the HTNV virus hindered the maturation of RBCs. Therefore, this work provides further insights on the role of and pathological changes in RBCs during HTNV infection.

Keywords: HFRS; HTNV; NRBC; folic acid (B9); vitamin B12 (B12).