Clinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis

Zhiqing Xiao; Minggui Lin; Ning Song; Xue Wu; Jingyu Hou; Lili Wang; XinLun Tian; Chunge An; Charles S Dela Cruz; Lokesh Sharma; De Chang

doi:10.1016/j.isci.2024.110110

Clinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis

iScience. 2024 May 25;27(6):110110. doi: 10.1016/j.isci.2024.110110. eCollection 2024 Jun 21.

Authors

Zhiqing Xiao^{1

2}, Minggui Lin³, Ning Song⁴, Xue Wu¹, Jingyu Hou⁴, Lili Wang³, XinLun Tian⁵, Chunge An¹, Charles S Dela Cruz⁶, Lokesh Sharma⁶, De Chang¹

Affiliations

¹ Department of Pulmonary and Critical Care Medicine at The Seventh Medical Center, College of Pulmonary and Critical Care Medicine of The Eighth Medical Center, Chinese PLA General Hospital, Beijing 100853, China.
² Hebei North University, Zhangjiakou 075000, Hebei, China.
³ Beijing Tsinghua Changgung Hospital, Tsinghua University School of Medicine, Beijing 102218, China.
⁴ Department of Infectious Diseases, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
⁵ Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
⁶ Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

Abstract

Increased cases of sepsis during COVID-19 in the absence of known bacterial pathogens highlighted role of viruses as causative agents of sepsis. In this study, we investigated clinical, laboratory, proteomic, and metabolomic characteristics of viral sepsis patients (n = 45) and compared them to non-sepsis patients with COVID-19 (n = 186) to identify molecular mechanisms underlying the pathology of viral sepsis in COVID-19. We identified unique metabolomic and proteomic signatures that suggest a substantial perturbation in the coagulation, complement, and platelet activation pathways in viral sepsis. Our proteomic data indicated elevated coagulation pathway protein (fibrinogen), whereas a decrease in many of the complement proteins was observed. These alterations were associated with the functional consequences such as susceptibility to secondary bacterial infections and potentially contributing to both local and systemic disease phenotypes. Our data provide novel aspect of COVID-19 pathology that is centered around presence of sepsis phenotype in COVID-19.

Keywords: health sciences; immunology; metabolomics; proteomics; virology.