Your browser doesn't support javascript.
Plasma metabolome and cytokine profile reveal glycylproline modulating antibody fading in convalescent COVID-19 patients.
Yang, Zhu; Wu, Di; Lu, Shanxin; Qiu, Yang; Hua, Zhengyi; Tan, Fancheng; Zhang, Cixiong; Zhang, Lei; Zhang, Ding-Yu; Zhou, Xi; Cai, Zongwei; Shang, You; Lin, Shu-Hai.
  • Yang Z; State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian 361102, China.
  • Wu D; National Institute for Data Science in Health and Medicine, Xiamen University, Fujian 361102, China.
  • Lu S; State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, China.
  • Qiu Y; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China.
  • Hua Z; Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology-Wuhan Jinyintan Hospital, Wuhan 430023, China.
  • Tan F; State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian 361102, China.
  • Zhang C; National Institute for Data Science in Health and Medicine, Xiamen University, Fujian 361102, China.
  • Zhang L; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China.
  • Zhang DY; Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology-Wuhan Jinyintan Hospital, Wuhan 430023, China.
  • Zhou X; State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian 361102, China.
  • Cai Z; National Institute for Data Science in Health and Medicine, Xiamen University, Fujian 361102, China.
  • Shang Y; State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian 361102, China.
  • Lin SH; National Institute for Data Science in Health and Medicine, Xiamen University, Fujian 361102, China.
Proc Natl Acad Sci U S A ; 119(34): e2117089119, 2022 08 23.
Article in English | MEDLINE | ID: covidwho-1984597
ABSTRACT
The COVID-19 pandemic has incurred tremendous costs worldwide and is still threatening public health in the "new normal." The association between neutralizing antibody levels and metabolic alterations in convalescent patients with COVID-19 is still poorly understood. In the present work, we conducted absolutely quantitative profiling to compare the plasma cytokines and metabolome of ordinary convalescent patients with antibodies (CA), convalescents with rapidly faded antibodies (CO), and healthy subjects. As a result, we identified that cytokines such as M-CSF and IL-12p40 and plasma metabolites such as glycylproline (gly-pro) and long-chain acylcarnitines could be associated with antibody fading in COVID-19 convalescent patients. Following feature selection, we built machine-learning-based classification models using 17 features (six cytokines and 11 metabolites). Overall accuracies of more than 90% were attained in at least six machine-learning models. Of note, the dipeptide gly-pro, a product of enzymatic peptide cleavage catalyzed by dipeptidyl peptidase 4 (DPP4), strongly accumulated in CO individuals compared with the CA group. Furthermore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination experiments in healthy mice demonstrated that supplementation of gly-pro down-regulates SARS-CoV-2-specific receptor-binding domain antibody levels and suppresses immune responses, whereas the DPP4 inhibitor sitagliptin can counteract the inhibitory effects of gly-pro upon SARS-CoV-2 vaccination. Our findings not only reveal the important role of gly-pro in the immune responses to SARS-CoV-2 infection but also indicate a possible mechanism underlying the beneficial outcomes of treatment with DPP4 inhibitors in convalescent COVID-19 patients, shedding light on therapeutic and vaccination strategies against COVID-19.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Convalescence / Cytokines / Dipeptides / Dipeptidyl-Peptidase IV Inhibitors / Antibodies, Neutralizing / COVID-19 / COVID-19 Drug Treatment / Antibodies, Viral Topics: Vaccines Limits: Animals / Humans Language: English Journal: Proc Natl Acad Sci U S A Year: 2022 Document Type: Article Affiliation country: Pnas.2117089119

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Convalescence / Cytokines / Dipeptides / Dipeptidyl-Peptidase IV Inhibitors / Antibodies, Neutralizing / COVID-19 / COVID-19 Drug Treatment / Antibodies, Viral Topics: Vaccines Limits: Animals / Humans Language: English Journal: Proc Natl Acad Sci U S A Year: 2022 Document Type: Article Affiliation country: Pnas.2117089119