BACKGROUND: Identifying immune correlates of COVID-19 disease severity is an urgent need for clinical management, vaccine evaluation, and drug development. Here, we present a temporal analysis of key immune mediators, cytokines, and chemokines in blood of hospitalized COVID-19 patients from serial sampling and follow-up over 4 weeks. METHODS: A total of 71 patients with laboratory-confirmed COVID-19 admitted to Beijing You'an Hospital in China with either mild (53 patients) or severe (18 patients) disease were enrolled with 18 healthy volunteers. We measured 34 immune mediators, cytokines, and chemokines in peripheral blood every 4-7 days over 1 month per patient using a bioplex multiplex immunoassay. RESULTS: We found that the chemokine RANTES (CCL5) was significantly elevated, from an early stage of the infection, in patients with mild but not severe disease. We also found that early production of inhibitory mediators including IL-10 and IL-1RA were significantly associated with disease severity, and a combination of CCL5, IL-1 receptor antagonist (IL-1RA), and IL-10 at week 1 may predict patient outcomes. The majority of cytokines that are known to be associated with the cytokine storm in virus infections such as IL-6 and IFN-γ were only significantly elevated in the late stage of severe COVID-19 illness. TNF-α and GM-CSF showed no significant differences between severe and mild cases. CONCLUSION: Together, our data suggest that early intervention to increase expression of CCL5 may prevent patients from developing severe illness. Our data also suggest that measurement of levels of CCL5, as well as IL-1RA and IL-10 in blood individually and in combination, might be useful prognostic biomarkers to guide treatment strategies.
BACKGROUND: Identifying immune correlates of COVID-19 disease severity is an urgent need for clinical management, vaccine evaluation, and drug development. Here, we present a temporal analysis of key immune mediators, cytokines, and chemokines in blood of hospitalized COVID-19 patients from serial sampling and follow-up over 4 weeks. METHODS: A total of 71 patients with laboratory-confirmed COVID-19 admitted to Beijing You'an Hospital in China with either mild (53 patients) or severe (18 patients) disease were enrolled with 18 healthy volunteers. We measured 34 immune mediators, cytokines, and chemokines in peripheral blood every 4-7 days over 1 month per patient using a bioplex multiplex immunoassay. RESULTS: We found that the chemokine RANTES (CCL5) was significantly elevated, from an early stage of the infection, in patients with mild but not severe disease. We also found that early production of inhibitory mediators including IL-10 and IL-1RA were significantly associated with disease severity, and a combination of CCL5, IL-1 receptor antagonist (IL-1RA), and IL-10 at week 1 may predict patient outcomes. The majority of cytokines that are known to be associated with the cytokine storm in virus infections such as IL-6 and IFN-γ were only significantly elevated in the late stage of severe COVID-19 illness. TNF-α and GM-CSF showed no significant differences between severe and mild cases. CONCLUSION: Together, our data suggest that early intervention to increase expression of CCL5 may prevent patients from developing severe illness. Our data also suggest that measurement of levels of CCL5, as well as IL-1RA and IL-10 in blood individually and in combination, might be useful prognostic biomarkers to guide treatment strategies.
Authors: O Dienz; J G Rud; S M Eaton; P A Lanthier; E Burg; A Drew; J Bunn; B T Suratt; L Haynes; M Rincon Journal: Mucosal Immunol Date: 2012-02-01 Impact factor: 7.313
Authors: Alison Crawford; Jill Marie Angelosanto; Kim Lynn Nadwodny; Shawn D Blackburn; E John Wherry Journal: PLoS Pathog Date: 2011-07-21 Impact factor: 6.823
Authors: Puja Mehta; Daniel F McAuley; Michael Brown; Emilie Sanchez; Rachel S Tattersall; Jessica J Manson Journal: Lancet Date: 2020-03-16 Impact factor: 79.321
Authors: Joseph Balnis; Alejandro P Adam; Amit Chopra; Hau C Chieng; Lisa A Drake; Nina Martino; Ramon Bossardi Ramos; Paul J Feustel; Katherine A Overmyer; Evgenia Shishkova; Joshua J Coon; Harold A Singer; Marc A Judson; Ariel Jaitovich Journal: Am J Physiol Regul Integr Comp Physiol Date: 2021-01-12 Impact factor: 3.619
Authors: Ali A Rabaan; Shamsah H Al-Ahmed; Mohammed A Garout; Ayman M Al-Qaaneh; Anupam A Sule; Raghavendra Tirupathi; Abbas Al Mutair; Saad Alhumaid; Abdulkarim Hasan; Manish Dhawan; Ruchi Tiwari; Khan Sharun; Ranjan K Mohapatra; Saikat Mitra; Talha Bin Emran; Muhammad Bilal; Rajendra Singh; Salem A Alyami; Mohammad Ali Moni; Kuldeep Dhama Journal: Pathogens Date: 2021-05-07
Authors: Samantha M Morrissey; Anne E Geller; Xiaoling Hu; David Tieri; Chuanlin Ding; Christopher K Klaes; Elizabeth A Cooke; Matthew R Woeste; Zachary C Martin; Oscar Chen; Sarah E Bush; Huang-Ge Zhang; Rodrigo Cavallazzi; Sean P Clifford; James Chen; Smita Ghare; Shirish S Barve; Lu Cai; Maiying Kong; Eric C Rouchka; Kenneth R McLeish; Silvia M Uriarte; Corey T Watson; Jiapeng Huang; Jun Yan Journal: JCI Insight Date: 2021-05-10
Authors: Jason Neidleman; Xiaoyu Luo; Ashley F George; Matthew McGregor; Junkai Yang; Cassandra Yun; Victoria Murray; Gurjot Gill; Warner C Greene; Joshua Vasquez; Sulggi A Lee; Eliver Ghosn; Kara L Lynch; Nadia R Roan Journal: Cell Rep Date: 2021-06-29 Impact factor: 9.423
Authors: Resmi Ravindran; Cindy McReynolds; Jun Yang; Bruce D Hammock; Aamer Ikram; Amna Ali; Adnan Bashir; Tanzeel Zohra; W L William Chang; Dennis J Hartigan-O'Connor; Hooman H Rashidi; Imran H Khan Journal: PLoS One Date: 2021-07-09 Impact factor: 3.240