Persistent immune and clotting dysfunction detected in saliva and blood plasma after COVID-19
Hyesun Jang,
Saibyasachi Choudhury,
Yanbao Yu,
Benjamin L. Sievers,
Terri Gelbart,
Harinder Singh,
Stephen A. Rawlings,
Amy Proal,
Gene S. Tan,
Yu Qian,
Davey Smith,
Marcelo Freire
Affiliations
Hyesun Jang
Genomic Medicine and Infectious Diseases, J. Craig Venter Institute, La Jolla, CA, and Rockville, MD, USA
Saibyasachi Choudhury
DGG-Genomics Division, Agilent, Technologies, Inc., La Jolla, CA 92037, USA
Yanbao Yu
Department of Chemistry & Biochemistry, University of Delaware, Newark, DE, USA, 19716
Benjamin L. Sievers
Genomic Medicine and Infectious Diseases, J. Craig Venter Institute, La Jolla, CA, and Rockville, MD, USA
Terri Gelbart
Genomic Medicine and Infectious Diseases, J. Craig Venter Institute, La Jolla, CA, and Rockville, MD, USA
Harinder Singh
Genomic Medicine and Infectious Diseases, J. Craig Venter Institute, La Jolla, CA, and Rockville, MD, USA
Stephen A. Rawlings
MMP Adult Infectious Disease, Maine Medical Center, South Portland, ME, 04106, USA
Amy Proal
PolyBio Research Foundation. Mercer Island, WA, USA
Gene S. Tan
Genomic Medicine and Infectious Diseases, J. Craig Venter Institute, La Jolla, CA, and Rockville, MD, USA; Division of Infectious Diseases and Global Public Health Department of Medicine, University of California San Diego, La Jolla, CA, USA
Yu Qian
Informatics, J. Craig Venter Institute, La Jolla, CA, and Rockville, MD, USA
Davey Smith
Division of Infectious Diseases and Global Public Health Department of Medicine, University of California San Diego, La Jolla, CA, USA
Marcelo Freire
Genomic Medicine and Infectious Diseases, J. Craig Venter Institute, La Jolla, CA, and Rockville, MD, USA; Division of Infectious Diseases and Global Public Health Department of Medicine, University of California San Diego, La Jolla, CA, USA; Corresponding author. Associate Professor Genomic Medicine and Infectious Diseases J. Craig Venter Institute 4120 Capricorn Lane, La Jolla, CA 92037, USA.
A growing number of studies indicate that coronavirus disease 2019 (COVID-19) is associated with inflammatory sequelae, but molecular signatures governing the normal versus pathologic convalescence process have not been well-delineated. Here, we characterized global immune and proteome responses in matched plasma and saliva samples obtained from COVID-19 patients collected between 20 and 90 days after initial clinical symptoms resolved. Convalescent subjects showed robust total IgA and IgG responses and positive antibody correlations in saliva and plasma samples. Shotgun proteomics revealed persistent inflammatory patterns in convalescent samples including dysfunction of salivary innate immune cells, such as neutrophil markers (e.g., myeloperoxidase), and clotting factors in plasma (e.g., fibrinogen), with positive correlations to acute COVID-19 disease severity. Saliva samples were characterized by higher concentrations of IgA, and proteomics showed altered myeloid-derived pathways that correlated positively with SARS-CoV-2 IgA levels. Beyond plasma, our study positions saliva as a viable fluid to monitor normal and aberrant immune responses including vascular, inflammatory, and coagulation-related sequelae.
