Microfluidic Immuno-Serolomic Assay Reveals Systems Level Association with COVID-19 Pathology and Vaccine Protection.
Dongjoo KimGiulia BianconZhiliang BaiJennifer VanOudenhoveYuxin LiuShalin KothariLohith GowdaJennifer M KwanNicholas Carlos Buitrago-PocasangreNikhil LeleHiromitsu AsashimaMichael K RackeJoDell E WilsonTara S GivensMary M TomaykoWade L SchulzErin E LongbrakeDavid A HaflerStephanie HaleneRong FanPublished in: Small methods (2023)
How to develop highly informative serology assays to evaluate the quality of immune protection against coronavirus disease-19 (COVID-19) has been a global pursuit over the past years. Here, a microfluidic high-plex immuno-serolomic assay is developed to simultaneously measure50 plasma or serum samples for50 soluble markers including 35proteins, 11 anti-spike/receptor binding domian (RBD) IgG antibodies spanningmajor variants, and controls. This assay demonstrates the quintuplicate test in a single run with high throughput, low sample volume, high reproducibilityand accuracy. It is applied to the measurement of 1012 blood samples including in-depth analysis of sera from 127 patients and 21 healthy donors over multiple time points, either with acute COVID infection or vaccination. The protein analysis reveals distinct immune mediator modules that exhibit a reduced degree of diversity in protein-protein cooperation in patients with hematologic malignancies or receiving B cell depletion therapy. Serological analysis identifies that COVID-infected patients with hematologic malignancies display impaired anti-RBD antibody response despite high level of anti-spike IgG, which can be associated with limited clonotype diversity and functional deficiency in B cells. These findings underscore the importance to individualize immunization strategies for these high-risk patients and provide an informative tool to monitor their responses at the systems level.
Keyphrases
- high throughput
- coronavirus disease
- end stage renal disease
- sars cov
- protein protein
- ejection fraction
- newly diagnosed
- chronic kidney disease
- peritoneal dialysis
- prognostic factors
- small molecule
- single cell
- stem cells
- mesenchymal stem cells
- bone marrow
- genome wide
- quality improvement
- intensive care unit
- cell therapy
- patient reported outcomes
- acute respiratory distress syndrome
- drug induced