Related Experiment Video
Updated: Aug 9, 2025
Prediction of Red Blood Cell Antibody Significance Using the Monocyte-Macrophage Assay
Published on: February 7, 2025
Early peripheral blood MCEMP1 and HLA-DRA expression predicts COVID-19 prognosis
Kuan Rong Chan1, Clara W T Koh1, Dorothy H L Ng2
1Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
Insights
Identifying key gene expression patterns in COVID-19 patients can predict severe disease. Elevated MCEMP1 and reduced HLA-DRA in CD14+ cells signal heightened risk, aiding early intervention for severe COVID-19.
Area of Science:
- Immunology and Molecular Biology
- Genomics and Transcriptomics
- Infectious Disease Research
Background:
- While mass vaccination reduced severe COVID-19, vulnerable populations remain at risk.
- Emerging SARS-CoV-2 variants and waning immunity necessitate reliable prognostic biomarkers.
- Prognostic biomarkers are crucial for early detection and patient triage for antiviral therapies.
Approach:
- Systematic review and re-analysis of 7 transcriptomics datasets (140 severe, 181 mild COVID-19 cases).
- Longitudinal monitoring of blood transcriptomics in an independent cohort to track gene expression changes.
- Single cell RNA-sequencing to identify specific immune cell subsets involved in differential gene expression.
Key Points:
- MCEMP1, HLA-DRA, and ETS1 were consistently differentially regulated in severe COVID-19 patients' peripheral blood.
- Elevated MCEMP1 and reduced HLA-DRA expression were observed as early as 4 days before respiratory function nadir.
- Differential expression of MCEMP1 and HLA-DRA predominantly occurred in CD14+ cells.
Conclusions:
- Early detection of elevated MCEMP1 and reduced HLA-DRA in CD14+ cells indicates a high risk of severe COVID-19.
- These gene expression changes serve as early prognostic indicators for severe disease progression.
- An online platform is available for querying gene expression differences in COVID-19 patients.
Background:
Mass vaccination has dramatically reduced the incidence of severe COVID-19, with most cases now presenting as self-limiting upper respiratory tract infections. However, those with co-morbidities, the elderly and immunocompromised, as well as the unvaccinated, remain disproportionately vulnerable to severe COVID-19 and its sequelae. Furthermore, as the effectiveness of vaccination wanes with time, immune escape SARS-CoV-2 variants could emerge to cause severe COVID-19. Reliable prognostic biomarkers for severe disease could be used as early indicator of re-emergence of severe COVID-19 as well as for triaging of patients for antiviral therapy.
Methods:
We performed a systematic review and re-analysis of 7 publicly available datasets, analysing a total of 140 severe and 181 mild COVID-19 patients, to determine the most consistent differentially regulated genes in peripheral blood of severe COVID-19 patients. In addition, we included an independent cohort where blood transcriptomics of COVID-19 patients were prospectively and longitudinally monitored previously, to track the time in which these gene expression changes occur before nadir of respiratory function. Single cell RNA-sequencing of peripheral blood mononuclear cells from publicly available datasets was then used to determine the immune cell subsets involved.
Findings:
The most consistent differentially regulated genes in peripheral blood of severe COVID-19 patients were MCEMP1, HLA-DRA and ETS1 across the 7 transcriptomics datasets. Moreover, we found significantly heightened MCEMP1 and reduced HLA-DRA expression as early as four days before the nadir of respiratory function, and the differential expression of MCEMP1 and HLA-DRA occurred predominantly in CD14+ cells. The online platform which we developed is publicly available at https://kuanrongchan-covid19-severity-app-t7l38g.streamlitapp.com/, for users to query gene expression differences between severe and mild COVID-19 patients in these datasets.
Interpretation:
Elevated MCEMP1 and reduced HLA-DRA gene expression in CD14+ cells during the early phase of disease are prognostic of severe COVID-19.
Funding:
K.R.C is funded by the National Medical Research Council (NMRC) of Singapore under the Open Fund Individual Research Grant (MOH-000610). E.E.O. is funded by the NMRC Senior Clinician-Scientist Award (MOH-000135-00). J.G.H.L. is funded by the NMRC under the Clinician-Scientist Award (NMRC/CSAINV/013/2016-01). S.K. is funded by the NMRC under the Transition Award. This study was sponsored in part by a generous gift from The Hour Glass.
