Proteomics in COVID-19 Pathogenesis

Proteomics has emerged as a pivotal tool in elucidating the mechanisms underlying COVID-19 pathogenesis. By enabling large-scale identification and quantification of proteins in biological samples, proteomic studies have characterised host–pathogen interactions, immune dysregulation and tissue-specific damage. Analyses of plasma proteomes have revealed signatures of inflammation, complement activation and coagulopathy that correlate with disease severity. Targeted and untargeted mass spectrometry workflows have identified prognostic biomarkers such as acute phase proteins, cytokine modulators and components of the extracellular matrix, shedding light on alveolar-capillary barrier disruption and vascular leakage in severe cases. Integration of temporal proteomic trajectories with clinical parameters has illuminated dynamic processes of immune suppression in early infection, transition to hyperinflammation in critical illness and subsequent tissue remodelling and repair. These findings underpin risk stratification strategies and inform therapeutic intervention points, from kinase inhibitors to extracellular matrix-modulating agents, thereby guiding precision-medicine approaches in the global effort to manage COVID-19.

Research from Nature Portfolio

Recent studies have applied longitudinal plasma profiling to hospitalised patients, monitoring over six thousand proteins to identify early predictors of critical illness. A panel of admission proteins accurately forecasts respiratory failure and highlights pathways of cellular adhesion, extracellular matrix turnover and tissue remodelling. Pharmacological modulation with tyrosine kinase inhibitors was shown to attenuate these proteomic perturbations, suggesting potential therapeutic avenues. In parallel, analysis of viral RNA in plasma has been juxtaposed with protein abundance trajectories, revealing that RNAemia correlates with mortality and complement pathway activation, while recovery of liver-derived proteins marks survival. Urine proteomics in early infection stages has delineated an initial immunosuppressive phase with tight junction impairment, followed by a hyperactivated immune response in severe cases, supporting a two-stage model of disease progression.

Proteomics in COVID-19 Pathogenesis publication trend

The graph below shows the total number of articles in proteomics in covid-19 pathogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

Proteomics: The large-scale study of the structure, function and interactions of proteins expressed by a genome.

Mass spectrometry: An analytical technique that measures the mass-to-charge ratio of ionised molecules to identify and quantify compounds in a sample.

Plasma proteome: The complete set of proteins present in blood plasma, reflecting physiological and pathological states.

RNAemia: The presence of viral RNA in the bloodstream, indicating systemic dissemination of the virus.

MALDI-TOF MS: A form of mass spectrometry in which a laser ionises matrix-embedded samples for rapid profiling of biomolecules based on their time of flight.

References

1. Longitudinal plasma proteomics reveals biomarkers of alveolar-capillary barrier disruption in critically ill COVID-19 patients. Nature Communications (2024).
2. Immune suppression in the early stage of COVID-19 disease. Nature Communications (2020).
3. SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care. Nature Communications (2021).
4. Engineered Receptor Capture Combined with Mass Spectrometry Enables High-Throughput Detection and Quantitation of SARS-CoV‑2 Spike Protein. JACS Au (2025).
5. MALDI‐TOF MS analysis of nasal swabs for the characterization of patients infected with SARS‐CoV‐2 Omicron. View (2024).
6. A time-resolved proteomic and prognostic map of COVID-19. Cell Systems (2021).