LAUSR

The rapid rise of monkeypox (MPX) cases outside previously endemic areas prompts for a better understanding of the disease. We studied the plasma proteome of a group of MPX patients with a similar infection history and clinical manifestation typical for the current outbreak. We report that MPX in this case series is associated with a strong plasma proteomic response among nutritional and acute phase response proteins. Moreover, we report a correlation between plasma proteins and disease severity. Contrasting the MPX host response with that of COVID‐19, we find a range of similarities, but also important differences. For instance, CFHR1 is induced in COVID‐19, but suppressed in MPX, reflecting the different roles of the complement system in the two infectious diseases. Of note, the spatial overlap in response proteins suggested that a COVID‐19 biomarker panel assay could be repurposed for MPX. Applying a targeted protein panel assay provided encouraging results and distinguished MPX cases from healthy controls. Hence, our results provide a first proteomic characterization of the MPX human host response and encourage further research on protein‐panel assays in emerging infectious diseases.