Disentangling the different stages of the star-formation process, in particular in the high-mass regime, is a challenge in astrophysics. Chemical clocks could help alleviating this problem, but their evolution strongly depends on many parameters, leading to degeneracy in the interpretation of the observational data. One of these uncertainties is the degree of CO depletion. We present here the first self-consistent magneto-hydrodynamic simulations of high-mass star-forming regions at different scales, fully coupled with a non-equilibrium chemical network, which includes C-N-O bearing molecules. Depletion and desorption processes are treated time-dependently. The results show that full CO-depletion (i.e. all gas-phase CO frozen-out on the surface of dust grains), can be reached very quickly, in one third or even smaller fractions of the free-fall time, whether the collapse proceeds on slow or fast timescales. This leads to a high level of deuteration in a short time both for typical tracers like N$_2$H$^+$, as well as for the main ion H$_3^+$, the latter being in general larger and more extended. N$_2$ depletion is slightly less efficient, and no direct effects on N-bearing molecules and deuterium fractionation are observed. We show that CO depletion is not the only driver of deuteration, and that there is a strong impact on $D_{frac}$ when changing the grain-size. We finally apply a two-dimensional gaussian Point Spread Function to our results to mimic observations with single-dish and interferometers. Our findings suggest that the low-values observed in high-mass star-forming clumps are in reality masking a full-depletion stage in the inner 0.1 pc region.
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