The TRAPPIST-1 system, consisting of an ultra-cool host star having seven known Earth-size planets will be a prime target for atmospheric characterization with JWST. However, the detectability of atmospheric molecular species may be severely impacted by the presence of clouds and/or hazes. In this work, we perform 3-D General Circulation Model (GCM) simulations with the LMD Generic model supplemented by 1-D photochemistry simulations at the terminator with the Atmos model to simulate several possible atmospheres for TRAPPIST-1e, 1f and 1g: 1) modern 2 Fauchez et al.Earth, 2) Archean Earth, and 3) CO 2 -rich atmospheres. JWST synthetic transit spectra were computed using the GSFC Planetary Spectrum Generator (PSG). We find that TRAPPIST-1e, 1f and 1g atmospheres, with clouds and/or hazes, could be detected using JWST's NIRSpec prism from the CO 2 absorption line at 4.3 µm in less than 15 transits at 3 σ or less than 35 transits at 5 σ. However, our analysis suggests that other gases would require hundreds (or thousands) of transits to be detectable. We also find that H 2 O, mostly confined in the lower atmosphere, is very challenging to detect for these planets or similar systems if the planets' atmospheres are not in a moist greenhouse state. This result demonstrates that the use of GCMs, self-consistently taking into account the effect of clouds and sub-saturation, is crucial to evaluate the detectability of atmospheric molecules of interest as well as for interpreting future detections in a more global (and thus robust and relevant) approach.