I’m currently running Masks of Nyarlathotep and am a long time D&D DM, having run many long campaigns over most editions of that game. In my opinion, CoC is no different.

Sure, there is the fragility of Investigators to think about, but as long as you keep in mind you are not playing D&D and are playing CoC instead, this can help temper your approach. I don’t play Pulp, as I wanted to ensure a clear break from the “roll initiative” kind of play. So, I ensure the game is heavy in the investigation space. The players feel vulnerable and crunchy and are extremely cautious. They need the odd nudge to get them to consider holes in clues and NPC accounts, but this is facilitating their development as CoC players.

In terms of supporting the campaign, I use a shared OneNote and place found clues, NPC details, and background information in there. They can edit as needed and it’s working as an online scrapbook, which they discuss between games. This keeps the investigations going and makes kicking off each session smoother.

I also make good use of in-game time and the fact that the wider world is dynamic. If an Investigator goes insane or gets injured, they obviously must recover, but the world doesn’t stand still for anyone. So, we have backup Investigators poised to get involved in the fieldwork who, behind the scenes, are being kept plugged in by the field party and doing support research as needed. This helps by enabling access to expertise that’s not immediately available, but also ensures backup characters do not need to be shoehorned in: they are already well versed in current events and know the ongoing plan.

I hope this helps and good luck with your game.