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Symbiotes
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- 1st appearance of Silence, a new symbiote, bonded to Andi Benton
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- 1st appearance of the symbiote that bonds with Gwen to becomes Gwenom
- 1st appearance of Dr. Elsa Brock, the Eddie Brock of Gwen Stacy's reality
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- 1st team appearance of the Resistance, heroes with symbiotes
- The Resistance led by Captain Venom
- 1st partial team appearance of The Poisons, a race of aliens devour symbiotes and their hosts
- Poisons: Hulk, Doctor Octopus, Spider-Man
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- 1st appearance and origin of Lee Price, bonds with the Venom symbiote
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- Origin of Gorr the God Butcher
- 1st cameo appearance of Knull the Symbiote God
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- 1st appearance of Gwen Stacy as Gwenom
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- April Parker becomes Mayhem, a clone of May Parker genetically and a hybrid human/symbiote
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- Preview appearance of Bile, a cannibalistic madman with the strength and eating habits of a spider
- Bile was presented as a joke in this issue but CBR posts an article about Donny Cates taking an interest in the character even though it seemed the tweet exchange was more conversational without future plans
- Character never appeared in a story but bears similar horror attributes as Spiders-Man of Earth 11580: See Spider-Verse button for more
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- Hulk bonds with the Venom symbiote
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- 1st appearance of Sleeper, the result of Eddie Brock bonding with the infant Symbiote
- [June 2021 - a character that is likely to play a significant role in the future alongside Dylan Brock]
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- 1st appearance of Patricia Robertson as Scream, formerly She-Venom
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- 1st appearance of Spider-Man's black costume
- Cover art inspired by Amazing Fantasy #15
- The symbiote costume was designed by a Marvel fan from Illinois named Randy Schueller. Editor-In-Chief Jim Shooter purchased the design idea from Randy for $220
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- 1st full appearance of Normie Osborn as Goblin Childe
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- 1st appearance of N'Jadaka, the new Emperor bonded to a symbiote
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- 1st appearance of Addy Brock, pilot of the mechanized Ven#m suit
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- 1st appearance of The Mercury Team, a US task force deployed to hunt down symbiotes equipped with the Life Foundation symbiotes: Phage, Lasher, Agony, Riot
- Mercury Team was a Sym-Soldier program that became known as Project Venom
- Copies ordered by retailers: 30,378