As C-Virus starts to rapidly spread through Taitchi district, Leon asks Chris to set off to an nearby underwater facility to rescue Sherry and Jake as the files provided by Sherry revealed that Jake's blood contains the antibodies that can be used to treat the infection, with Chris also telling Leon that his team killed Ada once they split up. Afterwards, him and Helena join the surviving BSAA operatives as they attempt to escape the district through small areas where viral gas didn't yet reach and to that end, head towards the tallest structure in the area; an skyscrapper known as Quad Tower. However, after navigating the district and surviving an helicopter crash during an attempt to hitch a ride to the tower, Leon and Helena are met by Ada, still inexplicably alive and piloting an armed helicopter which she uses to help them break into Quad Tower's central rotunda. However, once there, two agents are once again confronted by Simmons who, still alive despite having been hit by a train, yells at Ada as she circles the rotunda, accusing her of having experimented on Jake to enhance the C-Virus. As Simmons transforms once again, now into an massive, dinosaur-like creature, Leon and Helena fight him while assisted by Ada and eventually manage to bring him down, allowing the trio to head towards the top of the tower. However, as they ride the elevator upwards, building starts to inexplicably collapse and Simmons returns, forcing two agents to evacuate the elevator cabin as it falls and climb along the cables, witnessing Ada as she fights Simmons atop the glass walkway connecting two sections of the building as she has ditched her helicopter on the rooftop. With Simmons starting to gain upper hand, Leon jumps onto the walkway to assist Ada and quickly discovers that Simmons fully descended into insanity as he implies possessiveness towards her, implying that there was indeed something between Simmons and Ada once. After another fight, Simmons nearly manages to throw Leon off the walkway, only for Ada to save him by stabbing Simmons through the side and throwing both him and herself off the walkway, saving herself using her grappling hook while letting Simmons fall into the burning debris below, once again seemingly to his demise. With Ada departing on her own, Leon and Helena reunite and finally reach the Quad Tower's rooftop, intent on taking Ada's helicopter to leave the city. However, there, they quickly discover that Simmons is still alive, and is actively consuming zombies roaming the rooftop to fuel himself. After interrupting his grotesque feeding long enough to let zombies swarm him, Leon and Helena arrive to the very top of Quad Tower, only to once again be faced by Simmons, who consumed enough zombie biomass to transform into a giant fly whom they are forced to fight in order to reach the helipad. Despite his enormous size, Leon quickly figures out that Simmons will try to negate any damage done to him by consuming zombies roaming the rooftop and, with thunderstorm brewing over the city, uses the broken lightning rod to spear individual zombies and bait Simmons into consuming them to regenerate as their fight progresses, causing both the speared zombie and Simmons to be struck by lightning, with Leon and Helena ultimately weakening Simmons enough to jam the lightning rod into his head, with direct lightning strike causing him to fall off the rooftop and allowing them to finally get to the helicopter where Simmons faces them once again and tries to flatten the helicopter, with Leon finally getting rid of him for good by shooting him with an rocket launcher left near the helicopter, causing Simmons to fall again and regain his human form, ultimately ending up impaled on the sharp tip of the obelisk at the tower's central rotunda and finally dying from the rapid blood loss. With Simmons finally dead, Leon and Helena prepare to depart and find an makeup compact with hidden compartment in the backseat, whose contents are revealed to be the files that will prove that Leon and especially Helena, weren't traitors Simmons had attempted to paint them as, despite Helena being happy with simply getting even with Simmons for killing her sister.
Several weeks after the events in China, Leon and Hunnigan arrive to the cemetery where Deborah Harper was buried and tell Helena, who was visiting her sister's grave, that an decision has been made to reinstate her into Secret Service as internal investigation ruled her involvement in causing Tall Oaks outbreak as coercion by Simmons, and that the truth about the whole ordeal surrounding Tall Oaks outbreak and President Benford's death will never be disclosed to the public. Despite her shock at such resolution, Helena agrees to go with Leon and Hunnigan as they depart the cemetery...
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