The main difference is that colds and flu are caused by completely different viruses, leading to distinct symptoms. A cold, usually from rhinoviruses, comes on gradually with a focus on the head—runny nose, sneezing, and a sore throat. The flu, from influenza viruses, strikes suddenly and is a full-body illness. It brings a high fever, significant body aches, chills, and extreme tiredness that can knock you off your feet. The flu's systemic nature is what makes it more severe.