Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has wrought havoc on the world economy and people's daily lives. The inability to comprehensively control COVID-19 is due to the difficulty of early and timely diagnosis, the lack of effective therapeutic drugs, and the limited effectiveness of vaccines. The body contains billions of extracellular vesicles (EVs), which have shown remarkable potential in disease diagnosis, drug development, and vaccine carriers. Recently, increasing evidence has indicated that EVs may participate or assist the body in defence, antagonism, recovery and acquired immunity against SARS-CoV-2. On the one hand, intercepting and decrypting the general intelligence carried in circulating EVs from COVID-19 patients will provide an important hint for diagnosis and treatment; on the other hand, engineered EVs modified by gene editing in the laboratory will amplify the effectiveness of inhibiting infection, replication and destruction of ever-mutating SARS-CoV-2, facilitating tissue repair and making a better vaccine. To comprehensively understand the interaction between EVs and SARS-CoV-2, providing new insights to overcome some difficulties in the diagnosis, prevention and treatment of COVID-19, we conducted a rounded review in this area. We also explain numerous critical challenges that these tactics face before they enter the clinic, and this work will provide previous 'meet change with constancy' lessons for responding to future similar public health disasters. Extracellular vesicles (EVs) provide a 'meet changes with constancy' strategy to combat SARS-CoV-2 that spans defence, antagonism, recovery, and acquired immunity. Targets for COVID-19 diagnosis, therapy, and prevention of progression may be found by capture of the message decoding in circulating EVs. Engineered and biomimetic EVs can boost effects of the natural EVs, especially anti-SARS-CoV-2, targeted repair of damaged tissue, and improvement of vaccine efficacy.