Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible coronavirus responsible for the global COVID-19 pandemic. The study provides evidence that SARS-CoV-2 spreads through cell–cell contact in cultures, mediated by the spike glycoprotein. Compared with cell-free infection of SARS-CoV that caused SARS in 2003, cell-to-cell transmission of SARS-CoV-2 is refractory to inhibition by neutralizing antibody or convalescent sera of COVID-19 patients. The researchers then investigate the role of the angiotensin-converting enzyme 2 (ACE2) receptor, a protein on cell surfaces that acts as the gateway for entry of the virus that causes COVID-19. Surprisingly, there is no perfect correlation between SARS-CoV-2 infection and the level of ACE2. ACE2 may be needed for initial infection, but once the infection is established, the virus may not need ACE2 anymore because it can spread from cell to cell.