How do nocebo effects in placebo groups of randomized controlled trials provide a possible explicative framework for the COVID-19 pandemic?

Introduction: Randomized clinical trials (RCTs) are useful to study the role of individual and contextual factors in which therapies vs placebos are administered and to provide an important perspective for understanding the phenomenon of nocebo-related risks.Areas covered: The results of nocebo effects in RCT placebo groups, measured in terms of adverse events (AEs) and dropouts, will be presented as an explicative framework for the COVID-19 pandemic. Currently, SARS-CoV-2 vaccines are the only RCTs routinely conducted during the pandemic. Information about efficacy and safety of different vaccines represents a fertile ground for nocebo phenomena. Individual and contextual factors will be emphasized in order to understand the presence of a refusal of immunization associated with a specific vaccine considered less effective and safe. Critical aspects and some guidelines will be presented in order to counteract the nocebo effects and to improve adherence to drug treatments and the vaccination campaign.Expert opinion: The nocebo effect could explain the presence of strong resistance in European countries to immunization with a vaccine perceived as less effective, compared to others. Increased awareness of the nocebo effect would be relevant as it could lead to a greater participation in the vaccination campaign and in protecting individuals against SARS-CoV-2 infection.