ABSTRACT
The development of SARS-CoV-2 vaccines represents a significant breakthrough for managing the COVID-19 pandemic. However, their approval process has exposed a crucial limitation in clinical trial reports-that is, a disregard for sex differences in response to vaccines. Historically, males and females have shown different reactions to vaccines of many kinds, which have become apparent with the arrival of COVID-19 vaccines in late-2020. In this article, we review regulatory data from Phase III vaccine trials as well as peer-reviewed reports from vaccines administered to the general population, many of which failed to stratify results by sex. We also discuss the exclusion of pregnant and lactating persons in drug development and the regulatory guidelines for use of COVID-19 vaccines in such populations. We conclude by proposing some questions to stimulate discussion with the intent of advancing the field toward precision medicine.