This summary document focusses on Long COVID, also known as post-COVID syndrome or post-acute COVID-19, in the context of clinical development and vaccine efficacy trials. Long COVID is typically assessed in observational cohort studies. However, an assessment for Long COVID can be included as an exploratory objective in randomized clinical trials following an amendment to the study protocol. Long COVID is of public health relevance, and vaccine developers can consider implementing a more robust prospective, periodic assessment of solicited symptoms or a less robust but less expensive nested retrospective cohort study within efficacy clinical trials.
Prospective observational cohort studies have been widely used to assess different signs and symptoms of Long COVID and their duration post-acute COVID-19. In a randomized clinical trial, a vaccine effect on Long COVID can be explored by comparing the incidence and duration of Long COVID signs and symptoms. Long COVID is associated with COVID-19 severity. However, because very few clinically symptomatic breakthrough COVID-19 cases in vaccinees are severe or critical, a meaningful comparison between treatment arms will be restricted to mild to moderate severity graded COVID-19 cases, which will likely occur in both the vaccine and the control groups. Study sponsors should consider the follow up of study subjects with PCR-confirmed COVID-19 beyond 12 weeks after diagnosis for as long as is feasible and preferably at study conclusion.
There is no global consensus on the definition of Long COVID or the definitive symptoms. The National Institute for Health and Care Excellence describes Long COVID as signs and symptoms that develop or continue after acute COVID-19 and continue for more than 12 weeks and are not explained by an alternative diagnosis. In addition, the term Long COVID has been used to address both ongoing / post-acute symptomatic COVID-19 (from four to 12 weeks) and long-term post-COVID-19 syndrome (12 weeks or more). Long COVID can affect all age groups from children to older adults.
The Post COVID-19 Functional Status Scale can be considered as a general status functioning scale applicable for use after confirmed COVID-19 to assess changes in physical, mental, and social health status functionality. A baseline reference grading of functionality can be considered prior to SARS CoV-2 infection in study subjects. However, the PFCS scale should not replace but rather supplement assessment of any solicited and unsolicited adverse events during follow up visits.
- A Comparison of Study Population Inclusion and Exclusion Criteria reported in Advanced Stage Clinical Trial Protocols
- A Comparison of Vaccine Efficacy Elements in Advanced Stage Clinical Trial Protocols
- Early and Advanced Stage Clinical Development Core Elements- Comparison of the Guidance and Considerations