Upper age limits for convalescent plasma donation and treatment of COVID‐19 patients: A further marker of ageism

Abstract

To the Editor, With millions of people experiencing COVID-19, older subjects have a higher risk of severe clinical manifestations of COVID-19, including mortality. Besides drugs and monoclonal antibodies proposed for COVID-19 treatment, a possible therapeutic option, especially early in the course of disease, is convalescent plasma (CP). Given ample evidence of ageism in clinical trials, we investigated whether trials of CP in COVID-19 restricted either donors or recipients on the basis of age. We searched the WHO International Clinical Trials Registry Platform (WHO-ICTRP) on August 25, 2020 for clinical trials of CP for the treatment of COVID-19 illness (https://www.who.int/ictrp/en/). The following keywords were used: “COVID” as condition and “plasma” as intervention. We identified the most relevant data from the study protocol of each trial, adapting the methodology previously used in the PREDICT study. We evaluated trial design, contacting by email the researchers when information was not available. When the age limit for plasma donors was not specified and there was no response from the authors, the information was obtained consulting national regulations. Logistic regression models were used to identify variables associated with upper age limits on the basis of χ Wald statistics. After the exclusion of observational studies (105), interventional studies not using COVID-19 CP as treatment (151), expanded access studies (10) and studies on pediatric subjects (5), 157 studies were included (95 RCTs and 62 non-RCTs). We found that 64% of the studies had an upper age limit for plasma donors, and 33% for receiving patients. Moreover, 26% had upper age limits both for donors and recipients. In at least 18 studies, donor s age limits were set independently of the national regulations, which would have allowed higher limits. In the logistic regression, geographical area was the only characteristic related with upper age limits. No scientific reason can justify exclusion of patients for treatment on the basis of age and the Food and Drug Administration and the European Medical Agency strongly recommend against it. In the context of the COVID-19 pandemic, which presents a more severe disease with increasing age, the exclusion of older subjects from trials supporting an emergency therapy has a clear relevance. The main reason explaining the age limitation for donors are the criteria used for blood donation in each country, often based on past practice rather than on scientific evidence. WHO guidelines indicate an upper age limit of 65 years, with discretion after 65 for regular donors based on individual evaluation. In North America, upper age limits for donors have been abolished. Europe is generally aligned with WHO. The presence of an upper age limit for blood and plasma donation is scientifically unfounded. Donation does not pose safety issues to older adults: on the contrary, donation-related moderate and severe reactions, including vasovagal reactions and loss of consciousness, are less common in older donors, and there is no evidence that blood or plasma donated by older people produces negative consequences in recipients. Although part of the CP donors could be first-time donors and therefore at higher risk of adverse events, in the context of the pandemic emergency and in clinical trials it would have been possible and appropriate to consider a higher age limit for plasma donation. Upper age limits in blood and plasma donation are unnecessary and should be revised. In the context of COVID-19 pandemic, they reduce the number of older people who can provide their plasma and of those who can benefit from it, a particular irony for a condition whose most serious consequences occur among older people.