Among the various conditions that may strongly influence the immunogenicity of COVID-19 vaccines, immunosuppression plays a key role. Several lines of evidence now attest that patients taking a kaleidoscope of immunosuppressant agents display considerably lower vaccine immunogenicity, as reflected by a blunted generation of anti-SARS-CoV-2 neutralizing antibodies compared to people not receiving these medications. Based on the current evidence, at least three potential approaches could be advocated to overcome this matter, entailing temporary suspension (usually between 1–2 weeks) of immunosuppressant treatment upon receiving COVID-19 vaccination, or modification of standard vaccination protocols, either in terms of time between boosters or alterations in dosage. The choice of the most appropriate strategy entails a personalized approach, individualizing the relative risk of each strategy according to environmental risk and clinical aspects, at least until more solid evidence will provide support for the superiority of one strategy over the others.
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