Safety of third dose of COVID-19 vaccination in frail patients: Results from the prospective Italian VAX4FRAIL study

Abstract

Importance: Despite people with impaired immune competence due to an underlying disease or ongoing therapy, hereinafter frail patients, are (likely to be) the first to be vaccinated, they were usually excluded from clinical trials.

Objective: To report adverse reactions of frail patients after receipt of the third dose (booster) administered after completion of a two-dose mRNA vaccination and to compare with those reported after the receipt of the first two doses.

Design: A multicenter, observational, prospective study aimed at evaluating both the safety profile and the immune response of Pfizer-BioNTech or Moderna vaccines in frail patients.

Setting: National Project on Vaccines, COVID-19 and Frail Patients (VAX4FRAIL).

Participants: People consenting and included in the VAX4FRAIL trial.

Exposure: A series of three doses of COVID-19 mRNA vaccination from the same manufacturer.

Main outcomes and measures: Evaluation of a self-assessment questionnaire addressing a predefined list of eight symptoms on a five-item Likert scale. Symptoms were classified as severe if the patient rated them as severe or overwhelming.

Results: Among 320 VAX4FRAIL participants diagnosed/treated for hematological malignancies (N=105; 32.8%), solid tumors (N=48; 15.0%), immune-rheumatological diseases (N=60; 18.8%), neurological diseases (N=107; 33.4%), and receiving the booster dose, 70.3% reported at least one loco-regional or systemic reactions. Adverse events were mostly mild or moderate, none being life-threatening. Only six of the 320 (1.9%) patients had their treatment postponed due to the vaccine. The safety profile of the booster compared to previously administered two doses showed a stable prevalence of patients with one or more adverse events (73.5%, 79.7% and 73.9% respectively), and a slightly increment of patients with one or more severe adverse events (13.4%, 13.9% and 19.2% respectively).

Conclusions and relevance: The booster of the mRNA COVID-19 vaccine was safely administered in the largest prospective cohort of frail patients reported so far. VAX4FRAIL will continue to monitor the safety of additional vaccine doses, especially systemic adverse events that can be easily prevented to avoid interruption of continuity of care.

Clinical trial registration: https://ichgcp.net/clinical-trials-registry/NCT04848493, identifier NCT04848493.

Keywords: COVID – 19; adverse (side) effects; frail adults; safety; vaccination.

Conflict of interest statement

SDC reports payments as speaker bureau Pierre-Fabre, AstraZeneca, as hoc advisor MEDSIR, IQVIA. AMa reports royalties for reagents related to innate immunity, consulting fees and payment or honoraria as a consultant/advisory board member for Novartis, Roche, Ventana, Pierre Fabre, Verily, AbbVie, BMS, J&J, Imcheck, Myeloid Theraputics, Astra Zeneca, Biovelocita, BG Fund, Third Rock Venture, Violend Verseau Therapeutics, Macrophage pharma, Ellipses Pharma, and Olatec Therapeutics, and is the inventor of patents related to PTX3 and other innate immunity molecules. RM reports consulting fees paid to 2 author from Alexion, Argenx, and UCB, payment to author for lectures, presentations, speakers 3 bureaus, manuscript writing or educational events from Alexion, Argenx, Merck Serono, Reflexion 4 Medical Network, Sanofi Aventis, UCB, paid participation on Data Safety Monitoring or Advisory Board with Alexion, Argenx, Catalyst, and UCB. AU reports grants or contracts unrelated to this work from FISM, ALEXION, BIOGEN, ROCHE, MERCK SERONO, and COVAXIMS, participation on Data Safety Monitoring or Advisory Board for BD, BIOGEN, IQVIA, SANOFI, ROCHE, ALEXION, BRISTOL MYERS SQUIBB. NS reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Lilly, Roche, and Servier. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Di Cosimo, Lupo-Stanghellini, Costantini, Mantegazza, Ciceri, Salvarani, Zinzani, Mantovani, Ciliberto, Uccelli, Baldanti, Apolone, Delcuratolo, Morrone, Locatelli, Agrati and Silvestris.

Figures

Figure 1

Prevalence of solicited adverse events within 7 days following third-dose vaccination. (A) Any-grade local and systemic adverse events. (B) Severe local and systemic adverse events.