mRNA-COVID19 vaccination can be considered safe and tolerable for frail patients
Authors: Stanghellini Maria Teresa Lupo , Cosimo Serena Di , Costantini Massimo , Monti Sara , Mantegazza Renato , Mantovani Alberto , Salvarani Carlo , Zinzani Pier Luigi , Inglese Matilde , Ciceri Fabio , Apolone Giovanni , Ciliberto Gennaro , Baldanti Fausto , Morrone Aldo , Sinno Valentina , Locatelli Franco , Notari Stefania , Turola Elena , Giannarelli Diana , Silvestris Nicola 
Published: January 2022

BackgroundFrail patients are considered at relevant risk of complications due to COVID-19 infection and, for this reason, are prioritized candidates for vaccination. As these patients were originally not included in the registration trials, fear related to vaccine side-effects and disease worsening was one of the reasons for vaccine hesitancy. Herein we report the safety profile of the prospective, multicenter, national VAX4FRAIL study (NCT04848493) to evaluate vaccines in a large trans-disease cohort of patients with solid or hematological malignancies, neurological and rheumatological diseases.MethodsBetween March 3rd and September 2nd, 2021, 566 patients were evaluable for safety endpoint: 105 received the mRNA-1273 vaccine and 461 the BNT162b2 vaccine.Frail patients were defined per protocol as patients under treatment with hematological malignancies (131), solid tumors (191), immune-rheumatological diseases (86), and neurological diseases (158), including multiple sclerosis and generalized myasthenia.The impact of the vaccination on the health status of patients was assessed through a questionnaire focused on the first week after each vaccine dose.ResultsThe most frequently reported moderate-severe adverse events were pain at the injection site (60.3% after the first dose, 55.4% after the second), fatigue (30.1% - 41.7%), bone pain (27.4% - 27.2%) and headache (11.8% - 18.9%).Risk factors associated with the occurrence of severe symptoms after vaccine administration were identified through a multivariate logistic regression analysis: age was associated with severe fever presentation (younger patients vs. middle-aged vs. older ones), females presented a higher probability of severe pain at the injection site, fatigue, headache, and bone pain; the mRNA-1237 vaccine was associated with a higher probability of severe pain at the injection site and fever. After the first dose, patients presenting a severe symptom were at a relevant risk of recurrence of the same severe symptom after the second one.Overall, 11 patients (1.9%) after the first dose and 7 (1.2%) after the second one required to postpone or suspend the disease-specific treatment. Finally, 2 fatal events occurred among our 566 patients. These two events were considered unrelated to the vaccine.ConclusionsOur study reports that mRNA-COVID-19 vaccination is safe also in frail patients as expected side effects were manageable and had a minimum impact on patient care path.ImportanceOur study reports the safety analysis of the trial VAX4FRAIL confirming that mRNA-COVID-19 vaccination is safe in frail immunocompromised patients: expected side effects were manageable and had a minimum impact on patient care path.ObjectiveTo evaluate the safety of mRNA-COVID-19 vaccination in vulnerable patients.DesignVAX4FRAIL is a national, multicentric, observational, prospective trial (start date March 3rd, 2021 – primary completion date September 2nd, 2021).SettingMulticenter prospective trial.ParticipantsFrail patients were defined per protocol as patients under treatment with solid tumors (191), immune-rheumatological diseases (86), hematological malignancies (131), and neurological diseases (158), including multiple sclerosis and generalized myasthenia.ExposureOverall, 105 received the mRNA-1273 vaccine and 461 the BNT162b2 vaccine.Main OutcomeThe occurrence of adverse events after 1st and 2nd m-RNA-COVID-19 vaccination was analyzed. Adverse events were collected through a questionnaire comprising both open and closed questions.ResultsThe most frequently reported moderate-severe adverse events were pain at the injection site (60.3% after the first dose, 55.4% after the second), fatigue (30.1% - 41.7%), bone pain (27.4% - 27.2%) and headache (11.8% - 18.9%).Risk factors associated with the occurrence of severe symptoms after vaccine administration were identified through a multivariate logistic regression analysis: age was associated with severe fever presentation (younger patients vs. middle-aged vs. older ones), females presented a higher probability of severe pain at the injection site, fatigue, headache, and bone pain; the mRNA-1237 vaccine was associated with a higher probability of severe pain at the injection site and fever. Patients presenting a severe symptom after the first dose were at a relevant risk of recurrence of the same severe symptom after the second one.Overall, 11 patients (1.9%) after the first dose and 7 (1.2%) after the second one was required to postpone or suspend their disease-specific treatment. Finally, 2 fatal events occurred among our 566 patients, and these two events were due to disease progression and considered unrelated to the vaccine.Conclusion and RelevanceOur study reports that mRNA-COVID-19 vaccination is safe also in frail patients as expected side effects were manageable and had a minimum impact on patient care path.Study RegistrationA National, Multicentric, Observational, Prospective Study to Assess Immune Response to COVID-19 Vaccine in Frail Patients (VAX4FRAIL). NCT04848493https://clinicaltrials.gov/ct2/show/NCT04848493Key PointsQuestionCan m-RNA-COVID19 vaccination be considered safe for frail patients?FindingsIn this national, multicentric, observational, prospective trial (NCT04848493) that included 566 frail patients, the occurrence of both local and systemic adverse events was manageable and did not negatively impact on the general treatment program.MeaningmRNA-COVID19 vaccination is safe among frail immunocompromised patients.