mRNA-COVID19 vaccination can be considered safe and tolerable for frail patients

Background Frail 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. Methods Between March 3 rd and September 2 nd , 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. Results The 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. Conclusions Our 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. Importance Our 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. Objective To evaluate the safety of mRNA-COVID-19 vaccination in vulnerable patients. Design VAX4FRAIL is a national, multicentric, observational, prospective trial (start date March 3 rd , 2021 – primary completion date September 2 nd , 2021). Setting Multicenter prospective trial. Participants Frail 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. Exposure Overall, 105 received the mRNA-1273 vaccine and 461 the BNT162b2 vaccine. Main Outcome The occurrence of adverse events after 1 st and 2 nd m-RNA-COVID-19 vaccination was analyzed. Adverse events were collected through a questionnaire comprising both open and closed questions. Results The 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 Relevance Our 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 Registration A National, Multicentric, Observational, Prospective Study to Assess Immune Response to COVID-19 Vaccine in Frail Patients (VAX4FRAIL). NCT04848493 https://clinicaltrials.gov/ct2/show/NCT04848493 Key Points Question Can m-RNA-COVID19 vaccination be considered safe for frail patients? Findings In 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. Meaning mRNA-COVID19 vaccination is safe among frail immunocompromised patients.