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 (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04848493">NCT04848493</ext-link>) 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). <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04848493">NCT04848493</ext-link><ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT04848493">https://clinicaltrials.gov/ct2/show/NCT04848493</ext-link>

Key Points