Do you recommend additional SARS (Severe Acute Respiratory Syndrome) vaccine shots after initial 3-shot series?

Additional COVID-19 Vaccine Doses After Initial 3-Shot Series

For the general population, additional COVID-19 vaccine doses beyond the initial 3-shot series are recommended according to national guidelines, particularly for those at higher risk of severe disease or with compromised immune systems.

General Recommendations

• The European Alliance of Associations for Rheumatology (EULAR) supports a "better safe than sorry" approach regarding additional COVID-19 vaccine doses, acknowledging that while robust evidence on waning immunity is still developing, precautionary additional doses are reasonable 1
• Due to the uncertainty of antibody response persistence after vaccination, especially for patients on active treatment, hematological malignancy and hematopoietic stem cell transplant (HSCT) patients can receive 3rd and 4th doses according to national guidelines 1
• Evidence suggests that immunity decline rate after the booster dose is slower than after the second dose, suggesting longer protection from additional doses 2

Special Populations Requiring Additional Doses

• Immunocompromised individuals, including those on certain immunosuppressive or immunomodulatory drugs, may not mount an adequate protective response to the initial COVID-19 vaccination series 1
• Patients with hematological malignancies who were vaccinated before or during treatment should be assessed 6 months after treatment ends and re-vaccinated if they have low antibody titers 1
• HSCT recipients should receive a full COVID-19 vaccination program regardless of previous vaccination history, as the transplant procedure likely eliminates previously acquired immunity 1

Timing Considerations

• For HSCT recipients, vaccination should preferably be initiated at least 6 months after transplantation if community transmission of SARS-CoV-2 is low 1
• Patients with hematological malignancies who have a low response to initial vaccination should not have their second dose delayed unless mandated by individual circumstances 1
• The timing of additional doses should consider the patient's immune status, with antibody response assessment potentially helpful in guiding decisions 2

Safety and Efficacy

• Studies show that a third dose resulted in significant increases in SARS-CoV-2 antibodies in HSCT patients who responded poorly to the second dose, with no severe adverse events noted 1
• Among previously non-responsive patients, 41% mounted a detectable response after a third dose, and 85% of those with weak prior responses achieved good responses after an additional dose 1
• Booster doses have demonstrated high antibody titers 7 months after administration, comparable to levels seen 2 months after the second dose 2

Risk Mitigation Beyond Vaccination

• Whatever the measured vaccine response, immunocompromised patients should be informed of ongoing risk of COVID-19 despite vaccination and should adhere to hygiene and social distancing recommendations 1
• Vaccination of household contacts, including children (according to age-appropriate approvals), is strongly recommended for protection of vulnerable individuals 1
• Consistent and proper use of masks has been shown to be crucial for protection against SARS infection in healthcare settings 3

Common Pitfalls and Caveats

• There is a risk for worsening or eliciting graft-versus-host disease (GVHD) in allogeneic HSCT recipients after COVID-19 vaccination, which needs to be considered when deciding about timing for vaccination 1
• Pre-exposure prophylaxis with long-acting anti-SARS-CoV-2 monoclonal antibodies may be recommended for non-immunized patients at risk for severe COVID-19, particularly those who cannot mount adequate vaccine responses 1
• Some evidence suggests that patients who received three doses and subsequently had breakthrough infection developed even higher antibody levels than those who only received boosters, indicating natural infection may further enhance immunity 2