Immunocompromised patients, such as organ transplant recipients, are at a particular risk of experiencing severe symptoms from COVID-19. These patients have reduced resistance to infection, can become infected with fewer infectious particles and less aggressive strains, experience more rapid progression of infections, and have higher mortality rates (1,2). To date, the standard two-dose COVID-19 vaccination has been found to have suboptimal efficacy, fueling discussions about how to best protect this high-risk population (3,4). Data have shown that mRNA vaccine efficacy against new, more dangerous variants (such as the Delta B.1.617.2) reaches 88% at best in the normal population following the second dose, but remains significantly lower in immunocompromised patients (5,6). To this end, various studies assessing the benefits of a COVID-19 booster dose have been carried out in light of the increased vulnerability of organ transplant recipients.

One recent large case series demonstrated the safety and immunogenic efficacy of a third dose of the mRNA-1273 vaccine (Moderna) and 162b2 vaccine (Pfizer/BioNTech). Results revealed that antibody titers increased after the third dose in one third of patients who had negative antibody titers and in all patients who had low-positive antibody titers after the second dose (7). In another study, after clinicians administered a third dose of the mRNA vaccine (Moderna) to 159 kidney transplant patients who had generated little to no antibodies after two doses, 49% of these subsequently started to produce antibodies (8). Consistently, another study found that 68% of organ recipients produced antibodies after a third dose of the mRNA vaccine (Pfizer), up from 40% after two doses (4). In a recent double-blind randomized controlled trial, in which transplant recipients were assigned to receive either a third dose or a saline placebo two months after their second dose of the of the mRNA-1273 vaccine (Moderna), participants having received the third dose had substantially higher immunogenicity than controls, as reflected in a 71% virus neutralization rate, compared to 13% in the placebo group (9). Interestingly however, a small subgroup of patients who received a placebo did experience modest increases in antibody levels – potentially reflecting ongoing mRNA vaccine-induced B-cell stimulation (10). No hospitalizations or any cases of organ rejection were reported among the patients who received the booster dose of the mRNA vaccine. This said, it must be noted that in the clinical trial of Hall et al., even after the third dose, only 55% of the transplant recipients had antibody levels exceeding the protective threshold of 100 U per milliliter – highlighting that this remains an imperfect protection.

Overall, evidence supports that a booster third dose of the mRNA vaccine in solid organ transplant recipients is safe and effective, with evidence of improved immunogenicity and protection from COVID-19 infection. As a result, a federal advisory committee at the Centers for Disease Control and Prevention officially suggested that a third dose of vaccine would be beneficial in immunocompromised patients such as transplant recipients, and the U.S. Food and Drug Administration authorized COVID-19 vaccine booster shots for certain individuals with compromised immune systems (11).

In general, a third-dose booster COVID-19 vaccine should be considered for organ transplant recipients who have previously received two doses of an mRNA vaccine (Moderna or Pfizer-BioNTech). Further research is warranted, however, on how best to treat and manage this patient population. In the meantime, masks should still be worn and social distancing practiced in an effort to continue to use all tools aimed at curbing the COVID-19 pandemic.

References 

1. Fishman JA. Infection in Organ Transplantation. American Journal of Transplantation. 2017. doi:10.1111/ajt.14208 
2. Fishman JA. Opportunistic infections-coming to the limits of immunosuppression? Cold Spring Harb Perspect Med. 2013. doi:10.1101/cshperspect.a015669 
3. Boyarsky BJ, Werbel WA, Avery RK, Tobian AAR, Massie AB, Segev DL, et al. Antibody response to 2-doseSARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA – Journal of the American Medical Association. 2021. doi:10.1001/jama.2021.7489 
4. Kamar N, Abravanel F, Marion O, Couat C, Izopet J, Del Bello A. Three Doses of an mRNACOVID-19 Vaccine in Solid-Organ Transplant Recipients. N Engl J Med. 2021. doi:10.1056/nejmc2108861 
5. Sheikh A, McMenamin J, Taylor B, Robertson C. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. The Lancet. 2021.doi:10.1016/S0140-6736(21)01358-1 
6. Lopez Bernal J, Andrews N, Gower C, Gallagher E, Simmons R, Thelwall S, et al. Effectiveness ofCOVID-19 Vaccines against the B.1.617.2 (Delta) Variant. N Engl J Med. 2021. doi:10.1056/nejmoa2108891 
7. Werbel WA, Boyarsky BJ, Ou MT, Massie AB, Tobian AAR, Garonzik-Wang JM, et al. Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series. Ann Intern Med. 2021. doi:10.7326/l21-0282 
8. Benotmane I, Gautier G, Perrin P, Olagne J, Cognard N, Fafi-Kremer S, et al. Antibody Response after a Third Dose of the mRNA-1273 SARS-CoV-2 Vaccine in Kidney Transplant Recipients with Minimal Serologic Response to 2 Doses. JAMA – Journal of the American Medical Association. 2021. doi:10.1001/jama.2021.12339 
9. Hall VG, Ferreira VH, Ku T, Ierullo M, Majchrzak-Kita B, Chaparro C, et al. Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients. N Engl J Med. 2021. doi:10.1056/nejmc2111462 
10. Turner JS, O’Halloran JA, Kalaidina E, Kim W, Schmitz AJ, Zhou JQ, et al. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Nature. 2021. doi:10.1038/s41586-021-03738-2 
11. Coronavirus (COVID-19) Update: FDA Authorizes Additional Vaccine Dose for Certain Immunocompromised Individuals | FDA [Internet]. Available from: https://www.fda.gov/news-events/press-announcements/coronavirus-COVID-19-update-fda-authorizes-additional-vaccine-dose-certain-immunocompromised