TID COVID-19 Guidance Focused Review: SARS-CoV-2 Vaccines in Transplant Recipients

Date of Update: 1 March 2021

KEY POINTS

• Transplant recipients may be vaccinated with any of the COVID-19 vaccines, as soon as they become approved and available.
• All transplant recipients should receive the vaccine, irrespective of past COVID-19 infection or positive SARS CoV-2 antibodies. Case reports of reinfection in immunocompromised patients suggest that protection after a first infection is inadequate or wanes over time.
• For SOT recipients, the ideal timing of vaccination is uncertain in the post-transplantation setting. Vaccination should be delayed at least one month after transplant surgery or rejection treatment. Longer delays may be required for patients who have received anti-B (i.e. rituximab) or anti-T cell (anti-thymocyte globulin, alemtuzumab).  A risk-benefit assessment should weigh the community transmission risks against the likelihood of side effects.
• For HSCT, in regions with accelerated transmission rates, COVID-19 vaccination may start at the 3rd month of HSCT. In regions where the risk of community acquisition of Covid-19 is lower, it is reasonable to wait until the sixth month after HSCT when better vaccine response is expected.
• Organ donors who have received any COVID-19 vaccine may be used irrespective of time since vaccine; no vaccine would rule out a donor.
• SOT and HSCT candidates should also receive the COVID-19 vaccine.
• The concomitant administration of COVID-19 vaccines with other vaccines has not been studied. A few national guidelines advise separating them from other vaccines by at least 2 weeks.  It is not yet known if antibodies persist post-transplant or if revaccination is required.
• Organ offers for candidates who have been recently vaccinated or are between doses 1 and 2 should generally proceed to transplant.  Persistence of protection has not been studied.  Doses post-transplant should be delayed at least 1 month post-transplant.
• Transplant recipients are at risk of poor outcomes with COVID-19. Ideally, they should be prioritized for early vaccination, as allowable by local health authorities.
• Consider prioritizing household contacts of transplant recipients with recipients as transmission rates within households have been shown to be high.
• Note: The response to most vaccines are less robust in transplant recipients, compared with healthy persons. Recent use of T- and B-cell-depleting agents have also been associated with muted immune responses to vaccination.
• We do not recommend checking post-vaccine titers as correlates of immunity are not well established and there is significant variability in what is detected by various assays.
• Transplant recipients who have received the COVID-19 vaccine should continue to observe all current preventive measures, such as masking, hand hygiene and safe distancing. 

Introduction

According to the WHO update of February 26, 2021 on the development of COVID-19 vaccines, there are 182 vaccine candidates in pre-clinical development and 61 vaccines in clinical studies ¹.

So far, 10 different platforms have been used in the development of these vaccines: 1) protein subunit (PS); 2) inactivated virus (IV); 3) non-replicating viral vector (VVnr); 4) RNA; 5) DNA; 6) virus-like particle (VLP); 7) replicating viral vector (VVr); 8) live attenuated virus (LAV); 9) VVnr + antigen-presenting cell (APC); and 10) VVr + APC. The first 5 platforms represent 84% of the vaccine candidates in clinical phase of development.1 Currently, 14 developers have COVID-19 vaccines in phase 3 studies, as shown in Table 1.

To date, 12 SARS-CoV-2 vaccines have been authorized in several countries for emergency use (Pfizer/ BioNTech, Moderna, Gamaleya Sputnik V, Sinovac, Sinopharm, Sinopharm-Wuhan AstraZeneca/Oxford, Janssen/Johnson & Johnson, Bharat, Vector Institute) and have started to be administered to health professionals and the elderly in Europe, the Americas, the Eastern Mediterranean region and Singapore. In the healthy population, projected clinical efficacy based on phase 2 and phase 3 studies varies from more than 50% to 95%. ^2-10.

Despite the achievements in such a short time, many questions remain unanswered, such as the titers of neutralizing antibodies for a COVID-19 vaccine to protect humans, the duration of vaccine-induced immunity, the possibility of occurrence of antibody-dependent enhancement (ADE) phenomenon, antibody responses in transplant recipients, among others. These and other queries that may arise with the expanded use of the COVID-19 vaccines will likely be clarified over time.

Table 1.  Vaccines with EUA Approval or Advanced Development

None of the above vaccines are live virus vaccines or replication-competent viral vectors; all may be used in transplant recipients, candidates or donors.

COVID-19 vaccines in transplant recipients

While prioritization of vaccine is generally determined by the federal, state and local health authorities, transplant recipients should be included in groups for earlier vaccination due to the risk for severe COVID-19. Immunocompromised patients, including transplant recipients, have not been included in studies performed to date.  As such, transplant recipients should be counseled that the effectiveness and safety profile of these vaccines for them are not currently known. As these are not live virus vaccines, it is unlikely that these vaccines would pose additional risks. Transplant recipients may have decreased vaccine responses compared to the general population, and thus should be advised regarding the importance of maintaining all current guidance to protect themselves even after vaccination, including continuing to use masks, focus on hand hygiene and social distancing. Additionally, caregivers and household contacts should be strongly encouraged to get vaccinated when available to them to protect the patient.

Inactivated vaccines, protein subunit recombinant or virus-like vaccines are considered safe to be administered to transplant populations. Particle vaccines have been used for decades in transplant vaccination programs (e.g., influenza, hepatitis B and HPV vaccines). RNA vaccines (BioNTech/Pfizer, Moderna) and non-replicating viral vector vaccines (Oxford/AstraZeneca, Janssen/Johnson & Johnson, Gamaleya) are also considered safe vaccines, but have never been used in the transplant scenario. Vigilance will be necessary to determine if the induced protective immunity is not associated with an increased risk for rejection episodes or the development of graft versus host disease (GVHD).

Preliminary data of 187 SOT recipients who received their first SARS-CoV-2 vaccine doses has recently provided early insight into safety and efficacy of the mRNA vaccine in this population.  Equal numbers of recipients received the Pfizer and Moderna vaccines and had low rates of local (61% pain, 7% redness, 16% swelling at injection site) and system (4% fever, 9% chills, fatigue 38%, headache 32% and myalgias 15%) reactions.  No rejections were reported in these patients.¹¹

Live attenuated vaccines are generally contraindicated in SOT recipients and may be used with restrictions in HSCT recipients. Replicating viral vector vaccines are not recommended in transplant populations at this moment.

References:

1. Organization WH. Draft landscape of COVID-19 candidate vaccines. <https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines> Published 2020.

2. Baden LR, El Sahly HM, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2020.

3. Logunov DY, Dolzhikova IV, Zubkova OV, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020;396(10255): 887-897.

4. Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2020.

5. Zhang Y, Zeng G, Pan H, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2020.

6. Logunov DY, Dolzhikova IV, Zubkova OV, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020;396(10255): 887-897

7. Zhu FC, Guan XH, Li YH, et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2020;396(10249): 479-488.

8. Ramasamy MN, Minassian AM, Ewer KJ, et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Lancet. 2021;396(10267): 1979-1993.

9. Wu Z, Hu Y, Xu M, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2021.

10. Xia S, Zhang Y, Wang Y, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. Lancet Infect Dis. 2021;21(1): 39-51.

11. Boyarsky BJ, Ou MT, Greenberg RS, et al. Safety of the First Dose of SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients. Transplantation. 2021.