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Volume: 20 Issue: 9 September 2022

FULL TEXT

ARTICLE
COVID-19 Vaccination in Solid-Organ Transplant: A Real-World Multicenter Experience

Abstract

Objectives: India ranks third globally in organ procurement and transplant and has the second highest COVID-19 incidence rate, but data regarding COVID-19 vaccination in solid-organ transplant patients are scarce.
Materials and Methods: We created a cross-sectional, anonymous, online questionnaire and sent invitations to several transplant centers in India. We surveyed vaccine mandates, immunization coverage and side effects, administration timing, infection severity among solid-organ transplant recipients, and booster dosage recommendations.
Results: The survey results showed that vaccine policy is heterogeneous among centers; vaccination is voluntary at some centers (44.7%), but some centers have established COVID-19 vaccination as a requirement for transplant candidates (44.6%). CoviShield was the most common vaccine administered (89.3%), and more than 50% of transplant recipients and donors were
fully vaccinated. Survey results showed that the pretransplant wait time after full vaccination (both doses) is 2 to 4 weeks (48.9%), and the optimal time for vaccination after transplant is 3 to 6 months (59.3%). For vaccinated transplant patients, 89.4% of respondents reported an incidence rate for posttransplant breakthrough infection of less than 25%. For unvaccinated patients, 38.3% of respondents reported a 25% to 50% incidence rate of posttransplant COVID-19 infection. Booster doses are recommended at many transplant centers in India, as reported by 89.4% of survey respondents.
Conclusions: The results of the survey suggested that there are no substantial safety concerns Future targets should include increasing efficacy and increasing booster doses of the COVID-19 vaccine.


Key words : COVID-19 vaccine, Kidney transplant, Oxford vaccine, SARS-CoV-2, Solid-organ transplantation

Introduction

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, there have been more than 450 million confirmed cases of COVID-19 reported to the World Health Organization. Various vaccine formulations are available in different countries, including mRNA-based vaccines, inactivated viral vaccines, adenovirus-vectored vaccines, and protein subunit vaccines. The COVID-19 virus is associated with a higher risk of severe disease and mortality for solid-organ transplant recipients (SOTR), but the evidence remains ambiguous.1 Observational research has shown that transplant patients infected with COVID-19 have a higher mortality rate than the general population. According to recent findings, certain SOTR subgroups may have higher rates of morbidity.2 Compared with immunocompetent individuals, immunologic responses of SOTRs to COVID-19 vaccination are lower, and vaccine hesitancy puts the SOTR population at greater risk.3,4 India is ranked third globally for organ donations and transplants and also has the second highest COVID-19 incidence rate of any country in the world. The standard 2-dose regimen of COVID-19 vaccine has been administered to more than 70% of the Indian population; however, data regarding COVID-19 vaccination in organ transplant patients are scarce.5-7 We recently conducted a national survey at several indigenous organ transplant centers to determine vaccination coverage and administration, as well as to solicit recom-mendations.

Materials and Methods

We commenced a cross-sectional, anonymous, web-based survey using an online questionnaire. We solicited participation from several transplant centers in India. Institutional Ethical Committee permission was acquired before the start of the project. The study was mainly conducted online. The questionnaire included 19 questions about vaccine mandate, immunization coverage and side effects, administ-ration timing, infection severity among SOTR recipients, and booster dosage recommendations. The target population consisted of health care providers working at various organ transplant centers. The participants were informed that participation was entirely voluntary and that their agreement to participate was confirmed by the act of completing the survey.

Statistical analyses
No formal sample size computation was done. This was a cross-sectional survey. All responses from different professionals, irrespective of the centers, were collected and analyzed on a hierarchical basis, representing one center. The cumulative responses from each center were analyzed. Data are expressed as numbers and percentages. The data are presented as pie charts, depicting relative proportions. No statistical analyses were performed.

Results

The respondents (N = 47) were from a variety of major organ transplant centers. Our participants were mostly transplant nephrologists (93.5%). Gujarat (29.8%), Maharashtra (23.4%), and Karnataka (23.4%) were the states with the most responses.

Many centers (44.7% of respondents) do not have a mandate for vaccination, although counseling is mandated, whereas 42.6% of respondents reported that pretransplant vaccination is a mandatory requirement at their center. Concerns about putting undue strain on organ transplant recipients (27.7%) and insufficient evidence that a mandate would improve the safety of patients (25.5%) has led some centers to the decision that vaccination should be voluntary for their transplant candidates. With regard to scheduling a transplant, 48.9% of respondents stated that the wait time following the completion of transplant recipient’s COVID-19 vaccination before scheduling a transplant is 2 to 4 weeks at their center (Table 1, Figure 1, Figure 2, and Figure 3).

Discussion

The COVID-19 virus is still causing chaos over the planet in waves. With the second-highest number of COVID-19 cases worldwide, India encountered the challenges of vaccinating its population. In light of the large number of people awaiting various organ transplants, numbers of transplants were reduced significantly during the early stages of the pandemic in the United States (51%), France (90%), India (50%), and Spain (87%).8-10 These events were associated with an increase in morbidity; however, the introduction of vaccination campaigns are demonst-rating a rising trend.

To better understand the real-world COVID-19 vaccination scenarios for SOTR patients, we conducted an online survey among major transplant centers in India. Optimally, transplant candidates should be fully immunized while awaiting transplant. The COVID-19 vaccinations can reduce the risk of the ongoing pandemic, are progressively safer, and will help prevent the spread of the COVID-19 virus. Multiple studies have shown that vaccination helps avoid serious illness in patients who experience a COVID-19 breakthrough infection despite a previous vaccination infected with the virus.11,12 At present, vaccine mandates, vaccine hesitancy, and the treatment of patients who refuse vaccination are all prominent issues.13

International surveys have indicated that many transplant centers are reluctant to proceed with transplants without full vaccination of the candidates, whereas other centers proceed without full vaccination.14 Supporters of the vaccine mandate point to better patient coverage, the principle of beneficence, and the notable reduction in the severity of COVID-19 symptoms; opponents point to organ failure without organ transplant and potential serious COVID-19 infections.15,16 Presently, transplant centers in India have proceeded with a heterogeneous approach to vaccine mandate policies, such that 44.7% of centers do not mandate vaccination but 42.6% of centers have mandatory vaccination. Centers cited a variety of explanations for their decision against mandatory vaccination, and the most common explanations were (1) insufficient evidence that vaccination would improve overall safety of patients (25.5%) and (2) concern of the perception of coercion against transplant recipients (27.5%).

In India, COVID-19 vaccination coverage has exceeded 173 million people.17 According to the results of our survey, (1) CoviShield (ChAdOx1 nCoV-19) was the most common vaccine administered to organ transplant patients, (2) most transplant recipients and donors (>50%) received both doses of the standard vaccine regimen, and (3) less than 25% of transplant patients received only a single dose of the vaccine. According to the guidelines of the American Society of Transplantation Infectious Diseases Community of Practice, vaccinations should be completed at least 2 weeks before transplant and at least 1 month after transplant.18 Currently, according to our survey results, 48.9% of treating specialists in India wait for 2 weeks after full vaccination before scheduling a patient for transplant, with 59.3% selecting the optimal time to vaccinate patients after transplant of >3 months.

To improve COVID-19 vaccine effectiveness in transplant recipients, immunosuppression can be modulated or vaccine immunogenicity can be enhanced, as demonstrated in transplant patients infected with COVID-19 who developed more anti-spike protein antibodies compared with vaccinated patients.19 In a recent study, Schrezenmeier and colleagues documented that removing antimetabolite from maintenance immunosuppressive regimen would augment immunological response during booster vaccination in SOTR patients.20 According to our current survey, over 80% of respondents reported no reduction in immunosuppression and no indication of graft dysfunction after the vaccination. The degree of reactogenicity to vaccines observed in the original studies with immunocompetent volunteers was similar to that observed in SOTR patients who had received immunization with mRNA-based vaccine. Serious reactions were uncommon.21 Similarly, most centers in India that administered vector-based vaccines (CoviShield) and inactivated virion vaccines (Covaxin) reported minor adverse events following immunization (66% of respondents) and no reactions (31.9% of respondents) in transplant patients, observations that support the safety attributes of these vaccines.

One relevant aspect is antibody testing in patients with a history of COVID-19 infection or immu-nization. The Transplant Infectious Disease section of The Transplantation Society currently does not recommend serologic antibody testing, because the extent of protective antibodies and the duration of protection, particularly in transplant populations, has not yet been established.22 In a study by Malinis and colleagues, it was also observed that, despite low antibody levels in SOTR patients, breakthrough infections were uncommon in vaccinated recipients.23 Serologic antibody testing before transplant is also not performed in 70% of centers in India as per our survey; however, a study by Prasad and colleagues reported that both Covaxin and CoviShield vaccines resulted in increased seroconversion.13

Vaccinated organ transplant recipients can contract breakthrough infections, as reported at many centers around the world.24 Aslam and colleagues investigated breakthrough infections in their study to assess the therapeutic effectiveness of COVID-19 vaccination in SOTR patients; similarly, we inquired about breakthrough infection in transplant patients in our survey.25 According to our survey results, at several centers in India, among those patients who were fully vaccinated (89% of respondents), less than 25% contracted moderate to severe COVID-19, whereas those who were not vaccinated reported a substantially high number of moderate to severe cases (38% of respondents), and several other centers reported lower incidence of disease (51% of respondents), all of which suggest that vaccination does protect against moderate to severe illnesses. A third dose of the SARS-CoV-2 mRNA-based vaccine appears to improve immuno-genicity in the SOTR population and appears to be safe.26,27 The British Transplantation Society also recommends a booster dose.28 In India, most centers recommend the administration of a third dose (89.4% of respondents) (Table 2 and Table 3).

Limitations
This was an online survey; therefore, the centers might not have responded transparently to the actual practice of vaccine in their respective centers and we may not have reached all communities of health care professionals. This survey was conducted during the third wave of COVID-19 in India, in which the Omicron variant was found in most of the cases. The lethality of this wave of COVID-19 is lower than previous waves, which has enhanced the trend away from tighter policies for vaccination.

Conclusions

We reported on how COVID-19 vaccine practices and coverage are evolving in India in this cross-sectional survey. Among the centers we surveyed, there were no substantial safety concerns regarding the present COVID-19 vaccination protocols. Ongoing inquiries should focused on improvements in efficacy and enhanced uptake of booster doses of vaccine.


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Volume : 20
Issue : 9
Pages : 805 - 810
DOI : 10.6002/ect.2022.0090


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From the 1Department of Nephrology and the 2Department of Gynecology, Institute of Kidney Disease and Research Center, Institute of Transplantation Sciences, Ahmedabad; and the 3Department of Medicine, B. J. Medical College, Ahmedabad, Gujarat, India
Acknowledgements: We thank Prof. Mehmet Haberal, Founder, Baskent University, for his kind support in editing and guidance. The authors have not received any funding or grants in support of the presented research or for the preparation of this work and have no declarations of potential conflicts of interest.
Corresponding author: Vivek B. Kute, Department of Nephrology, Institute of kidney disease and research center, IKDRC-ITS, Ahmedabad, Gujarat, India
Phone: +91 90 99927543
E-mail: drvivekkute@rediffmail.com