The safety of the SARS-CoV-2 mRNA vaccines in solid organ transplant recipients (SOTRs) is unknown because immunosuppressed individuals were generally excluded from phase 1-3 studies. To better understand perivaccination reactogenicity in immunosuppressed individuals, we studied SOTRs who underwent early vaccination.
SOTRs in the United States were recruited to participate in this study by invitation through their transplant centers or social media. Participants completed a detailed online questionnaire 1 week following their first dose. This study was approved by the Institutional Review Board at the Johns Hopkins School of Medicine.
We studied 187 SOTRs who received their first SARS-CoV-2 vaccination dose between December 16, 2020 and January 16, 2021, of whom 64% identified as front-line healthcare workers. Median (IQR) age was 48 (37-59) years; 69% were female, and 87% were White, and 6% Hispanic/Latino. Median (IQR) years since transplantation was 6 (3-13); 52% were kidney, 19% liver, 14% heart, 9% lung, 3% kidney/pancreas, and 3% other multiorgan recipients. Maintenance immunosuppression included tacrolimus (87%), mycophenolate (69%) or azathioprine (11%), and steroids (55%).
Participants received the Pfizer/BioNTech (50%) or Moderna (50%) mRNA vaccines. There were no self-reported cases of PCR-confirmed SARS-CoV-2 diagnoses between vaccination and study participation, nor were there any reported cases of acute rejection, neurological diagnoses (Guillain-Barré syndrome, Bell's Palsy or neuropathy) or allergic reactions requiring epinephrine. Two participants reported development of a new infection (1 was acute-on-chronic pouchitis, the second was influenza A) requiring treatment. Local site reactions included mild pain (61%), mild redness (7%), and mild swelling (16%) (Table 1). Systemic reactions such as fever and chills were uncommon (4% and 9%), although more-than-baseline fatigue was reported by 38%, headache by 32%, and myalgias by 15%.
Table 1.
Local site and systemic adverse reactions in solid organ transplant recipients within the first week following the first dose of the SARS-CoV-2 vaccination.
| None | Mild1 | Moderate2 | Severe3 | |
|---|---|---|---|---|
| Local site reaction | ||||
| Pain, % | 10 | 61 | 27 | 2 |
| Redness, % | 92 | 7 | 1 | 0 |
| Swelling, % | 82 | 16 | 2 | 0 |
| Systemic adverse effect | ||||
| Fever, % | 96 | 2 | 1 | 1 |
| Chills, % | 91 | 7 | 1 | 1 |
| Fatigue4, % | 62 | 27 | 10 | 1 |
| Headache, % | 68 | 24 | 7 | 1 |
| Vomiting, % | 95 | 3 | 1 | 1 |
| Diarrhea, % | 92 | 6 | 1 | 1 |
| Myalgias, % | 85 | 11 | 3 | 1 |
Mild: does not interfere with activity.
Moderate: some interference with activity.
Severe: prevents daily activity.
More than baseline.
Similar to the randomized trials of these vaccines,1,2 adverse events were largely consistent with expected vaccine reactogenicity, with mostly mild local reactions such as injection-site pain; systemic reactions, such as fever, were uncommon.3 Furthermore, transplant rejection, which remains a theoretical concern triggered by vaccination, was not seen during early follow-up.4
Strengths of this study include a national sample and novel, early data to inform major concerns among SOTRs and their providers.5 Limitations include a relatively small sample size, lack of longer-term safety data and less granular ascertainment of side effects than the original trials. Further study will be needed to explore unexpected safety issues, and longer-term follow-up is vital to explore additional adverse effects. It is also important to note that this was a nonrandomized, early, observational study leveraging a convenience sample of SOTRs with access to the vaccine, and as such not designed to evaluate vaccine efficacy.
In this first group of SOTRs to be vaccinated against SARS-CoV-2 in the United States, we observed expected, typically mild, minimal perivaccine reactogenicity after the first dose, similar to reported rates in non-SOTRs. There were no reported episodes of acute rejection, SARS-CoV-2 diagnoses, neurological diagnoses or major allergic reactions. These early, reassuring safety data in SOTRs may ease anxiety among patients and providers and provide some evidence for targeted counseling to address critical concerns such as vaccine refusal and hesitancy.
Acknowledgments
This research was made possible with generous support of the Ben-Dov family. This work was supported by grant number F32DK124941 (Boyarsky), K01DK101677 (Massie), and K23DK115908 (Garonzik-Wang) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), K24AI144954 (Segev) from National Institute of Allergy and Infectious Diseases (NIAID), and by a grant from the Transplantation and Immunology Research Network of the American Society of Transplantation (Werbel). The analyses described here are the responsibility of the authors alone and do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. We also acknowledge the following individuals for their assistance with this study: Aaron A.R. Tobian MD PhD; Oliver B. Laeyendecker PhD; William A. Clarke PhD; Yukari C. Manabe MD, Christine M. Durand MD, Teresa Po-Yu Chiang MD MPH, Alexandra T. Strauss MD, Amber B. Kernodle MD MPH, Kayleigh M. Herrick-Reynolds, MD, Mackenzie A. Eagleson MD, Andrew M. Hallett MD, Victoria A. Bendersky, MD, Richard Wang BA, Jake A. Ruddy BS, Leyla R. Herbst BA, Michelle R. Krach MS.
ABBREVIATIONS
- SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
- SOTR
solid organ transplant recipient
- COVID-19
Coronavirus disease 2019
- PCR
polymerase chain reaction
Footnotes
DISCLOSURE
The authors of this manuscript have no financial disclosures or conflicts of interest to disclose as described by Transplantation.
References
- 1.Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603–2615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Walsh EE, Frenck RW Jr., Falsey AR, et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med. 2020;383(25):2439–2450. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Rubin EJ, Longo DL. SARS-CoV-2 vaccination - an ounce (actually, much less) of prevention. N Engl J Med. 2020;383(27):2677–2678. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Duchini A, Goss JA, Karpen S, et al. Vaccinations for adult solid-organ transplant recipients: current recommendations and protocols. Clin Microbiol Rev. 2003;16(3): 357–364. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Kates OS, Stohs EJ, Pergam SA, et al. The limits of refusal: an ethical review of solid organ transplantation and vaccine hesitancy [published online ahead of print December 28, 2020]. Am J Transplant. doi: 10.1111/ajt.16472. [DOI] [PMC free article] [PubMed] [Google Scholar]