Failure to Protect the Most Vulnerable: COVID-19 Vaccine Safety and Efficacy Issues Loom Large for Transplant and Immunosuppressed Communities
Introduction
The three COVID-19 vaccines authorized by the United States — Pfizer, Moderna, and, most recently, Johnson & Johnson — have been proven safe and effective in the general population. However, it has consistently been quite challenging to locate vaccine safety and efficacy information for those within the transplant and immunocompromised communities, who are more vulnerable to the pandemic due to multiple risk factors. The lack of representation in clinical trials led to an information vacuum in how COVID-19 vaccine doses behave in transplant recipients and people on immunosuppressant medications. The good news is that a number of research teams around the world have launched studies to provide crucial insights into this question. In this update, we want to share with you three ongoing studies aiming to examine the effects of COVID-19 vaccines specifically in transplant recipients and immunocompromised individuals. They are the COVaRiPAD study and National Vaccine Research Study for Transplant Recipients in the United States and the OCTAVE study in the United Kingdom.
As transplant recipients and immunosuppressed patients, why were we not represented in clinical trials for COVID-19 vaccines?
As briefly discussed in our previous update, initial trials of any vaccine are usually conducted in healthy, immunocompetent adults.1 Thus, the initial participants represent the population that is at low risk of infection against which the vaccine protects. The World Health Organization (WHO) advises that after protective effects are established in healthy populations, later phases of the vaccine trial should recruit participants vulnerable to the disease. Since COVID-19 vaccines are relatively new, their initial studies did not include persons on immunosuppressive treatments or those with weakened immune systems, such as transplant recipients. So far, there is very limited evidence to assess vaccine safety and efficacy in transplant recipients and immunosuppressed patients.
What are these studies looking at?
At Washington University School of Medicine (WUSM), researchers have launched a study on COVID-19 Vaccine Responses in Patients with Autoimmune Disease, or the COVaRiPAD study. The clinical trial is intended to evaluate the safety and effectiveness of COVID-19 vaccines in people taking immunosuppressive medications. Such drugs often are prescribed to treat autoimmune diseases, such as arthritis, Crohn’s disease, and psoriasis. Immunosuppressants are also essential to transplant recipients because they prevent and treat rejection. However, these drugs may blunt the body’s antibody response to vaccines2. To get a better understanding of how well COVID-19 vaccines work in immunosuppressed patients, the research team evaluates the quantity and quality of the antibody response normally generated from vaccination.
Johns Hopkins University School of Medicine, on the other hand, has launched the National Vaccine Research Study for Transplant Recipients. This observational study aims to examine levels of COVID-19 antibodies in organ transplant recipients who have received the COVID-19 vaccines. The researchers have also pointed out that transplant recipients may be less likely to mount a durable immune response due to the immunosuppressant medications. Moreover, since solid organ transplant recipients are often prevented from participating in vaccine trials, they hope to bridge this knowledge gap and learn more about how COVID-19 vaccines behave in transplant recipients.
In addition to efforts in the United States, researchers in the United Kingdom have recently launched a new study, called the OCTAVE trial, aiming to better understand the immune response to COVID-19 vaccinations in patients with certain immunosuppressed conditions including cancer. The OCTAVE trial is a collaborative research project between the Universities of Birmingham, Glasgow, Oxford, Liverpool, Imperial College London, and Leeds Teaching Hospitals NHS Trust. Scientists will build on years of expertise in investigating the immune system in the context of chronic conditions, to better determine the effectiveness of COVID-19 vaccines in these vulnerable patient groups.
What types of patients are being included in current studies?
In the Johns Hopkins study, researchers are recruiting adult transplant recipients as study participants through online registration. Participants will be asked to complete a short survey regarding the COVID-19 as well as at-home, do-it-yourself blood collection before receiving a vaccination as well as at sequential time points after vaccination. With the blood samples, researchers will be able to evaluate levels of antibodies, proteins that are part of the immune system to eliminate foreign objects such as viruses. The quality and quantity of antibody response can effectively reflect the level of immunity against the COVID-19.
The COVaRiPAD and the OCTAVE studies follow similar rationales. In the COVaRiPAD study, the research team will recruit participants who are taking immunosuppressive drugs and determine the quantity and quality of the antibody response normally generated from COVID-19 vaccines. The OCTAVE study, on the other hand, aims to investigate the effectiveness of COVID-19 vaccines authorized in the United Kingdom in 2021. The study will be conducted in up to 5,000 participants with immunosuppressed conditions who are vaccinated in the national vaccination program. With the aid of a variety of state-of-the-art immune tests, researchers will determine patients’ COVID-19 immune response by testing blood samples taken before and/or after vaccination. The results from the study group will be compared against control groups of healthy individuals who also received COVID-19 vaccines.
What are the initial results?
Initial reports from the Johns Hopkins study demonstrated that Moderna and Pfizer messenger RNA (mRNA) vaccines are safe for organ transplant patients. The research team documented reactions of nearly 200 solid organ transplant recipients, 36 of whom had received liver transplants, after their first shots. They found that the occurrences of systemic adverse reactions, such as fever and chills, were very low and similar to those seen in the general population. They also found, importantly, that organ rejection did not occur in any of the participants. The initial study results suggest that Moderna and Pfizer can be safely administered in immunocompromised populations.
The latest report, published on March 15, shows that among 436 participants who had received organ transplants in recent years and were getting the Pfizer or Moderna vaccines, only 17% had developed antibodies against the COVID-19 a few weeks after the first dose. This finding indicates poor antibody responses in transplant recipients after the first dose of mRNA vaccines, suggesting that they remain at higher early risk for COVID-19 despite vaccination3. Dr. Dorry Segev, a transplant surgeon at the Johns Hopkins Hospital and a co-author of the study, commented that although data is not sufficient at this point, transplant recipients are expected to acquire better protection after the second dose. He also called on the Centers for Disease Control (CDC) to update their new guidelines with a more nuanced message about post-vaccination precautions for transplant recipients, stressing that transplant patients should not assume that they are safe after being vaccinated and may need post-vaccination blood tests to be sure, to which the CDC did not offer an immediate comment.4
Researchers leading the same study at Johns Hopkins have discovered in a separate study that organ transplant recipients can develop immunity after contracting COVID-19 despite immunosuppression. They followed 18 recipients of kidney, liver, lung, and composite tissue allograft transplants who were taking immunosuppressive medications and who developed COVID-19 post-transplant. Through antibody testing, researchers observed that most participants had neutralizing immunity, the ability to prevent reinfection if exposed to the virus again. With the new understanding of the post-transplant immune response to the COVID-19, practitioners will be better able to treat transplant recipients who develop the disease and refine vaccine protocols to meet their special needs.
Further, another group of scientists at the Johns Hopkins Bloomberg School of Public Health found that immunosuppressive drugs do not contribute to the severity of COVID-19 in a study conducted at the Johns Hopkins Medicine in Baltimore, MD, and Washington, D.C., between March 4 and Aug. 29, 2020. They found that demonstrated that compared to immunocompetent patients, COVID-19 patients with immunosuppressed conditions prior to their COVID-19 hospitalization did not show worse COVID-19 outcomes, as measured by factors like the longer length of hospitalization, death in hospital, or the use of a ventilator.
So far, the COVaRiPAD and OCTAVE studies have not published their initial results.
Why are these studies important for me?
These timely studies will play a crucial role in filling the knowledge gap in the COVID-19 vaccination for our transplant and immunocompromised communities. While scientists agree that vaccines are most likely safe for those individuals, we are looking to understand how effective vaccines are in immunosuppressed conditions. Hopefully, with the new study results being updated on a regular basis, the physician and patient communities are able to make more informed decisions about the ideal timing of vaccination.
Source: Transplant recipients. (2021, March 12). Retrieved March 17, 2021, from https://transplantvaccine.org/covid-19-vaccine-in-transplant-recipients-transplant-recipients/
How can I sign up to participate in the studies?
The Johns Hopkins study is continuing to welcome new participants.5 To participate, you need to be a transplant recipient over 18 years of age who has received or will be receiving a COVID-19 vaccine.6 To sign up, please fill out the online registration form on their website to determine your eligibility. After the initial screening, you will receive further instructions on how to complete blood collection at home or vouchers for a draw at LabCorp.. As a participant, you will:
- Collect samples of your blood prior to receiving the first vaccine dose, in-between the two doses for Moderna and Pfizer vaccines, and then 1 month, 3 months, 6 months, and 1 year from the last vaccine dose, if you have not been vaccinated;
- Collect your blood samples according to individualized instructions, if you are already vaccinated;
- Not be required for in-person at any point of the study;
- Not be provided vaccines or guidance as to whether or not you should be vaccinated, meaning that you will need to locate a vaccine appointment yourself.
In the COVaRiPAD study, researchers will enroll up to 500 adults ages 18 and older in the St. Louis region. They are recruiting health-care workers at the School of Medicine and patients seen in Washington University outpatient clinics. Eligible patients who have pre-registered for the COVID-19 vaccine will be contacted to assess their interest in being recruited into the study. For information about participating in the trial, please email covaripad@wustl.edu or contact either Alia El-Qunni at 314-249-1151 or Lily McMorrow at 314-280-3894.
Researchers leading the OCTAVE study have begun recruiting patients at sites across the United Kingdom who receive COVID-19 vaccines as part of the national vaccination program. Unfortunately, there is currently no information available about signing up for the study as a non-UK resident.
Conclusion
Although many looming questions remain unanswered, scientists have revealed some of the information that is key to properly and effectively vaccinating organ transplant and immunocompromised communities based on current research. Specifically, we would like to highlight four issues that are of particular concern:
- Despite their known vulnerability to COVID-19, as suggested by multiple authorities including the CDC, there is still a lack of prioritization of transplant recipients and persons with immunosuppressed conditions in COVID-19 vaccine research and allocation.
- It is currently not clear as to how many mRNA vaccine shots are needed to optimize protection for transplant recipients, and it is possible that more than two shots are necessary due to their poor antibody responses after the first dose of mRNA vaccines, as shown in the Johns Hopkins study7.
- People with weakened immune systems are known to be more likely to spread COVID-19 to others and to incubate SARS-CoV-2 variants that can potentially make the disease more dangerous and vaccines less effective.8 9 10 11
- Recent supply chain disruptions and the push to reopen the economy have exacerbated vaccine shortage and inequity, which come at the cost of the wellbeing of immunocompromised people who are already struggling with other life-threatening conditions.
In the end, it is time to recognize the urgent need to direct funding, research, and life-saving vaccine resources to the most vulnerable in our society. The failure to prioritize patients within these communities is a public health and moral crisis.
Other useful information
Lastly, we would like to share some resources that might be helpful to you.
- The Global Healthy Living Foundation has launched the Free COVID-19 Support Program for Chronic Disease Patients and Their Families. This patient support program aims to provide up-to-date information about COVID-19 for patients with chronic conditions and their family members. As always, we hope that you are staying safe and healthy.
- Please continue to follow updates about your eligibility for the vaccine in your state/country. A guide for checking vaccine eligibility and sign-up can be found on the The Wall Street Journal COVID-19 Vaccine State-by-State Guide.
Sources
(1) Singh, K., & Mehta, S. (2016). The clinical development process for a novel preventive vaccine: An overview. Retrieved March 17, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944327/
(2) COVID-19 FAQs: Medications, Treatments and Vaccines. (2021, March 2). Arthritis Foundation. https://www.arthritis.org/health-wellness/about-arthritis/related-conditions/other-diseases/covid-19-faqs-medication-treatment-and-vaccines
(3) Boyarsky, B. J., Werbel, W. A., Avery, R. K., Tobian, A. A., Massie, A. B., Segev, D. L., & Garonzik-Wang, J. M. (2021). Immunogenicity of a Single Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients. JAMA. https://doi.org/10.1001/jama.2021.4385
(4) How Well Do COVID Vaccines Protect after Organ Transplant? (2021, March 15). Independent Digital News and Media. www.independent.co.uk/news/how-well-do-covid-vaccines-protect-after-organ-transplant-vaccines-covid-johns-hopkins-university-pfizer-moderna-b1817611.html.
(5) Segev, D. (2021, March 15). COVID Vax in the Immunosuppressed: Reason for Concern. Retrieved March 16, 2021, from https://www.medpagetoday.com/infectiousdisease/vaccines/91631
(6) Transplant Recipients. (2021, March 12). COVID-19 Vaccine in Transplant Recipients. transplantvaccine.org/covid-19-vaccine-in-transplant-recipients-transplant-recipients/.
(7) Boyarsky, B. J., Werbel, W. A., Avery, R. K., Tobian, A. A., Massie, A. B., Segev, D. L., & Garonzik-Wang, J. M. (2021). Immunogenicity of a Single Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients. JAMA. https://doi.org/10.1001/jama.2021.4385
(8) Centers for Disease Control and Prevention. If You Are Immunocompromised, Protect Yourself From COVID-19. Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/immunocompromised.html.
(9) Weintraub, K. (2021, March 15). People with immune issues – at 'high risk' for COVID-19 – remain hesitant about vaccination. Here's what experts say. Retrieved March 16, 2021, from https://www.usatoday.com/story/news/health/2021/03/15/covid-19-vaccines-immune-issues-cancer-organ-transplants-hiv/4639884001/
(10) Mandavilli, A. (2021, March 15). Virus Variants Likely Evolved Inside People With Weak Immune Systems. Retrieved March 16, 2021, from https://www.nytimes.com/2021/03/15/health/coronavirus-variants-immunocompromised-patients.html
(11) Antibodies from vaccines less effective against SARS-CoV-2 variants. (2021, March 15). Retrieved March 17, 2021, from https://www.drugtargetreview.com/news/86189/antibodies-from-covid-19-vaccines-less-effective-against-sars-cov-2-variants/
