Novel Research Approach

Besides stimulating research that has provided information that can guide management decisions, the pandemic spurred innovation in how research itself is conducted. For example, transplant surgeon Dorry L. Segev, MD, PhD, professor of surgery and epidemiology at Johns Hopkins University, described to ATC attendees how he and colleagues conducted large-scale COVID-19 vaccine studies with SOT recipients while keeping participants safe.5

“We launched this study during what was the third wave of the pandemic in the United States,” he said. “It was dangerous for transplant patients to leave the house, let alone go to a health care center, enroll in a study, do exams, do lab work, and things like that.”

The mRNA vaccines became available for use in the United States in December 2020. Knowing that SOT recipients would be scattered across the country, his team used social media to openly enroll any transplant recipient who wanted to participate and who had access to the vaccine starting in December. “By March, we were already able to quantify responses to the vaccine,” Dr Segev related.


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Thousands of patients participated in the study “and we’ve never met any of them in person,” Dr Segev said. “Everything has been done online, over the phone, remotely.”

One of the novel approaches used in conducting the study was to send patients automated blood collection devices they could attach to their upper arm and painlessly draw about 200 microliters of blood. The team made an instructional video to educate patients how to use the devices. Patients would then use a return mailer to send the devices containing the sample back to Johns Hopkins.

Dr Segev and colleagues originally published findings from these studies in research letters in JAMA, one on March 15 and another on May 5. These reports described the effects of the first dose and second dose, respectively, of the 2 FDA approved mRNA vaccines (Moderna and Pfizer-BioNTech) in SOT recipients without a prior COVID-19 diagnosis. The vaccines are designed to stimulate an immune response to the spike protein of SARS-CoV-2, the novel coronavirus that causes COVID-19. At the congress, Dr Segev reported updated findings from larger numbers of patients.

The March 15 research letter discussed findings from 436 transplant patients, of whom 76 (17%) had detectable antibodies at a median of 20 days after receiving the first vaccine dose.6 The updated findings, based on 1112 patients, showed that 208 (19%) developed antibodies at a median of 21 days after the first dose.

The May 5 report described results from 658 patients, of whom 357 (54%) had detectable antibodies at a median of 29 days after the second dose. Updated findings from 873 patients showed that antibodies developed in 495 (57%) at a median of 30 days after the second dose.7

Based on the latest findings, Dr Segev concluded that the mRNA vaccines are safe in SOT recipients, but they elicit poor anti-spike protein antibody responses. SOT recipients, he said, may be at higher risk for COVID-19 despite vaccination, but he cautioned that the studies only looked at antibody response, which at best is a surrogate measure of protection against SARS-CoV-2 and may not accurately reflect patients’ level of protection.

The Pandemic’s Lessons

The Johns Hopkins COVID-19 vaccine studies, which were designed in response to the exigencies presented by the pandemic, have shown what can be achieved by streamlining large-scale studies, Dr Avery said. Investigators were able to get answers more quickly by enrolling patients online, providing ways for patients to send in blood samples by mail, and communicating remotely. This is important because “the whole thing with pandemic science is the faster we get answers, the better we can implement interventions for these patients,” she said.

Transplant recipients typically are excluded from initial randomized trials of new treatments, and the pandemic underscored the need to find out quickly which therapies are effective in this population, she said.

Physicians learned a lot about managing immunosuppression in SOT recipients hospitalized with COVID-19, such as the need to withhold mycophenolate to allow the immune system to control the virus, Dr Avery noted. “However, we’ve also learned that you need to have some immunosuppression on board because you still want to mitigate the inflammatory phase [of COVID-19].”

Another consequence of the pandemic was that transplant center physicians and nurses became more adept at managing larger numbers of transplant recipients as outpatients to avoid exposing them to possible infection during in-person visits, she said. They have gained proficiency in the use of telehealth encounters and remote monitoring, she said.

“We’ve learned a lot from this pandemic,” Dr Avery said. “My hope is that on a societal level we are better prepared in terms of hospital resources, ability to ramp up production of drugs and vaccines rapidly, and things of that nature.”

 References

2. Fernandez A, Anjan S, Chandorkar A, et al. Clinical outcomes of solid organ transplant recipients treated with remdesivir and convalescent plasma for Covid-19 at the largest transplant center in the United States. Presented at: ATC 2021 held June 4-9, 2021. Abstract 21.

3. Riella LV, Mothi SS, Akalin E, Cravedi P.COVID-19 and kidney transplantation: Results from the TANGO International Transplant Consortium. Presented at: Kidney Week 2020 Reimagined virtual conference, October 19 to 25. PO0765.

4. Agarwal G, Vinson A, Dai R, et al. COVID-19 in solid organ transplantation: results of the National COVID Cohort Collaborative (N3C). Presented at: ATC 2021 held June 4-9, 2021. Abstract 126.

5. Segev D. A US-wide study of COVID vaccine safety, immune response, and durability in 3000 transplant patients. Video presentation at the 2021 American Transplant Congress on June 6, 2021.

6. Boyarsky BJ, Werbel WA, Avery RK, et al. Immunogenicity of a single dose of SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients. JAMA. 2021;325:184-1786. Published online March 15, 2021. doi:10.1001/jama.2021.4385

7. Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325:2204-2206. Published online May 5, 2021. doi:10.1001/jama.2021.7489

This article originally appeared on Renal and Urology News