Solid organ transplant recipients is at an increased risk for COVID-19 because they are immunosuppressed and have frequent contact with the health care system.
Risk of transmission
I. Potential for donor-derived infection
· To date, one episode of donor-derived infection involving a lung transplant recipient has been reported.
· Blood-borne transmission has not been reported.
II. Post transplantation risk
· Chronic immuno-suppression may lower the infectious dose needed to cause COVID- 19 and impair adequate immune control once infection is established.
Pre transplantation screening
· Donors with known or suspected active COVID-19 based on symptoms or chest imaging should generally be declined or deferred.
· Donors with known or suspected COVID-19 within the past 21 days should generally be declined or deferred.
Studies have shown that many organ recipients don’t produce corona virus-fighting antibodies even after two doses of the highly effective messenger RNA (mRNA) vaccines— an indication their bodies are unable to mount a strong defense against SARS-CoV-2.Severe cases of corona virus disease 2019 (Covid-19) have also been reported in transplant recipients who had received two doses of vaccine. People who receive solid organ transplants (such as hearts, lungs and kidneys) often must take drugs to suppress their immune systems and prevent rejection.
Such regimens may interfere with a transplant recipient’s ability to make antibodies to foreign substances, including the protective ones produced in response to vaccines. This may mean that despite vaccination, transplant recipient may still get COVID-19 and it might progress to severe disease.
Three studies found that the antibody response to a two-dose mRNA vaccine is substantially lower in solid organ transplant recipients when compared with the general population. In a study involving 658 transplant recipients, just 54% of patients given two doses of an mRNA vaccine developed antibodies to protect them against the pandemic corona virus.
Dorry Segev, a transplant surgeon with Johns Hopkins University and colleagues obtained SARS-CoV-2 infection and testing data on more than 18,000 fully vaccinated recipients of large organs like kidneys or lungs at 17 transplant centers across the United States. They found that 151 of these patients caught the virus. Of those that became infected, more than half were hospitalized with COVID-19 symptoms and nearly one in 10 died. The rate of infection in the study was low, just 0.83%. But it’s still 82 times higher than in the general vaccinated public and the rate of serious illness was 485 times higher.
ANOTHER CASE STUDY
The new study evaluated immunogenic response following the second dose of either of the two messenger RNA (mRNA) vaccines (made by Moderna and Pfizer-BioNTech) for 658 transplant recipients, none of whom had a prior diagnosis of COVID-19. The participants completed their two-dose regimen between Dec. 16, 2020, and March 13, 2021.
The researchers found that only 98 of the 658 study participants (15%) had detectable antibodies to SARS-CoV-2 at 21 days after the first vaccine dose. At 29 days following the second dose, the number of participants with detectable antibodies rose to 357 out of 658 (54%). Among the participants, the most likely to develop an antibody response were younger, did not take immunosuppressive regimens including anti-metabolite drugs.
Given these observations, transplant recipients should not assume that two vaccine doses guarantee sufficient immunity against SARS-CoV-2 any more than it did after just one dose. A potential solution is a third shot of vaccine. Segev, and other researchers are studying whether a booster dose could give transplant recipients better COVID-19 protection. These reports prompted the French National Authority for Health to recommend the use of a third dose in immunosuppressed patients.
Antibody Response After a Third Dose of the mRNA Vaccine in Kidney Transplant Recipients
The antibody response of kidney transplant recipients who did not respond to 2 doses and received a third dose (100 μg) of the mRNA-1273 vaccine (Moderna) was measured in this study. The median age of all the participants was 57.6 years.One month after the second dose, 159 kidney transplant recipients had IgG levels less than 50 AU/mL.
The third dose was injected of 51 days after the second dose. The antibody response was measured 28 days after the third vaccine injection, and 78 patients (49%) had antibody levels greater than 50 AU/mL.
Patients
who had a weak response after the second dose were more likely to develop an
antibody response after the third
dose compared with those without an antibody response. None of the patients developed COVID-19 after their
third dose. No severe adverse events were observed after the third dose. Limitations of this study include that
detailed B- and T-cell studies were not performed.
Another case series reported by Dorry Segev,
MD, PhD, of Johns Hopkins
University cited that the
third dose was likewise safe and got all of the initially low-positive patients
to high antibody titers and a third
of the initially-negative patients to at least low-positive titers. A major
aspect that is missing from the
current evidence is risk to the transplanted organ in the context of the immune activation from the third dose. The
measures to be taken incase of persistently low or negative antibody levels even after a third vaccine
dose isn't clear as of now.
Third doses aren’t yet an officially recommended course of action for immune-compromised people in most countries, but as more data come out, policies are shifting. The French government endorsed third doses for transplant patients in April. The United Kingdom’s National Health Service also plans to begin to offer a third vaccine dose to immuno- compromised individuals beginning at the end of September, this year.
Conclusion
A three-dose COVID-19 vaccine regimen may provide protection for some immune- compromised patients who have not had adequate immunological response after two doses. The risks of a three-dose regimen – including organ rejection and autoimmune disease exacerbation – have not been adequately studied. Organ transplant recipients should continue to adhere to protective measures (such as masking and social distancing) despite vaccination.
Gautham Gopakumar - II Pharm D
