The Paper's reporter He Liping intern Lu Jinyang
Vaccination has become an important means of combating COVID-19. There are already a variety of vaccines available worldwide, and the world health organization certified vaccine protection rate generally exceeds 50%. For organ transplanters, the COVID-19 vaccine is less effective. As research progresses, researchers have also proposed potential responses such as booster vaccine injections.
Recently, a research team such as Johns Hopkins University in the United States published a study in the journal Transplantation: compared with the general population, organ transplanters have low resistance to new coronavirus infection after vaccination. The researchers called for organ transplanters to continue to practice preventive measures such as wearing masks and social distancing.
In general, vaccines fight the virus by triggering specific immune memories. Specific immunity consists of cellular immunity and humoral immunity. Vaccine-induced protective humoral immunity acts through a collaborative interaction between CD4+ T cell subsets and activated B cells within a growth center (GC), in the process also producing a memory cd4+ T cell population and B cell. At the same time, an effective vaccine can also trigger the expansion and differentiation of CD8+ T cells, which can quickly develop into lymphocytes, which can kill cells infected by the virus. Multiple doses of vaccines can enhance the primary immune response triggered by initial vaccination by providing supplementary innate immune activation signals that promote further expansion of T cell and B cell clones and promote antibody production.
However, many of these immune responses are weakened in organ transplant recipients. As previously reported in Science, transplant recipients require a lifelong course of immunosuppression, usually consisting of a combination of calciuretic acid inhibitors (such as tacrolimus), steroids, and/or antimetabolites (such as mycophenolic acid or mycophenolates, MMF). These courses non-specifically inhibit T and B cells to prevent rejection of transplanted organs. However, while preventing rejection, this also increases the risk of infection in patients. A previous study of 658 organ transplant recipients showed that only 54 percent of patients developed antibodies after two doses of the mRNA vaccine.
In the study, the researchers estimated the rate of breakthrough infection after organ transplanters received the mRNA covid-19 vaccine and compared it to the infection rate in the general population. According to the Centers for Disease Control and Prevention (CDC), breakthrough infections are when a person who has tested positive for COVID-19 more than 14 days after completing vaccinations (Johnson & Johnson, Pfizer, and Modena).
The study data showed that the organ transplanters in the study had an 82-fold higher risk of breakthrough infection and a 485-fold higher risk of developing breakthrough infection with hospitalization and death compared to the general population. Of the 18,215 fully vaccinated organ transplanters in 17 organ transplant centers, 151 had breakthrough infections (0.83%), of which 87 patients were hospitalized (0.48%) and 14 died (0.077%). The mortality rate was 9.3% among organ transplants with breakthrough infection, and the rate of breakthrough infection at the center-level ranged from 0.23% to 2.52%. In contrast, cdc reported 10,262 (0.0102%) of the 101 million fully vaccinated adults in the United States as of April 30, 2021, of which 995 were hospitalized (0.00099%) and 160 died (0.00016%).
Data from the study were collected in a pooled fashion, and other researchers were contacted through the PudMed and Scopus databases to identify 17 transplant centers that could provide information about studies related to organ transplant recipients. However, the researchers also point out that it is challenging to fully count data such as organ transplant recipients who have been vaccinated. In most cases, these numbers should be considered estimates. Even so, even with twice the current statistics of vaccinated organ transplant recipients, the risk of breakthrough infection would still be 41 times higher than in the general population.
In addition, many organ transplant centers that provide data for researchers also said that the number of coronavirus infections among organ transplant recipients treated at their centers is not a complete number. Patients may be present at other hospitals, by doctors from other departments in the same hospital, or if they test positive in the community without notifying the transplant center. As a result, the researchers believe that the current number of breakthrough infections among organ transplant recipients is likely to be underestimated.
Given the high rate of breakthrough infections in this population, the researchers call for organ transplant recipients to continue to implement recommended safety precautions, such as wearing masks and social distancing, in addition to vaccinates as much as possible for transplant recipients' families, and other potential strategies to protect this group.
It's worth noting that although studies have shown that organ transplants have a much higher risk of breakthrough infection compared to the average person, vaccination does seem to provide protection. Most vaccinated organ transplanters produced antibodies, and the breakthrough infection rate in the study was lower than the 5% rate of new infections among unvaccinated organ transplanters. In addition, the mortality rate for breakthrough infections in the study was lower than the 20.5 percent mortality rate for new infections in unvaccinated organ transplanters, which are usually reported. Therefore, researchers believe that vaccination is very important for organ transplanters.
How can vaccine protection be more effective for organ transplanters? Recent studies of COVID-19 vaccination strategies for organ transplanters have also supported the potential efficacy of third doses and booster vaccines. A June study in the New England Journal of Medicine, including 101 participants, showed that injecting a third dose of Pfizer into organ transplant recipients significantly increased the immunogenicity of the vaccine. A July study in the Journal of the American Medical Association found that a third dose of the mRNA-1273 vaccine induced a serological response in 49 percent of kidney transplant recipients. It is worth noting that although the third dose of the vaccine improves the level of vaccine protection in organ transplant populations, it still has limitations. In addition, there are still a subset of organ transplant recipients who are unable to produce a protective response even in the form of a boosted dose or frequency.
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