COVID-19 Vaccine Antibody Response Rates in Kidney Transplant Patients Vary by Age Over 50 and Medication Use
Background
Organ transplant recipients must take immunosuppressants to prevent rejection, making them vulnerable to viral infections and at higher risk for severe complications than the general population. Since the early stages of the COVID-19 pandemic, the high risk of infection and mortality among kidney transplant recipients has been a long-standing challenge in nephrology.
While the risk of severe disease in the general population has plummeted with the distribution of mRNA vaccines, cases of seronegativity—where protective antibodies fail to develop even after the second dose—have continued among immunosuppressed groups. Previous studies were limited to reporting decreased antibody formation without clearly identifying which clinical factors drive vaccine non-responsiveness. There was an urgent need for data to quantitatively analyze the specific impact of patient age, medications, and antibody levels on infection rates.
Key Findings
Researchers at Hamad Medical Corporation in Qatar conducted a retrospective analysis of immune data from 372 adult patients who received two doses of the COVID-19 mRNA vaccine after kidney transplantation. They measured the receptor-binding domain (RBD) binding antibody titers of the SARS-CoV-2 spike protein in serum at least 14 days after the second dose. The patient group was categorized by previous infection history, seropositive/seronegative status, and high/low titer groups based on a 121 U/mL threshold.
Analysis revealed that the presence or absence of antibody formation determined the actual infection rate. The subsequent COVID-19 infection rate in the seronegative group reached 36%, compared to 26% in the seropositive group and 13% in the group with previous infection history (P=0.02). Even among seropositive patients, a clear disparity in protective efficacy was observed according to antibody titers. The infection rate in the low-titer group was 33%, whereas it was significantly lower at 20% in the high-titer group (P=0.02). This serves as evidence that higher vaccine-induced antibody titers are associated with sustained viral defense.
Multivariable logistic regression analysis also identified factors associated with differences in immune response. Older patients over 52 years old had a 1.94 times higher risk of vaccine non-responsiveness (seronegativity) compared to patients aged 52 or younger (adjusted Odds Ratio [aOR]=1.94; 95% Confidence Interval [CI]: 1.12-3.36; P=0.018). Regarding gender, male patients showed a 57% lower risk of non-responsiveness than female patients (aOR=0.43; 95% CI: 0.24-0.77; P=0.004).
Disparities based on the type of immunosuppressant were also prominent. Patients treated with azathioprine, a purine synthesis inhibitor, had a 74% lower risk of vaccine non-responsiveness compared to those taking other immunosuppressants (aOR=0.26; 95% CI: 0.07-0.91; P=0.035). The probability of achieving high antibody titers (≥ 121 U/mL) was significantly lower in patients over 51 years old compared to those aged 51 or younger, with an adjusted odds ratio of 0.43 (aOR=0.43; 95% CI: 0.24-0.75; P=0.003). In racial comparisons, the probability of high-titer antibody formation was higher in African (aOR=2.82; 95% CI: 1.11-7.16; P=0.03) and South Asian (aOR=2.27; 95% CI: 1.08-4.75; P=0.03) groups compared to those of Middle Eastern descent.
Implications and Outlook
This study demonstrates that applying a uniform two-dose regimen to kidney transplant recipients creates blind spots in immune response. It is interpreted as highlighting the reality that elderly patients aged 50 and older, and those taking specific immunosuppressants, may struggle to establish sufficient immune protection through standard vaccination alone.
These results support the need to transition infection prevention guidelines for transplant recipients toward a personalized system. For patients identified as high-risk for vaccine non-responsiveness, early additional booster doses or proactive follow-up based on antibody titers should be implemented. This necessitates an immunosuppressant prescription strategy that comprehensively considers both the prevention of transplant rejection and the formation of antibodies against infection.
As a single-institution retrospective analysis, the study has limitations, such as not addressing neutralizing capacity against variants or the persistence of T-cell responses. Future large-scale multicenter studies are required to clarify the detailed impact of dosage adjustments of specific drugs on immunogenicity.
Kidney transplant recipients are vulnerable to developing severe coronavirus disease 2019 (COVID-19) infection. Although mRNA vaccines have significantly improved outcomes, seropositivity rates remain variable in immunosuppressed patients. This study aimed to evaluate the antibody response to COVID-19 mRNA vaccines, identify factors affecting immunogenicity, and examine the association between antibody titers and subsequent SARS-CoV-2 infection and COVID-19-related hospitalization among kidney transplant recipients. We retrospectively studied 372 adult kidney transplant recipients who received two doses of COVID-19 mRNA vaccine after transplantation and had anti-SARS‑CoV‑2 spike protein receptor-binding domain antibodies measured ≥ 14 days after the second dose and prior to receiving a third dose. We categorized patients based on previous COVID-19 infection, post-vaccination antibody status (seropositive or seronegative), and antibody titers (low or high). Factors associated with poor vaccine response (seronegativity) and with high antibody titers (antibody titer ≥ 121 U/mL) were determined using multivariable regression models. The proportion of patients with subsequent COVID-19 infection was higher in the seronegative group than in the seropositive or previous infection groups (36% vs. 26% vs. 13%, respectively; P = 0.02). Multivariable regression analysis revealed higher odds of poor response to the mRNA vaccine among patients aged > 52 years compared with those aged ≤ 52 years (aOR = 1.94; 95% CI: 1.12-3.36; P = 0.018). Lower odds were observed among male patients (aOR = 0.43; 95% CI: 0.24-0.77; P = 0.004) and those taking azathioprine (aOR = 0.26; 95% CI: 0.07-0.91; P = 0.035). The proportion of patients with subsequent COVID-19 was also higher in the low-antibody group than in the high-antibody group (33% vs. 20%; P = 0.02). Multivariable logistic regression analysis showed lower odds of high SARS-CoV-2 antibody titers among patients aged > 51 years compared w
The results of this study can serve as specific indicators for individualizing vaccination schedules in outpatient clinical settings for kidney transplant recipients. For transplant recipients aged 50 years or older or patients undergoing high-risk immunosuppressive therapy, it is advisable to introduce a protocol for routine RBD antibody testing two weeks after the standard two-dose regimen. This enables strategic resource allocation, such as assigning immediate additional booster shots or prioritizing monoclonal antibody prophylaxis for patients identified as having titers below 121 U/mL or being seronegative.
The pharmaceutical industry and transplant medicine community are clearly presented with the target patient group for developing next-generation vaccine formulations and optimizing adjuvants specifically for immunocompromised individuals. In immunosuppressant administration protocols, it provides scientific evidence to consider switching to agents that cause less reduction in antibody response or making temporary dosage adjustments, provided the patient's condition permits during periods of infection outbreaks.