Humoral Response to the Third Dose of Sars-Cov-2 Vaccine in Kidney Transplant Recipients.

BACKGROUND: Most solid organ transplant recipients did not develop an appreciable serologic response after 2 doses of the mRNA SARS-CoV-2 vaccine. METHODS: We analyzed the humoral response after a third dose of the BNT162b2 vaccine in 130 kidney transplant recipients, compared to 48 health care workers, and associated factors, including prevaccine cellular immune response, by evaluating intracellular cytokine production after stimulation of donor's peripheral blood mononuclear cells. RESULTS: After 2 doses, most of the controls (47 out of 48, 98%) and only 40% of kidney recipients (52 of 130) kidney recipients were seropositive (P < .001). Most seronegative recipients developed a serologic response after the booster (47 out 78, 60%), thus bringing the total number of seropositive recipients to 99 out of 130 (76%). After the third dose, there was a significant increase in antibodies titers in both groups. Decreased humoral response was significantly associated with an older age, lower lymphocyte count, and a lower level of antibodies before booster administration. CD4+TNFα+ and CD4+INFγ+ were correlated with mean increase in antibody titers. CONCLUSIONS: A third dose of the BNT162b2 mRNA vaccine in kidney recipients is safe and effectively results in increased IgG anti-S levels, including in individuals who were seronegative after 2 doses. Long-term studies of the length of the immune response and protection are required.

The effect of a third-dose BNT162b2 vaccine on anti-SARS-CoV-2 antibody levels in immunosuppressed patients.

OBJECTIVES: The recent surge in coronavirus disease 2019 cases led to the consideration of a booster vaccine in previously vaccinated immunosuppressed individuals. However, the immunogenic effect of a third-dose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in immunosuppressed patients is still unknown. METHODS: This was an observational cohort study of 279 previously vaccinated immunosuppressed patients followed at a single tertiary hospital in Israel. Patients were administered a third dose of the Pfizer-BioNTech mRNA vaccine (BNT162b2) between July 14 and July 21, 2021. Levels of IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 were measured 3 to 4 weeks after vaccination. RESULTS: Of the cohort of 279 patients, 124 (44.4%) had haematologic malignancies, 57 (20.4%) had rheumatologic diseases, and 98 (35.1%) were solid organ-transplant recipients. Anti-SARS-CoV-2 antibody levels increased in 74.9% of cases. Across the entire cohort, the median absolute antibody levels (expressed in AU/mL) increased from 7 (interquartile range (IQR), 0.1-69) to 243 (IQR, 2-4749) after the booster dose. The response significantly varied across subgroups: The transplant cohort showed the greatest increase in absolute antibody levels (from 52 (IQR, 7.25-184.5) to 1824 (IQR, 161-9686)), followed by the rheumatology (from 22 (IQR, 1-106) to 1291 (IQR, 6-6231)) and haemato-oncology (from 1 (IQR, 0.1-7) to 7.5 (IQR, 0.1-407.5)) cohorts. The χ2 test was 8.30 for difference in fold change (p = 0.016). Of the 193 patients who were seronegative at baseline, 76 became seropositive after vaccination, corresponding to a 39.4% (95% CI, 32.8%-46.4%) seroconversion rate. Transplant patients had the highest seroconversion rate (58.3% (95% CI, 44.3%-71.2%)), followed by rheumatology (44.1% (95% CI, 28.9%-60.5%)) and haemato-oncology (29.7% (95% CI, 22%-38.8%); χ2 = 11.87; p = 0.003) patients. DISCUSSION: A third dose of BNT162b2 is immunogenic in most immunosuppressed individuals, although antibody response may differ based on the type of disease and immunosuppression. The antibody level that correlates with protection is still unknown; thus, future studies are needed to evaluate clinical outcomes.

Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients.

BACKGROUND & AIMS: Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk of lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population. METHODS: LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 IgG antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10-20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records. RESULTS: Eighty LT recipients were enrolled. Mean age was 60 years and 30% were female. Twenty-five healthy volunteer controls were younger (mean age 52.7 years, p = 0.013) and mostly female (68%, p = 0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p <0.001). Antibody titer was also significantly lower in this group (mean 95.41 AU/ml vs. 200.5 AU/ml in controls, p <0.001). Predictors for negative response among LT recipients were older age, lower estimated glomerular filtration rate, and treatment with high dose steroids and mycophenolate mofetil. No serious adverse events were reported in either group. CONCLUSION: LT recipients developed substantially lower immunological response to the Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibody responses include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population. LAY SUMMARY: The Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine elicited substantially inferior immunity in liver transplant recipients. Less than half of the patients developed sufficient levels of antibodies against the virus, and in those who were positive, average antibody levels were 2x less compared to healthy controls. Factors predicting non-response were older age, renal function and immunosuppressive medications.

Kidney transplant recipients vaccinated before transplantation maintain superior humoral response to SARS-CoV-2 vaccine.

Majority of transplant recipients did not develop an appreciable humoral response following SARS-CoV-2 vaccine, in contrast to dialysis patients and healthy individuals. We analyzed the serologic response to BNT162b2 (Pfizer-BioNTech) vaccine in a cohort of 19 kidney transplant recipients, vaccinated prior to transplantation, compare to 109 recipients vaccinated after transplantation, and to 39 healthcare workers, by determining the level of anti-spike antibodies after transplantation. All controls and 17 of 19 (90%) of recipients vaccinated before transplant were seropositive, while only 49 of 109 (45%) recipients vaccinated post-transplant had positive serology (P < .001). Median anti-spike IgG in the group of kidney transplant recipients vaccinated after transplantation (10.7 AU/ml, [IQR 0-62.5]) was lower than the patients vaccinated before transplantation (66.2 AU/ml [21.6-138]), which was significantly lower than in the controls (156 AU/ml [99.7-215.5]). Negative humoral response was associated with vaccination post transplantation (odds ratio 22.4), older age (OR = 1.04), and longer time on dialysis (OR = 1.02), while higher lymphocyte count at time of vaccination was protective (OR = .52). Our findings of sustained superior humoral response to SARS-CoV-2 vaccine in kidney transplant recipients vaccinated prior to transplantation strongly support the recommendations of SARS-CoV-2 vaccination of transplant candidates, especially those younger than 60 years.

Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus.

COVID-19 is associated with increased morbidity and mortality in transplant recipients. There are no efficacy data available regarding these patients with any of the available SARS-CoV-2 vaccines. We analyzed the humoral response following full vaccination with the BNT162b2 (Pfizer-BioNTech) in 136 kidney transplant recipients, and compared it to 25 controls. In order to exclude prior exposure to the virus, only participants with negative serology to SARS-CoV-2 nucleocapsid protein were included. All controls developed a positive response to spike protein, while only 51 of 136 transplant recipients (37.5%) had positive serology (p < .001). Mean IgG anti-spike level was higher in the controls (31.05 [41.8] vs. 200.5 [65.1] AU/mL, study vs. control, respectively, p < .001). Variables associated with null humoral response were older age (odds ratio 1.66 [95% confidence interval 1.17-2.69]), high-dose corticosteroids in the last 12 months (1.3 [1.09-1.86]), maintenance with triple immunosuppression (1.43 [1.06-2.15]), and regimen that includes mycophenolate (1.47 [1.26-2.27]). There was a similar rate of side effects between controls and recipients, and no correlation was found between the presence of symptoms and seroconversion. Our findings suggest that most kidney transplant recipients remain at high risk for COVID-19 despite vaccination. Further studies regarding possible measures to increase recipient's response to vaccination are required.