Risk factors associated with poor response to COVID-19 vaccination in kidney transplant recipients
Authors: Yorg Azzi, Harith Raees, Tao Wang, Levi Cleare, Luz Liriano-Ward, Pablo Loarte-Campos, Cindy Pynadath, Maria Ajaimy, Omar Alani, Yi Bao, Liise-anne Pirofski, Enver Akalin
Journal: Kidney International (2021)

The case fatality ratio of coronavirus disease 2019 (COVID-19) in kidney transplant recipients is between 10% and 30%,1Azzi Y. Parides M. Alani O. et al.COVID-19 infection in kidney transplant recipients at the epicenter of pandemics.Kidney Int. 2020; 98: 1559-1567Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar,2Azzi Y. Bartash R. Scalea J. et al.COVID-19 and solid organ transplantation: a review article.Transplantation. 2021; 105: 37-55Crossref PubMed Scopus (227) Google Scholar underscoring the importance of vaccination to prevent COVID-19. However, kidney transplant recipients have a reduced response to COVID-19 vaccines (18%–54%).3Boyarsky B.J. Werbel W.A. Avery R.K. et al.Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients.JAMA. 2021; 325: 2204-2206Crossref PubMed Scopus (758) Google Scholar,4Benotmane I. Gautier-Vargas G. Cognard N. et al.Weak anti–SARS-CoV-2 antibody response after the first injection of an mRNA COVID-19 vaccine in kidney transplant recipients.Kidney Int. 2021; 99: 1487-1489Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar We determined severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike IgG (anti–spike IgG) responses to COVID-19 vaccination in 65 kidney transplant recipients who received BNT162b2 (Pfizer–BioNTech), 29 who received mRNA-1273 (Moderna), and 4 who received Janssen Ad26.CoV2.S (Johnson & Johnson) vaccines at a median of 4 years (range, 3 mo–22 yr) after transplantation (Supplementary Table S1). Twenty-one patients had prior COVID-19 infection, and 11 (52%) had SARS-CoV-2 nucleocapsid IgG (anti–nucleocapsid IgG) before vaccination, of whom 20 (95%) generated anti–spike IgG. However, only 24 (32%) of 76 patients without a previous history of COVID-19 and a negative anti–nucleocapsid IgG before vaccination generated an anti–spike IgG response. The median anti–spike IgG level was significantly higher in those with prior COVID-19 (median signal-to-cutoff ratio, 13.3 [95% CI, 7.59–16.20] vs. 6.3 [95% CI, 1.22–15.6]; P < 0.01). African Americans, those on full-dose anti-metabolite therapy, and those with lower median CD3 and CD4 T-cell and serum IgM levels had reduced responses (Table 1). A total of 65% of those with CD4 counts >400 and 57% of those with CD3 counts >1000 responded, but only 17% and 13%, respectively, of those with CD4 counts <400 and CD3 counts <500 responded (Supplementary Figure S1A and S1B). In summary, a lack of response to COVID-19 vaccines was associated with African American race; being on high-dose anti-metabolite therapy; and having lower prevaccination CD3, CD4 T-cell, and serum IgM levels.Table 1Baseline demographics of kidney transplant recipients without previous history of COVID-19 and completed COVID-19 vaccinationVariableAnti-spike IgG negative (N = 52)Anti-spike IgG positive (N = 24)P valueAge, yr63 (54–69)58 (41–70)0.22 <6565671 ≥653533Male sex63500.39Race White1233 African American52250.04 Hispanic2925 Other817Transplant type Deceased donor83670.21 Living donor1734Cause of ESRD Diabetes mellitus3525 Hypertension31250.67 Glomerular disease2946 Others64Comorbidities Diabetes mellitus52460.8 Hypertension1001001 Heart disease39170.1 Lung disease12170.8 Cancer15250.49BMI, kg/m229.5 (23.7–32.4)30.3 (25.5–34.3)0.31Vaccine type BNT162B2 (Pfizer–BioNTech)64630.94 mRNA-1273 (Moderna)3133 Adenovirus (Johnson & Johnson)54Time to vaccination from transplant, mo54 (24–98)39 (12–100)0.47Induction with anti-thymocyte globulin69480.13Immunosuppressive regimen CNI981001 MPA/MMF87670.043 Prednisone1001001No MPA/MMF1433P value for 3 groups = 0.093MPA/MMF ≤720/1000 mg/d3333MPA/MMF >720/1000 mg/d5433P value for no MPA/MMF vs. MPA/MMF >720/1000 mg/d = 0.045eGFR , ml/min55 (36–77)62 (44–84)0.23PRA before vaccination, mean (SD) Class I21 (35)16 (29)0.35 Class II17 (31)11 (26)0.29CD3 count, cells/μl652 (427–1204)1176 (653–1422)0.032CD4 count, cells/μl303 (185–503)632 (249–858)0.046CD8 count, cells/μl314 (184–507)454 (223–562)0.2IgM, mg/dl67.5 (39–92)100 (60–141)0.009IgA, mg/dl156.5 (133.8–246.3)194 (147.5–277.5)0.31IgG, mg/dl1114.5 (801.5–1340)954 (885–1183)0.5BMI, body mass index; CNI, calcineurin inhibitor; COVID-19, coronavirus disease 2019; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; IQR, interquartile range; MMF, mycophenolate mofetil; MPA, mycophenolic acid; PRA, panel reactive antibody.Values are presented as percentage or median (interquartile range), unless otherwise indicated. Open table in a new tab BMI, body mass index; CNI, calcineurin inhibitor; COVID-19, coronavirus disease 2019; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; IQR, interquartile range; MMF, mycophenolate mofetil; MPA, mycophenolic acid; PRA, panel reactive antibody. Values are presented as percentage or median (interquartile range), unless otherwise indicated. Download .pdf (.37 MB) Help with pdf files Supplementary File (PDF) COVID-19 infection in kidney transplant recipients at the epicenter of pandemicsKidney InternationalVol. 98Issue 6PreviewWe investigated the prevalence and clinical outcomes of COVID-19 in recipients of kidney transplants in the Bronx, New York, one of the epicenters of the pandemic. Between March 16 and June 2, 2020, 132 kidney transplant recipients tested positive by SARS-CoV-2 RT-PCR. From May 3 to July 29, 2020, 912 kidney transplant recipients were screened for SARS-CoV-2 IgG antibodies during routine clinic visits, of which 16.6% tested positive. Fifty-five of the 152 patients had previously tested positive by RT-PCR, while the remaining 97 did not have significant symptoms and had not been previously tested by RT-PCR. Full-Text PDF Weak anti–SARS-CoV-2 antibody response after the first injection of an mRNA COVID-19 vaccine in kidney transplant recipientsKidney InternationalVol. 99Issue 6PreviewInternational recommendations on coronavirus disease 2019 (COVID-19) vaccine distribution have given priority to immunocompromised patients, including kidney transplant recipients (KTRs).1,2 Unfortunately, this guidance has been released without inclusion of this clinical population in vaccine clinical trials. In an effort to shed light on the efficacy and safety of an mRNA COVID-19 vaccine in KTRs, this preliminary study was undertaken to investigate the anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response after the first injection. Full-Text PDF