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Waleed H Mahallawi,1 Wael A Alharbi,1 Sultan A Aloufi,1 Nadir A Ibrahim,1 Muntasir M Abdelrahman,2 Bader A Alhomayeed,2 Moutasem S Aboonq,3 Saeed Awad M Alqahtani,3 Emad S Rajih,4 Abdulaziz M Bakhsh,4 Ibrahim Sandokji5 1Medical Laboratory Technology Department, College of Applied Medical Sciences, Taibah University, Madinah, Saudi Arabia; 2King Fahad Hospital, Ministry of Health, Madinah, Saudi Arabia; 3Department of Physiology, College of Medicine, Taibah University, Madinah, Saudi Arabia; 4Urology Department, College of Medicine, Taibah University, Madinah, Saudi Arabia; 5Department of Pediatrics, College of Medicine, Taibah University, Madinah, Saudi ArabiaCorrespondence: Waleed H Mahallawi, Medical Laboratory Technology Department, College of Applied Medical Sciences, Taibah University, Madinah, Saudi Arabia, Email wmahallawi@gmail.comBackground: Kidney transplant recipients (KTRs) commonly suffer from impaired immunity. KTRs’ compromised immune response to COVID-19 vaccines indicates urgent revision of immunisation policies.Methods: A cross-sectional study was conducted in Madinah, Saudi Arabia of 84 KTRs who had received at least one dose of a COVID-19 vaccine. ELISA was used to evaluate anti-spike SARS-CoV-2 IgG and IgM antibody levels in blood samples obtained one month and seven months after vaccination. Univariate and multivariate analyses were performed to identify associations between seropositive status and factors such as the number of vaccine doses, transplant age, and immunosuppressive therapies.Results: The mean age of KTRs was 44.3 ± 14.7 years. The IgG antibody seropositivity rate (n=66, 78.5%) was significantly higher than the seronegativity rate (n=18, 21.4%) in the whole cohort (p< 0.001). In KTRs seroconverting after one month (n=66), anti-SARS-CoV-2 IgG levels declined significantly between one month (median [IQR]:3 [3– 3]) and seven months (2.4 [1.7– 2.6]) after vaccination (p< 0.01). In KTRs with hypertension, IgG levels significantly decreased between one and seven months after vaccination (p< 0.01). IgG levels also decreased significantly in KTRs with a transplant of > 10 years (p=0.02). Maintenance immunosuppressive regimens (triple immunosuppressive therapy and steroid-based and antimetabolite-based regimens) led to a significant decrease in IgG levels between the first and second sample (p< 0.01). KTRs receiving three vaccine doses showed higher antibody levels than those receiving a single dose or two doses, but the levels decreased significantly between one (median [IQR]: 3 [3– 3]) and seven months (2.4 [1.9– 2.6]) after vaccination (p< 0.01).Conclusion: KTRs’ humoral response after SARS-CoV-2 vaccination is dramatically inhibited and wanes. Antibody levels show a significant decline over time in KTRs with hypertension; receiving triple immunosuppressive therapy or steroid-based or antimetabolite-based regimens; receiving mixed mRNA and viral vector vaccines; and with a transplant of > 10 years.Keywords: SARS-CoV-2, kidney transplant recipients, booster, immunosuppression, COVID-19 vaccines, humoral immune response