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Maintenance hemodialysis (MHD) patients exhibit compromised immune responses, leading to lower immunogenicity to the COVID‐19 vaccine than the general population. The metabolomic factors influencing COVID‐19 vaccine response in MHD patients remain elusive. A cross‐sectional study was conducted with 30 MHD patients, divided into three vaccine regimen groups (N= 10 per group): homologous CoronaVac® (SV‐SV), homologous ChAdOx1 nCoV‐19 (AZ‐AZ), and heterologous prime‐boost (SV‐AZ). Plasma samples were collected at baseline and at 28 days after the final dose to analyze 92 metabolomic levels using targeted metabolomics. The study included 30 MHD patients (mean age 56.67 ± 10.79 years) with similar neutralizing antibody (nAb) levels across vaccine regimens. The most significant differences in metabolomics were found between AZ‐AZ and SV‐SV, followed by SV‐AZ versus SV‐SV, and AZ‐AZ versus SV‐AZ. Overall, the metabolomic changes involved amino acids like glutamate and phenylalanine, and phospholipids. Prevaccination metabolomic profiles, including PG (38:1), lysoPE (20:2), lysoPC (18:2), lysoPI (18:1), and PC (34:2), exhibited negative correlations with postvaccination nAb levels. Different COVID‐19 vaccine regimens had unique interactions with the immune response in MHD patients. Amino acid and phospholipid metabolisms play crucial roles in nAb formation, with the phospholipid metabolism being a potentially predictive marker of vaccine immunogenicity among MHD patients. [ABSTRACT FROM AUTHOR]

Abstract Maintenance hemodialysis (MHD) patients exhibit compromised immune responses, leading to lower immunogenicity to the COVID‐19 vaccine than the general population. The metabolomic factors influencing COVID‐19 vaccine response in MHD patients remain elusive. A cross‐sectional study was conducted with 30 MHD patients, divided into three vaccine regimen groups (N= 10 per group): homologous CoronaVac® (SV‐SV), homologous ChAdOx1 nCoV‐19 (AZ‐AZ), and heterologous prime‐boost (SV‐AZ). Plasma samples were collected at baseline and at 28 days after the final dose to analyze 92 metabolomic levels using targeted metabolomics. The study included 30 MHD patients (mean age 56.67 ± 10.79 years) with similar neutralizing antibody (nAb) levels across vaccine regimens. The most significant differences in metabolomics were found between AZ‐AZ and SV‐SV, followed by SV‐AZ versus SV‐SV, and AZ‐AZ versus SV‐AZ. Overall, the metabolomic changes involved amino acids like glutamate and phenylalanine, and phospholipids. Prevaccination metabolomic profiles, including PG (38:1), lysoPE (20:2), lysoPC (18:2), lysoPI (18:1), and PC (34:2), exhibited negative correlations with postvaccination nAb levels. Different COVID‐19 vaccine regimens had unique interactions with the immune response in MHD patients. Amino acid and phospholipid metabolisms play crucial roles in nAb formation, with the phospholipid metabolism being a potentially predictive marker of vaccine immunogenicity among MHD patients.