Effects of Short-Term Corticosteroid Use on Reactogenicity and Immunogenicity of the First Dose of ChAdOx1 nCoV-19 Vaccine

Abstract

The effects of corticosteroid use on the reactogenicity and immunogenicity of ChAdOx1 nCoV-19 (ChAd) vaccine were evaluated. Healthcare workers (HCWs) who took low-dose corticosteroid agents around the time of the first dose of ChAd (ChAdPd group) were recruited and the reactogenicity and immunogenicity were compared with those of ChAd (ChAd group) and BNT162b2 vaccination (BNT group) of HCWs without corticosteroid exposure. The immunogenicity was measured three weeks after vaccination using quantitative anti-SARS-CoV-2 spike protein (S) antibody electrochemiluminescence immunoassay and interferon gamma (IFN-γ) release assay. A total of 67 HCWs comprising 24 ChAd, 29 BNT, and 14 ChAdPd was included. The median total corticosteroid dose of the ChAdPd group was 30 mg prednisolone equivalents (interquartile range (IQR) 20–71.3 mg). HCWs in the ChAdPd group experienced significantly milder reactogenicity (median total score 7.5, IQR 4.0–18.0) compared to those in the ChAd group (median 23.0, IQR 8.0–43.0, P=0.012) but similar to that in the BNT group (median 5.0, IQR 3.0–9.0, P=0.067). The S antibody concentration of the ChAdPd group (62.4 ± 70.0 U/mL) was higher than that of the ChAd group, though without statistical significance (3.45 ± 57.6 U/mL, P=0.192). The cellular immune response was most robust in the ChAdPd group, with significantly higher IFN-γ concentration (5.363 ± 4.276 IU/mL), compared to the ChAd (0.978 ± 1.181 IU/mL, P=0.002) and BNT (1.656 ± 1.925 IU/mL, P=0.009) groups. This finding suggest that short-term corticosteroid reduces reactogenicity of the first dose of ChAd without hindering immunogenicity.

Humoral and Cellular Responses to BNT162b2 as a Booster Following Two Doses of ChAdOx1 nCov-19 Determined Using Three SARS-CoV-2 Antibody Assays and an Interferon-Gamma Release Assay: A Prospective Longitudinal Study in Healthcare Workers

“…It has been shown that cellular immunity was detectable at 8 months after two doses of BNT162b2, although antibody levels declined significantly ( 20 ). A study investigating the immunogenicity of 23 healthcare workers after the first dose of BNT162b2 or ChAdOx1 nCov-19 presented 67.7% positivity determined using Covi-FERON IGRA ( 21 ). The median values for BNT162b2 and ChAdOx1 nCov-19 were 1.656 and 0.978 IU/mL, respectively.…”

“…The Covi-FERON ELISA kit (SD Biosensor, Suwon, Korea) was used to detect cell-mediated immune responses to SARS-CoV-2 antigens by measuring IFN-γ secreted by T cells in response to the SARS-CoV-2 antigen ( 21 ). Blood samples collected in heparinized tubes were aliquoted (in 1 mL aliquots) into five tubes for Nil, Mitogen, original spike protein (SP1) antigen, variant spike protein antigen (SP2), and nucleocapsid protein (NP) antigens.…”

“…Cellular responses have been measured using various methods ( 8 , 19 ). SARS-CoV-2-specific interferon-γ (IFN-γ) release assay, based on a methodology similar to that utilized for tuberculosis blood tests, has been introduced to determine cellular immunity, implicating sustained responses after vaccination ( 20 , 21 ).…”

Immunogenicity of COVID-19 mRNA vaccines in immunocompromised patients: a systematic review and meta-analysis

“…They also showed that the duration of tocilizumab administration did not impact the response to the vaccine. Also, another recent study showed that although short-term corticosteroid therapy reduces reactogenicity of the first dose of ChAdOx1 nCoV-19, it does not weaken its immunogenicity [ 67 ]. On the other hand, a preliminary report (preprint) shows that methotrexate might hamper humoral and cellular immune response to COVID-19 mRNA vaccines [ 68 ].…”

Severity-Adjusted Dexamethasone Dosing and Tocilizumab Combination for Severe COVID-19

“…17 Cell-mediated immunity was evaluated by measuring interferon-gamma (IFN-γ) secreted by T-cells in response to SARS-CoV-2-specific antigens using a SARS-CoV-2-specific IFN-γ release assay (IGRA) kit with enzyme-linked immunosorbent assay (ELISA) (Covi-FERON ELISA; SD Biosensor, Suwon, Republic of Korea). 18 The test kit consists of nil, SARS-CoV-2 spike protein antigen (Sp)1, Sp2, mitogen tubes, and IFN-γ ELISA. The Sp1 tube contained spike protein antigens derived from the original SASR-CoV-2 strain and its alpha variant, and the Sp2 tube contained those derived from the beta and gamma variants.…”