Factors associated with poor antibody response to third-dose SARS-CoV-2 vaccination in patients with rheumatic and musculoskeletal diseases

Connolly, Cynthia; Chiang, Teresa Po‐Yu; Teles, Mayan; Frey, Sarah; Alejo, Jennifer L; Massie, Allan B.; Shah, Ami A.; Albayda, Jemima; Christopher‐Stine, Lisa; Werbel, William A; Segev, Dorry L.; Paik, Julie J

doi:10.1016/s2665-9913(22)00065-0

Cited by 9 publications

(18 citation statements)

References 10 publications

(11 reference statements)

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“…Of note, the percentage of non-responders or suboptimal-responders ASD patients who experienced an increase of serum NAb titers after the booster dose is extremely variable in the previous reports (from 16.3% to 92%) [ [20] , [21] , [22] , [23] , [24] , [25] , [26] ]. Thus, it is possible to hypothesize that the reported discrepancies in the improvement of booster-related immunogenicity may reflect a variable contribution of several factors; in particular, the differences among various patients’ series investigated in ASD subtype composition and/or in the treatments employed in the peri-vaccination period.…”

Section: Discussionmentioning

confidence: 99%

“…A number of reports, generally on small patients series, often focusing on single autoimmune disorders, underlined effective seroconversion produced by the booster dose of vaccine [ 20 , 21 , [24] , [25] , [26] ], as well as the weak response to the booster vaccine in ASD patients previously treated with RTX or MMF [ 21 , 22 , [24] , [25] , [26] ].…”

Section: Discussionmentioning

confidence: 99%

“…Few studies regarding the effects of the third dose in ASD subjects are available in the literature [ [20] , [21] , [22] , [23] , [24] , [25] , [26] ]. In addition, the comparison between our results and previous reports is quite difficult because of several differences regarding the size and disease composition of the patients’ series, the timing of the NAb dosages, and the concomitant treatments [ [20] , [21] , [22] , [23] , [24] , [25] , [26] ].…”

Section: Discussionmentioning

confidence: 99%

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Absent or suboptimal response to booster dose of COVID-19 vaccine in patients with autoimmune systemic diseases

Ferri

Gragnani

Raimondo³

et al. 2022

Journal of Autoimmunity

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Absent or suboptimal response to booster dose of COVID-19 vaccine in patients with autoimmune systemic diseases

Ferri

Gragnani

Raimondo³

et al. 2022

Journal of Autoimmunity

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“…While we observed significantly diminished antibody titers in BS patients, especially in those treated with anti-TNF agents compared to healthy individuals among Cor-onaVac recipients, no such difference was detected in the BioNTech group. We and others have previously shown that immunocompromised patients often fail to show an adequate response to SARS-CoV-2 vaccines, as indicated by lower protective immune response rates compared with healthy individuals [5][6][7][8][24][25][26][27][28][29][30][31][32][33][34][35][36]. Almost all DMARDs including mycophenolate mofetil, methotrexate, rituximab, abatacept and glucocorticoids have been shown to blunt humoral responses [7,[24][25][26][31][32][33].…”

Section: Discussionmentioning

confidence: 99%

Higher antibody responses after mRNA-based vaccine compared to inactivated vaccine against SARS-CoV-2 in Behcet’s syndrome

et al. 2022

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There are limited data about humoral response to vaccine in Behçet's syndrome (BS). We compared SARS-CoV-2 antibody response after two doses of inactivated (Sinovac/CoronaVac) or mRNA (Pfizer/BioNTech) vaccines in patients with BS and healthy controls (HCs). We studied 166 (92M/74F) patients with BS (mean age: 42.9 ± 9.6 years) and 165 (75M/90F) healthy controls (mean age: 42.4 ± 10.4 years), in a single-center cross-sectional design between April 2021 and October 2021. A total of 80 patients with BS and 89 HCs received two doses of CoronaVac, while 86 patients with BS and 76 HCs were vaccinated with BioNTech. All study subjects had a negative history for COVID-19. Serum samples were collected at least 21 days after the second dose of the vaccine. Anti-spike IgG antibody titers were measured quantitatively using a commercially available immunoassay method. We found that the great majority in both patient and HC groups had detectable antibodies after either CoronaVac (96.3% vs 100%) or BioNTech (98.8% vs 100%). Among those vaccinated with CoronaVac, BS patients had significantly lower median (IQR) titers compared to ) vs 102 (59-180), p < 0.001]. On the other hand, antibody titers did not differ among patients with BS and HCs who were vaccinated with BioNTech [1648BioNTech [ .5 (527.0-3693.8) vs 1516BioNTech [ .0 (836.3-2599), p = 0.512). Among different treatment regimen subgroups in both vaccine groups, those who were using anti-TNF-based treatment had the lowest antibody titers. However, the difference was statistically significant only among those vaccinated with CoronaVac. Among patients vaccinated with BioNTech, there was no statistically significant difference between different treatment regimen groups. Compared to inactivated COVID-19 vaccine, mRNA-based vaccine elicited higher antibody titers among BS patients. Only in the CoronaVac group, patients especially those using anti-TNF agents were found to have low titers compared to healthy subjects. BS patients vaccinated with BioNTech were found to have similar seroconversion rates and antibody levels compared to healthy controls. Further studies should assess whether the low antibody titers are associated with diminished protection against COVID-19 in both vaccine groups.

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“…With regard to anti-SARS-CoV-2 vaccination, prime immunization may be especially impaired by age ≥60 years, prednisone, and some specific immunosuppressive and biological drugs [ 1 , 7 , 8 ], reinforcing the need for additional doses. Both homologous and heterologous third dose of anti-SARS-CoV-2 vaccination have been associated with robust humoral response in this population [ 9 , 10 ]. Furthermore, a recent small sized study of a fourth anti-SARS-CoV-2 dose demonstrated enhanced immunogenicity in ARD patients, although still impaired by MMF [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Strong response after fourth dose of mRNA COVID-19 vaccine in autoimmune rheumatic diseases patients with poor response to inactivated vaccine

et al. 2022

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Objectives To assess immunogenicity of a heterologous 4th dose of a mRNA (BNT162b2) SARS-CoV-2 vaccine in autoimmune rheumatic diseases (ARD) patients with poor/non-response to inactivated vaccine (Sinovac-CoronaVac). Methods 164 ARD patients who were COVID-19 poor/non-responders (negative anti-SARS-CoV-2 S1/S2 IgG and/or neutralising antibodies—NAb) to the 3rd dose of Sinovac-CoronaVac received an additional heterologous dose of mRNA (BNT162b2) three months after last dose. IgG and NAb were evaluated before and after the 4th dose. Results Significant increases were observed after 4th dose in IgG (66.4% vs 95.1%, p< 0.001), NAb positivity (5.5% vs 83.5%, p< 0.001) and GMT (29.5 vs 215.8 AU/ml, p< 0.001), and 28 (17.1%) remained poor/non-responders. Patients with negative IgG after 4th dose were more frequently under rituximab (p= 0.001). Negative NAb was associated with older age (p= 0.015), rheumatoid arthritis (p= 0.002), systemic sclerosis (p= 0.026), leflunomide (p= 0.016), and rituximab use (p= 0.007). In multiple logistic regression analysis, prednisone dose ≥7.5 mg/day (OR = 0.34; p= 0.047), leflunomide (OR = 0.32, p= 0.036) and rituximab use (OR = 0.19, p= 0.022) were independently associated with negative NAb after the 4th vaccine dose. Conclusions This is the largest study to provide evidence of a remarkable humoral response after the 4th dose of heterologous mRNA SARS-CoV-2 vaccination in ARD patients with poor/no-response to the 3rd dose of an inactivated vaccine. We further identified that treatment, particularly rituximab and prednisone, impaired antibody response to this additional dose. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, CoronavRheum #NCT04754698

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Factors associated with poor antibody response to third-dose SARS-CoV-2 vaccination in patients with rheumatic and musculoskeletal diseases

Cited by 9 publications

References 10 publications

Absent or suboptimal response to booster dose of COVID-19 vaccine in patients with autoimmune systemic diseases

Absent or suboptimal response to booster dose of COVID-19 vaccine in patients with autoimmune systemic diseases

Higher antibody responses after mRNA-based vaccine compared to inactivated vaccine against SARS-CoV-2 in Behcet’s syndrome

Strong response after fourth dose of mRNA COVID-19 vaccine in autoimmune rheumatic diseases patients with poor response to inactivated vaccine

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