Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases

Abstract

ObjectiveTo determine the immunogenicity of the third dose of CoronaVac vaccine in a large population of patients with autoimmune rheumatic diseases (ARD) and the factors associated with impaired response.MethodsAdult patients with ARD and age-balanced/sex-balanced controls (control group, CG) previously vaccinated with two doses of CoronaVac received the third dose at D210 (6 months after the second dose). The presence of anti-SARS-CoV-2 S1/S2 IgG and neutralising antibodies (NAb) was evaluated previously to vaccination (D210) and 30 days later (D240). Patients with controlled disease suspended mycophenolate mofetil (MMF) for 7 days or methotrexate (MTX) for 2 weekly doses after vaccination.ResultsARD (n=597) and CG (n=199) had comparable age (p=0.943). Anti-S1/S2 IgG seropositivity rates significantly increased from D210 (60%) to D240 (93%) (p<0.0001) in patients with ARD. NAb positivity also increased: 38% (D210) vs 81.4% (D240) (p<0.0001). The same pattern was observed for CG, with significantly higher frequencies for both parameters at D240 (p<0.05). Multivariate logistic regression analyses in the ARD group revealed that older age (OR=0.98, 95% CI 0.96 to 1.0, p=0.024), vasculitis diagnosis (OR=0.24, 95% CI 0.11 to 0.53, p<0.001), prednisone ≥5 mg/day (OR=0.46, 95% CI 0.27 to 0.77, p=0.003), MMF (OR=0.30, 95% CI 0.15 to 0.61, p<0.001) and biologics (OR=0.27, 95% CI 0.16 to 0.46, p<0.001) were associated with reduced anti-S1/S2 IgG positivity. Similar analyses demonstrated that prednisone ≥5 mg/day (OR=0.63, 95% CI 0.44 to 0.90, p=0.011), abatacept (OR=0.39, 95% CI 0.20 to 0.74, p=0.004), belimumab (OR=0.29, 95% CI 0.13 to 0.67, p=0.004) and rituximab (OR=0.11, 95% CI 0.04 to 0.30, p<0.001) were negatively associated with NAb positivity. Further evaluation of COVID-19 seronegative ARD at D210 demonstrated prominent increases in positivity rates at D240 for anti-S1/S2 IgG (80.5%) and NAb (59.1%) (p<0.0001).ConclusionsWe provide novel data on a robust response to the third dose of CoronaVac in patients with ARD, even in those with prevaccination COVID-19 seronegative status. Drugs implicated in reducing immunogenicity after the regular two-dose regimen were associated with non-responsiveness after the third dose, except for MTX.Trial registration numberNCT04754698.

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

“…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 ].…”

“…We recently reported a substantial increase in antibody response after a third dose of Sinovac-CoronaVac in a large cohort of ARD patients. However, almost 20% of patients were still negative for anti-SARS-CoV-2 IgG or neutralizing antibodies (NAb) after three-dose homologous vaccination [ 10 ], and possibly remained at high risk for severe COVID-19 [ 11 ]. The analysis of factors associated with a reduced third dose response in our cohort of 875 patients revealed that older age, prednisone ≥5 mg/day, MMF and biologic drugs, particularly abatacept, belimumab and rituximab, were the main factor impairing vaccine-induced antibody response [ 10 ].…”

Characteristics of Patients with Hematologic Malignancies Without Seroconversion Post-COVID19 Third Vaccine Dosing

“…A third dose of the mRNA vaccine ('3V') has shown to be particularly beneficial for HM patients given the reduced response to the standard two dose series. 13 With the increased likelihood of seroconversion among individuals who may have been less responsive to the standard series there is added protection against COVID19 associated morbidity and mortality with 3V; however, research is emerging to show that this may not be true for all HM conditions and/or underlying treatments and responses. This current study builds off a previous study conducted by the same team that assessed the characteristics of a large cohort of HM patients who had received a 3V dose of the mRNA COVID19 vaccine.…”

COVID-19 vaccine booster strategy: striving for best practice

“…Zeng and colleagues 3 reported that neutralising antibody titres induced by two doses of CoronaVac declined to near or below the lower limit of seropositivity after 6 months; however, a third dose given 8 months after the second dose led to a strong boost in immune response. Aikawa and colleagues 4 showed that a third dose of CoronaVac 6 months after the completion of an initial two-dose CoronaVac series resulted in a robust immunogenicity response even in patients with autoimmune rheumatic diseases, with a greater benefit in those who were still seronegative for COVID-19 after the first two vaccinations. Khong and colleagues 5 reported that different combinations of CoronaVac and BNT162b2 (BNT162b2-CoronaVac-BNT162b2 or CoronaVac-CoronaVac-BNT162b2) vaccines in a three-dose regimen induced high neutralising antibody titres even for the delta (B.1.617.2) variant, but a much lower titre for the omicron BA.1 subvariant.…”