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Humoral immune-response to a SARS-CoV-2-BNT162b2 booster in inflammatory arthritis patients who received an inactivated virus vaccine
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  1. Josefina Durán1,
  2. Paula Isabel Burgos1,
  3. Nicole Le Corre2,
  4. Cinthya Ruiz Tagle3,
  5. Constanza Martinez-Valdebenito2,
  6. Mauricio Castro4,
  7. Valentina Metcalfe5,
  8. Paula Niemann5,
  9. M Elvira Balcells3
  1. 1 Department of Rheumatology, Pontificia Universidad Católica de Chile, Santiago, Chile
  2. 2 Department of Pediatric Immunology and Infectious Diseases, Pontificia Universidad Católica de Chile, Santiago, Chile
  3. 3 Department of Infectious Diseases, Pontificia Universidad Católica de Chile, Santiago, Chile
  4. 4 Department of Statistics, Pontifiicia Universidad Católica de Chile, Santiago, Chile
  5. 5 Pontificia Universidad Católica de Chile, Santiago, Chile
  1. Correspondence to Dr Josefina Durán, Rheumatology, Pontificia Universidad Católica de Chile, Santiago, Chile; jgduran{at}uc.cl

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CoronaVac, an inactivated SARS-CoV-2 vaccine, has been administered in over 100 countries worldwide, but its immunity wanes quickly over time.1 In consequence, boosters are being recommended.

We evaluated the immunogenicity of an mRNA vaccine booster (BNT162b2) in inflammatory arthritis (IA) patients with biologic treatments previously vaccinated with CoronaVac. Consenting adults with IA followed at Red Salud UC-CHRISTUS (Chile), who were on anti-TNF, anti-IL6 or anti-IL17 biologics, vaccinated with CoronaVac (0, 28), were eligible. Those with a SARS-CoV-2 infection history were excluded. Humoral response was assessed by measuring IgG SARS-CoV-2 total antibody (Tab) and neutralising antibody (Nab) within 7 days and 4 weeks after the booster. DMARDs were not discontinued.

The primary outcome was the proportion of participants with positive SARS-CoV-2 Nab 4 weeks after the BTN162b2 booster. A neutralisation of 30% or more at a 1:10 dilution was considered positive.2 Dichotomous and continuous variables were compared using the McNemar or Wilcoxon signed-rank test. Confounding and effect modifiers of covariates were explored using binary regression models.

Seventy-six individuals were included. Mean age was 51.9 (SD 11.3) and 73.6% were female. Mean years since diagnosis were 6.2 years (SD 7.4), 74% had rheumatoid arthritis (RA), 24% psoriatic arthritis, 1% juvenile idiopathic arthritis and 1% ankylosing spondylitis. Overall, 45% used low dose prednisone, 36% methotrexate, 21% leflunomide and 14% sulfasalazine. The median (IQR) number of days between the second CoronaVac dose and the BNT162b2 booster was 157 (143-170). At baseline, 18 participants (24%) had Nab and 40 (53%) had positiveTab. Age was inversely and independently associated with the probability of having detectable Nab at baseline (p value 0.006). In the same model, neither gender, prednisone, methotrexate nor time between CoronaVac vaccination and the booster predicted baseline Nab serostatus. Four weeks after receiving a BNT162b2 booster, 71 (94%) and 73 (96%) individuals had positive Nab and Tab, respectively. The median (IQR) neutralising activity rose from 17% (11%–29%) to 97% (80%–99%) after boosting (figure 1). Five participants (6.8%) remained Nab-seronegative; all had RA, received steroids and four of them used methotrexate. Sixty-two per cent of patients reported adverse events, all mild.

Figure 1

Humoral response against SARS-CoV-2 4 weeks after the booster dose. Distribution for (A) neutralising activity (median (IQR) of percentage of inhibition), (B) neutralising antibodies positivity (≥30% of inhibition rate), (C) total IgG anti S1 GMC (95% CI),RU/mL, (D) frequency of total IgG anti S1 positivity (≥11 relative units per mL, RU/mL).

Multivariate analysis found no association among age, gender, prednisone, methotrexate and postbooster Nab levels. Response was not correlated to the time elapsed since the second dose of CoronaVac.

No COVID-19 cases were reported after the booster (follow-up 1–3 months).

After an mRNA vaccine booster, our sample of IA patients using biologics and vaccinated with CoronaVac significantly improved their humoral immune response against SARS-CoV-2. Little is known about response to vaccine boosters following inactivated vaccines. One study compared BNT162b2 versus CoronaVac in 80 healthy individuals with low antibody response to CoronaVac. Nab seroconversion was observed in 96.8% and 57.7% of participants receiving BNT162b2 or CoronaVac boosters, respectively.3 A recent study of a homologous booster of CoronaVac in patients with rheumatic disease showed 81.4% of subjects produced Nab.4 Booster doses have also been explored in rheumatologic patients vaccinated with mRNA vaccines. A small study in RA patients unresponsive to BNT162b2 showed that after a homologous booster plus DMARDS discontinuation, 15 of 17 participants reached adequate Tab titers.5

Similarly, 16 out of 18 autoimmune disease patients vaccinated with mRNA vaccines and boosted with mRNA or viral-vectored vaccines increased Tabs.6

Our study limitations include the lack of assessment of cellular response and the short postbooster clinical follow-up. Results should not be generalised to patients receiving other biologics.

In conclusion, our study suggests that IA patients on biologic drugs receiving inactivated COVID-19 vaccines should receive a booster dose. A mix-and-match approach with mRNA vaccines is well tolerated and highly immunogenic.

Ethics statements

Patient consent for publication

Ethics approval

This study involves human participants and was approved by Pontificia Universidad Catolica de Chile Ethics Commitee (ID210726002). Participants gave informed consent to participate in the study before taking part.

Acknowledgments

We are very grateful for the collaboration of Dr Marcela Ferrés, head of the Laboratorio de Infectología y Virología Molecular, Red de Salud UC-CHRISTUS for storing samples and to the study nurse, Nancy Vásquez.

References

Footnotes

  • Handling editor Josef S Smolen

  • Contributors Authors report no competing interests, and all significantly contributed to this work. JD, MEB and MC: acquisition, interpretation of data, drafting the work and final approval of the version to be published. PIB, NLC, CRT, CM-V, VM and PN: acquisition, interpretation of data and drafting the work and final approval of the version to be published. All authors have agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding This work was supported by PANLAR Stimulus Award 2021, PANLAR.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.