Background/Purpose: Brazil is among the countries with the highest numbers of confirmed cases and deaths by COVID-19. CoronaVac (SARS-CoV-2 inactivated vaccine) has been largely used as the main available immunogen for COVID-19 in several countries and it is reported to have 50.7% efficacy. However, its immunogenicity in immunocompromised individuals has not been established. The objective is to evaluate the immunogenicity and safety of the inactivated virus vaccine against SARS-CoV-2 (CoronaVac) in autoimmune rheumatic diseases (ARD) patients.

Methods: This was a prospective controlled study of 910 adult ARD patients and 182 age- and sex-matched control group (CG) who received two doses of CoronaVac. Both groups had negative serology and neutralizing antibodies for COVID-19 at baseline. Anti-SARS-CoV-2 IgG and neutralizing antibodies (NAb) were assessed prior to each vaccine shot (D0 and D28) and 6 weeks after the 2^nd dose (D69). Blood samples were collected from all participants for quantitative serological testing for IgG antibodies against SARS-CoV-2 S1/S2 proteins (DiaSorin) and NAb (GenScript). The primary outcome was immunogenicity (seroconversion rate of anti-SARS-CoV-2 IgG, and frequency of patients with NAb) at D69. Geometric mean titers (GMT) and factor increase in GMT (FI-GMT) of anti-SARS-CoV-2 IgG, and median (interquartile) percentage of neutralizing activity of NAb were also calculated. ARD patients and CG were vaccinated with standardized schedule (28-days interval) and evaluated using COVID-19 symptoms and adverse events (AE) diaries, three face-to-face visits, and 24-hs available phone, Whatsapp and e-mail contact. Symptomatic cases were tested by RT-PCR for SARS-CoV-2 and a subgroup of positive samples were evaluated for the presence of variants of concern (P.1, B.1.1.7, and B.1.351 lineages).

Results: We observed significant lower anti-SARS-Cov-2 IgG seroconversion (70.4% vs. 95.5%,p< 0.001) and GMT [12.1(95%CI 11.0-13.2) vs. 29.7(95%CI 26.3-33.5),p< 0.001], frequency of NAb (56.3% vs. 79.3%),p< 0.001) and median (interquartile range) neutralization activity [58.7(43.1-77.2)% vs. 64.5(48.4-81.4)%,p=0.013] in ARD patients compared to CG. Vaccine safety analysis revealed similar AE between the groups, with no moderate/severe event. Thirty-nine incident symptomatic cases of COVID-19 confirmed by RT-PCR were observed among ARD patients and CG [36/910 (4%) vs. 3/182 (1.6%), p=0.186] throughout the study. Frequency of cases occurring from D0-D39 (up to 10 days after the second dose) was higher compared to D40-D79 [33/1092 (3.0%) vs. 6/1057 (0.6%), p< 0.0001]. Four ARD patients were hospitalized (up to 10 days after second dose) and none deceased due to COVID-19.

Conclusion: CoronaVac has an excellent safety profile and reasonable rates of seroconversion (70.4%) and adequate neutralization activity (56.3%) in ARD patients. The impact of this reduced immunogenicity in vaccine effectiveness warrants further evaluation.

Results are expressed in geometric mean (95%CI) and n (%). GMT – Geometric mean titers (AU/mL); SC – seroconversion (defined as post vaccination titer > 15 AU/mL – Indirect ELISA, LIAISON® SARS-CoV_2 S1/S2 IgG, DiaSorin, Italy); FI-GMT – factor increase of Geometric mean titers; ARD – autoimmune rheumatic diseases; CG – control group; CIA – chronic inflammatory arthritis (rheumatoid arthritis, axial spondyloarthritis and psoriatic arthritis); Other ARD– systemic lupus erythematosus, primary vasculitis, systemic sclerosis, primary Sjögren syndrome, idiopathic inflammatory myopathies and primary antiphospholipid syndrome; * – p < 0.001 in comparison among ARD and CG at the same time points; # - p < 0.001 for longitudinal comparisons of GMT in ARD at D28 and D69 vs. baseline; α - p < 0.001 for longitudinal comparison of GMT in ARD at D69 vs. D28; Ŧ - p < 0.001 for longitudinal comparison of GMT in CG at D28 and D69 vs. baseline; β - p < 0.001 for longitudinal comparison of GMT in CG at D69 vs. D28.

Results are expressed in median (interquartile range) and n (%). Positivity for Nab defined as a neutralizing activity ≥30 % (cPass sVNT Kit, GenScript, Piscataway, USA) ***p < 0.05, **p < 0.01 and *p < 0.001 in comparison to CG ARD – autoimmune rheumatic diseases; CG – control group; CIA – chronic inflammatory arthritis (rheumatoid arthritis, axial spondyloarthritis and psoriatic arthritis); Other ARD – systemic lupus erythematosus, primary vasculitis, systemic sclerosis, primary Sjögren syndrome, idiopathic inflammatory myopathies and primary antiphospholipid syndrome.

Results are expressed in median (interquartile range) and n (%). ARD – autoimmune rheumatic disease; CIA – chronic inflammatory arthritis (rheumatoid arthritis, axial spondyloarthritis and psoriatic arthritis); Other ARD – systemic lupus erythematosus, primary vasculitis, systemic sclerosis, primary Sjögren syndrome, idiopathic inflammatory myopathies and primary antiphospholipid syndrome. SC – seroconversion defined as a positive serology (IgG titer > 15 AU/ml) for anti-SARS-CoV_2 S1/S2 IgG antibodies after vaccination (Indirect ELISA, LIAISON® SARS-CoV_2 S1/S2 IgG, DiaSorin, Italy). Positivity for Nabs defined as a neutralizing activity ≥ 30 % (cPass sVNT Kit, GenScript, Piscataway, USA).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunogenicity-and-safety-of-an-inactivated-virus-vaccine-against-sars-cov-2-in-patients-with-autoimmune-rheumatic-diseases/