Abstract
Objective: To analyse the safety, immunogenicity and factors affecting antibody response to Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) vaccination in patients with SSc.
Methods: This is a phase 4 prospective study within a larger trial of two doses of inactivated SARS-CoV-2 vaccine (CoronaVac) in 51 SSc patients compared with 153 controls. Anti-SARS-CoV-2-IgG and neutralizing antibodies (NAb) were assessed at each vaccine shot (D0/D28) and 6 weeks after the second dose(D69), only in individuals with negative baseline IgG/NAb and those who did not have coronavirus-19(COVID19) during follow-up. Vaccine safety was also assessed in all participants.
Results: Patients and controls had comparable median ages [48(38.5-57) vs 48(38-57) years, P =0.945]. Patients had mostly diffuse SSc (68.6%) and the majority (74.5%) had interstitial lung disease. Most patients were under immunosuppressive therapy (72.5%), mainly MMF (52.9%). After full vaccination (D69), anti-SARS-CoV-2-IgG frequency (64.1% vs 94.2%, P < 0.001) and NAb positivity (53.8% vs 76.9%; P =0.006) were moderate, although lower than controls. The first dose response (D28) was low and comparable for both seroconvertion rates (SC) (P =0.958) and NAb positivity (P =0.537). SSc patients under MMF monotherapy vs other (no therapy/other DMARDs) had lower immunogenicity (SC: 31.3% vs 90%, P < 0.001) and NAb(18.8% vs 85%, P < 0.001). Multiple regression analysis confirmed that MMF use, but not disease subtype, is associated with insufficient seroconversion [odds ratio (OR)=0.056(95% CI: 0.009, 0.034), P =0.002] and NAb positivity [OR = 0.047(95% CI: 0.007, 0.036), P =0.002]. No moderate/severe side-effects were observed.
Conclusion: CoronaVac has an excellent safety profile and moderate response to anti-SARS-CoV-2 vaccine in SSc. Vaccine antibody response is not influenced by disease subtype and is greatly affected by MMF, reinforcing the need for additional strategies to up-modulate vaccine response in this subgroup of patients.
Trial registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT04754698 .
Keywords: SARS-CoV-2; immunogenicity; mycophenolate; systemic sclerosis; vaccine.
【저자키워드】 SARS-CoV-2, immunogenicity, vaccine., Systemic sclerosis, mycophenolate, 【초록키워드】 neutralizing antibody, Vaccine, vaccination, therapy, Trial, Antibody Response, Prospective Study, CoronaVac, Interstitial lung disease, anti-SARS-CoV-2, SARS-CoV-2 vaccine, Seroconversion, vaccine response, Patient, Control, Follow-up, respiratory, monotherapy, disease, moderate, safety profile, inactivated, Frequency, dose, immunosuppressive, regression analysis, Factor, Side-effect, Participants, first dose, median age, individual, Multiple, controls, affected, Most patient, majority, comparable, affecting, baseline, MMF, subgroup of patients, were assessed, 【제목키워드】 therapy, SARS-CoV-2 vaccine, Patient, disease,