SARS-CoV-2 Inactivated Vaccine in Naïve ANCA-Associated Vasculitis: Impact of Glucocorticoid Use

Background: There are no reports focusing specifically on ANCA-associated vasculitis(AAV) vaccinated with COVID-19 vaccine. This condition raises special concern regarding SARS-CoV-2 complications due to its typical airway and kidney involvement. The aim of this study was to evaluate CoronaVac immunogenicity and safety in these patients, and also to assess the impact of disease activity and immunosuppressive drugs(IS) in vaccine response.Method: We analyzed 53 naive AAV patients and 106 controls from the CoronavRheum phase 4 trial(NCT04754698), who received two doses of the inactivated CoronaVac. The primary outcome was immunogenicity assessed by seroconversion rates(SC) of anti-SARS-CoV-2 S1/S2 IgG and presence of neutralizing antibodies(NAb) six weeks after the second vaccine dose(day 69). Secondary outcomes were immunogenicity at day 28 and vaccine safety. Factors associated with SC and NAb positivity were evaluated including BVAS. Adverse events and COVID-19 incident cases were carefully followed.Findings: SC(65·1% vs. 96·8%,p=0·0001), IgG GMT(213UA/mL vs. 67·7UA/mL,p<0·001) and percentage of subjects with positive NAb(53·7% vs. 80·6%,p=0·001) were moderate but lower in patients compared to controls, whereas the median of NAb activity was similar between the groups(p=0·952).The frequencies of IS (93·3% vs. 53·3%,p=0·015) and mycophenolate mofetil(20% vs. 0%,p=0·037) were significantly higher in patients without SC compared to those with SC, and a trend of prednisone use(60·0% vs. 28·6%,p=0·057). NAb negativity in AAV patients was associated with prednisone treatment(57·9% vs. 18·2%,p=0·015) and IS(84·2% vs. 55·0%,p=0·046) compared to those with NAb positivity. Logistic regression analysis models showed that only the use of prednisone was associated with lower seroconversion(OR=0·20, 95%CI0·05-0·86,p=0·030)and with lower NAb positivity(OR=0·20, 95%CI 0·05-0·88,p=0·034).No moderate/severe adverse events were observed.Interpretation: This study provides novel data of safety and reduced, but acceptable, short-term immunogenicity of an inactivated SARS-CoV-2 vaccine in AAV patients, mainly hampered by glucocorticoid use. The trial is still ongoing to evaluate additional doses six-months after the full vaccination schedule.Trial Registration Details: This prospective controlled trial is within a large phase 4 study (CoronavRheum clinicaltrials.gov #NCT04754698) conducted at a single tertiary center in Sao Paulo (Brazil) that assessed immunogenicity and safety of the CoronaVac COVID-19 vaccine in a large sample of ARD patients.Funding Information: Sponsored by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo(FAPESP)(#2015/03756-4 to NEA and EB); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, #305556/2017-7 to RMRP, #305242/2019-9 to EB, #303379/2018-9 to SKS), and B3 - Bolsa de Valores do Brasil. Instituto Butantan supplied the study product and had no other role in the trial.Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: This prospective controlled trial is within a large phase 4 study (CoronavRheum clinicaltrials.gov #NCT04754698) conducted at a single tertiary center in Sao Paulo (Brazil) that assessed immunogenicity and safety of the CoronaVac COVID-19 vaccine in a large sample of ARD patients.