Immunogenicity and safety of two doses of the CoronaVac SARS-CoV-2 vaccine in SARS-CoV-2 seropositive and seronegative patients with autoimmune rheumatic diseases in Brazil: a subgroup analysis of a phase 4 prospective study

Abstract

Background We aimed to examine the immunogenicity pattern induced by the inactivated SARS-CoV-2 vaccine CoronaVac (Sinovac Life Sciences, Beijing, China) in SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases compared with seropositive controls, seronegative patients with autoimmune rheumatic diseases, and seronegative controls. Methods CoronavRheum is an ongoing, prospective, controlled, phase 4 study, in which patients aged 18 years or older with autoimmune rheumatic diseases, and healthy controls were recruited from a single site (Rheumatology Division of Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo) in São Paulo, Brazil Participants were vaccinated with two doses of CoronaVac (intramuscular injection, 3 μg in 0·5 mL of β-propiolactone inactivated SARS-CoV-2) on day 0 and on day 28. Blood samples were taken pre-vaccination on day 0, day 28, and also on day 69. For this subgroup analysis, participants were defined as being SARS-CoV-2 seropositive or seronegative prevaccination via anti-SARS-CoV-2 spike (S)1 or S2 IgG (cutoff of 15·0 arbitrary units [AU] per mL) or neutralising antibody titres (cutoff of ≥30%) and were matched for age and sex, via convenience sampling, in a 1:3:1:1 ratio (seropositive patients to seronegative patients to seropositive controls to seronegative controls). The primary outcomes were rates of anti-SARS-CoV-2 S1 and S2 IgG seropositivity and SARS-CoV-2 neutralising antibody positivity at day 28 and day 69 and immunogenicity dynamics assessed by geometric mean titres (GMTs) of IgG and median neutralising activity in seropositive patients with autoimmune rheumatic diseases compared with seronegative patients and seropositive and seronegative controls. We assessed safety in all participants randomly selected for this subgroup analysis. This study is registered with ClinicalTrials.gov , NCT04754698 , and is ongoing for long-term immunogenicity evaluation. Findings Between Feb 4 and Feb 8, 2021, 1418 patients and 542 controls were recruited, of whom 1685 received two vaccinations (1193 patients and 492 controls). After random sampling, our immunogenicity analysis population comprised 942 participants, of whom 157 were SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases, 157 were seropositive controls, 471 were seronegative patients, and 157 were seronegative controls; the median age was 48 years (IQR 38–56) and 594 (63%) were female and 348 (37%) were male. For seropositive patients and controls, an increase in anti-SARS-CoV-2 S1 and S2 IgG titres (seropositive patients GMT 52·3 [95% CI 42·9–63·9] at day 0 vs 128·9 [105·6–157·4] at day 28; seropositive controls 53·3 [45·4–62·5] at day 0 vs 202·0 [174·8–233·4] at day 28) and neutralising antibody activity (seropositive patients 59% [IQR 39–83] at day 0 vs 82% [54–96] at day...

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

“…10 A more robust response was observed in individuals with ARD pre-exposed to COVID-19, with a high plateau of response after a single Coro-naVac dose. 13 Neutralising antibodies' (NAb) response dynamics in patients who have recovered from COVID-19 may vary greatly. 14 We further demonstrated a substantial decline of anti-SARS-CoV-2 antibodies in patients with ARD 6 months after a two-dose schedule of CoronaVac.…”

Distinct immune response to CoronaVac in SARS-CoV-2 seropositive and seronegative patients with autoimmune rheumatic disease

“…This study provides evidence that, in patients with autoimmune rheumatic diseases who have been exposed to natural SARS-CoV-2 infection, a single dose of CoronaVac might be sufficient to produce robust antibody responses, by contrast with unexposed individuals who need at least two doses. 3 Several previous studies of other COVID-19 vaccines showed similar results in the general population or in patients with autoimmune diseases. A single dose of mRNA vaccine or adenovirus-vectored vaccine in patients who had recovered from COVID-19 has been found to elicit similar humoral immunity as elicited by two doses of vaccine in unexposed patients, which is possibly related to the enhanced recall response of pre-existing memory B cells compared with the primary response.…”

“…In The Lancet Rheumatology, Nadia E Aikawa and colleagues report a subgroup analysis of the CoronavRheum study, 3 comparing CoronaVac immunogenicity in patients with autoimmune rheumatic disease who were SARS-CoV-2 seropositive or seronegative with controls who were seropositive or seronegative. 942 participants were included in the subgroup analysis, of whom 157 were seropositive patients, 157 were seropositive controls, 471 were seronegative patients with autoimmune rheumatic diseases and 157 were seronegative controls (median age was 48 years [IQR 38–56] and 594 [63%] were female and 348 [37%] were male).…”

“… 4 , 5 , 6 , 7 To date, more than 294 million doses of CoronaVac have been deployed for use in dozens of countries and regions worldwide, and uninfected individuals who have received two doses of CoronaVac are recommended to get an additional dose after 6 months. 1 However, Aikawa and colleagues 3 found that the antibody responses of SARS-CoV-2-exposed populations did not increase within 6 weeks after the second dose of vaccine, and so whether this population would need an additional dose remains to be determined in longer-term studies, and the effects of previous SARS-CoV-2 exposure also need to be verified in further clinical trials.…”

Effect of an exercise bout before the booster dose of an inactivated SARS-CoV-2 vaccine on immunogenicity in immunocompromised patients

“…However, vaccine responses largely vary between individuals. This is the case of immunocompromised individuals who generally exhibit lower immunogenicity to SARS-CoV vaccines, likely due to the disease-related immune dysfunction and the use immunosuppressive, glucocorticoid, and/or biological therapies ( 2 – 5 ). Prolonged SARS-CoV-2 shedding, decreased SARS-CoV-2 clearance, and enhanced viral genomic evolution have been reported in immunocompromised patients, which underscores the relevance of improving vaccine responses in this population to ultimately prevent the emergence of new variants ( 6 , 7 ).…”