mmunogenicity 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 stud

Author(s):Show less -

Aikawa, Nadia E. ^{[1, 2]} ; Kupa, Leonard V. K. ^[1] ; Pasoto, Sandra G. ^[1] ; Medeiros-Ribeiro, Ana C. ^[1] ; Yuki, Emily F. N. ^[1] ; Saad, Carla G. S. ^[1] ; Pedrosa, Tatiana ^[1] ; Fuller, Ricardo ^[1] ; Shinjo, Samuel K. ^[1] ; Sampaio-Barros, Percival D. ^[1] ; Andrade, Danieli C. O. ^[1] ; Pereira, Rosa M. R. ^[1] ; Seguro, Luciana P. C. ^[1] ; Valim, Juliana M. L. ^[1] ; Waridel, Filipe ^[1] ; Sartori, Ana Marli C. ^[3] ; Duarte, Alberto J. S. ^[4] ; Antonangelo, Leila ^[4] ; Sabino, Ester C. ^[5] ; Menezes, Paulo Rossi ^[6] ; Kallas, Esper G. ^[3] ; Silva, Clovis A. ^{[1, 2]} ; Bonfa, Eloisa ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Med, Rheumatol Div, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Inst Crianca & Adolescente, Pediat Rheumatol Unit, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med, Dept Infect & Parasit Dis, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med, Cent Lab Div, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Hosp Micas, Fac Med, Inst Med Trop, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Fac Med, Dept Prevent Med, Sao Paulo - Brazil

• Document type: Journal article
• Source: LANCET RHEUMATOLOGY; v. 4, n. 2, p. E113-E124, FEB 2022.
• Web of Science Citations: 1

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 Clinicas, Faculdade de Medicina da Universidade de Sao Paulo) in Sao Paulo, Brazil Participants were vaccinated with two doses of CoronaVac (intramuscular injection, 3 mu g in 0middot5 mL of beta-propiolactone inactivated SARSCoV-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 15middot0 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-SARSCoV-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 52middot3 {[}95% CI 42middot9-63middot9] at day 0 vs 128middot9 {[}105middot6-157middot4] at day 28; seropositive controls 53middot3 {[}45middot4-62middot5] at day 0 vs 202middot0 {[}174middot8-233middot4] at day 28) and neutralising antibody activity (seropositive patients 59% {[}IQR 39-83] at day 0 vs 82% {[}54-96] at day 28; seropositive controls 58% {[}41-79] at day 0 vs 92% {[}79-96] at day 28), was observed from day 0 to day 28, without further increases from day 28 to day 69 (at day 69 seropositive patients' GMT was 137middot1 {[}116middot2-161middot9] and neutralising antibody activity was 79% {[}57-94]); and seropositive controls' GMT was 188middot6 {[}167middot4-212middot6] and neutralising antibody activity was 92% {[}75-96]). By contrast, for seronegative patients and controls, the second dose was required for maximum response at day 69, which was lower in seronegative patients than in seronegative controls. GMTs in seronegative patients were 2middot3 (95% CI 2middot2-2middot3) at day 0, 5middot7 (5middot1-6middot4) at day 28, and 29middot6 (26middot4-33middot3) at day 69, and in seronegative controls were 2middot3 (2middot1-2middot5) at day 0, 10middot6 (8middot7-13middot1) at day 28, and 71middot7 (63middot5-81middot0) at day 69; neutralising antibody activity in seronegative patients was 15% (IQR 15-15) on day 0, 15% (15-15) at day 28, and 39% (15-65) at day 69, and in seronegative controls was 15% (15-15) at day 0, 24% (15-37) at day 28, and 61% (37-79) at day 69. Neither seronegative patients nor seronegative controls reached the GMT or antibody activity levels of seropositive patients at day 69. Interpretation By contrast with seronegative patients with autoimmune rheumatic diseases, seropositive patients have a robust response after a single dose of CoronaVac. Our findings raise the possibility that the reduced immunogenicity observed in seronegative patients might not be the optimum response potential to SARS-CoV-2 vaccination, and therefore emphasise the importance of at least a single booster vaccination in these patients. (AU)

• FAPESP's process: 17/14352-7 - Assessment of relevance of blood levels of drugs in the monitoring rheumatic autoimmune diseases: safety, effectiveness and adherence to therapy
• Grantee: Tatiana Do Nascimento Pedrosa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/17272-0 - Relevance of monitoring blood levels compared to salivar levels of drugs used in rheumatic autoimmune diseases: adherence and understanding the possible underlying mechanisms involved in effectiveness and in adverse effects
• Grantee: Leonard de Vinci Kanda Kupa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/03756-4 - Assessment of relevance of blood levels of drugs in the monitoring rheumatic autoimmune diseases: safety, effectiveness and adherence to therapy
• Grantee: Eloisa Silva Dutra de Oliveira Bonfá
• Support Opportunities: Research Projects - Thematic Grants