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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.
Aikawa, Nadia E; Kupa, Leonard V K; Pasoto, Sandra G; Medeiros-Ribeiro, Ana C; Yuki, Emily F N; Saad, Carla G S; Pedrosa, Tatiana; Fuller, Ricardo; Shinjo, Samuel K; Sampaio-Barros, Percival D; Andrade, Danieli C O; Pereira, Rosa M R; Seguro, Luciana P C; Valim, Juliana M L; Waridel, Filipe; Sartori, Ana Marli C; Duarte, Alberto J S; Antonangelo, Leila; Sabino, Ester C; Menezes, Paulo Rossi; Kallas, Esper G; Silva, Clovis A; Bonfa, Eloisa.
  • Aikawa NE; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Kupa LVK; Pediatric Rheumatology Unit, Instituto da Criança e do Adolescente, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Pasoto SG; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Medeiros-Ribeiro AC; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Yuki EFN; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Saad CGS; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Pedrosa T; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Fuller R; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Shinjo SK; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Sampaio-Barros PD; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Andrade DCO; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Pereira RMR; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Seguro LPC; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Valim JML; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Waridel F; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Sartori AMC; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Duarte AJS; Department of Infectious and Parasitic Diseases, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Antonangelo L; Central Laboratory Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Sabino EC; Central Laboratory Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Menezes PR; Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Instituto de Medicina Tropical, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Kallas EG; Department of Preventive Medicine, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Silva CA; Department of Infectious and Parasitic Diseases, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
  • Bonfa E; Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Lancet Rheumatol ; 4(2): e113-e124, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1649499
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 ß-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 1311 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 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 137·1 [116·2-161·9] and neutralising antibody activity was 79% [57-94]); and seropositive controls' GMT was 188·6 [167·4-212·6] 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 2·3 (95% CI 2·2-2·3) at day 0, 5·7 (5·1-6·4) at day 28, and 29·6 (26·4-33·3) at day 69, and in seronegative controls were 2·3 (2·1-2·5) at day 0, 10·6 (8·7-13·1) at day 28, and 71·7 (63·5-81·0) 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.

FUNDING:

Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and B3-Bolsa de Valores do Brasil. TRANSLATION For the Portuguese translation of the abstract see Supplementary Materials section.

Full text: Available Collection: International databases Database: MEDLINE Type of study: Observational study / Randomized controlled trials Topics: Vaccines Country/Region as subject: South America / Brazil Language: English Journal: Lancet Rheumatol Year: 2022 Document Type: Article Affiliation country: S2665-9913(21)00327-1

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Observational study / Randomized controlled trials Topics: Vaccines Country/Region as subject: South America / Brazil Language: English Journal: Lancet Rheumatol Year: 2022 Document Type: Article Affiliation country: S2665-9913(21)00327-1