ABSTRACT
Objetivos: Avaliar as taxas de seroconversao apos duas doses da vacina contra SARS-CoV-2 em pacientes com Leucemia Mieloide Cronica (LMC). Material e Metodos: Foram coletadas amostras para teste sorologico de triagem para avaliacao da presenca de anticorpos IgG (CMIA, SARS-CoV-2 IgM, IgG - Alinity System, Abbott Laboratories, Ireland) no periodo de 1-3 meses apos duas doses de vacina para COVID-19. Nas amostras positivas, foi realizada analise quantitativa de IgG (anti-S1 - SARS-CoV-2 IgG II Quant, Alinity System, Abbott Laboratories, Ireland) e os Titulos de Anticorpos Neutralizantes (TAN), que detectam o efeito citopatico do virus em cultura celular induzidos pelas vacinas (Vero CCL-81 cells). Resultados: Entre agosto e novembro de 2021, foram avaliados 102 pacientes com LMC com media de idade de 56,2 anos (33-85), sendo 58,8% do sexo masculino, 98,5% em Fase Cronica (FC), 80% apresentavam ao menos Resposta Molecular Maior (RMM). 87% dos pacientes estavam em uso de ITQ e 13% estavam em descontinuacao da medicacao. 66,7% receberam a vacina ChAdOx1 nCoV-19 (AZD1222)-Covishield (Oxford/AstraZeneca/Fiocruz), 29,41% CoronaVac (Sinovac/Butatan), 1,96% BNT162b2 (Pfeizer/BioNTech/Fosun Pharma) e 1,96% Ad26.COV2.S (Janssen-Cilag). 15% dos pacientes apresentaram COVID-19 antes da vacinacao. O teste sorologico de triagem (CMIA) foi positivo em 25% dos pacientes. COVID-19 previa foi associada a presenca de anticorpos IgG (p<=0,001). Os TAN foram maiores que 1:320 em 13/26 casos, dentre os quais 5 haviam apresentado COVID-19 antes de completar o esquema vacinal. Neste grupo, 76% receberam a vacina ChAdOx1 nCoV-19, 19% Coronavac e 1% BNT162b2. Dentre os casos com infeccao previa pelo SARS-CoV-2, 7 apresentaram confirmacao laboratorial e 2 tinham quadro clinico sugestivo. Oito casos ocorreram antes da vacinacao e um paciente apresentou quadro leve, apos ter recebido a primeira dose da vacina ChAdOx1 nCoV-19. Onze pacientes estavam em tratamento com Imatinibe, 6 com Dasatinibe e um com Nilotinibe (6 com RMM), 5 em terceira ou quarta linha (sem RMM) e 3 pacientes em descontinuacao de ITQ. A proporcao de pacientes com TAN >1:320 foi superior no grupo que recebia terceira ou quarta linha (p=0,022). Entretanto, neste grupo havia mais pacientes com infeccao previa por COVID-19. Nao houve diferenca estatistica entre as taxas de seroconversao (CMIA, IgM and IgG) entre pacientes que receberam Coronavac ou ChAdOx1 nCoV-19. Nao houve diferencas nas taxas de seroconversao entre pacientes que receberam ITQ e naqueles em descontinuacao (p=0,77). Discussao: Estudos observacionais demonstraram que pacientes com LMC-FC produzem anticorpos em niveis semelhantes a populacao geral, apos receberem as vacinas ChAdOx1 nCoV-19 ou BNT162b2. No estudo conduzido por Rotterdam et al., 100/101 pacientes apresentaram seroconversao apos duas doses. Outro estudo avaliou as taxas de conversao em pacientes que receberam Coronavac, demonstrando menores taxas de conversao se comparados a vacina BNT162b2. Nosso estudo demonstrou que a resposta sorologica apos duas doses de vacina contra SARS-CoV-2 foi menor do que a descrita previamente na literatura. Conclusoes: Nao foram demonstradas diferencas entre os tipos de vacina (Coronavac vs. ChAdOx1 nCoV-19) ou em relacao a fase da doenca na taxa de seroconversao. Duas doses de vacinas para COVID-19 foram insuficientes para imunizacao adequada em pacientes com LMC. Agradecimentos: Brazilian National Council for Scientific and Technological Development (CNPq), grant ndegree 401977/2020-0. Copyright © 2022
ABSTRACT
Background: Although initially considered at higher risk for severe presentations of COVID-19, observational studies with SCD patients have mostly pointed to clinical severity similar to the general population. However, the level of vulnerability of these individuals to become infected and the determinants for their contagion are still uncertain. Aims: To assess the prevalence of SARS-Cov-2 antibodies in SCD patients followed at a Brazilian center and its correlation with phenotypic and socioeconomic determinants. Methods: A questionnaire was applied regarding demographics, socioeconomic status, use of Hydroxyurea, working status and income, COVID-19 symptoms, and the perceptions about social isolation measures. Blood samples were taken for chemoluminescence IgG (anti-N) and IgM (anti-S) anti-SARS-CoV-2 tests (Abbott Architect™, Ireland);specific neutralizing antibody titers were accessed observing the cytopathic effect in cells incubated with patient serum-virus mixture. Results: From Jul/20 to Jan/21, 214 serological tests were performed on135 patients (86% of SCD patients registered at the center): 82 HbSS (61%), 41HbSC (30%), 8Sβ+ (6%), 4Sβ0 (3%);57% male and median age 42 (19-74). 66% were using Hydroxyurea and 4% were on chronic transfusion. In the analyzed period, 61 (45%) patients had vasoocclusive crises;37 (27%) had symptoms suggestive of COVID-19, but only 2 patients had a positive PCR for SARS-Cov-2. When questioned, only12% of patients did not consider themselves vulnerable to infection, and only17% believed that individual and collective protection measures were expendable. In fact, 91% stated that they were able to adopt basic social distance measures, with 76% reporting cancellation of social events and 64% managed to reduce the use of public transport, but only 44% could work or study remotely. Regarding serological evaluation, 57 patients (42%) were tested more than1 time during this period: 46 with 2 tests,11 with ≥ 3 tests. Among all patients,15 had positive results: 9 IgG/IgM+ and 6 IgG+ only, therefore with an overall seroprevalence of11%. Seroconversion was documented for only1 patient during the study period and, interestingly, with no signs and symptoms of infection. Moreover, 2 patients lost positivity for IgG 3 months after the initial positive test. The search for functionally neutralizing antibodies resulted in 9 patients with low titers (□1:40) and only 3 patients with remarkably high titers (≥1:640). There were no correlations between test positivity and education, income, number of household contacts and maintenance of work outside the home;however, serological positivity was associated with older age (40.3 x 22.9, p<.001) and regular use of public transport (Fisher exact test, p=0.02). Only1 patient in this cohort needed hospitalization for COVID-19, including mechanical ventilation and exchange transfusions, but was discharged after14 days Summary/Conclusion: These data attest to the effectiveness of social distancing instructions given to patients in our SCD clinic throughout the pandemic, considering the low overall positivity and only1 seroconversion during the study period. The fact that only1 patient in our center had severe disease agrees with other reports showing less severity for SCD than initially expected. In fact, the transient positivity of serological tests and the low levels of functional neutralizing antibodies in SCD patients may indicate the acquisition of protective immune responses that are not dependent on antibodies and that still need to be better evaluated.