Imunogenicidade natural e induzida pelas vacinas contra a Covid-19 em uma coorte de trabalhadores da saúde
Nenhuma Miniatura disponível
Data
2024-11-18
Autores
Gouvea, Maria da Penha Gomes
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Federal do Espírito Santo
Resumo
The clinical profile of COVID-19 has been linked to age, pre-existing comorbidities, viral load, immunological profile, and individual vaccination status. This study resulted from two consecutive projects. Objectives: In the first phase, monitoring of symptoms and antibody production in a cohort of unvaccinated healthcare professionals over six months. The aim of the second phase was to evaluate the immunogenicity and duration of humoral response of the CoronaVac and AstraZeneca (ChAdOx1) vaccines in a cohort of workers for 180 days after the primary schedule and 180 days after booster dose with ChAdOx1 or Pfizer/BioNTech (BNT 162b2), in homologous and heterologous schemes. Method: Observational longitudinal study. The first phase included healthcare workers diagnosed with COVID-19 confirmed by RT-PCR. The presence of anti-nucleocapsid IgG and IgM antibodies against SARS-CoV-2 was detected by chemiluminescent microparticle immunoassay (ARCHITECT i1000SR, Abbott Laboratories, IL, USA). IgG results > 1.4 AU/mL and IgM > 1.0 AU/mL were considered seroconverted (group A), and those with values below were non-seroconverted (group B). Serologic tests were conducted at 15, 30, 45, 60, 90, and 180 days after COVID-19 symptoms onset. The second phase included healthcare workers which were immunized with two doses of CoronaVac or ChAdOx1 followed by a booster dose with ChAdOx1 or BNT 162b2 (BNT). Subjects underwent 8-9 blood collections for IgG anti-spike antibody levels (IgG-S) measurement, immediately before the first dose, 28 days after the first dose, immediately before the second dose, 28 days and 180 days after the second dose (*), immediately before the third dose, 28, 90, and 180 after the booster dose (#). IgG antibody titers to the SARS-CoV-2 spike receptor binding domain (IgG-S) were determined using a chemiluminescent microparticle immunoassay (CMIA) (ARCHITECT i1000SR, SARS-CoV-2 IgG II Quant assay, Abbott Laboratories, Abbott Park, IL, USA). Results were expressed in arbitrary units per mL (AU/mL) and converted to Binding Antibody Units per mL (BAU/mL), as standardized by the World Health Organization (WHO). Results: The first phase included 73 healthcare workers with COVID-19. 4 subjects were separately evaluated due to reinfection. COVID-19 evolved mildly to moderately in all 69 subjects. Mean age was 40 (±10) years, 74% female, 78.3% with previous comorbidities, and 21.7% used at least one medication for chronic disease. Common initial symptoms were muscle pain (76.9%), headache (75.5%), anosmia (59.6%), ageusia (63.8%), rhinorrhea (58.4%), fever (52.2%), and cough (52.2%). After 30 days, persistent symptoms included anosmia (18.9%), asthenia (18.9%), adynamia (14.5%), muscle pain and ageusia (7.3%). IgG serology curve peaked on the 30th day with an average value of 3.25 AU/mL, and IgM peaked on the 15th day with an average value of 7.2 AU/mL, both showing progressive decline in subsequent serologies. Non-seroconversion for IgG or IgM was observed in 26% of participants (n=18). Among IgG seropositive individuals, 28.3% (n=15) maintained IgG reactivity for 180 days. The symptom Diarrhea had a 4-fold higher likelihood of IgM seropositivity, while sore throat and shortness of breath increased the likelihood by 6-fold for reactive IgG after 180 days. The 4 patients with recurrent infection belonged to the non-seropositive group. The mean period between infection and reinfection was 112 (± 65) days. The recurrence rate was 5.47%. Symptomatic period duration ranged from 3 to 22 days for the first infection and 5 to 19 days for the second infection. RT-PCR cycle threshold (Ct) data showed lower Ct values during COVID-19 recurrence in the four cases. All four participants became IgM and IgG seropositive during reinfection, with symptoms considered more severe in one participant requiring medical care and non-invasive respiratory support for 24 hours. In the second phase of this study, serological results from the first blood collection showed 42.8% IgG-S reactivity in the VAC group and 29.7% in the AZV group. In both groups, IgG-S levels increased [Geometric Mean Titers (95% CI)], with CoronaVac or ChAdOx1 [D28 = 12(10–15) vs. 71(57–88) and D28* = 115(96–137) vs. 488(407–586)]. Seroconversion rate at D28* was 100% in both groups. At D180, 88% of VAC participants remained reactive, and 100% in the AZV group. Sharp decline in titers averaged 3.73 times and 2.61 times in seronegative groups, and averaged 2.16 times and 1.66 times in seropositive, VAC and AZV groups, respectively. Six months after primary vaccination (D180), the geometric mean titer significantly decreased in VAC [30(24–39)] and AZV [186(155–226)]. Confirming this, PRNT neutralizing antibody test demonstrated higher geometric mean titers in the AZV group compared to VAC, regardless of serological status [237 (181–311) vs. 43 (34–55) seronegative and 748 (534–1,048) vs. 145 (111–189) seropositive], with high correlation (r = 0.93, p < 0.001). In the VAC seronegative group, soluble plasma mediators were increased at D28* compared to D28 and compared to AZV. The AZV seropositive group showed high levels of soluble plasma mediators at D28 and D28* compared to the VAC group. Levels of soluble immune mediators were reduced at D28 compared to D0 in both seronegative groups. At D28*, the CCL3, CCL2, IL-1B, IL-6, IFN-y, IL-5, VEGF, and PDGF set was increased, while the IL-12, IL-15, IL-17, IL-10, IL-13, FGF-basic, G-CSF, GM-CSF, and IL-2 set remained unchanged. Soluble mediators that differed between vaccine schemes were CCL11, CXCL8, CCL4, CCL5, CXCL10, TNF-a, IL-1Ra, IL-4, and IL-9, with the VAC seronegative group showing higher levels than AZV at D28*. On the booster day (D0#), all AZV group participants remained seropositive, while in the VAC group, seropositivity rate was 16% lower. Heterologous groups were formed: VAC/BNT, VAC/AZV, AZV/BNT, and 1 homologous group AZV/AZV. At D28#, heterologous groups showed stronger titers with VAC/AZV and VAC/BNT (45 times and 118 times, respectively) compared to AZV/BNT (29 times), while the homologous AZV/AZV scheme showed a slight increase (3.9 times). Heterologous schemes induced higher neutralizing antibody titers against the Wuhan ancestral lineage, Delta, and Omicron variants. Seropositivity rate for the Omicron variant was significantly lower in the homologous scheme (VAC/AZV = 93%; VAC/BNT = 100%; AZV/BNT = 100% vs. AZV/AZV = 64%). Following booster dose, antibody response in VAC or AZV groups showed exponential growth. VAC/BNT scheme induced titers as high as AZV/BNT and maintained them up to 180 days after the booster dose. Conclusion: IgM and IgG peak approximately 15/30 days after symptom onset. Natural infection with SARS CoV-2 does not provide similar protection in all individuals, and absence of specific antibodies may increase reinfection risk. Exacerbated symptoms in second infection may be associated with higher viral load. 28 days after the second dose, CoronaVac and AstraZeneca vaccines induced seroconversion in 100% of patients. CoronaVac induced lower titers and shorter duration of immunity compared to AstraZeneca. Higher activation of inflammatory response biomarkers was observed in the VAC group compared to the AZV group, possibly due to the multiplicity of antigens present in the inactivated virus vaccine. Heterologous booster with AstraZeneca or BNT 162b2 provided protection against the ancestral strain and Delta and Omicron variants, regardless of primary immunization scheme. Overall, kinetic analysis of IgGS reactivity reinforces the efficacy of the heterologous scheme in inducing antibody response to SARS-CoV-2. Additionally, the heterologous scheme produced higher geometric mean titers than the homologous regimen. Lower titers and faster decline of specific antibody levels suggest the need for a booster dose.
Descrição
Palavras-chave
Vacina , Resposta imunológica natural , Resposta imune adaptativa