Korelasi Antara Kadar Serum Α-Tocopherol Dengan Kadar Anti-S-Rbd Dan Ifn-Γ Pada Kasus Breakthrough Setelah Vaksinasi Sinovac Pada Tenaga Kesehatan Di Rsud Dr. Saiful Anwar Malang

Kesuma, Tanti Adelia and Prof. Dr. dr. Kusworini Handono, M.Kes, Sp.PK Subsp.I.K.(K) and Prof. Dr. dr. Handono Kalim, Sp.PD-KR (2024) Korelasi Antara Kadar Serum Α-Tocopherol Dengan Kadar Anti-S-Rbd Dan Ifn-Γ Pada Kasus Breakthrough Setelah Vaksinasi Sinovac Pada Tenaga Kesehatan Di Rsud Dr. Saiful Anwar Malang. Magister thesis, Universitas Brawijaya.

Abstract

Petugas kesehatan terutama yang bertugas di Instalasi Gawat Darurat dan/atau melakukan tindakan swab nasofaring memiliki risiko tinggi terpapar dan menularkan COVID-19 akibat eksposur intens tanpa bisa menjaga jarak fisik, sehingga mereka diprioritaskan untuk vaksinasi. Di RS Saiful Anwar, Malang, pada tahap awal, vaksinasi menggunakan Sinovac. Namun, WHO melaporkan bahwa antibodi dari vaksin ini menurun setelah tiga bulan. Infeksi breakthrough masih bisa terjadi pada orang yang sudah divaksinasi. Efektivitas vaksin dapat dipengaruhi oleh faktor virus, usia, komorbiditas, dan kekebalan host. α-tocopherol sebagai antioksidan kuat melindungi membran sel dari peroksidasi lipid dan memperkuat respons imun, baik humoral maupun seluler. Dalam respons humoral, α-tocopherol mendukung produksi antibodi spesifik terhadap domain pengikat reseptor (anti-S-RBD), penting untuk netralisasi SARS-CoV-2. Pada respons seluler, α-tocopherol meningkatkan produksi interferon gamma (IFN-γ), yang berperan penting dalam aktivasi sel T dan pertahanan imun terhadap virus. Penelitian ini merupakan studi observasional analitik dengan rancangan potong lintang, yang bertujuan menganalisis hubungan kadar α-tocopherol serum dengan anti-S-RBD dan IFN-γ pada kasus breakthrough dan non-breakthrough pasca vaksinasi Sinovac. Infeksi breakthrough dikonfirmasi melalui RT-PCR SARS-CoV-2 dengan mendeteksi RNA atau antigen dari usap nasofaring dalam rentang ≥14 hari hingga <26 minggu setelah dosis kedua Sinovac. Pemilahan sampel dilakukan berdasarkan kriteria inklusi dan eksklusi. Kadar α-tocopherol diukur menggunakan ELISA kit (BT Lab), IFN-γ diukur menggunakan ELISA kit (The BioLegend), dan keduanya dibaca dengan microplate reader. Anti-S-RBD dideteksi menggunakan ECLIA pada alat Roche Cobas e411. Data dianalisis menggunakan uji normalitas Shapiro-Wilk, uji beda Mann-Whitney dan Kruskal Wallis, serta korelasi Spearman. Penelitian ini melibatkan 89 responden dengan 49 kasus infeksi breakthrough (55%), yang sebagian besar terjadi pada individu dengan komorbid seperti asma, dislipidemia, dan hipertensi. Insiden infeksi breakthrough meningkat secara signifikan tiga bulan setelah vaksinasi. Secara keseluruhan, rerata kadar α-Tocopherol, IFN-γ, dan anti-S-RBD pada kelompok non-breakthrough lebih tinggi dibandingkan dengan kelompok breakthrough, meskipun perbedaannya tidak signifikan secara statistik (p=0.494; p=0.125; p=0.291). Namun, analisis lebih vii lanjut dengan mempertimbangkan komorbiditas menunjukkan perbedaan signifikan pada kadar α-Tocopherol dan IFN-γ. Kadar α-Tocopherol secara signifikan lebih tinggi pada kelompok non-breakthrough tanpa komorbiditas (rata rata 108,28 µmol/L) dibandingkan kelompok lainnya (p=0.001). Kadar IFN-γ pada kelompok non-breakthrough tanpa komorbiditas (rata-rata 166,20 pg/mL) juga secara signifikan lebih tinggi dibandingkan dengan kelompok lainnya (p=0.001). Di sisi lain, kadar anti-S-RBD antara kasus breakthrough dan non-breakthrough, baik dengan atau tanpa komorbiditas, tidak menunjukkan perbedaan signifikan (p=0.473). α-Tocopherol tidak menunjukkan korelasi yang signifikan terhadap kadar anti-S-RBD (p>0.05), namun memiliki korelasi positif yang signifikan dengan kadar IFN-γ, yang berarti peningkatan kadar α-Tocopherol dihubungkan dengan peningkatan kadar IFN-γ (p=0.000). Berdasarkan penelitian ini, dapat disimpulkan bahwa setelah tiga bulan pasca pemberian dua dosis vaksin Sinovac (vaksin homolog) pada tenaga kesehatan di RSUD Saiful Anwar menunjukkan peningkatan kasus infeksi breakthrough hingga lima kali lipat dibandingkan dengan laporan infeksi pada tenaga kesehatan di tempat lain, dengan kasus lebih banyak ditemukan pada kelompok dengan komorbiditas. Selain itu, serum α-Tocopherol berperan signifikan dalam meningkatkan respons imun seluler, tetapi tidak menunjukkan hasil signifikan dalam respons humoral. Temuan ini mungkin dipengaruhi oleh riwayat infeksi COVID-19 sebelumnya, yang dapat memengaruhi hasil pengukuran kadar anti-S-RBD.

English Abstract

Healthcare workers, particularly those working in Emergency Departments and/or performing nasopharyngeal swab tests, are at high risk of contracting and transmitting COVID-19 due to intense exposure and the inability to maintain physical distance. As a result, they were prioritized for vaccination. At Saiful Anwar Hospital in Malang, the initial vaccination used the Sinovac vaccine. However, the WHO has reported that antibodies from this vaccine decline after three months. Breakthrough infections can still occur in vaccinated individuals. The effectiveness of the vaccine can be influenced by factors such as viral characteristics, age, comorbidities, and the host immune system. α-Tocopherol, as a potent antioxidant, protects cell membranes from lipid peroxidation and strengthens both humoral and cellular immune responses. In the humoral response, α-tocopherol supports the production of specific antibodies against the receptor-binding domain (anti-S RBD), which is crucial for neutralizing SARS-CoV-2. In the cellular response, α tocopherol enhances the production of interferon gamma (IFN-γ), which plays an important role in T-cell activation and immune defense against the virus. This study is an observational analytic study with a cross-sectional design, aiming to analyze the relationship between serum α-tocopherol levels with anti-S RBD and IFN-γ in breakthrough and non-breakthrough cases after Sinovac vaccination. Breakthrough infection was confirmed by RT-PCR for SARS-CoV-2 through detection of RNA or antigens from nasopharyngeal swabs within the range of ≥14 days to <26 weeks after the second dose of Sinovac. Sample selection was based on inclusion and exclusion criteria. α-Tocopherol levels were measured using the ELISA kit (BT Lab), while IFN-γ levels were measured using the ELISA kit (The BioLegend), both read with a microplate reader. Anti-S-RBD was detected using ECLIA on the Roche Cobas e411 device. Data were analyzed using the Shapiro-Wilk normality test, Mann-Whitney test, Kruskal-Wallis test, and Spearman's correlation. This study involved 89 respondents, with 49 cases of breakthrough infection (55%), most of which occurred in individuals with comorbidities such as asthma, dyslipidemia, and hypertension. The incidence of breakthrough infections increased significantly three months after vaccination. Overall, the average levels of α-tocopherol, IFN-γ, and anti-S-RBD in the non-breakthrough group were higher than in the breakthrough group, although the differences were not statistically ix significant (p=0.494; p=0.125; p=0.291). However, further analysis considering comorbidities showed significant differences in α-tocopherol and IFN-γ levels. α Tocopherol levels were significantly higher in the non-breakthrough group without comorbidities (mean 108.28 µmol/L) compared to other groups (p=0.001). IFN-γ levels in the non-breakthrough group without comorbidities (mean 166.20 pg/mL) were also significantly higher than in other groups (p=0.001). On the other hand, anti-S-RBD levels between breakthrough and non-breakthrough cases, with or without comorbidities, did not show significant differences (p=0.473). α-Tocopherol did not show a significant correlation with anti-S-RBD levels (p>0.05), but it had a significant positive correlation with IFN-γ levels, indicating that increased α tocopherol levels were associated with increased IFN-γ levels (p=0.000). Based on this study, it can be concluded that three months after the administration of two doses of the Sinovac vaccine (homologous vaccine) in healthcare workers at Saiful Anwar Hospital, there was a five-fold increase in breakthrough infection cases compared to reports of infection in healthcare workers elsewhere, with more cases found in the group with comorbidities. Additionally, serum α-tocopherol plays a significant role in enhancing the cellular immune response, but did not show significant results in the humoral response. These findings may be influenced by the history of prior COVID-19 infection, which could affect the measurement of anti-S-RBD levels.

Item Type:	Thesis (Magister)
Identification Number:	042406
Divisions:	Profesi Kedokteran > Spesialis Patologi Klinik, Fakultas Kedokteran
Depositing User:	Unnamed user with username nova
Date Deposited:	16 Oct 2024 01:55
Last Modified:	16 Oct 2024 01:55
URI:	http://repository.ub.ac.id/id/eprint/230888

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