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"Latar Belakang Penelitian ini meneliti potensi peningkatan resistensi insulin dan obesitas dalam 12 bulan pasca COVID-19 pada penyintas COVID-19 dengan status glikemik beragam. Analisis retrospektif dilakukan untuk mengidentifikasi faktor metabolik dan respons inflamasi yang berkontribusi, termasuk proporsi sel T memori spesifik SARS-CoV-2 yang fungsional dan yang mengalami disfungsi, kadar sitokin, serta polarisasi makrofag. Metode Penelitian kohort ini melibatkan 47 pasien terinfeksi SARS-CoV-2 yang dipantau selama lima periode: fase akut (baseline), bulan ke-1, ke-3, ke-9, dan ke-12 fase konvalesen. Partisipan dikelompokkan menjadi tiga berdasarkan status obesitas dan peningkatan HOMA-IR, yaitu non-obes (NO), obes tanpa peningkatan HOMA-IR (O), dan obes dengan peningkatan HOMA-IR (O-IR). Peningkatan HOMA-IR didefinisikan sebagai rasio HOMA-IR bulan ke-12/bulan ke-1 ≥ 1,21. Pada setiap periode, dilakukan pengukuran komposisi tubuh, kadar kendali glikemik, serta isolasi PBMC. Identifikasi sel T CD4+ dan CD8+ memori spesifik SARS-CoV-2 dilakukan melalui inkubasi PBMC dengan antigen SARS-CoV-2 selama 24 jam. Supernatan hasil inkubasi PBMC dengan antigen digunakan untuk menilai kadar sitokin yang diproduksi dan kecenderungan polarisasi makrofag. Hasil Sebanyak 35,3% pasien non-DM, 75% pasien DM baru, dan 59,1% pasien DM mengalami peningkatan HOMA-IR ≥ 21% dalam 12 bulan pasca COVID-19. Kelompok O-IR tidak mengalami penurunan total lemak tubuh, rasio lemak/otot, dan lingkar perut dalam 12 bulan follow up. Selain itu, kelompok O-IR memiliki proporsi sel T memori spesifik SARS-CoV-2 fungsional lebih rendah, sementara sel yang mengalami disfungsi lebih tinggi, kadar sitokin lebih rendah, tetapi rasio TNF-α/IL-10 lebih tinggi dibandingkan dengan kelompok lain. Supernatan dari PBMC dari kelompok O-IR menurunkan ekspresi IL-10 pada makrofag M2. Sehingga ekspresi IL10 ini tidak mampu menekan ekspresi IL-6 makrofag M1. Kesimpulan Disfungsi sel T memori spesifik SARS-CoV-2 meningkatkan resistensi insulin 12 bulan pasca COVID-19 pada kelompok obes yang tidak mengalami penurunan kadar lemak dan obesitas sentral.

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Background: A retrospective analysis to investigate the increased of insulin resistance and obesity within 12 months after COVID-19 was conducted to identify contributing metabolic factors and inflammatory responses, including the proportion of functional and dysfunctional SARS-CoV-2-specific memory T cells, cytokine levels, and macrophage polarization.

Methods:

This cohort study involved 47 SARS-CoV-2-confirmed patients, who were followed-up at five periods: the acute phase (baseline) and months 1, 3, 9, and 12 of the convalescent phases. Participants were categorized into three groups based on obesity status and increased HOMA-IR: non-obese (NO), obese without HOMA-IR increase (O), and obese with HOMA-IR increase (O-IR). Increased of HOMA-IR was defined as a HOMA-IR ratio of 12th/1st month ≥ 1.21. At each period, body composition and glycemic indices were measure and PBMC was isolated. The PBMC was incubated with SARS-CoV-2 antigen for 24 hours to identify SARS-CoV-2-specific CD4+ and CD8+ memory T cells The PBMC supernatant was used to evaluate cytokine production and macrophage polarization. Results:

A 35.3% of non-DM patients, 75% of newly diagnosed DM patients, and 59.1% of DM patients experienced increased of HOMA-IR ≥21% within 12 months postCOVID-19. The O-IR group did not show a reduction in total body fat, fat-tomuscle ratio, or waist circumference over the 12-month follow-up. Additionally, the O-IR group had a lower proportion of functional SARS-CoV-2-specific memory T cells, a higher proportion of dysfunctional cells, lower cytokine levels, but a higher TNF-α/IL-10 ratio compared to other groups. The PBMC supernatant from the O-IR group reduced IL-10 expression in M2 macrophages, which failed to suppress IL-6 expression in M1 macrophages.

Conclusion:

The dysfunctional SARS-CoV-2 memory T cells may increase the risk of elevated insulin resistance within 12 months post COVID-19, particularly in obese individual who do not experience body fat and central obesity reduction."

"COVID-19 merupakan penyakit menular yang disebabkan oleh SARS-CoV-2 dan ditetapkan sebagai pandemi global pada 11 Maret 2020 oleh WHO. Pemerintah Republik Indonesia mulai melaksanakan program vaksinasi booster untuk meningkatkan durabilitas sistem imun, khususnya pada tenaga kesehatan untuk memicu reaksi imunogenitas pada tubuh melalui produksi antibodi netralisasi (NAb). Namun, NAb memiliki durabilitas tertentu dan mungkin akan mengalami penurunan yang turut dipengaruhi oleh adanya SARS-CoV-2 varian baru yang muncul seperti varian Delta dan Omicron. Tujuan dari penelitian ini adalah mengevaluasi antibodi netralisasi yang dihasilkan oleh tenaga kesehatan di Jakarta sebelum dan setelah 12 bulan vaksinasi booster COVID-19, mengevaluasi antibodi netralisasi setelah 12 bulan vaksinasi booster COVID-19 terhadap 4 varian SARS-CoV-2 berupa varian wild type, Delta, Omicron (B.1.1.529), dan Omicron (BA.2), dan mengevaluasi antibodi netralisasi pada partisipan yang mengalami breakthrough infection dengan partisipan yang tidak mengalami breakthrough setelah 12 bulan vaksinasi booster COVID-19. Metode yang digunakan dalam penelitian ini adalah uji Surrogate Virus Neutralization Test (sVNT) yang sesuai untuk digunakan dalam mendeteksi antibodi netralisasi karena memiliki hasil yang baik dengan waktu deteksi singkat. Hasil penelitian yang diperoleh adalah terdapat kenaikan antibodi netralisasi yang signifikan pada saat 12 bulan pascavaksinasi booster dibandingkan dengan saat pravaksinasi booster. Selain itu, terdapat perbedaan kadar antibodi netralisasi antara keempat varian dengan penurunan antibodi netralisasi yang cukup signifikan sekitar 10—20% pada varian Omicron (B.1.1.529 dan BA.2). Tidak terdapat perbedaan antibodi netralisasi yang signifikan pada partisipan yang mengalami breakthrough infection dengan partisipan yang tidak mengalami breakthrough infection, namun, seluruh partisipan breakthrough infection memiliki tingkat keparahan COVID-19 kategori ringan. Kesimpulan penelitian ini adalah vaksinasi booster pertama pada partisipan menunjukkan durabilitas imun pada bulan ke-12 pascavaksinasi booster pertama yang masih tergolong baik dan kemungkinan berpengaruh terhadap rendahnya tingkat keparahan gejala COVID-19 pada partisipan yang mengalami breakthrough infection. Varian baru SARS-CoV-2 seperti Omicron (B.1.1.529 dan BA.2) menyebabkan penurunan respons kekebalan tubuh sehingga perlu dilaksanakan vaksinasi booster lanjutan.

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COVID-19 is an infectious disease caused by SARS-CoV-2 and was declared as global pandemic on 11 March 2020 by WHO. The Government of the Republic of Indonesia has started implementing a booster vaccination program to increase the durability of the immune system, especially for healthcare workers to trigger an immunogenic reaction in the body through the production of neutralizing antibodies (NAb). However, NAb has a certain durability and may experience a decrease which is also influenced by the emergence of new SARS-CoV-2 variants such as the Delta and Omicron variants. The purpose of this study was to evaluate the neutralization antibodies produced by healthcare workers in Jakarta before and after 12 months of the COVID-19 booster vaccination, to evaluate the neutralization antibodies after 12 months of the COVID-19 booster vaccination against 4 variants of SARS-CoV-2 in the form of wild type variants, Delta, Omicron (B.1.1.529), and Omicron (BA.2), and evaluated neutralizing antibodies in participants who experienced a breakthrough infection with participants who did not experience a breakthrough after 12 months of the COVID-19 booster vaccination. The method used in this study is the Surrogate Virus Neutralization Test (sVNT) which is suitable for detecting neutralizing antibodies because it has good results with a short detection time. The results of the study were that there was a significant increase in neutralizing antibodies 12 months after the booster vaccination compared to the prevaccination booster. In addition, there were differences in neutralizing antibody levels between the four variants with a significant decrease in neutralizing antibodies of around 10—20% in the Omicron variants (B.1.1.529 and BA.2). There was no significant difference in neutralizing antibodies in participants who experienced a breakthrough infection and participants who did not experience a breakthrough infection. However, all breakthrough infection participants had a mild level of COVID-19 severity. The conclusion of this study is that the first booster vaccination in participants shows immune durability at the 12th month after the first booster vaccination which is still relatively good and may have an effect on the lower severity of COVID-19 symptoms in participants who experience a breakthrough infection. New variants of SARS-CoV-2 such as Omicron (B.1.1.529 and BA.2) cause a decrease in the body's immune response so that further booster vaccinations are necessary."

"Salah satu terapi COVID-19 adalah plasma konvalesen yang disiapkan Unit Transfusi Darah dari donor yang telah sembuh dari COVID-19. Plasma konvalesen mengandung antibodi netralisasi yang menghambat interaksi antara protein S dengan reseptor ACE2 dengan persyaratan minimal titer 1:160 sehingga diperlukan sistem deteksi antibodi netralisasi seperti tes serologi berbasis ELISA kompetitif yang mudah, murah, cepat dan tidak membutuhkan BSL 3 atau 2. Uji ini membutuhkan protein rekombinan spike S1 yang dapat diekspresikan pada sistem ekspresi mamalia. Penelitian ini bertujuan untuk mendeteksi antibodi spesifik SARS-CoV-2 pada plasma konvalesen COVID-19 menggunakan protein rekombinan Spike S1.Penelitian ini menggunakan plasmid pD609 sebagai vektor ekspresi yang terdapat gen spike S1. DNA ditransfeksi secara transien ke sel CHO. Immunostaining dilakukan setelah transfeksi untuk melihat ekspresi protein rekombinan spike S1 pada sel CHO. Supernatan media sel CHO post transfeksi dianalisis dengan western blot dan ELISA untuk melihat reaktifitas terhadap serum konvalesen COVID-19. Hasil immunostaining menunjukkan plasmid pD609 S1 Spike Foldon-His dapat mengekspresikan protein rekombinan spike S1 SARS-CoV-2 pada sel CHO. Hasil Western Blot dan ELISA menunjukkan supernatan media sel kultur CHO post transfeksi reaktif terhadap serum konvalesen COVID-19. Protein rekombinan spike S1 memiliki potensi untuk dikembangkan dan digunakan dalam uji antibodi spesifik namun hasil ekspresi protein masih rendah.

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One of the therapies for COVID-19 is convalescent plasma prepared by the Blood Transfusion Unit from donors who have recovered from COVID-19. Convalescent plasma contains neutralizing antibodies that inhibit the interaction between S protein and ACE2 receptors with a minimum requirement of a titer of 1:160 so that a neutalizing antibody detection system is needed such as a competitive ELISA-based serological test that is easy, inexpensive, fast, and does not require BSL 3 or 2. S1 spike recombinant protein that can be expressed in mammalian expression systems. This study aims to detect SARS-CoV-2 specific antibodies in COVID-19 convalescent plasma using recombinant Spike S1 protein. This study used the pD609 plasmid as an expression vector containing the spike S1 gene. DNA was transiently transfected into CHO cells. Immunostaining was performed after transfection to see the expression of the S1 spike recombinant protein in CHO cells. The post-transfected CHO cell media supernatans were analyzed by western blot and ELISA to see the reactivity to COVID19 convalescent serum. Immunostaining results showed that the plasmid pD609 S1 Spike Foldon-His could express the SARS-CoV-2 spike S1 recombinant protein in CHO cells. The results of Western blot and ELISA showed that the post-transfection CHO cell culture media supernatant was reactive to COVID-19 convalescent serum. S1 spike recombinant protein has the potential to be developed and used in specific antibody assays, but the results of protein expression is still low."

"Golongan usia anak merupakan golongan usia yang paling ringan terdampak infeksi COVID-19. Salah satu kemungkinan penyebab keadaan tersebut adalah perlindungan dari efek nonspesifik vaksinasi rutin yang diterima anak sebelumnya. Vaksinasi rutin yang diterima anak dapat memodulasi sistem imun anak terhadap infeksi lain di luar target imunisasi yang dituju melalui mekanisme imunitas heterolog. Bukti-bukti penelitian terdahulu menimbulkan hipotesis antigen vaksin DTP berpotensi menimbulkan imunitas heterolog dengan SARS-CoV-2. Hal ini berdasarkan kemiripan epitop antara antigen SARS-CoV-2 dengan antigen pada vaksin DTP. Belum diketahui bagaimana pengaruh vaksinasi DT booster terhadap respons imun (antibodi S-RBD SARS-CoV-2 dan IFN-ɤ-sel T spesifik SARS-CoV-2) pascavaksinasi COVID-19 inaktif pada anak usia 6–7 tahun. Penelitian ini bertujuan mengetahui pengaruh pemberian vaksinasi DT booster pada anak yang mendapat vaksinasi COVID-19 inaktif terhadap respons imun humoral dan selular anak.Studi potong lintang dilakukan dengan didahului tahapan pengambilan data pada orang tua subjek penelitian di wilayah Senen, Jakarta Pusat. Pengambilan data menggunakan kuesioner yang disebarkan secara luring kepada orang tua melalui guru sekolah anaknya. Dari kuesioner didapatkan data status vaksinasi anak, yang dibedakan dalam 4 kelompok yaitu COVID+/DT+, COVID+/DT–, COVID–/DT+ dan COVID–/DT–, dan diukur antibodi S-RBD, IFN-ɤ-sel T spesifik SARS-CoV-2 dan IgG antidifteri.Hasil penelitian menunjukkan 113 dari 154 subjek penelitian (73,4%) telah memiliki status relative immune terhadap difteri, dengan hasil IgG antidifteri > 0,1 IU/mL. Terdapat imunitas heterolog vaksinasi DT booster terhadap COVID-19 dengan adanya perbedaan bermakna kadar antibodi S-RBD SARS-CoV-2 antara anak yang sudah mendapat vaksin DT booster dibanding yang belum (1182 U/mL vs. 612,5 U/mL, p = 0,026), dan perbedaan bermakna IFN-ɤ-sel T spesifik SARS-CoV-2 pada anak COVID+/DT+ dibanding COVID+/DT– (560,87 mIU/mL vs. 318,03 mIU/mL, p = 0,03). Tidak didapatkan korelasi antara IgG antidifteri dan S-RBD SARS-CoV-2. Selain hasil penelitian data laboratorium, didapatkan pula data keinginan orang tua untuk vaksinasi COVID-19 bagi anaknya adalah sebesar 69,7%.Disimpulkan vaksin DT booster dapat berperan menguatkan respons imun spesifik SARS-CoV-2 pada anak yang menerima vaksin COVID-19 inaktif.

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Corona Virus Disease 2019 (COVID-19) in children tends to be mild. A possible cause is existing protection from the routine vaccination previously received by children. Routine vaccinations can modulate the child's immune system against other pathogen, presumably through a mechanism of heterologous immunity. Previous research had suggested that the Diphtheria-Tetanus-Pertussis (DTP) vaccine antigen has potential to incite heterologous immunity towards SARS-CoV-2, due to similarities between SARS-CoV-2 epitopes and various epitopes found within the DTP vaccine. It was not known whether the Diphtheria-Tetanus (DT) vaccination could modulate the SARS-CoV-2-specific immune response among children aged 6–7 years who received inactivated COVID-19 vaccine.

This study thus aimed to assess the impact of DT booster immunization in SARS-CoV-2-specific humoral and cellular immune responses among children who received two doses of CoronaVac.

A cross-sectional study was performed on children aged 6–7 years old in the Senen area, Central Jakarta. This study was started with data collection from parents of eligible subjects using questionnaire that was distributed to parents via their children’ school teachers. Based on the collected demographic data and the child's vaccination status, eligible subjects were further screened. The participating subjects were subsequently classified into 4 groups, i.e., COVID+/DT+, COVID+/DT-, COVID-/DT+ and COVID-/DT-. Blood collections were performed to determine anti-diphtheria toxoid antibodies, anti-S-RBD antibodies and SARS-CoV-2-specific T cell-produced IFN-ɤ.

The results showed that 113 of 154 subjects (73.4%) had relative immune-status against diphtheria as the result of the anti–diphtheria toxoid antibodies was > 0.1 IU/mL. There was a heterologous immunity of DT booster and COVID-19 vaccine, as there was significant difference in anti-S-RBD antibody titers between the group with DT booster compared to non-DT booster (1182 U/mL vs. 612.5 U/mL, p = 0.026), and a significant difference in IFN-ɤ concentration between the group of COVID+/DT+ and COVID+/DT- (560.87 mIU/mL vs. 318.03 mIU/mL, p = 0.03). No correlation was found between anti-diphtheria and anti-S-RBD antibodies. In addition, our data indicated that parental intention to vaccinate their children against COVID-19 in the Senen area was 69.7%.

In conclusion, our results suggested that DT booster vaccine might able to enhance SARS-CoV-2-specific immune responses among children who received inactivated COVID-19 vaccine."

"COVID-19 merupakan penyakit yang disebabkan oleh virus SARS-CoV-2 yang mengakibatkan pandemi global. Jakarta adalah salah satu kota di Indonesia dengan angka kasus dan kematian tertinggi akibat COVID-19. Salah satu cara paling efektif untuk mengurangi keparahan dan resiko penularan COVID-19 adalah dengan vaksinasi. Vaksin dapat merangsang respons imunitas humoral tubuh yang menghasilkan antibodi netralisasi. Selain vaksin, antibodi netralisasi dapat diinduksi secara natural oleh imunitas tubuh. Hybrid immunity merupakan gabungan antara antibodi netralisasi yang diinduksi secara natural dan yang diinduksi oleh vaksin. SARS-CoV-2 terus bermutasi memunculkan berbagai varian yang menyebabkan peningkatan jumlah kasus dan munculnya gelombang COVID-19 baru di Indonesia, yaitu gelombang Delta pada Juni 2021 dan gelombang Omicron pada Januari 2022. Penelitian ini bertujuan untuk mengevaluasi perubahan antibodi netralisasi 3 bulan setelah vaksinasi dosis lengkap dari beberapa jenis vaksin, yaitu vaksin virus inaktivasi (CoronaVac), vaksin viral vektor (ChAdOx1 nCoV-19), dan vaksin mRNA (BNT162b2) serta pengaruh riwayat infeksi SARS-CoV-2 pada penerima vaksin terhadap berbagai varian SARS-CoV-2 (Wuhan, Delta, Omicron B.1.1.529 dan BA.2). Penelitian dilakukan dengan menggunakan uji Surrogate Virus Neutralization Test (sVNT) yang memiliki prinsip kerja seperti enzyme-linked immunosorbent assay (ELISA) dan meniru interaksi antara receptor binding domain (RBD) dan angiotensin-converting enzyme 2 (ACE2) dalam pelat ELISA dengan RBD dan ACE2 yang telah mengalami pemurnian dengan sampel serum partisipan populasi umum (n = 76). Hasil penelitian menunjukkan adanya perbedaan signifikan antara antibodi netralisasi sebelum dan 3 bulan setelah vaksinasi dosis lengkap, tetapi tidak terdapat perbedaan signifikan pada antibodi netralisasi yang dihasilkan dari masing-masing jenis vaksin. Hal tersebut kemungkinan disebabkan oleh waktu pengambilan sampel setelah terjadi gelombang Omicron COVID-19 sehingga terjadi hybrid immunity yang menyebabkan tingginya kadar antibodi netralisasi yang merata pada setiap jenis vaksin. Partisipan dengan riwayat infeksi SARS-CoV-2 memiliki kadar antibodi netralisasi yang lebih tinggi. Terdapat perbedaan antibodi netralisasi yang signifikan terhadap berbagai varian SARS-CoV-2 dengan penurunan kadar antibodi netralisasi yang signifikan terhadap varian Omicron B.1.1.529 dan BA.2. Kesimpulan dari penelitian ini adalah vaksinasi dosis lengkap berhasil meningkatkan kadar antibodi netralisasi hingga 3 bulan pascavaksinasi yang dipengaruhi oleh riwayat infeksi SARS-CoV-2.

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COVID-19 is a disease caused by the SARS-CoV-2 virus which has resulted in a global pandemic. Jakarta is one of the cities in Indonesia with the highest number of COVID-19 cases and deaths. One of the most effective ways to reduce the severity and transmission risk of COVID-19 is by getting vaccinated. Vaccines can stimulate the body's humoral immune response to produce neutralizing antibodies. Apart from vaccines, neutralizing antibodies can be induced naturally by the body's immunity. Hybrid immunity is a combination of naturally induced neutralizing antibodies and those induced by vaccines. The continuously mutating SARS-CoV-2 has led to the emergence of various variants which have resulted in an increase in the number of cases and the emergence of new COVID-19 waves in Indonesia, namely the Delta variant which appeared in June 2021 and the Omicron variant in January 2022. This study aims to evaluate changes in neutralizing antibodies 3 months after complete doses of several types of vaccines, namely inactivated virus vaccine (CoronaVac), viral vector vaccine (ChAdOx1 nCoV-19), and mRNA vaccine (BNT162b2) and the effect of a history of SARS-CoV-2 infection in vaccine recipients against various variants SARS-CoV-2 (Wuhan, Delta, Omicron B.1.1.529 and BA.2). The study was conducted using the Surrogate Virus Neutralization Test (sVNT) test which has a working principle like the enzyme-linked immunosorbent assay (ELISA) and mimics the interaction between the receptor binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2) in ELISA plates using RBD and ACE2 that had undergone purification with sera samples of general population participants (n = 76). The results showed that there were significant differences between the neutralizing antibodies before and 3 months after the full dose of vaccination, but there were no significant differences in the neutralizing antibodies produced from each type of vaccine. This was probably caused by the sampling time after the Omicron COVID-19 wave occurred, resulting in hybrid immunity which resulted in high levels of neutralizing antibodies that were evenly distributed in each type of vaccine. Participants with a history of SARS-CoV-2 infection had higher levels of neutralizing antibodies. There were significant differences in neutralizing antibodies against various variants of SARS-CoV-2 with a significant decrease in levels of neutralizing antibodies against Omicron B.1.1.529 and BA.2 variants. The conclusion of this study is that full dose vaccination has succeeded in increasing neutralizing antibody levels for up to 3 months after vaccination which are affected by a history of SARS-CoV-2 infection."

"Pembuatan Stable Cell Line sendiri membutuhkan proses pengantaran materi genetik untuk mencapai tahap ekspresi gen rekombinan secara berkelanjutan. Metode ini menggunakan transfeksi untuk membantu mencapai tahapan tersebut. Badan Riset dan Inovasi Nasional (BRIN) Indonesia telah berhasil membuat konstruksi plasmid rekombinan pengekspresi protein Spike SARS-CoV-2. Namun, belum dilakukan penelitian lebih lanjut terkait penggunaan konstruksi plasmid rekombinan tersebut. Oleh karena itu, tujuan penelitian ini adalah untuk memvalidasi ekspresi protein rekombinan dari plasmid rekombinan pengekspresi Spike SARS-CoV-2 yang akan digunakan dalam pembuatan Stable Cell Line pada galur sel mamalia 293T. Validasi ekspresi dari empat protein SARS-CoV-2 (Spike Full, Subunit S1, Subunit S2, dan Receptor Binding Domain) dilakukan melalui metode Immunofluorescence Assay (IFA) dan Western Blot (WB). Hasil menunjukkan bahwa dari empat ragam protein (Spike Full, Subunit S1, Subunit S2, dan Receptor Binding Domain) terbukti fungsional secara ekspresi dan sesuai dengan ukuran protein yang sesuai. Uji IFA menunjukkan bahwa terdapat dua nilai rata-rata Corrected Total Cell Fluorescence (CTCF) yang unggul yaitu pada protein Spike Full dan Subunit S2 (118.813 dan 264.159 CTCF) sel pasca transfeksi yang menandakan bahwa terdapat perbedaan kemampuan ekspresi dari masing-masing protein. Uji western blot telah membuktikan dua protein (Spike Full dan Subunit S2) memiliki ukuran molekul yang sesuai (142,5 dan 66,0 kDa). Sehingga, dapat disimpulkan bahwa plasmid rekombinan yang dikonstruksi oleh BRIN terbukti fungsional dan dapat dilanjutkan ke dalam penggunaannya untuk pembuatan Stable Cell Line.

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Making a Stable Cell Line requires a process of delivering genetic material to reach the continuous recombinant gene expression stage. This method uses transfection to help achieve this stage. The National Research and Innovation Agency of Indonesia (BRIN) has successfully constructed a recombinant plasmid expressing the SARS-CoV-2 Spike protein. However, no further research has been carried out regarding using these recombinant plasmid constructs. Therefore, this study aimed to validate the expression of recombinant proteins from the SARS-CoV-2 Spike-expressing recombinant plasmid to manufacture Stable Cell Line in mammalian cell line 293T. Validation of the expression of four SARS-CoV-2 proteins (Spike Full, Subunit S1, Subunit S2, and Receptor Binding Domain) was carried out using Immunofluorescence Assay (IFA) and Western Blot (WB) methods. The results showed that the four protein variants (Spike Full, S1 Subunit, S2 Subunit, and Receptor Binding Domain) were functional in expression and according to the appropriate protein size. The IFA test showed two superior Corrected Total Cell Fluorescence (CTCF) values: the Spike Full protein and the S2 Subunit (118.813 and 264159 CTCF) of post-transfection cells, which indicated that there were differences in the expression ability of each protein. The Western Blot test has proven that two proteins (Spike Full and Subunit S2) have the appropriate molecular size (142.5 and 66.0 kDa). Thus, it can be concluded that the recombinant plasmid constructed by BRIN is proven to be functional and can be used to manufacture Stable Cell Lines."

"Latar belakang: Clinically significant prostate cancer (csPCa) merupakan kanker prostat yang mempunyai kemungkinan progresi lokal, metastasis, rekurensi, dan kematian yang sedang hingga tinggi, serta tata laksana yang lebih agresif. Penelitian ini bertujuan untuk membantu diagnosis antara csPCa dan bukan csPCa menggunakan rasio apparent diffusion coefficient (rADC) lesi prostat dengan urine. Metode: Penelitian dilakukan pada lesi prostat kategori 3-5 prostate imaging-reporting and data system yang telah dibiopsi prostat transperineal tertarget magnetic resonance imaging (MRI) dengan ultrasound/MRI fusion software di Rumah Sakit Umum Pusat Nasional Dokter Cipto Mangunkusumo pada Juni 2019 hingga Maret 2021. rADC lesi prostat dengan urine merupakan perbandingan rerata nilai apparent diffusion coefficient (ADC) lesi prostat dan urine di vesica urinaria pada MRI prostat peta ADC potongan aksial multi-institusi. rADC lesi prostat dengan urine antara csPCa (adenokarsinoma asinar prostat dengan skor Gleason ≥7) dan bukan csPCa (jaringan prostat nonneoplastik atau adenokarsinoma asinar prostat dengan skor Gleason 6) dibandingkan dan ditentukan nilai titik potongnya menggunakan receiver operating curve. Hasil: Terdapat perbedaan rADC lesi prostat dengan urine yang bermakna antara 19 lesi prostat yang merupakan csPCa dan 35 lesi prostat yang bukan merupakan csPCa, dengan nilai tengah rADC lesi prostat dengan urine pada csPCa 0,21 (0,11-0,33), nilai tengah rADC lesi prostat dengan urine pada bukan csPCa 0,43 (0,30-0,61), dan nilai p <0,001. Nilai titik potong rADC lesi prostat dengan urine dalam membedakan csPCa dan bukan csPCa adalah 0,30 dengan sensitivitas 94,73% dan spesifisitas 100%, area under curve 0,998 (IK95% 0,994-1,000), serta nilai p <0,001. Kesimpulan: rADC lesi prostat dengan urine dapat membantu diagnosis csPCa dan bukan csPCa pada lesi prostat sebelum biopsi prostat yang tidak invasif, mudah dikerjakan, serta tidak membutuhkan persiapan dan pemeriksaan tambahan.

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Background: Clinically significant prostate cancer (csPCa) is prostate cancer with moderate to high probability of local progression, metastasis, recurrence, and death, as well as more aggressive management. This study aims to aid diagnose between csPCa and non-csPCa using apparent diffusion coefficient ratio (rADC) of prostate-lesion-to-urine.

Methods: This study analyze prostate lesions with prostate imaging-reporting and data system category 3-5 that underwent magnetic resonance imaging (MRI)-targeted transperineal prostate biopsy using ultrasound/MRI fusion software at Rumah Sakit Umum Pusat Nasional Dokter Cipto Mangunkusumo from June 2019 to March 2021. rADC of prostate-lesion-to-urine is defined as comparison between mean apparent diffusion coefficient (ADC) value of prostate lesion and urine in urinary bladder from axial section of ADC map of multi-institutional prostate MRI. rADC of prostate-lesion-to-urine between csPCa (acinar adenocarcinoma of the prostate with Gleason score ≥7) and non-csPCa (non-neoplastic prostate tissue or acinar adenocarcinoma of the prostate with Gleason score 6) is compared and the cutoff point is determined using receiver operating curve.

Results: There is significance rADC of prostate-lesion-to-urine difference between 19 prostate lesions with csPCa and 35 prostate lesions with non-csPCa, with mean rADC of prostate-lesion-to-urine in csPCa is 0.21 (0.11-0.33), mean rADC of prostate-lesion-to-urine in non-csPCa is 0.43 (0.30-0.61), and p value is <0.001. The cut-off value of rADC of prostate-lesion-to-urine to differentiate between csPCa and non-csPCa is 0.30, with 94.73% sensitivity and 100% specificity, area under curve is 0.998 (CI95% 0.994-1.000), and p value is <0.001.

Conclusion: rADC of prostate-lesion-to-urine may help diagnose between csPCa and non-csPCa in prostate lesions before prostate biopsy, which is non-invasive, easy to perform, does not require additional preparation and examination."

"Latar Belakang: Pandemi COVID-19 menyebabkan mortalitas dan morbiditas yang tinggi khususnya pada tenaga kesehatan di Indonesia, Studi mengenai manfaat dari vaksin booster mRNA-1273 yang diawali vaksinasi primer Coronavac masih minim sehingga diperlukan penelitian lebih lanjut.Tujuan: Penelitian ini dilakukan untuk mengetahui faktor yang berhubungan dengan insiden COVID-19 pasca vaksinasi booster mRNA-1273 yang diberikan vaksinasi primer Coronavac sebelumnya serta profil antibodi pada tenaga kesehatan di Indonesia.Metode: Penelitian ini menggunakan gabungan desain kohort retrospektif dan potong lintang pada 300 tenaga kesehatan yang dipilih secara acak dari data penerima vaksin booster mRNA-1273 di salah satu RS tersier (RSCM). Subjek yang terpilih kemudian dilakukan wawancara mendalam mengenai riwayat vaksinasi COVID-19, riwayat terinfeksi COVID-19, komorbiditas dan dilakukan pengambilan sampel darah untuk menilai kadar antibodi IgG sRBD. Dari hasil wawancara kemudian dinilai faktor-faktor yang berhubungan terhadap kejadian COVID-19 pasca vaksinasi booster mRNA-1273 serta profil antibodi subjek.Hasil: 56 orang (18,6%) mengalami COVID-19 setelah divaksinasi booster dalam 5 bulan. Incidence rate per person per month sebesar 3,2%. Median antibodi IgG sRBD dalam 8 bulan 6627 AU/ml (min-max, 729-20374 AU/ml) dan tidak berhubungan dengan variabel usia, jenis kelamin, komorbiditas, KIPI pasca booster ataupun riwayat infeksi pasca booster. Usia, jenis kelamin, diabetes melitus tipe 2, hipertensi, obesitas dan KIPI pasca booster tidak berhubungan terhadap insiden COVID-19 pasca booster. Riwayat COVID-19 sebelum vaksinasi booster berhubungan signifikan terhadap penurunan kejadian COVID-19 pasca vaksinasi booster dengan RR 0,20 (95 % CI: 0,09-0,45).Simpulan: Insiden COVID-19 mencapai 18,6% dalam 5 bulan pasca vaksinasi booster dengan riwayat COVID-19 sebelum vaksinasi booster berperan dalam menurunkan risiko kejadian COVID-19 pasca vaksinasi booster.

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Background: COVID-19 pandemic has caused high mortality and morbidity especially among healthcare workers in Indonesia. Studies on the benefits of the mRNA-1273 booster vaccine preceded with Coronavac primary vaccine are still minimal so further studies are needed.

Purpose: Knowing the factors associated with the incidence rate of SARS-CoV-2 infection after mRNA-1273 booster vaccination starting with the Coronavac primary vaccination and the antibody profile of healthcare workers in Indonesia.

Method: This study used combined design of retrospective cohort and cross sectional study. Three hundreds healthcare workers at one of tertiary hospital in Indonesia that obtain mRNA-1273 booster vaccine minimal after 5 months were randomly selected. Subjects were then interviewed regarding their history of COVID-19 vaccination, history of SARS-CoV-2 infection, comorbidities and blood samples were taken to assess IgG sRBD antibody levels. Factors related to antibody profile and incidence of SARS-CoV-2 infection after the mRNA-1273 booster vaccination were then analyzed.

Results: 56 subjects (18.6%) experienced SARS-CoV-2 infection after mRNA-1273 booster vaccination. Median antibody IgG sRBD in 8 months was 6627 AU/ml (min-max, 729-20374 AU/ml) and not related to age, gender, comorbidities, AEFI after booster and infection after booster. Age, gender, diabetes type 2, hypertension, obesity, AEFI after booster were not related to COVID-19 incidence after booster. History of SARS-CoV-2 infection before booster vaccination was significantly associated with reduced risk of SARS-CoV-2 infection after booster vaccination with RR 0,20 (95 % CI: 0,09-0,45).

Conclusion: Cumulative incidence of SARS-CoV-2 infection in 5 months was 18,6% with history of COVID-19 before booster correlated with reduced risk of COVID-19 after booster."

"Respons antibodi spesifik SARS-CoV-2 dapat diperoleh dari paparan virus ketika infeksi ataupun dari vaksinasi. Studi mengenai rasio CD4+/CD8+ sebagai penanda status imunitas masih belum banyak dilakukan pada dewasa sehat. Vitamin D yang memiliki efek imunomodulatori pada sistem imun adaptif dan alamiah, mampu memodulasi pembentukan antibodi dan regulasi dari sel T. Penelitian ini bertujuan melihat hubungan kadar 25(OH)D serum terhadap titer antibodi SARS-CoV-2 dan rasio CD4+/CD8+ sebagai penanda status imunitas individu. Studi potong lintang ini dilakukan terhadap tenaga kesehatan di tiga rumah sakit rujukan COVID-19 di Jakarta dan Depok pada periode Juli–Desember 2021. Pengambilan data yang dilakukan berupa wawancara kuesioner data sosiodemografik, pemeriksaan tanda-tanda vital, pengukuran antropometri, dietary assessment menggunakan 24-h food recall dan SQ-FFQ. Pengambilan sampel darah dilakukan untuk menilai kadar 25(OH)D serum, rasio CD4+/CD8+, dan titer antibodi SARS-CoV-2. Didapatkan 154 tenaga kesehatan usia 22-53 tahun dalam kondisi sehat dan tanpa riwayat penyakit kronis. Median asupan vitamin D subjek penelitian sebesar 2,42 mcg/hari (1,23–4,00) dengan 94,7% subjek memiliki asupan vitamin D yang kurang. Median kadar serum 25(OH)D pada subjek sebesar 14,4 ng/mL (9,50–18,62) dengan 81,8% subjek mengalami defisiensi dan 14,9% subjek mengalami insufisiensi vitamin D. Median rasio CD4+/CD8+ 1,14 (0,88–1,34), 85,7% subjek memiliki titer antibodi SARS-CoV-2 >250 U/mL dan 14,3% subjek memiliki titer antibodi ≤250. Tidak ditemukan adanya hubungan yang siginifikan antara kadar 25(OH)D dengan titer antibodi SARS-CoV-2 (p 0,209 OR 4,101 95% CI 0,45–37,04) dan Rasio CD4/CD8 (p 0,385 𝛃 -0,005 95% CI -0,0015–0,006). Asupan dan kadar vitamin D pada subjek penelitian masih tergolong rendah. Penelitian ini tidak berhasil membuktikan adanya hubungan antara kadar serum 25(OH)D dengan rasio CD4+/CD8+ dan titer antibodi SARS-CoV-2.

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SARS-CoV-2 specific antibody response can be generated from exposure to the virus during infection or from vaccination. There is limited data on CD4+/CD8+ ratio in healthy individuals as a marker of immunity status. Vitamin D, which has an immunomodulatory effect on both  innate and adaptive immune systems, is able to modulate antibody formation and regulation of T cells. This study aimed to examine the association between serum 25(OH)D levels and SARS-CoV-2 antibody titers along with CD4+/CD8+ ratio as a marker of immunity status. This cross-sectional study was conducted on healthcare workers at three COVID-19 referral hospitals in Jakarta and Depok in the period of July–December 2021. Data collection was carried out using questionnaire, examination of vital signs, anthropometric measurements, dietary assessment using 24-h food recall, and SQ-FFQ. Blood samples were taken to assess serum 25(OH)D levels, CD4+/CD8+ ratio, and SARS-CoV-2 antibody titers. 154 healthcare workers aged 22-53 years who were in good health and had no history of chronic disease were examined in this study. The median intake of vitamin D was 2.42 mcg/day (1.23-4.00), with 94.7% of participants having insufficient intake of vitamin D. The median serum 25(OH)D level was 14.4 ng/mL (9.50-18.62), with 81.8% participants are vitamin D deficiency and 14.9% are insufficient. Median CD4+/CD8+ ratio was 1.14 (0.88 to 1.34). 85.7% participants had SARS-CoV-2 antibody titers >250 U/mL, while 14.3% were below 250 U/mL. There was no significant relationship of serum 25(OH)D levels to SARS-CoV-2 antibody titers (p 0.209 OR 4.101 95% CI 0.45–37.04) and CD4+/CD8+ ratio (p 0.385 o-0.005 95% CI -0.0015–0.006). Vitamin D intake and serum 25(OH)D levels are relatively low. This study disproves relationship between serum 25(OH)D levels with CD4+/CD8+ ratio and SARS-CoV-2 antibody."

"Latar Belakang: COVID-19 merupakan penyakit yang disebabkan oleh infeksi SARS-CoV-2 yang dapat mengalami mutasi sehingga membentuk beberapa varian baru. Perubahan varian tersebut dapat menyebabkan proses transmisi virus yang cepat hingga meningkatnya mortalitas dan morbiditas pada pasien COVID-19. Adanya mikrobiota pada saluran pernafasan yang merupakan bagian dari sistem kekebalan tubuh dapat memberikan perlindungan dari infeksi dan pathogenesis SARS-CoV-2 pada tubuh manusia. Akan tetapi, patogenesis virus dari beberapa varian SARS-CoV-2 yang berbeda dapat menghambat homeostasis dari komunitas mikroba pada saluran pernafasan. Oleh sebab itu perlu dilakukan identifikasi varian SARS-CoV-2 dan profil komunitas bakteri pada sampel swab naso/orofaring pasien COVID-19, untuk mendapatkan data awal profil komunitas mikroba dan korelasinya dengan varian SARS-CoV-2.Metode: Penelitian menggunakan sampel swab naso/orofaring pasien COVID-19. Sekuensing sampel dilakukan sebanyak dua kali. Sekuensing pertama bertujuan untuk mengidentifikasi varian SARS-CoV-2 menggunakan Whole Genome Sequencing (WGS) dari Oxford Nanopore Technologies (ONT). Sekuensing kedua bertujuan untuk mengidentifikasi keragaman bakteri pada naso/orofaring pasien COVID-19 menggunakan amplifikasi gen 16S rRNA. Kemudian analisis bioinformatika dilakukan untuk memperoleh profil komunitas mikroba pada beberapa varian SARS-CoV-2.Hasil: Ditemukan enam varian SARS-CoV-2 yang dideteksi pada sampel terpilih yang dikoleksi selama bulan Maret-Juni 2021, dengan hasil varian yang mendominasi adalah varian Delta, Alpha, dan Lokal. Pada varian Alpha dan Delta didominasi oleh genus bakteri Streptococcus, Prevotella, dan Veillonella. Pada varian lokal, genus yang mendominasi yaitu Corynebacterium, Staphylococcus, dan Salmonella.Kesimpulan: Komunitas bakteri yang ditemukan pada sampel swab naso/orofaring pasien COVID-19 memiliki tingkat keragaman yang signifikan antar varian SARS-CoV-2. Komunitas bakteri yang ditemukan didominasi oleh genus Prevotella, Streptococcus, Corynebacterium, dan Veillonella. Persentase jumlah bakteri paling banyak yaitu genus Prevotella sebesar 27%. Genus bakteri Prevotella dan Veillonella banyak ditemukan pada varian SARS-COV-2 Alpha dan Delta, yang memiliki potensi meningkatkan inflamasi dan tingkat keparahan pada pasien COVID-19.

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Background: COVID-19 is a disease caused by infection of a SARS-CoV-2 virus that can undergo mutations to form several new variants. These variants could lead to a more rapid transmission, which increases mortality and morbidity in COVID-19 patients. The presence of microbiota in the respiratory tract as part of the immune system provides protection from viral infections and pathogenesis in the human body. However, pathogenesis of different SARS-CoV-2 variants plays a role in inhibiting the homeostasis of the microbial community in the respiratory tract. Therefore, it is necessary to identify the SARS-CoV-2 variants and profile the bacterial community profile in naso/oropharynx using swab samples of COVID-19 patients, to obtain initial data regarding the microbial community profile of COVID-19 patients and potential correlation with the SARS-CoV-2 variants.

Methods: This study used naso/oropharyngeal swab samples from COVID-19 patients. Sample sequencing was performed twice. The first sequencing aims to identify variants of SARS-CoV-2 using Whole Genome Sequencing (WGS) with Oxford Nanopore Technologies (ONT) platform. The second sequencing aims to identify bacterial diversity in the naso/oropharynx of COVID-19 patients using 16S rRNA gene amplification followed by profiling of the microbial community using bioinformatic analysis.

Results: Six variants of SARS-CoV-2 were identified in the selected samples collected during March-June 2021, with the dominant variants being Delta, Alpha, and Local variants. The microbial community of samples belonging to the Alpha and Delta variants was dominated by the bacterial genera Streptococcus, Prevotella, and Veillonella. Meanwhile, in the samples identified as having local variant, the dominant genera were Corynebacterium, Staphylococcus, and Salmonella.

Conclusion: The bacterial diversity in the swab samples naso/oropharyngeal of COVID-19 patients varied significantly among SARS-CoV-2 variants. The bacterial community was dominated by the genera Prevotella, Streptococcus, Corynebacterium, and Veillonella. The highest percentage of genus was Prevotella by 27%. The genera Prevotella and Veillonella were found in the SARS-CoV-2 Alpha and Delta variants, which have the potential to increase inflammation and severity in COVID-19 patients."