The first case of coronavirus disease (COVID-19) in humans was discovered in Wuhan City, China. This disease is caused by SARS-CoV-2. According to the World Health Organization (WHO), in 2020, COVID-19 is the third disease caused by a coronavirus, spreading faster and more extensively than SARS and MERS. Studies show that COVID-19 patients admitted to the hospital experience severity as low as 1.4 % and as high as 61.5 % in critical stages. According to data compiled by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU), as of January 12th, 2022, there have been over 314.019.135 confirmed cases of COVID-19 since the first cases were discovered in 2019, resulting in 5507,370 deaths.
In general, COVID-19 symptoms include fever, headache, fatigue, diarrhea, loss of taste and smell, and a dry cough that can lead to respiratory distress and death. A recent study by Geneva University Hospitals found that symptoms of SARS-CoV-2 infection typically appear 2–3 days after infection, and about 32 % of participants reported experiencing at least one symptom. Symptoms can affect functional capacity up to 12 months post-infection. As of April 2020, there were 1790 confirmed cases of COVID-19, with 170 deaths and 112 recoveries. Indonesia experienced a sharp surge in COVID-19 cases from December 2020 to February 2021, with a peak of 14,224 confirmed cases in a single day on January 16, 2021. In the second wave of COVID-19 spread on July 15, 2021, the number of cases increased dramatically to 56,757 per day.
The present study focuses on synthesizing CDs using CA and 2-aminophenyl boronic acid (APBA). CA is a carbon source with a carboxyl group, facilitating essential dehydration and carbonization reactions. CA exhibits respectable biocompatibility and low cytotoxicity in healthy cells. APBA is a carbon and nitrogen source during the CDs synthesis. This strategic combination of CA and APBA contributes to successfully fabricating CDs with desirable properties for potential biomedical applications [20]. Nanoparticles (i.e., quantum dots, gold nanoparticles (GNPs), and silver nanoparticles) have been widely used in COVID-19 antibody marker assays. The alteration of these nanoparticles’ optical properties is a reliable indicator for detection. For instance, gold nanoparticles (GNPs) have demonstrated changes in absorption and emission when in contact with IgG or IgM antibodies.
This phenomenon has been extensively studied, showcasing the potential for precise detection methods. However, exploring modified CDs absorption and emission changes in the presence of IgG and IgM antibodies for COVID-19 detection remains uncharted territory and emerges a notable gap in research that warrants investigation. The present study will examine alterations in the absorption and emission of Boron-modified CDs in the presence of IgG and IgM antibodies, which could significantly contribute to filling this gap. By demonstrating the efficacy of modified CDs in detecting IgG and IgM antibodies of COVID-19 patients, this research could pave the way for innovative diagnostic approaches, thus advancing the field of nanoparticle-based detection methods for infectious diseases. Considering all the advantages of this developed APBA-CDs marker, it emerges as a promising auxiliary diagnostic method for COVID-19. It can potentially be crucial in global efforts to contain the ongoing pandemic.
COVID-19 antibody
This research investigates how carbon dots (CDs) can be utilized as markers for COVID-19 antibodies, taking advantage of their biocompatibility and low toxicity. CDs were synthesized using citric acid (CA) and APBA with boronic acid, enabling the detection of COVID-19 IgG antibodies with increased absorbance and fluorescence. Comprehensive analyses confirmed the successful synthesis of APBA-CDs, prompting further exploration of their impact on SARS-CoV-2 RNA. Increased absorbance levels were observed in categories K1, K2, and K3, attributed to the introduction of CDs into plasma, indicating effective binding of APBA-CDs to COVID-19 antibodies. In addition, the fluorescence tests consistently showed heightened levels across all categories, emphasizing the effective binding of APBA-CDs with COVID-19 antibodies, particularly in positive plasma samples. As a part of our analysis, we conducted a PCA test to validate the data, which revealed that APBA-CDs are specific to IgG+ antibodies. The results showed a sensitivity rate of 74 % and a specificity rate of 53 %, while, when tested for IgM antibodies, the sensitivity and specificity rates were 63 % and 27 %, respectively. These findings highlight the potential of APBA-CDs as a sensitive and specific marker for COVID-19 antibody detection, offering potential for diagnostic tool development.
During the marker test, the absorbance and fluorescence results of the APBA-CDs compound were compared with those of plasma alone without using any compound markers (as illustrated in Fig. 1). The absorbance test was conducted using four different wavelengths such as 360 nm (Fig. 1a), 380 nm (Fig. 1b), 400 nm (Fig. 1c), and 450 nm (Fig. 1d). The results showed a significant increase in absorbance levels for categories K1 (IgG positive and IgM negative), K2 (IgG negative and IgM positive), and K3 (IgG positive and IgM positive). The notable enhancement is attributed to the introduction of CDs into the plasma, as CDs exhibit higher absorbance levels than plasma. These results suggest that APBA-CDs are effectively bound to antibodies in blood plasma, indicating a positive presence of COVID-19. Furthermore, boronic acid, employed as a guide for CDs to the COVID-19 virus, selectively reacts with 1,2- or 1,3-cis diol groups, resembling the existing gp120 binding agent in the Human Immunodeficiency Virus (HIV). Moreover, a previous study confirmed that diol groups could block viral processes within the host. It was confirmed that both IgG and IgM consist of a large number of hydroxyl group and cis-diol, formation of the boronated complex resulted from the boronic acid of APBA and cis-diols of the antibodies became the fundamental reason for the effectiveness of the APBA-CDs marker and is potentially developed as a specific marker for detecting the COVID-19 virus.
Conclusion
The research highlights the promising potential of APBA-CDs as sensitive and specific markers for COVID-19 antibody detection. Their biocompatibility, low toxicity, and stability in physiological conditions make them suitable candidates for diagnostic tool development. This innovative approach could enhance current diagnostic methods, providing a supplementary screening tool to RT-PCR, particularly in resource-limited settings. The study paves the way for further exploration and optimization of carbon dot-based biosensors in the fight against COVID-19 and other infectious diseases.
Author: Prof. Mochamad Zakki Fahmi, S.Si., M.Si., Ph.D.
Link : https://www.sciencedirect.com/science/article/pii/S0731708524002826?pes=vor#sec0040
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