COVID-19 Associated Thyroid Dysfunction and Other Comorbidities and Its Management Using Phytochemical-Based Therapeutics- A Natural Way.

The present severe acute respiratory syndrome-2 (SARS-CoV-2) mediated Coronavirus pandemic (COVID-19) and post-COVID-19 complications affect human life drastically. Patients who have been cured of COVID-19 infection are now experiencing post-COVID-19 associated comorbidities, which have increased mortality rates.  The SARS-CoV-2 infection distresses the lungs, kidneys, gastrointestinal tract, and various endocrine glands, including the thyroid. The emergence of variants which includes Omicron (B.1.1.529) and its lineages threaten the world severely. Among different therapeutic approaches, phytochemical-based therapeutics are not only cost-effective but also have lesser side effects. Recently a plethora of studies have shown the therapeutic efficacy of various phytochemicals for the treatment of COVID-19. Besides this, various phytochemicals have been found efficacious in treating several inflammatory diseases, including thyroid-related anomalies. The method of the phytochemical formulation is quick and facile and the raw materials for such herbal preparations are approved worldwide for human use against certain disease conditions. Owing to the advantages of phytochemicals, this review primarily discusses the COVID-19-related thyroid dysfunction and the role of key phytochemicals to deal with thyroid anomaly and post-COVID-19 complications. Further, this review shed light on the mechanism via which COVID-19 and its related complication affect organ function of the body, along with the mechanistic insight into the way by which phytochemicals could help to cure post-COVID-19 complications in thyroid patients. Considering the advantages offered by phytochemicals as a safer and cost-effective medication they can be potentially used to combat COVID-19-associated comorbidities.

Synergistically functionalized molybdenum disulfide-reduced graphene oxide nanohybrid based ultrasensitive electrochemical immunosensor for real sample analysis of COVID-19.

Herein, we have proposed a straightforward and label-free electrochemical immunosensing strategy supported on a glassy carbon electrode (GCE) modified with a biocompatible and conducting biopolymer functionalized molybdenum disulfide-reduced graphene oxide (CS-MoS2/rGO) nanohybrid to investigate the SARS-CoV-2 virus. CS-MoS2/rGO nanohybrid-based immunosensor employs recombinant SARS-CoV-2 Spike RBD protein (rSP) that specifically identifies antibodies against the SARS-CoV-2 virus via differential pulse voltammetry (DPV). The antigen-antibody interaction diminishes the current responses of the immunosensor. The obtained results indicate that the fabricated immunosensor is extraordinarily capable of highly sensitive and specific detection of the corresponding SARS-CoV-2 antibodies with a LOD of 2.38 zg mL-1 in phosphate buffer saline (PBS) samples over a broad linear range between 10 zg mL-1-100 ng mL-1. In addition, the proposed immunosensor can detect attomolar concentrations in spiked human serum samples. The performance of this immunosensor is assessed using actual serum samples from COVID-19-infected patients. The proposed immunosensor can accurately and substantially differentiate between (+) positive and (-) negative samples. As a result, the nanohybrid can provide insight into the conception of Point-of-Care Testing (POCT) platforms for cutting-edge infectious disease diagnostic methods.

Internet-of-medical-things integrated point-of-care biosensing devices for infectious diseases: Toward better preparedness for futuristic pandemics.

Microbial pathogens have threatened the world due to their pathogenicity and ability to spread in communities. The conventional laboratory-based diagnostics of microbes such as bacteria and viruses need bulky expensive experimental instruments and skilled personnel which limits their usage in resource-limited settings. The biosensors-based point-of-care (POC) diagnostics have shown huge potential to detect microbial pathogens in a faster, cost-effective, and user-friendly manner. The use of various transducers such as electrochemical and optical along with microfluidic integrated biosensors further enhances the sensitivity and selectivity of detection. Additionally, microfluidic-based biosensors offer the advantages of multiplexed detection of analyte and the ability to deal with nanoliters volume of fluid in an integrated portable platform. In the present review, we discussed the design and fabrication of POCT devices for the detection of microbial pathogens which include bacteria, viruses, fungi, and parasites. The electrochemical techniques and current advances in this field in terms of integrated electrochemical platforms that include mainly microfluidic- based approaches and smartphone and Internet-of-things (IoT) and Internet-of-Medical-Things (IoMT) integrated systems have been highlighted. Further, the availability of commercial biosensors for the detection of microbial pathogens will be briefed. In the end, the challenges while fabrication of POC biosensors and expected future advances in the field of biosensing have been discussed. The integrated biosensor-based platforms with the IoT/IoMT usually collect the data to track the community spread of infectious diseases which would be beneficial in terms of better preparedness for current and futuristic pandemics and is expected to prevent social and economic losses.

Biosensors based detection of novel biomarkers associated with COVID-19: Current progress and future promise.

The pandemic situation of COVID-19 has caused global alarm in health care, devastating loss of lives, strangled economy, and paralysis of normal livelihood. The high inter-individual transmission rate created havoc in the global community. Although tremendous efforts are pitching in from across the globe to understand this disease, the clinical features seemed to have a wide range including fever, cough, and fatigue are the prominent features. Congestion, rhinorrhea, sore throat, and diarrhea are other less common features observed. The challenge of this disease lies in the difficulty in maneuvering the clinical course causing severe complications. One of the major causative factors for multi-organ failure in patients with severe COVID-19 complications is systemic vasculitis and cytokine-mediated coagulation disorders. Hence, effective markers trailing the disease severity and disease prognosis are urgently required for prompt medical treatment. In this review article, we have emphasized currently identified inflammatory, hematological, immunological, and biochemical biomarkers of COVID-19. We also discussed currently available biosensors for the detection of COVID-19-associated biomarkers & risk factors and the detection methods as well as their performances. These could be effective tools for rapid and more promising diagnoses in the current pandemic situation. Effective biomarkers and their rapid, scalable, & sensitive detection might be beneficial for the prevention of serious complications and the clinical management of the disease.

Functionalized Titanium Dioxide Nanoparticle-Based Electrochemical Immunosensor for Detection of SARS-CoV-2 Antibody.

The advancement in biosensors can overcome the challenges faced by conventional diagnostic techniques for the detection of the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, the development of an accurate, rapid, sensitive, and selective diagnostic technique can mitigate adverse health conditions caused by SARS-CoV-2. This work proposes the development of an electrochemical immunosensor based on bio-nanocomposites for the sensitive detection of SARS-CoV-2 antibodies through the differential pulse voltammetry (DPV) electroanalytical method. The facile synthesis of chitosan-functionalized titanium dioxide nanoparticles (TiO2-CS bio-nanocomposites) is performed using the sol-gel method. Characterization of the TiO2-CS bio-nanocomposite is accomplished using UV-vis spectroscopy, Raman spectroscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM). The electrochemical performance is studied using cyclic voltammetry (CV), DPV, and electrochemical impedance spectroscopy (EIS) for its electroanalytical and biosensing capabilities. The developed immunosensing platform has a high sensitivity with a wide range of detection from 50 ag mL-1 to 1 ng mL-1. The detection limit of the SARS-CoV-2 antibody in buffer media is obtained to be 3.42 ag mL-1 and the limit of quantitation (LOQ) to be 10.38 ag mL-1. The electrochemical immunosensor has high selectivity in different interfering analytes and is stable for 10 days. The results suggest that the developed electrochemical immunosensor can be applicable for real sample analysis and further high-throughput testing.

Polydopamine decorated MoS2 nanosheet based electrochemical immunosensor for sensitive detection of SARS-CoV-2 nucleocapsid protein in clinical samples.

The outbreak of the highly contagious disease COVID-19, which is triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demands a rapid, low-cost, and highly sensitive immunosensor that can detect and identify the virus efficiently. Here, an electrochemical immunosensor based on a nanocomposite consisting of molybdenum disulfide nanosheets decorated with polydopamine (MoS2-PDA) is developed for highly sensitive detection of SARS-CoV-2 nucleocapsid protein (N protein). The MoS2-PDA nanocomposite possesses various hydroxyl and amine groups that have excellent chemistry with crosslinkers and act as adhesive agents to bind with the working electrode surface. Furthermore, the optical, functional, structural, vibrational, and morphological properties of the MoS2-PDA nanocomposite are studied using various characterization techniques such as UV-vis, FTIR, and Raman spectroscopies, XRD, and TEM. The electrochemical immunosensor is fabricated by functionalizing the MoS2-PDA nanocomposite with anti-SARS-CoV-2 nucleocapsid IgG antibody (Ab) and has a very high sensitivity against the N protein with a linear range between 10 ag mL-1 and 100 ng mL-1. The electrochemical immunosensor exhibits a lowest limit of detection (LOD) of 2.80 ag mL-1 and a limit of quantification (LOQ) of 8.48 ag mL-1via electrochemical impedance spectroscopy (EIS). Furthermore, the electrochemical immunosensor is successfully employed to detect the N protein in nasopharyngeal swab specimens and displays good consistency with the conventional RT-PCR test results. The results show that the MoS2-PDA nanocomposite-based electrochemical platform can serve as a highly sensitive and selective detector of N protein and will pave the way for the development of a point-of-care (POC) electrochemical immunosensor for rapid detection of other infectious viruses.

Advanced high-throughput biosensor-based diagnostic approaches for detection of severe acute respiratory syndrome-coronavirus-2

Given the global Coronavirus disease-2019 (COVID-19) pandemic, the transmission, and mortality rate increased drastically and affected the healthcare, financial sectors, and livelihood of the common man. The use of conventional diagnostic tools like reverse transcription-polymerase chain reaction enabled to screen and detecting the spread at a normal pace that had few limitations embedded into their operation, such as complex operation, slow response time, inaccurate results, single laboratory-based operation, and limited sample processing capacity. Consequently, the biosensors have merits that helped in point of care testing, rapid response, simple operation, and multiplex detection among others. Moreover, other advancements in diagnostic tools provided the ability of multiplexing and multioperation attributes for the detection of severe acute respiratory syndrome-Coronavirus-2 that enabled the high-throughput diagnosis of the viral infection in real samples with faster and accurate results. Further, modifications in their methodology, design and detection strategy facilitated their high-throughput property to help in the effective management of the COVID-19 pandemic.

3D printed human organoids: High throughput system for drug screening and testing in current COVID-19 pandemic.

In the current pandemic, scenario the world is facing a huge shortage of effective drugs and other prophylactic medicine to treat patients which created havoc in several countries with poor resources. With limited demand and supply of effective drugs, researchers rushed to repurpose the existing approved drugs for the treatment of COVID-19. The process of drug screening and testing is very costly and requires several steps for validation and treatment efficacy evaluation ranging from in-vitro to in-vivo setups. After these steps, a clinical trial is mandatory for the evaluation of treatment efficacy and side effects in humans. These processes enhance the overall cost and sometimes the lead molecule show adverse effects in humans and the trial ends up in the final stages. Recently with the advent of three-dimensional (3D) organoid culture which mimics the human tissue exactly the process of drug screening and testing can be done in a faster and cost-effective manner. Further 3D organoids prepared from stems cells taken from individuals can be beneficial for personalized drug therapy which could save millions of lives. This review discussed approaches and techniques for the synthesis of 3D-printed human organoids for drug screening. The key findings of the usage of organoids for personalized medicine for the treatment of COVID-19 have been discussed. In the end, the key challenges for the wide applicability of human organoids for drug screening with prospects of future orientation have been included.

Highly Sensitive Electrochemical Immunosensor Platforms for Dual Detection of SARS-CoV-2 Antigen and Antibody based on Gold Nanoparticle Functionalized Graphene Oxide Nanocomposites.

In this work, we report a facile synthesis of graphene oxide-gold (GO-Au) nanocomposites by electrodeposition. The fabricated electrochemical immunosensors are utilized for the dual detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen and SARS-CoV-2 antibody. The GO-Au nanocomposites has been characterized by UV-vis spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS) for its biosensing properties. The linear detection range of the SARS-CoV-2 antigen immunosensor is 10.0 ag mL-1 to 50.0 ng mL-1, whereas that for the antibody immunosensor ranges from 1.0 fg mL-1 to 1.0 ng mL-1. The calculated limit of detection (LOD) of the SARS-CoV-2 antigen immunosensor is 3.99 ag mL-1, and that for SARS-CoV-2 antibody immunosensor is 1.0 fg mL-1 with high sensitivity. The validation of the immunosensor has also been carried out on patient serum and patient swab samples from COVID-19 patients. The results suggest successful utilization of the immunosensors with a very low detection limit enabling its use in clinical samples. Further work is needed for the standardization of the results and translation in screen-printed electrodes for use in portable commercial applications.

A machine learning-based approach to determine infection status in recipients of BBV152 (Covaxin) whole-virion inactivated SARS-CoV-2 vaccine for serological surveys.

Data science has been an invaluable part of the COVID-19 pandemic response with multiple applications, ranging from tracking viral evolution to understanding the vaccine effectiveness. Asymptomatic breakthrough infections have been a major problem in assessing vaccine effectiveness in populations globally. Serological discrimination of vaccine response from infection has so far been limited to Spike protein vaccines since whole virion vaccines generate antibodies against all the viral proteins. Here, we show how a statistical and machine learning (ML) based approach can be used to discriminate between SARS-CoV-2 infection and immune response to an inactivated whole virion vaccine (BBV152, Covaxin). For this, we assessed serial data on antibodies against Spike and Nucleocapsid antigens, along with age, sex, number of doses taken, and days since last dose, for 1823 Covaxin recipients. An ensemble ML model, incorporating a consensus clustering approach alongside the support vector machine model, was built on 1063 samples where reliable qualifying data existed, and then applied to the entire dataset. Of 1448 self-reported negative subjects, our ensemble ML model classified 724 to be infected. For method validation, we determined the relative ability of a random subset of samples to neutralize Delta versus wild-type strain using a surrogate neutralization assay. We worked on the premise that antibodies generated by a whole virion vaccine would neutralize wild type more efficiently than delta strain. In 100 of 156 samples, where ML prediction differed from self-reported uninfected status, neutralization against Delta strain was more effective, indicating infection. We found 71.8% subjects predicted to be infected during the surge, which is concordant with the percentage of sequences classified as Delta (75.6%-80.2%) over the same period. Our approach will help in real-world vaccine effectiveness assessments where whole virion vaccines are commonly used.

Antibacterial and antiviral high-performance nanosystems to mitigate new SARS-CoV-2 variants of concern.

The increased severity of the COVID-19 infection due to new SARS-CoV-2 variants has resonated pandemic impact which made health experts to re-evaluate the effectiveness of pandemic management strategies. This becomes critical owing to the infection in large population and shortcomings in the existing global healthcare system worldwide. The designing of high-performance nanosystems (NS) with tunable performances seems to be the most efficient method to tackle infectious SARS-CoV-2 variants including recently emerged omicron mutation. In this direction, experts projects the versatile functionalized NS and their capabilities to mitigate SARS-CoV-2 propagation pathways by sensitization, antipathogenicity, photocatalysis, photothermal effects, immune response, developing efficient diagnostics assays or associated, selective biomarkers detection, and targeted drug delivery systems. To achieve these tasks, this opinion article project the importance of the fabrication of nano-enabled protective gear, masks, gloves, sheets, filtration units, nano-emulsified disinfectants, antiviral/bacterial paints, and therangostics to facilitate quarantine strategies via protection, detection, and treatment needed to manage COVID-19 pandemic in personalized manners. These functional protective high-performance antibacterial and antiviral NS can efficiently tackle the SARS-CoV-2 variants transmission through respiratory fluids and pollutants within water droplets, aerosols, air, and particulates along with their severe infection via neutralizing or eradicating the virus.

From Nanosystems to a Biosensing Prototype for an Efficient Diagnostic: A Special Issue in Honor of Professor Bansi D. Malhotra.

It has been proven that rapid bioinformatics analysis according to patient health profiles, in addition to biomarker detection at a low level, is emerging as essential to design an analytical diagnostics system to manage health intelligently in a personalized manner. Such objectives need an optimized combination of a nano-enabled sensing prototype, artificial intelligence (AI)-supported predictive analysis, and Internet of Medical Things (IoMT)-based bioinformatics analysis. Such a developed system began with a prototype demonstration of efficient diseases diagnostics performance is the future diseases management approach. To explore these aspects, the Special Issue planned for the nano-and micro-technology section of MDPI's Biosensors journal will honor and acknowledge the contributions of Prof. B.D. Malhotra, Ph.D., FNA, FNASc has made in the field of biosensors.

High throughput molecularly imprinted polymers based electrochemical nanosensors for point-of-care diagnostics of COVID-19.

The importance of early diagnosis of infectious disease has been revealed well by the COVID-19 pandemic. The current methods for testing SARS-CoV-2 mainly utilize biorecognition elements. The process of production of these biorecognition elements is not only tedious, time-consuming but also costly. The molecularly imprinted polymers recently have gained considerable attention as they are stable and also offer high selectivity and specificity than conventional labels. The present review discussed the MIPs-based electrochemical nano-sensors diagnostic of SARS-CoV-2.

Rapid detection of SARS-CoV-2 using graphene-based IoT integrated advanced electrochemical biosensor.

Unique characteristics like large surface area, excellent conductivity, functionality, ease of fabrication, etc., of graphene and its derivatives, have been extensively studied as potential candidates in healthcare applications. They have been utilized as a potential nanomaterial in biosensor fabrication for commercialized point-of-care (POC) devices. This review concisely provided innovative graphene and its derivative-based-IoT (Internet-of-Things) integrated electrochemical biosensor for accurate and advanced high-throughput testing of SARS-CoV-2 in POC setting.

High-performance antiviral nano-systems as a shield to inhibit viral infections: SARS-CoV-2 as a model case study.

Despite significant accomplishments in developing efficient rapid sensing systems and nano-therapeutics of higher efficacy, the recent coronavirus disease (COVID-19) pandemic is not under control successfully because the severe acute respiratory syndrome virus (SARS-CoV-2, original and mutated) transmits easily from human to -human and causes life-threatening respiratory disorders. Thus, it has become crucial to avoid this transmission through precautions and keep premises hygienic using high-performance anti-viral nanomaterials to trap and eradicate SARS-CoV-2. Such an antiviral nano-system has successfully demonstrated useful significant contribution in COVID-19 pandemic/endemic management effectively. However, their projection with potential sustainable prospects still requires considerable attention and efforts. With this aim, the presented review highlights various severe life-threatening viral infections and the role of multi-functional anti-viral nanostructures with manipulative properties investigated as an efficient precative shielding agent against viral infection progression. The salient features of such various nanostructures, antiviral mechanisms, and high impact multi-dimensional roles are systematically discussed in this review. Additionally, the challenges associated with the projection of alternative approaches also support the demand and significance of this selected scientific topic. The outcomes of this review will certainly be useful to motivate scholars of various expertise who are planning future research in the field of investigating sustainable and affordable high-performance nano-systems of desired antiviral performance to manage not only COVID-19 infection but other targeted viral infections as well.

Rapid diagnosis of SARS-CoV-2 using potential point-of-care electrochemical immunosensor: Toward the future prospects.

Coronavirus disease (COVID-19) is an emerging and highly infectious disease making global public health concern and socio-economic burden. It is caused due to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). It has the tendency to spread rapidly through person-to-person. Currently, several molecular diagnostic platforms such as PCR, qRT-PCR, reverse transcription loop-mediated isothermal amplification (RT-LAMP), CRISPR are utilized for the diagnosis of SARS-CoV-2. These conventional techniques are costly, time consuming and require sophisticated instrumentation facility with well trained personnel for testing. Hence, it is tough to provide testing en-masse to the people in developing countries. On the other hand, several serological biosensors such as lateral flow immunosensor, optical, electrochemical, microfluidics integrated electrochemical/fluorescence is currently utilized for the diagnosis of SARS-CoV-2. In current pandemic situation, there is an urgent need of rapid and efficient diagnosis on mass scale of SARS-CoV-2 for early stage detection. Early monitoring of viral infections can help to control and prevent the spreading of infections in large chunk of population. In this review, the SARS-CoV-2 and their biomarkers in biological samples, collection of samples and recently reported potential electrochemical immunosensors for the rapid diagnosis of SARS-CoV-2 are discussed.

Insights from a Pan India Sero-Epidemiological survey (Phenome-India Cohort) for SARS-CoV2.

To understand the spread of SARS-CoV2, in August and September 2020, the Council of Scientific and Industrial Research (India) conducted a serosurvey across its constituent laboratories and centers across India. Of 10,427 volunteers, 1058 (10.14%) tested positive for SARS-CoV2 anti-nucleocapsid (anti-NC) antibodies, 95% of which had surrogate neutralization activity. Three-fourth of these recalled no symptoms. Repeat serology tests at 3 (n = 607) and 6 (n = 175) months showed stable anti-NC antibodies but declining neutralization activity. Local seropositivity was higher in densely populated cities and was inversely correlated with a 30-day change in regional test positivity rates (TPRs). Regional seropositivity above 10% was associated with declining TPR. Personal factors associated with higher odds of seropositivity were high-exposure work (odds ratio, 95% confidence interval, p value: 2.23, 1.92-2.59, <0.0001), use of public transport (1.79, 1.43-2.24, <0.0001), not smoking (1.52, 1.16-1.99, 0.0257), non-vegetarian diet (1.67, 1.41-1.99, <0.0001), and B blood group (1.36, 1.15-1.61, 0.001).

SERS Based Lateral Flow Immunoassay for Point-of-Care Detection of SARS-CoV-2 in Clinical Samples.

The current scenario, an ongoing pandemic of COVID-19, places a dreadful burden on the healthcare system worldwide. Subsequently, there is a need for a rapid, user-friendly, and inexpensive on-site monitoring system for diagnosis. The early and rapid diagnosis of SARS-CoV-2 plays an important role in combating the outbreak. Although conventional methods such as PCR, RT-PCR, and ELISA, etc., offer a gold-standard solution to manage the pandemic, they cannot be implemented as a point-of-care (POC) testing arrangement. Moreover, surface-enhanced Raman spectroscopy (SERS) having a high enhancement factor provides quantitative results with high specificity, sensitivity, and multiplex detection ability but lacks in POC setup. In contrast, POC devices such as lateral flow immunoassay (LFIA) offer rapid, simple-to-use, cost-effective, reliable platform. However, LFIA has limitations in quantitative and sensitive analyses of SARS-CoV-2 detection. To resolve these concerns, herein we discuss a unique modality that is an integration of SERS with LFIA for quantitative analyses of SARS-CoV-2. The miniaturization ability of SERS-based devices makes them promising in biosensor application and has the potential to make a better alternative of conventional diagnostic methods. This review also demonstrates the commercially available and FDA/ICMR approved LFIA kits for on-site diagnosis of SARS-CoV-2.

Telemedicine Technologies for Confronting COVID-19 Pandemic: A Review

Telemedicine (TM) is used to treat patients in a remote location by using telecommunication technology. It exchanges the medical information and data from one location to another through advanced technological innovation. During this COVID-19 pandemic, there is a lockdown in almost all countries. TM is beneficial to healthcare to minimize social distance. This review paper briefs about TM and discusses how this technology works for the COVID-19 pandemic and its significant benefits. An extensive search is made on the known research engines of PubMed, SCOPUS, Google Scholar, and ResearchGate using the appropriate keywords to extract meaningful and relevant articles. Ten major applications of TM for COVID-19 are identified and discussed with a brief description of each provided. The major technological processes involved in TM, which create advancement in the medical field, are also discussed. This technology helps avoid visits to the doctor and hospital during the lockdown and provides a suitable treatment option. It collects the medical information and data, which can be helpful for better treatment of the patient. Telemedicine adopts virtualized treatment approaches for the patient. Now patients can receive better quality treatment without leaving their homes during COVID-19 lockdown.