Ultrasensitive and Reusable Graphene Oxide-Modified Double-Interdigitated Capacitive (DIDC) Sensing Chip for Detecting SARS-CoV-2.

This research reveals the promising functionalization of graphene oxide (GrO)-glazed double-interdigitated capacitive (DIDC) biosensing platform to detect severe acute respiratory syndrome coronavirus (SARS-CoV-2) spike (S1) proteins with enhanced selectivity and rapid response. The DIDC bioactive surface consisting of Pt/Ti featured SiO2 substrate was fabricated using GrO/EDC-NHS/anti-SARS-CoV-2 antibodies (Abs) which is having layer-by-layer interface self-assembly chemistry method. This electroactive immune-sensing platform exhibits reproducibility and sensitivity with reference to the S1 protein of SARS-CoV-2. The outcomes of analytical studies confirm that GrO provided a desired engineered surface for Abs immobilization and amplified capacitance to achieve a wide detection range (1.0 mg/mL to 1.0 fg/mL), low limit of detection (1 fg/mL) within 3 s of response time, good linearity (18.56 nF/g), and a high sensitivity of 1.0 fg/mL. Importantly, the unique biochip was selective against blood-borne antigens and standby for 10 days at 5 °C. Our developed DIDC-based SARS-CoV-2 biosensor is suitable for point-of-care (POC) diagnostic applications due to portability and scaling-up ability. In addition, this sensing platform can be modified for the early diagnosis of severe viral infections using real samples.

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.

Aspects of Point-of-Care Diagnostics for Personalized Health Wellness.

Advancements in analytical diagnostic systems for point-of-care (POC) application have gained considerable attention because of their rapid operation at the site required to manage severe diseases, even in a personalized manner. The POC diagnostic devices offer easy operation, fast analytical outcome, and affordable cost, which promote their advanced research and versatile adoptability. Keeping advantages in view, considerable efforts are being made to design and develop smart sensing components such as miniaturized transduction, interdigitated electrodes-based sensing chips, selective detection at low level, portable packaging, and sustainable durability to promote POC diagnostics according to the needs of patient care. Such effective diagnostics systems are in demand, which creates the challenge to make them more efficient in every aspect to generate a desired bio-informatic needed for better health access and management. Keeping advantages and scope in view, this mini review focuses on practical scenarios associated with miniaturized analytical diagnostic devices at POC application for targeted disease diagnostics smartly and efficiently. Moreover, advancements in technologies, such as smartphone-based operation, paper-based sensing assays, and lab-on-a-chip (LOC) which made POC more sensitive, informative, and suitable for major infectious disease diagnosis, are the main focus here. Besides, POC diagnostics based on automated patient sample integration with a sensing platform is continuously improving therapeutics interventions against specific infectious disease. This review also discussed challenges associated with state-of-the-art technology along with future research opportunities to design and develop next generation POC diagnostic systems needed to manage infectious diseases in a personalized manner.

Internet of medical things (IoMT)-integrated biosensors for point-of-care testing of infectious diseases.

On global scale, the current situation of pandemic is symptomatic of increased incidences of contagious diseases caused by pathogens. The faster spread of these diseases, in a moderately short timeframe, is threatening the overall population wellbeing and conceivably the economy. The inadequacy of conventional diagnostic tools in terms of time consuming and complex laboratory-based diagnosis process is a major challenge to medical care. In present era, the development of point-of-care testing (POCT) is in demand for fast detection of infectious diseases along with "on-site" results that are helpful in timely and early action for better treatment. In addition, POCT devices also play a crucial role in preventing the transmission of infectious diseases by offering real-time testing and lab quality microbial diagnosis within minutes. Timely diagnosis and further treatment optimization facilitate the containment of outbreaks of infectious diseases. Presently, efforts are being made to support such POCT by the technological development in the field of internet of medical things (IoMT). The IoMT offers wireless-based operation and connectivity of POCT devices with health expert and medical centre. In this review, the recently developed POC diagnostics integrated or future possibilities of integration with IoMT are discussed with focus on emerging and re-emerging infectious diseases like malaria, dengue fever, influenza A (H1N1), human papilloma virus (HPV), Ebola virus disease (EVD), Zika virus (ZIKV), and coronavirus (COVID-19). The IoMT-assisted POCT systems are capable enough to fill the gap between bioinformatics generation, big rapid analytics, and clinical validation. An optimized IoMT-assisted POCT will be useful in understanding the diseases progression, treatment decision, and evaluation of efficacy of prescribed therapy.

Nanomedicine for the SARS-CoV-2: State-of-the-Art and Future Prospects.

The newly emerged ribonucleic acid (RNA) enveloped human beta-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection caused the COVID-19 pandemic, severely affects the respiratory system, and may lead to death. Lacking effective diagnostics and therapies made this pandemic challenging to manage since the SARS-CoV-2 transmits via human-to-human, enters via ACE2 and TMPSSR2 receptors, and damages organs rich in host cells, spreads via symptomatic carriers and is prominent in an immune-compromised population. New SARS-CoV-2 informatics (structure, strains, like-cycles, functional sites) motivated bio-pharma experts to investigate novel therapeutic agents that act to recognize, inhibit, and knockdown combinations of drugs, vaccines, and antibodies, have been optimized to manage COVID-19. However, successful targeted delivery of these agents to avoid off-targeting and unnecessary drug ingestion is very challenging. To overcome these obstacles, this mini-review projects nanomedicine technology, a pharmacologically relevant cargo of size within 10 to 200 nm, for site-specific delivery of a therapeutic agent to recognize and eradicate the SARS-CoV-2, and improving the human immune system. Such combinational therapy based on compartmentalization controls the delivery and releases of a drug optimized based on patient genomic profile and medical history. Nanotechnology could help combat COVID-19 via various methods such as avoiding viral contamination and spraying by developing personal protective equipment (PPE) to increase the protection of healthcare workers and produce effective antiviral disinfectants surface coatings capable of inactivating and preventing the virus from spreading. To quickly recognize the infection or immunological response, design highly accurate and sensitive nano-based sensors. Development of new drugs with improved activity, reduced toxicity, and sustained release to the lungs, as well as tissue targets; and development of nano-based immunizations to improve humoral and cellular immune responses. The desired and controlled features of suggested personalized therapeutics, nanomedicine, is a potential therapy to manage COVID-19 successfully. The state-of-the-art nanomedicine, challenges, and prospects of nanomedicine are carefully and critically discussed in this report, which may serve as a key platform for scholars to investigate the role of nanomedicine for higher efficacy to manage the COVID-19 pandemic.

Functionalized terahertz plasmonic metasensors: Femtomolar-level detection of SARS-CoV-2 spike proteins.

Effective and efficient management of human betacoronavirus severe acute respiratory syndrome (SARS)-CoV-2 virus infection i.e., COVID-19 pandemic, required sensitive and selective sensors with short sample-to-result durations for performing desired diagnostics. In this direction, one appropriate alternative approach to detect SARS-CoV-2 virus protein at low level i.e., femtomolar (fM) is exploring plasmonic metasensor technology for COVID-19 diagnostics, which offers exquisite opportunities in advanced healthcare programs, and modern clinical diagnostics. The intrinsic merits of plasmonic metasensors stem from their capability to squeeze electromagnetic fields, simultaneously in frequency, time, and space. However, the detection of low-molecular weight biomolecules at low densities is a typical drawback of conventional metasensors that has recently been addressed using toroidal metasurface technology. This research is focused on the fabrication of a miniaturized plasmonic immunosensor based on toroidal electrodynamics concept that can sustain robustly confined plasmonic modes with ultranarrow lineshapes in the terahertz (THz) frequencies. By exciting toroidal dipole mode using our quasi-infinite metasurface and a judiciously optimized protocol based on functionalized gold nanoparticles (AuNPs) conjugated with the specific monoclonal antibody specific to spike protein (S1) of SARS-CoV-2 virus onto the metasurface, the resonance shifts for diverse concentrations of the spike protein are monitored. Possessing molecular weight around ~76 kDa allowed to detect the presence of SARS-CoV-2 virus protein with significantly low as limit of detection (LoD) was achieved as ~4.2 fM. We envisage that outcomes of this research will pave the way toward the use of toroidal metasensors as practical technologies for rapid and precise screening of SARS-CoV-2 virus carriers, symptomatic or asymptomatic, and spike proteins in hospitals, clinics, laboratories, and site of infection.

Electrochemical SARS-CoV-2 Sensing at Point-of-Care and Artificial Intelligence for Intelligent COVID-19 Management

To manage the COVID-19 pandemic, development of rapid, selective, sensitive diagnostic systems for early stage β-coronavirus severe acute respiratory syndrome (SARS-CoV-2) virus protein detection is emerging as a necessary response to generate the bioinformatics needed for efficient smart diagnostics, optimization of therapy, and investigation of therapies of higher efficacy. The urgent need for such diagnostic systems is recommended by experts in order to achieve the mass and targeted SARS-CoV-2 detection required to manage the COVID-19 pandemic through the understanding of infection progression and timely therapy decisions. To achieve these tasks, there is a scope for developing smart sensors to rapidly and selectively detect SARS-CoV-2 protein at the picomolar level. COVID-19 infection, due to human-to-human transmission, demands diagnostics at the point-of-care (POC) without the need of experienced labor and sophisticated laboratories. Keeping the above-mentioned considerations, we propose to explore the compartmentalization approach by designing and developing nanoenabled miniaturized electrochemical biosensors to detect SARS-CoV-2 virus at the site of the epidemic as the best way to manage the pandemic. Such COVID-19 diagnostics approach based on a POC sensing technology can be interfaced with the Internet of things and artificial intelligence (AI) techniques (such as machine learning and deep learning for diagnostics) for investigating useful informatics via data storage, sharing, and analytics. Keeping COVID-19 management related challenges and aspects under consideration, our work in this review presents a collective approach involving electrochemical SARS-CoV-2 biosensing supported by AI to generate the bioinformatics needed for early stage COVID-19 diagnosis, correlation of viral load with pathogenesis, understanding of pandemic progression, therapy optimization, POC diagnostics, and diseases management in a personalized manner.

COVID-19: Review of a 21st Century Pandemic from Etiology to Neuro-psychiatric Implications.

COVID-19 is a severe infectious disease that has claimed >150,000 lives and infected millions in the United States thus far, especially the elderly population. Emerging evidence has shown the virus to cause hemorrhagic and immunologic responses, which impact all organs, including lungs, kidneys, and the brain, as well as extremities. SARS-CoV-2 also affects patients', families', and society's mental health at large. There is growing evidence of re-infection in some patients. The goal of this paper is to provide a comprehensive review of SARS-CoV-2-induced disease, its mechanism of infection, diagnostics, therapeutics, and treatment strategies, while also focusing on less attended aspects by previous studies, including nutritional support, psychological, and rehabilitation of the pandemic and its management. We performed a systematic review of >1,000 articles and included 425 references from online databases, including, PubMed, Google Scholar, and California Baptist University's library. COVID-19 patients go through acute respiratory distress syndrome, cytokine storm, acute hypercoagulable state, and autonomic dysfunction, which must be managed by a multidisciplinary team including nursing, nutrition, and rehabilitation. The elderly population and those who are suffering from Alzheimer's disease and dementia related illnesses seem to be at the higher risk. There are 28 vaccines under development, and new treatment strategies/protocols are being investigated. The future management for COVID-19 should include B-cell and T-cell immunotherapy in combination with emerging prophylaxis. The mental health and illness aspect of COVID-19 are among the most important side effects of this pandemic which requires a national plan for prevention, diagnosis and treatment.

Convalescent plasma in the management of moderate COVID-19 in India: An open-label parallel-arm phase II multicentre randomized controlled trial (PLACID Trial)

ObjectivesConvalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. DesignOpen-label, parallel-arm, phase II, multicentre, randomized controlled trial. SettingThirty-nine public and private hospitals across India. ParticipantsHospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 [≤] 93% on room air). InterventionParticipants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome MeasureComposite of progression to severe disease (PaO2/FiO2< 100) or all-cause mortality at 28 days post-enrolment. ResultsBetween 22nd April to 14th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: -0.61 to 1.83]. InterpretationCP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19. Trial registrationThe trial was registered with Clinical Trial Registry of India (CTRI); CTRI/2020/04/024775.