In Vitro Diagnostic Assay to Detect SARS-CoV-2-Neutralizing Antibody in Patient Sera Using Engineered ACE-2 Mini-Protein.

The recent development and mass administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines allowed for disease control, reducing hospitalizations and mortality. Most of these vaccines target the SARS-CoV-2 Spike (S) protein antigens, culminating with the production of neutralizing antibodies (NAbs) that disrupt the attachment of the virus to ACE2 receptors on the host cells. However, several studies demonstrated that the NAbs typically rise within a few weeks after vaccination but quickly reduce months later. Thus, multiple booster administration is recommended, leading to vaccination hesitancy in many populations. Detecting serum anti-SARS-CoV-2 NAbs can instruct patients and healthcare providers on correct booster strategies. Several in vitro diagnostics kits are available; however, their high cost impairs the mass NAbs diagnostic testing. Recently, we engineered an ACE2 mimetic that interacts with the Receptor Binding Domain (RBD) of the SARS-2 S protein. Here we present the use of this engineered mini-protein (p-deface2 mut) to develop a detection assay to measure NAbs in patient sera using a competitive ELISA assay. Serum samples from twenty-one patients were tested. Nine samples (42.8%) tested positive, and twelve (57.1%) tested negative for neutralizing sera. The data correlated with the result from the standard commercial assay that uses human ACE2 protein. This confirmed that p-deface2 mut could replace human ACE2 in ELISA assays. Using bacterially expressed p-deface2 mut protein is cost-effective and may allow mass SARS-CoV-2 NAbs detection, especially in low-income countries where economical diagnostic testing is crucial. Such information will help providers decide when a booster is required, reducing risks of reinfection and preventing the administration before it is medically necessary.

Neurology and Telemedicine: The Way Forward

Objective: During the coronavirus-2019 (COVID-19) times, we have all learned to appreciate the advantages of communicating with each other on the digital or virtual format. This included both social, commercial and professional settings. This was necessitated through the restrictions on direct physical contact mandated by the pandemic. Through innovations and adaptations, the practice of medicine has also changed with telemedicine, triggered by ‘necessity is the mother of invention’ concept being embraced by both patients and physicians. Neurology, traditionally seen as a complex speciality and the preserve of a couple of thousand practising neurologists in the country, has opened itself up to the telemedicine or tele-neurology format very easily in the anecdotal and a few pilot studies conducted globally and in India. Design: Despite the initial misgivings and anticipation of patient reluctance to adopt this technology, the real-world experience has been, to the contrary, where both young and old patients have readily embraced the new medium and cooperated with the neurologists to improve their care, which would otherwise have been severely restricted in the COVID-19 times. The neurologists have also adapted to the new way of working to deliver optimum diagnosis and care plans. Outcome measures: There have been technical glitches (in form of internet connectivity, smartphone hardware and software problems and lighting and camera angle and image stabilization issues to name a few), which have been reduced with practice and innovation. Feedback from neurologists, patients, and their carers via regular audits and questionnaires are being circulated, and practice parameters are being improved (IFNR survey- Ref 5). The contribution of national regulatory agencies, such as the Ministry of Health and Family Welfare (MoHFW), and stakeholders, such as the Telemedicine Society of India (TSI), has been phenomenal to facilitate the tele-neurology practice and make it safe for all stakeholders. Results: In a country of 1.37 billion population and only 2,500 accredited neurologists, there is a need for tele-neurology to be able to serve patients living in remote areas in mountains and coastal areas, and also in poorly connected areas on the plains. This becomes paramount for patients requiring specialised acute neurological care and to improve access, which now becomes a practical feasibility on the digital format to bring neurology to the doorsteps of the people. Follow-up care of patients, epidemiological studies of various neurological chronic illnesses and their audit will become realities cutting down on costs and time to access quality neurological care using the digital format for 21st-century India. Conclusions: Tele-neurology is no longer a vision, but a reality precipitated by the pandemic, the needs and aspirations of the Indian population, and the technological infrastructure India has achieved in the last 20 years.

Tele-Neurorehabilitation During the COVID-19 Pandemic: Implications for Practice in Low- and Middle-Income Countries.

The importance of neurorehabilitation services for people with disabilities is getting well-recognized in low- and middle-income countries (LMICs) recently. However, accessibility to the same has remained the most significant challenge, in these contexts. This is especially because of the non-availability of trained specialists and the availability of neurorehabilitation centers only in urban cities owned predominantly by private healthcare organizations. In the current COVID-19 pandemic, the members of the Task Force for research at the Indian Federation of Neurorehabilitation (IFNR) reviewed the context for tele-neurorehabilitation (TNR) and have provided the contemporary implications for practicing TNR during COVID-19 for people with neurological disabilities (PWNDs) in LMICs. Neurorehabilitation is a science that is driven by rigorous research-based evidence. The current pandemic implies the need for systematically developed TNR interventions that is evaluated for its feasibility and acceptability and that is informed by available evidence from LMICs. Given the lack of organized systems in place for the provision of neurorehabilitation services in general, there needs to be sufficient budgetary allocations and a sector-wide approach to developing policies and systems for the provision of TNR services for PWNDs. The pandemic situation provides an opportunity to optimize the technological innovations in health and scale up these innovations to meet the growing burden of neurological disability in LMICs. Thus, this immense opportunity must be tapped to build capacity for safe and effective TNR services provision for PWNDs in these settings.

Dataset on optimization and development of a point-of-care glucometer-based SARS-CoV-2 detection assay using aptamers.

We present supplementary data for the published article, "Hitting the diagnostic sweet spot: Point-of-care SARS-CoV-2 salivary antigen testing with an off-the-shelf glucometer" [1]. The assay described is designed to be performed at home or in a clinic without expensive instrumentation or professional training. SARS-CoV-2 is detected by an aptamer-based assay that targets the Nucleocapsid (N) or Spike (S) antigens. Binding of the N or S protein to their respective aptamer results in the competitive release of a complementary antisense-invertase enzyme complex. The released enzyme then catalyzes the conversion of sucrose to glucose that is measured by an off-the-shelf glucometer. The data presented here describe the optimization of the assay parameters and their contribution to developing this aptamer-based assay to detect SARS-CoV-2. The assay performance was checked in a standard buffer, contrived samples, and patient samples validated with well-established scientific methods. The resulting dataset can be used to further develop glucometer-based assays for diagnosing other communicable and non-communicable diseases.

A systematic review and meta-analysis on correlation of weather with COVID-19.

This study presents a systematic review and meta-analysis over the findings of significance of correlations between weather parameters (temperature, humidity, rainfall, ultra violet radiation, wind speed) and COVID-19. The meta-analysis was performed by using 'meta' package in R studio. We found significant correlation between temperature (0.11 [95% CI 0.01-0.22], 0.22 [95% CI, 0.16-0.28] for fixed effect death rate and incidence, respectively), humidity (0.14 [95% CI 0.07-0.20] for fixed effect incidence) and wind speed (0.58 [95% CI 0.49-0.66] for fixed effect incidence) with the death rate and incidence of COVID-19 (p < 0.01). The study included 11 articles that carried extensive research work on more than 110 country-wise data set. Thus, we can show that weather can be considered as an important element regarding the correlation with COVID-19.

Hitting the diagnostic sweet spot: Point-of-care SARS-CoV-2 salivary antigen testing with an off-the-shelf glucometer.

Significant barriers to the diagnosis of latent and acute SARS-CoV-2 infection continue to hamper population-based screening efforts required to contain the COVID-19 pandemic in the absence of widely available antiviral therapeutics or vaccines. We report an aptamer-based SARS-CoV-2 salivary antigen assay employing only low-cost reagents ($3.20/test) and an off-the-shelf glucometer. The test was engineered around a glucometer as it is quantitative, easy to use, and the most prevalent piece of diagnostic equipment globally, making the test highly scalable with an infrastructure that is already in place. Furthermore, many glucometers connect to smartphones, providing an opportunity to integrate with contact tracing apps, medical providers, and electronic health records. In clinical testing, the developed assay detected SARS-CoV-2 infection in patient saliva across a range of viral loads - as benchmarked by RT-qPCR - within 1 h, with 100% sensitivity (positive percent agreement) and distinguished infected specimens from off-target antigens in uninfected controls with 100% specificity (negative percent agreement). We propose that this approach provides an inexpensive, rapid, and accurate diagnostic for distributed screening of SARS-CoV-2 infection at scale.

Anosmia, Ageusia and COVID-19.

COVID-19 is certainly the greatest global health problem now and for the foreseeable future. Clinicians and scientists from all over the world have been producing evidence to understand the epidemiology, clinical profile and prognostic factors of COVID-19. In the last six months a large list of COVID-19 symptoms including loss of taste and smell have emerged which can be used for screening and risk stratification. Robust workup of this evidence will help to reach strong conclusions to advance clinical medicine, epidemiology, public health, immunology and evidence-based treatment options in the spectrum of disease that we now know as COVID-19.