Recent Advances in Novel Lateral Flow Technologies for Detection of COVID-19.

The development of reliable and robust diagnostic tests is one of the most efficient methods to limit the spread of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, most laboratory diagnostics for COVID-19, such as enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR), are expensive, time-consuming, and require highly trained professional operators. On the other hand, the lateral flow immunoassay (LFIA) is a simpler, cheaper device that can be operated by unskilled personnel easily. Unfortunately, the current technique has some limitations, mainly inaccuracy in detection. This review article aims to highlight recent advances in novel lateral flow technologies for detecting SARS-CoV-2 as well as innovative approaches to achieve highly sensitive and specific point-of-care testing. Lastly, we discuss future perspectives on how smartphones and Artificial Intelligence (AI) can be integrated to revolutionize disease detection as well as disease control and surveillance.

Aspects of Nanotechnology for COVID-19 Vaccine Development and Its Delivery Applications.

Coronavirus, a causative agent of the common cold to a much more complicated disease such as "severe acute respiratory syndrome (SARS-CoV-2), Middle East Respiratory Syndrome (MERS-CoV-2), and Coronavirus Disease 2019 (COVID-19)", is a member of the coronaviridae family and contains a positive-sense single-stranded RNA of 26-32 kilobase pairs. COVID-19 has shown very high mortality and morbidity and imparted a significantly impacted socioeconomic status. There are many variants of SARS-CoV-2 that have originated from the mutation of the genetic material of the original coronavirus. This has raised the demand for efficient treatment/therapy to manage newly emerged SARS-CoV-2 infections successfully. However, different types of vaccines have been developed and administered to patients but need more attention because COVID-19 is not under complete control. In this article, currently developed nanotechnology-based vaccines are explored, such as inactivated virus vaccines, mRNA-based vaccines, DNA-based vaccines, S-protein-based vaccines, virus-vectored vaccines, etc. One of the important aspects of vaccines is their administration inside the host body wherein nanotechnology can play a very crucial role. Currently, more than 26 nanotechnology-based COVID-19 vaccine candidates are in various phases of clinical trials. Nanotechnology is one of the growing fields in drug discovery and drug delivery that can also be used for the tackling of coronavirus. Nanotechnology can be used in various ways to design and develop tools and strategies for detection, diagnosis, and therapeutic and vaccine development to protect against COVID-19. The design of instruments for speedy, precise, and sensitive diagnosis, the fabrication of potent sanitizers, the delivery of extracellular antigenic components or mRNA-based vaccines into human tissues, and the administration of antiretroviral medicines into the organism are nanotechnology-based strategies for COVID-19 management. Herein, we discuss the application of nanotechnology in COVID-19 vaccine development and the challenges and opportunities in this approach.

Ancestral SARS-CoV-2-Driven Antibody Repertoire Diversity in an Unvaccinated Individual Correlates with Expanded Neutralization Breadth.

Understanding the quality of immune repertoire triggered during natural infection can provide vital clues that form the basis for development of a humoral immune response in some individuals capable of broadly neutralizing pan-SARS-CoV-2 variants. In the present study, we report variations in neutralization potential against Omicron variants of two novel neutralizing monoclonal antibodies (MAbs), THSC20.HVTR11 and THSC20.HVTR55, isolated from an unvaccinated convalescent individual that represent distinct B cell lineage origins and epitope specificity compared to five MAbs we previously reported that were isolated from the same individual. In addition, we observed neutralization of Omicron variants by plasma antibodies obtained from this particular individual postvaccination with increased magnitude. Interestingly, this observation was found to be comparable with six additional individuals who initially were also infected with ancestral SARS-CoV-2 and then received vaccines, indicating that hybrid immunity can provide robust humoral immunity likely by antibody affinity maturation. Development of a distinct antigen-specific B cell repertoire capable of producing polyclonal antibodies with distinct affinity and specificities offers the highest probability of protecting against evolving SARS-CoV-2 variants. IMPORTANCE Development of robust neutralizing antibodies in SARS-CoV-2 convalescent individuals is known; however, it varies at the population level. We isolated monoclonal antibodies from an individual infected with ancestral SARS-CoV-2 in early 2020 that not only varied in their B cell lineage origin but also varied in their capability and potency to neutralize all the known variants of concern (VOCs) and currently circulating Omicron variants. This indicated establishment of unique lineages that contributed in forming a B cell repertoire in this particular individual immediately following infection, giving rise to diverse antibody responses that could complement each other in providing a broadly neutralizing polyclonal antibody response. Individuals who were able to produce polyclonal antibody responses with higher magnitude have a higher chance of being protected from evolving SARS-CoV-2 variants.

School reopening: Back to classroom. A systematic review of strategies and their implementation during COVID-19 pandemic.

School closure has affected millions of students worldwide. After more than a year of school closure, steps have been taken to re-start in-person schooling. These strategies have worked well for many setups; however, there are some gaps that have led to repeated sessions of closure and reopening of schools. We have studied these plans of reopening schools and looked into changes that can improve their execution. In this study, we have studied the impact of school reopening in the transmission of SARS CoV-2 in various countries, both developed and developing nations. We have reviewed the measures taken in different countries to reopen schools. We have studied how effective these measures were so as to chart out plans from them to execute our strategies in the country. Both urban and rural setups have been taken in to account. We have searched the electronic databases, PubMed and MEDLINE, and bibliographies of relevant studies were included. We have used the keywords "COVID-19," "school," "reopening," "prevention," "strategies," and "transmission." We have manually searched for studies addressing school reopening during the COVID-19 pandemic. PRISMA approach has been adopted to study the articles systematically. After reviewing different studies on school reopening, a low transmission rate among students was noted in 12 out of 13 studies. Measures such as hand hygiene, masks, and contact tracing are fundamental in preventing the spread of infection in schools.

In vitro effect of Withania somnifera, AYUSH-64, and remdesivir on the activity of CYP-450 enzymes: Implications for possible herb-drug interactions in the management of COVID-19.

Ayurvedic medicines Withania somnifera Dunal (ashwagandha) and AYUSH-64 have been used for the prevention and management of COVID-19 in India. The present study explores the effect of Ashwagandha and AYUSH-64 on important human CYP enzymes (CYP3A4, CYP2C8, and CYP2D6) to assess their interaction with remdesivir, a drug used for COVID-19 management during the second wave. The study also implies possible herb-drug interactions as ashwagandha and AYUSH-64 are being used for managing various pathological conditions. Aqueous extracts of ashwagandha and AYUSH-64 were characterized using LC-MS/MS. A total of 11 and 24 phytoconstituents were identified putatively from ashwagandha and AYUSH-64 extracts, respectively. In addition, in silico studies revealed good ADME properties of most of the phytoconstituents of these herbal drugs and suggested that some of these might possess CYP-450 inhibitory activity. In vitro CYP-450 studies with human liver microsomes showed moderate inhibition of CYP3A4, 2C8, and 2D6 by remdesivir, while ashwagandha had no inhibitory effect alone or in combination with remdesivir. AYUSH-64 also exhibited a similar trend; however, a moderate inhibitory effect on CYP2C8 was noticed. Thus, ashwagandha seems to be safe to co-administer with the substrates of CYP3A4, CYP2C8, and CYP2D6. However, caution is warranted in prescribing AYUSH-64 along with CYP2C8 substrate drugs. Furthermore, preclinical and clinical PK studies would be helpful for their effective and safer use in the management of various ailments along with other drugs.

Fluorescent nanodiamond-based spin-enhanced lateral flow immunoassay for detection of SARS-CoV-2 nucleocapsid protein and spike protein from different variants.

SARS-CoV-2 viruses, responsible for the COVID-19 pandemic, continues to evolve into new mutations, which poses a significant threat to public health. Current testing methods have some limitations, such as long turnaround times, high costs, and professional laboratory requirements. In this report, the novel Spin-Enhanced Lateral Flow Immunoassay (SELFIA) platform and fluorescent nanodiamond (FND) reporter were utilized for the rapid detection of SARS-CoV-2 nucleocapsid and spike antigens from different variants, including wild-type (Wuhan-1), Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529). The SARS-CoV-2 antibodies were conjugated with FND via nonspecific binding, enabling the detection of SARS-CoV-2 antigens via both direct and competitive SELFIA format. Direct SELFIA was performed by directly adding the SARS-CoV-2 antibodies-conjugated FND on the antigens-immobilized nitrocellulose (NC) membrane. Conversely, the SARS-CoV-2 antigen-containing sample was first incubated with the antibodies-conjugated FND, and then dropped on the antigen-immobilized NC membrane to carry out the competitive SELFIA. The results suggested that S44F anti-S IgG antibody can be efficiently used for the detection of wild-type, Alpha, Delta, and Omicron variants spike antigens. Findings were comparable in direct SELFIA, competitive SELFIA, and ELISA. A detection limit of 1.94, 0.77, 1.14, 1.91, and 1.68 ng/mL can be achieved for SARS-CoV-2 N protein, wild-type, Alpha, Delta, and Omicron S proteins, respectively, via competitive SELFIA assay. These results suggest that a direct SELFIA assay can be used for antibody/antigen pair screening in diagnosis development, while the competitive SELFIA assay can serve as an accurate quantitative diagnostic tool. The simplicity and rapidity of the SELFIA platform were demonstrated, which can be leveraged in the detection of other infectious diseases in the near future.

Reducing error in drug prescribing in a neonatal unit (RED quality improvement project)

1008 Figure 1[Figure omitted. See PDF] 1008 Figure 2[Figure omitted. See PDF]ConclusionPrescribing is a complex, challenging task and a high-risk area of clinical practice.1 Preventing prescribing errors is critical to improving patient safety.2 Studies have identified a range of factors underpinning poor prescribing at individual, environmental and organizational levels.3 Through our project, we have demonstrated that these errors can be reduced to a minimum by sheer commitment, effective team engagement, supervision, teaching, and training of the staff. Currently the biggest barrier to sustaining the change are staffing issues within the department and the impact of COVID-19, however going forward embedding the correct culture is paramount.ReferencesDepartment of Health. Building a Safer NHS for Patients. London: NHS, 2001.Bruna Carolina de Araújo. How to Prevent or Reduce Prescribing Errors: An Evidence Brief for Policy. Front Pharmacol. Published online 2019 Jun 12. doi:10.3389/fphar.2019.00439Ross S, Loke YK. Do educational interventions improve prescribing by medical students and junior doctors? A systematic review. Br J Clin Pharmacol 2009;67: 662–70.

Clinical profile and in-hospital outcomes of COVID-19 patients: Findings from secondary data analysis.

Background: Uttarakhand, a hilly state in north India, reported the first coronavirus disease (COVID) case on 15 March 2020. Since then, the case numbers rose multiple folds. As Uttarakhand has been on a 'war-footing' amidst the recent second wave and is gearing up to fight against the third wave, the present study aims to uncover baseline clinical profile and in-hospital outcomes of COVID patients in Dehradun district (Uttarakhand) during the first wave. Methods: A record-based descriptive analysis was carried out for 671 COVID patients admitted to a private dedicated COVID hospital in Dehradun district between August 2020 and February 2021. Data was collected from medical records on a standardized abstraction form. Data was entered and analyzed using Statistical Package for Social Sciences (SPSS) version 20. Results: The present study showed most admitted COVID patients were males, aged 40 years and above, moderately ill, had co-morbidities with about one-fourth lately succumbed to death. The proportions of deaths, moderate-to-severe and severe category of illness were invariably high for those with co-morbidities irrespective of the gender. Females, age <60 years, and absence of co-morbidities had overall high mean survival estimates from COVID. Conclusion: Females, younger age group, and absence of co-morbidities are more likely to survive from COVID than males, older age groups, and those with co-morbidities.

Inpatient virtual shared medical appointments to improve health literacy, increase patient self-efficacy, and reduce provider burnout in acute cerebrovascular pathology patients and their caregivers: a pilot study.

OBJECTIVE: Admission to the hospital for an acute cerebrovascular condition such as stroke or brain hemorrhage can be a traumatic and disorienting experience for patients and their family members. The COVID-19 pandemic has further intensified this experience in addition to exacerbating clinician and resident burnout. To ameliorate some of these concerns, a team of resident and medical student trainees implemented a virtual shared medical appointment (vSMA) program for inpatients with acute cerebrovascular disorders and their caregivers. The authors hypothesized that an early intervention in the form of a vSMA improves patient and caregiver health literacy and preparedness while simultaneously educating clinical trainees on effective communication skills and reducing clinician burnout. METHODS: Patients and caregivers of admitted patients were identified through a census of neurosurgery, neurocritical care, and neurology electronic medical records. A weekly 60-minute secure virtual session consisted of introductions and a 10-minute standardized presentation on cerebrovascular disease management, followed by participant-guided discussion. Participants completed presession and postsession surveys. Through this small feasibility study data were obtained regarding present challenges, both expected and unforeseen. RESULTS: A total of 170 patients were screened, and 13 patients and 26 caregivers participated in at least 1 vSMA session. A total of 6 different healthcare providers facilitated sessions. The vSMA program received overwhelmingly positive feedback from caregivers. Survey responses demonstrated that 96.4% of caregivers and 75% of patients were satisfied with the session, 96.4% of caregivers and 87.5% of patients would recommend this type of appointment to a friend or family member, and 88.8% of providers reported feeling validated by conducting the session. The participant group had a 20% greater percentage of patients discharged home without home needs compared to the nonparticipant group. The primary obstacles encountered included technological frustrations with the consent process and the sessions themselves. CONCLUSIONS: Implementation of a vSMA program at a tertiary care center during a pandemic was feasible. Themes caregivers expressed on the postsession survey included better understanding of caring for a stroke patient and coping with the unpredictability of a patient's prognosis. The pandemic has precipitated shifts toward telehealth, but this study highlights the importance of avoiding marginalization of elderly and less technologically inclined populations.

COVID-19 and tuberculosis: the double whammy of respiratory pathogens.

Prior to coronavirus disease 2019 (COVID-19), tuberculosis (TB) was the worst killer among infectious diseases. The union of these two obnoxious respiratory diseases can be devastating, with severe public health implications. The COVID-19 pandemic has affected all TB-elimination programmes due to the severe burden on healthcare systems and the diversion of funds and attention towards controlling the pandemic. The emerging data show that the COVID-19 pandemic caused a marked decrease in case notifications and bacille Calmette-Guérin immunisations, ultimately promoting disease transmission and increasing the susceptible population. The similarity between the clinical characteristics of TB and COVID-19 adds to the public health complications, with evidence of immune dysregulation in both cases leading to severe consequences. Clinical evidence suggests that severe acute respiratory syndrome coronavirus 2 infection predisposes patients to TB infection or may lead to reactivation of latent disease. Similarly, underlying TB disease can worsen COVID-19. Treatment options are limited in COVID-19; therefore, using immunosuppressive and immunomodulatory regimens that can modulate the concomitant bacterial infection and interaction with anti-TB drugs requires caution. Thus, considering the synergistic impact of these two respiratory diseases, it is crucial to manage both diseases to combat the syndemic of TB and COVID-19.

Life and Death Decisions and COVID-19: Investigating and Modeling the Effect of Framing, Experience, and Context on Preference Reversals in the Asian Disease Problem.

Prior research in judgment and decision making (JDM) has investigated the effect of problem framing on human preferences. Furthermore, research in JDM documented the absence of such reversal of preferences when making decisions from experience. However, little is known about the effect of context on preferences under the combined influence of problem framing and problem format. Also, little is known about how cognitive models would account for human choices in different problem frames and types (general/specific) in the experience format. One of the primary objectives of this research is to investigate the presence of preference reversals under the influence of problem framing (gain/loss), problem format (experience/description), and problem type (general/specific). Another objective of this research is to develop cognitive models to account for human choices across different problem frames and types in the experience format. A total of 320 participants from India were randomly assigned to one of eight between-subjects conditions that differed in problem frame, format, and type. Results revealed preference reversals in the description condition; however, they were absent in the experience condition. Moreover, preference reversals were less pronounced in the general problem framing compared to the specific problem framing. Furthermore, specific problems influenced risk-seeking behavior among participants. We developed cognitive and heuristics models using instance-based learning theory and natural mean heuristic. Results reveal models' dependency on recent and frequent observations during information sampling. These experience-based cognitive models could help build artificial intelligence models with fewer preference reversals.

Mucormycosis: Why Incidence Rate is more in Covid -19 patients

This article aims to review existing evidence and evaluate the documented reasons of high association of Mucormycosis with Covis-19 patients. A literature search was conducted using CDC, MedlinePlus, PubMed, Medscape and Researchgate databases.

Clinical Presentation and Course of SARS-CoV-2 Infection in Health-Care Personnel Working in Dedicated COVID-19 Hospital During 2 Pandemic Waves in India.

INTRODUCTION: Health-care personnel (HCPs) are predisposed to infection during direct or indirect patient care as well as due to the community spread of the disease. METHODS: We observed the clinical presentation and course of severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) infection in HCPs working in a dedicated coronavirus disease 2019 (COVID-19) care hospital during the first and the second wave. RESULTS: A total of 100 and 223 HCPs were enrolled for the first wave and the second wave, respectively. Cough, shortness of breath, sore throat, runny nose, and headache was seen in 40 (40%) and 152 (68%) (P < 0.01), 15 (15%) and 64 (29%) (P = 0.006), 40 (40%) and 119 (53.3%) (P = 0.03), 9 (9%) and 66 (30%) (P < 0.01), 20 (20%) and 125 (56%) (P < 0.01), respectively. Persistent symptoms at the time of joining back to work were seen in 31 (31%) HCPs and 152 (68%) HCPs, respectively (P ≤ 0.01). Reinfection was reported in 10 HCPs. CONCLUSIONS: Most of the HCPs had mild to moderate infections. Symptoms persist after joining back to work. Upgradation of home-based care and teleconsultation facilities for active disease and redressal of residual symptoms will be helpful.

SARS-CoV-2 seroprevalence rates of children seeking medical care in Louisiana during the state stay at home order.

Serologic testing of residual blood samples from 812 children from a hospital in New Orleans, LA, between March and May 2020, demonstrated a SARS-CoV-2 seroprevalence of 6.8% based on S and N protein IgG; Black and Hispanic children, and children living in zip codes with lower household incomes were over-represented.

Diagnostic and Therapeutic Challenges of Cerebral Venous Thrombosis in SARS-CoV-2 Infection: A Case Report and Review of Literature.

Headache, a common prodromal symptom of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, can also be a manifestation of cerebral venous thrombosis (CVT), secondary to COVID-19. CVT management continues to evolve, with direct oral anticoagulants (DOACs) emerging as an alternative to warfarin. A 44-year-old Asian female, with no past medical history, presented to the emergency room (ER) with complaints of nonproductive cough and left-sided headache. She denied a history of COVID-19 vaccination, and SARS-CoV-2 testing (with reverse transcriptase-polymerase chain reaction) was positive. Non-contrast computed tomography (CT) of the head revealed left transverse sinus hyperdensity, consistent with dense vein sign, and magnetic resonance venography (MRV) confirmed the presence of thrombus. The initial treatment included subcutaneous enoxaparin with headache resolution, and she was discharged on apixaban. Five weeks later, a non-contrast head CT showed resolution of the dense vein sign and recanalisation of left transverse sinus was seen on MRV. This report has highlighted the need for increased awareness of coagulopathy and thrombotic events, including cerebral venous thrombosis, in patients infected with SARS-CoV-2. Unremitting headache, in context of SARS-CoV-2 infection, should be evaluated with appropriate neurovascular imaging. Controlled studies are required to compare the safety and efficacy of DOACs with warfarin for management of cerebral venous thrombosis.

A novel compound active against SARS-CoV-2 targeting uridylate-specific endoribonuclease (NendoU/NSP15): in silico and in vitro investigations.

NendoU (NSP15) is an Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond. Our in-house library was subjected to high throughput virtual screening (HTVS) to identify compounds with potential to inhibit NendoU enzyme, high-rank compounds (those that bound to multiple target structures) were further subjected to 100 nanoseconds MD simulations. Among these, one was found to be bound highly stable within the active site of the NendoU protein structure. Here, we are reporting a derivative of piperazine based '(2S,3S)-3-amino-1-(4-(4-(tert-butyl)benzyl)piperazin-1-yl)-4-phenylbutan-2-ol' (IV) from our in-house libraries having potential efficacy against SARS-CoV-2 in in vitro assays. This compound demonstrated inhibition of viral replication at the same level as Ivermectin, a known SARS-CoV-2 inhibitor, which is not used due to its toxicity at a higher than the currently approved dosage. Compound IV was not toxic to the cell lines up to a 50 µM concentration and exhibited IC50s of 4.97 µM and 8.46 µM in viral entry and spread assay, respectively. Therefore, this novel class of NendoU inhibitor could provide new insights for the development of treatment options for COVID-19.

Antiviral evaluation of hydroxyethylamine analogs: Inhibitors of SARS-CoV-2 main protease (3CLpro), a virtual screening and simulation approach.

The continued toll of COVID-19 has halted the smooth functioning of civilization on a global scale. With a limited understanding of all the essential components of viral machinery and the lack of structural information of this new virus, initial drug discovery efforts had limited success. The availability of high-resolution crystal structures of functionally essential SARS-CoV-2 proteins, including 3CLpro, supports the development of target-specific therapeutics. 3CLpro, the main protease responsible for the processing of viral polypeptide, plays a vital role in SARS-CoV-2 viral replication and translation and is an important target in other coronaviruses. Additionally, 3CLpro is the target of repurposed drugs, such as lopinavir and ritonavir. In this study, target proteins were retrieved from the protein data bank (PDB IDs: 6 M03, 6LU7, 2GZ7, 6 W63, 6SQS, 6YB7, and 6YVF) representing different open states of the main protease to accommodate macromolecular substrate. A hydroxyethylamine (HEA) library was constructed from harvested chemical structures from all the series being used in our laboratories for screening against malaria and Leishmania parasites. The database consisted of ∼1000 structure entries, of which 70% were new to ChemSpider at the time of screening. This in-house library was subjected to high throughput virtual screening (HTVS), followed by standard precision (SP) and then extra precision (XP) docking (Schrodinger LLC 2021). The ligand strain and complex energy of top hits were calculated by Molecular Mechanics Generalized Born Surface Area (MM/GBSA) method. Promising hit compounds (n = 40) specifically binding to 3CLpro with high energy and average MM/GBSA scores were then subjected to (100-ns) MD simulations. Using this sequential selection followed by an in-silico validation approach, we found a promising HEA-based compound (N,N'-((3S,3'S)-piperazine-1,4-diylbis(3-hydroxy-1-phenylbutane-4,2-diyl))bis(2-(5-methyl-1,3-dioxoisoindolin-2-yl)-3-phenylpropanamide)), which showed high in vitro antiviral activity against SARS-CoV-2. Further to reduce the size of the otherwise larger ligand, a pharmacophore-based predicted library of âˆ¼42 derivatives was constructed, which were added to the previous compound library and rescreened virtually. Out of several hits from the predicted library, two compounds were synthesized, tested against SARS-CoV-2 culture, and found to have markedly improved antiviral activity.

Repercussions of lockdown on primary health care in India during COVID 19.

Primary health care is a comprehensive care with a wide range of essential services for people living in the rural and hard-to-reach areas. However, the primary healthcare delivery system in India is still in its initial stages and lacks human resources. With the COVID-19 pandemic around the corner, there has been a diversion of resources for controlling corona pandemic leading to undermining availability and accessibility of health services. This article highlights a few case scenarios and the multidimensional impact of lockdown on primary healthcare services. The article suggests certain appropriate measures that can be implemented as the lockdown simply cannot stop the transmission with no definite treatment and vaccine. There should be a multipronged strategy for breaking the chain of transmission and for future preparedness in case of such situations and to strengthen our primary healthcare system.