Barriers and Facilitators of COVID-19 Vaccination Outreach Program in Rural India: A Qualitative Study.

Background Primary health centres are in charge of effectively implementing the COVID-19 vaccination program in rural areas. So, the study was planned to seek insight into the challenges faced by health personnel in the effective implementation of the COVID-19 vaccination program. Methodology The study was conducted in a rural area of Akola district which lies in the western parts of Maharashtra State and belongs to the Vidarbha region and is said to be one of the progressive districts in the region. A qualitative study was planned to understand the barriers and facilitators of the COVID-19 vaccine implementation program at rural and tribal areas. The study participants were medical officers from rural and tribal areas who actively planned and implemented COVID-19 vaccination at the primary health centre. A total of 30 medical officers were interviewed. Interview questions were focussed on the planning of COVID-19 vaccination in their area. Other questions were the problem faced during the implementation of the COVID-19 vaccination program and how it has been tackled. Results The factors identified were grouped into three groups: Health system factors, Human resource factors and Community level factors. Health system factors like shortage of vaccines and syringes, tablet paracetamol, online digital method of vaccination registration, overcrowding at the initial stage, and inadequate infrastructure were barriers to vaccination. Fear about vaccine adverse events, even in healthcare workers (HCWs), and overburdened healthcare workers were also factors affecting vaccination. At the community level, high resistance initially and misconception about the vaccine, and also the fear about post-vaccination side effects have an impact on the COVID-19 vaccination program in rural and tribal areas. Conclusion The successful vaccination rate among the population needs community leadership and a community-centred approach when conducting outreach and strengthening primary health care in terms of infrastructure, manpower, and capacity building of healthcare staff.

Stem cell therapy: a novel approach against emerging and re-emerging viral infections with special reference to SARS-CoV-2.

The past several decades have witnessed the emergence and re-emergence of many infectious viral agents, flaviviruses, influenza, filoviruses, alphaviruses, and coronaviruses since the advent of human deficiency virus (HIV). Some of them even become serious threats to public health and have raised major global health concerns. Several different medicinal compounds such as anti-viral, anti-malarial, and anti-inflammatory agents, are under investigation for the treatment of these viral diseases. These therapies are effective improving recovery rates and overall survival of patients but are unable to heal lung damage caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, there is a critical need to identify effective treatments to combat this unmet clinical need. Due to its antioxidant and immunomodulatory properties, stem cell therapy is considered a novel approach to regenerate damaged lungs and reduce inflammation. Stem cell therapy uses a heterogeneous subset of regenerative cells that can be harvested from various adult tissue types and is gaining popularity due to its prodigious regenerative potential as well as immunomodulatory and anti-inflammatory properties. These cells retain expression of cluster of differentiation markers (CD markers), interferon-stimulated gene (ISG), reduce expression of pro-inflammatory cytokines and, show a rapid proliferation rate, which makes them an attractive tool for cellular therapies and to treat various inflammatory and viral-induced injuries. By examining various clinical studies, this review demonstrates positive considerations for the implications of stem cell therapy and presents a necessary approach for treating virally induced infections in patients.

Microfluidic nanodevices for drug sensing and screening applications.

The outbreak of pandemics (e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 in 2019), influenza A viruses (H1N1 in 2009), etc.), and worldwide spike in the aging population have created unprecedented urgency for developing new drugs to improve disease treatment. As a result, extensive efforts have been made to design novel techniques for efficient drug monitoring and screening, which form the backbone of drug development. Compared to traditional techniques, microfluidics-based platforms have emerged as promising alternatives for high-throughput drug screening due to their inherent miniaturization characteristics, low sample consumption, integration, and compatibility with diverse analytical strategies. Moreover, the microfluidic-based models utilizing human cells to produce in-vitro biomimetics of the human body pave new ways to predict more accurate drug effects in humans. This review provides a comprehensive summary of different microfluidics-based drug sensing and screening strategies and briefly discusses their advantages. Most importantly, an in-depth outlook of the commonly used detection techniques integrated with microfluidic chips for highly sensitive drug screening is provided. Then, the influence of critical parameters such as sensing materials and microfluidic platform geometries on screening performance is summarized. This review also outlines the recent applications of microfluidic approaches for screening therapeutic and illicit drugs. Moreover, the current challenges and the future perspective of this research field is elaborately highlighted, which we believe will contribute immensely towards significant achievements in all aspects of drug development.

Updated Insights into the T Cell-Mediated Immune Response against SARS-CoV-2: A Step towards Efficient and Reliable Vaccines.

The emergence of novel variants of SARS-CoV-2 and their abilities to evade the immune response elicited through presently available vaccination makes it essential to recognize the mechanisms through which SARS-CoV-2 interacts with the human immune response. It is essential not only to comprehend the infection mechanism of SARS-CoV-2 but also for the generation of effective and reliable vaccines against COVID-19. The effectiveness of the vaccine is supported by the adaptive immune response, which mainly consists of B and T cells, which play a critical role in deciding the prognosis of the COVID-19 disease. T cells are essential for reducing the viral load and containing the infection. A plethora of viral proteins can be recognized by T cells and provide a broad range of protection, especially amid the emergence of novel variants of SARS-CoV-2. However, the hyperactivation of the effector T cells and reduced number of lymphocytes have been found to be the key characteristics of the severe disease. Notably, excessive T cell activation may cause acute respiratory distress syndrome (ARDS) by producing unwarranted and excessive amounts of cytokines and chemokines. Nevertheless, it is still unknown how T-cell-mediated immune responses function in determining the prognosis of SARS-CoV-2 infection. Additionally, it is unknown how the functional perturbations in the T cells lead to the severe form of the disease and to reduced protection not only against SARS-CoV-2 but many other viral infections. Hence, an updated review has been developed to understand the involvement of T cells in the infection mechanism, which in turn determines the prognosis of the disease. Importantly, we have also focused on the T cells' exhaustion under certain conditions and how these functional perturbations can be modulated for an effective immune response against SARS-CoV-2. Additionally, a range of therapeutic strategies has been discussed that can elevate the T cell-mediated immune response either directly or indirectly.

Positivity of typhidot test in COVID cases: An observational cohort study from the second wave of the pandemic

Introduction: Typhidot has been known to cross-react with a variety of viral illnesses. There has been some communication throwing light on the possible false-positive results in COVID cases, but overall there is a dearth of studies directly investigating the association. This is a small-sized observational cohort study to detect and analyze the association between these two conditions. Materials and Methods: During a period of 1 month, starting from April 1, 2021, to April 30, 2021, all patients admitted with a Reverse Transcriptase- Polymerase Chain Reaction (RT-PCR)- positive report for SARS-CoV-2 to a nursing home in Ghaziabad were prescribed typhidot immunoglobulin M (IgM) test. Other parameters such as the radiological computed tomography score, hemoglobin levels, total leukocyte counts, serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase enzyme levels, and the cycle threshold values of the RT-PCR test were recorded. The data thus collected were entered into a structured electronic data collection system and analyzed. Results: Thirty-seven percent of patients who were admitted with a diagnosis of RT-PCR-positive mild-to-moderate COVID pneumonia were also positive for typhoid IgM antibody. The distribution of this positive typhidot test was equal among both genders and was not found to be significantly associated with any of the other test variables. Conclusion: Our study reveals the anamnestic response of typhoid IgM antibodies against SARS-CoV-2. A positive typhidot test should not mislead or delay the diagnosis of any other viral respiratory illness.

Microfluidic nanodevices for drug sensing and screening applications

The outbreak of pandemics (e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 in 2019), influenza A viruses (H1N1 in 2009), etc.), and worldwide spike in the aging population have created unprecedented urgency for developing new drugs to improve disease treatment. As a result, extensive efforts have been made to design novel techniques for efficient drug monitoring and screening, which form the backbone of drug development. Compared to traditional techniques, microfluidics-based platforms have emerged as promising alternatives for high-throughput drug screening due to their inherent miniaturization characteristics, low sample consumption, integration, and compatibility with diverse analytical strategies. Moreover, the microfluidic-based models utilizing human cells to produce in-vitro biomimetics of the human body pave new ways to predict more accurate drug effects in humans. This review provides a comprehensive summary of different microfluidics-based drug sensing and screening strategies and briefly discusses their advantages. Most importantly, an in-depth outlook of the commonly used detection techniques integrated with microfluidic chips for highly sensitive drug screening is provided. Then, the influence of critical parameters such as sensing materials and microfluidic platform geometries on screening performance is summarized. This review also outlines the recent applications of microfluidic approaches for screening therapeutic and illicit drugs. Moreover, the current challenges and the future perspective of this research field is elaborately highlighted, which we believe will contribute immensely towards significant achievements in all aspects of drug development.

A Cold Chain-Independent Specimen Collection and Transport Medium Improves Diagnostic Sensitivity and Minimizes Biosafety Challenges of COVID-19 Molecular Diagnosis.

Equitable and timely access to COVID-19-related care has emerged as a major challenge, especially in developing and low-income countries. In India, ∼65% of the population lives in villages where infrastructural constraints limit the access to molecular diagnostics of COVID-19 infection. Especially, the requirement of a cold chain transport for sustained sample integrity and associated biosafety challenges pose major bottlenecks to the equitable access. Here, we developed an innovative clinical specimen collection medium, named SupraSens microbial transport medium (SSTM). SSTM allowed a cold chain-independent transport at a wide temperature range (15°C to 40°C) and directly inactivated SARS-CoV-2 (<15 min). Evaluation of SSTM compared to commercial viral transport medium (VTM) in field studies (n = 181 patients) highlighted that, for the samples from same patients, SSTM could capture more symptomatic (∼26.67%, 4/15) and asymptomatic (52.63%, 10/19) COVID-19 patients. Compared to VTM, SSTM yielded significantly lower quantitative PCR (qPCR) threshold cycle (Ct) values (mean ΔCt > -3.50), thereby improving diagnostic sensitivity of SSTM (18.79% [34/181]) versus that of VTM (11.05% [20/181]). Overall, SSTM had detection of COVID-19 patients 70% higher than that of VTM. Since the logistical and infrastructural constraints are not unique to India, our study highlights the invaluable global utility of SSTM as a key to accurately identify those infected and control COVID-19 transmission. Taken together, our data provide a strong justification to the adoption of SSTM for sample collection and transport during the pandemic. IMPORTANCE Approximately forty-four percent of the global population lives in villages, including 59% in Africa (https://unhabitat.org/World%20Cities%20Report%202020). The fast-evolving nature of SARS-CoV-2 and its extremely contagious nature warrant early and accurate COVID-19 diagnostics across rural and urban population as a key to prevent viral transmission. Unfortunately, lack of adequate infrastructure, including the availability of biosafety-compliant facilities and an end-to-end cold chain availability for COVID-19 molecular diagnosis, limits the accessibility of testing in these countries. Here, we fulfill this urgent unmet need by developing a sample collection and transport medium, SSTM, that does not require cold chain, neutralizes the virus quickly, and maintains the sample integrity at broad temperature range without compromising sensitivity. Further, we observed that use of SSTM in field studies during pandemic improved the diagnostic sensitivity, thereby establishing the feasibility of molecular testing even in the infrastructural constraints of remote, hilly, or rural communities in India and elsewhere.

Parental Coronavirus Disease 2019 Testing of Hospitalized Children: Rethinking Infection Control in a Pandemic.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) poses a challenge to infection control within hospital systems. Asymptomatic children and their caretakers carry the risk of silently spreading infection in pediatric emergency departments and hospital units. Our current knowledge is evolving, and infection control measures are frequently changing depending on new emerging data. METHODS: We conducted a point-prevalence study to assess SARS-CoV-2 Real-Time Polymerase Chain Reaction (SARS-CoV-2 RT-PCR) results of hospitalized children, their asymptomatic caretakers, and caretaker-child test concordance at a major community hospital in New York City. We screened Children and caretakers with temperature measurements and the presence of COVID-19 symptoms before pediatric emergency department evaluation. Children requiring hospitalization and their caretakers had nasopharyngeal swabs for SARS-CoV-2 RT-PCR. The paired results are used to identify the infection control level at the appropriate pediatric unit. RESULTS: Forty consecutive asymptomatic caretaker-child pairs had SARS-CoV-2 RT-PCR testing between May 28th to June 22nd, 2020. The rate of asymptomatic COVID-19 was 2.5% in hospitalized children and 7.5% in caretakers. The caretaker-child SARS-CoV-2 RT-PCR test concordance was evident in 95% of the cohort. CONCLUSION: This cohort had a low asymptomatic SARS-CoV-2 PCR positive rate in children and their caretakers with a high concordance rate of paired test results. It suggests that children's SARS-CoV-2 PCR test result will likely correspond to their accompanying caretaker at healthcare facilities where admission screening is performed.

Crisis clinical pathway for COVID-19.

The pandemic of COVID-19 has been particularly severe in the New York City area, which has had one of the highest concentrations of cases in the USA. In March 2020, the EDs of New York-Presbyterian Hospital, a 10-hospital health system in the region, began to experience a rapid surge in patients with COVID-19 symptoms. Emergency physicians were faced with a disease that they knew little about that quickly overwhelmed resources. A significant amount of attention has been placed on the problem of limited supply of ventilators and intensive care beds for critically ill patients in the setting of the ongoing global pandemic. Relatively less has been given to the issue that precedes it: the demand on resources posed by patients who are not yet critically ill but are unwell enough to seek care in the ED. We describe here how at one institution, a cross-campus ED physician working group produced a care pathway to guide clinicians and ensure the fair and effective allocation of resources in the setting of the developing public health crisis. This 'crisis clinical pathway' focused on using clinical evaluation for medical decision making and maximising benefit to patients throughout the system.

Conscious Proning: An Introduction of a Proning Protocol for Nonintubated, Awake, Hypoxic Emergency Department COVID-19 Patients.

The novel coronavirus, or COVID-19, has rapidly become a global pandemic. A major cause of morbidity and mortality due to COVID-19 has been the worsening hypoxia that, if untreated, can progress to acute respiratory distress syndrome (ARDS) and respiratory failure. Past work has found that intubated patients with ARDS experience physiological benefits to the prone position, because it promotes better matching of pulmonary perfusion to ventilation, improved secretion clearance, and recruitment of dependent areas of the lungs. We created a systemwide multi-institutional (New York-Presbyterian Hospital enterprise) protocol for placing awake, nonintubated, emergency department patients with suspected or confirmed COVID-19 in the prone position. In this piece, we describe the background literature and the approach we have taken at our institution as we care for a high burden of COVID-19 cases with respiratory symptoms.