Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV (preprint)

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that causes severe and often lethal respiratory illness in humans. The MERS-CoV spike (S) protein is the viral fusogen and the target of neutralizing antibodies, and has therefore been the focus of vaccine design efforts. Currently there are no licensed vaccines against MERS-CoV and only a few candidates have advanced to Phase I clinical trials. Here we developed MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for SARS-CoV-2. Two-component protein nanoparticles displaying MERS-CoV S-derived antigens induced robust neutralizing antibody responses and protected mice against challenge with mouse-adapted MERS-CoV. Electron microscopy polyclonal epitope mapping and serum competition assays revealed the specificities of the dominant antibody responses elicited by immunogens displaying the prefusion-stabilized S-2P trimer, receptor binding domain (RBD), or N-terminal domain (NTD). An RBD nanoparticle vaccine elicited antibodies targeting multiple non-overlapping epitopes in the RBD, whereas anti-NTD antibodies elicited by the S-2P- and NTD-based immunogens converged on a single antigenic site. Our findings demonstrate the potential of two-component nanoparticle vaccine candidates for MERS-CoV and suggest that this platform technology could be broadly applicable to betacoronavirus vaccine development.

Immature platelet fraction in patients infected with COVID-19

The Paradigm of Immune Dysregulation in COVID-19 Infection (preprint)

The COVID-19 pandemic cost 7-8 million deaths worldwide, creating an unprecedented health and economic crisis. Affecting 700 million people globally, the magnitude of this pandemic is far from anything that humanity has encountered in recent times. A detailed investigation revealed that more than the SARS-CoV2 virus, the hyperactive immune system mediated injury as the real cause of mortality. Cytokine storm following viral infection leads to the surge of proinflammatory cytokines resulting in ARDS and lung injury. Anti-inflammatory intervention with anti-IL6 (anti-IL-6 receptor monoclonal antibodies (mAbs) (e.g., sarilumab, tocilizumab) and anti-IL-6 mAbs (i.e., siltuximab) and /or steroid-based approach lead to substantial protection and prevent death thereby implying the role of inflammation in COVID-19. In this short review, we summarized the dysregulated immune system in COVID-19 infection, investigating in detail the virus–host immune cross talks and presenting the possibilities of therapeutic intervention.

White blood cell parameters in COVID-19 infection

Platelet parameters in COVID-19 infection

Management of Laryngotracheal Trauma During the COVID 19 Pandemic: Our Experience.

Objective To study the outcomes in terms of airway, voice and swallowing as well as the economic impact of the trauma on patients' finances and the constrained health infrastructure due to the pandemic. Materials and methods Study design Retrospective study. Setting : Tertiary care teaching hospital. Subjects and methods: A retrospective study was done of the 19 subjects who sustained acute laryngotracheal trauma during the SARS CoV-2 pandemic and was managed at our institution from January 2020 to September 2021. Results Change in voice was the most common presenting symptom and thyroid cartilage fractures were the commonest cartilage injury noted. It was found that 93% (decannulated) of the patients had good functional outcome and 90% of them required financial support to meet the medical expenses. Conclusion During the COVID 19 pandemic, it was not only, early presentation, timely detection and intervention by the treating team, but also the multidisciplinary teamwork and the support system that facilitated the recuperation and restoration of these traumatized individuals back into society with good laryngeal function.

Feasibility and acceptability pilot of video-based direct observed treatment (vDOT) for supporting antitubercular treatment in South India: a cohort study.

OBJECTIVES: The objective of this study was to assess the feasibility and acceptability of video-based anti-tuberculosis (TB) treatment adherence support in patients with TB (PwTB) in South India. DESIGN: An exploratory cohort. SETTING: Participants were recruited at the TB treatment centre (direct observed treatment short centre) of a tertiary-level teaching facility in Bangalore, Karnataka, South India. PARTICIPANTS: The study enrolled 25 PwTB, with replacement. Adult PwTB who were on drug-sensitive treatment regimens were included, while those who had drug resistant TB were excluded from the study. INTERVENTION: Participants received scheduled adherence reminders and were trained to videorecord themselves swallowing their medication via a mobile application. The application was automated to submit these videos for evaluation. Participants were followed up monthly till treatment completion or withdrawal. OUTCOME MEASURES: Adherence rate and acceptability of video-based directly observed treatment (vDOT). RESULTS: The mean±SD age of the participants was 33±14 years, majority were females (16, 64%), residing in urban areas (24,96%), married (17, 68%) and had access to smart phones (23,92%). A total of 3193 person days of follow-up was completed; of the videos submitted within the first 6 months of enrollment (2501), 94% (2354/2501) were considered 'acceptable' and 16 (64%) participants were optimally adherent (ie, ≥80%). Participant videos improved in quality and a higher proportion met acceptability criteria over time. Twenty-one (84%) participants stated that they found the application easy to learn; 13 (52%) preferred vDOT over DOT. Mixed model logistic regression showed that those who are married are more likely have daily adherence to anti-TB treatment. CONCLUSION: Video-based mobile phone interventions are acceptable to PwTB and the ease of using the application increases with time. To provide patient-centred care, vDOT is a promising option that can be offered to patients for treatment support and adherence monitoring.

Virtual Reality to Assess Resident Recognition of Impending Respiratory Failure During COVID-19.

OBJECTIVES: To assess the performance of pediatric residents in recognizing a decompensating patient with impending respiratory failure and appropriately escalating care using a virtual reality (VR) simulated case of an infant with bronchiolitis after an extended period of decreased clinical volumes during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Sixty-two pediatric residents at a single academic pediatric referral center engaged in a 30-minute VR simulation on respiratory failure in a 3-month-old admitted to the pediatric hospital medicine service with bronchiolitis. This occurred in a socially distant manner across the Zoom platform during the COVID-19 pandemic (January-April 2021). Residents were assessed on their ability to (1) recognize altered mental status (AMS), (2) designate clinical status as "(impending) respiratory failure," and (3) escalate care. Statistical differences between and across postgraduate year (PGY) levels were examined using χ2 or Fisher's exact test, followed by pairwise comparison and posthoc multiple testing using the Hochberg test. RESULTS: Among all residents, 53% successfully recognized AMS, 16% identified respiratory failure, and 23% escalated care. No significant differences were seen across PGY levels for recognizing AMS or identifying respiratory failure. PGY3+ residents were more likely to escalate care than PGY2 residents (P = .05). CONCLUSIONS: In the setting of an extended period with decreased clinical volumes during the COVID-19 pandemic, pediatric residents across all PGY levels demonstrated challenges with identifying (impending) respiratory failure and appropriately escalating care during VR simulations. Though limited, VR simulation may serve as a safe adjunct for clinical training and assessment during times of decreased clinical exposure.

Can Prenatal Ultrasound Predict Adverse Neonatal Outcomes in SARS-CoV-2 Affected Pregnancies?

BACKGROUND: Based on available data, at least one ultrasound assessment of pregnancies recovering from SARS-CoV-2 infection is recommended. Reports, however, on prenatal imaging findings and potential associations with neonatal outcomes following SARS-CoV-2 infection in pregnancy have been inconclusive. OBJECTIVE: We aim to describe the sonographic characteristics of pregnancies after confirmed SARS-CoV-2 infection and assess the association of prenatal ultrasound (US) findings with adverse neonatal outcomes (ANO). STUDY DESIGN: This is an observational prospective cohort study of pregnancies diagnosed with SARS-CoV-2 by reverse transcription polymerase chain reaction between March 2020 and May 2021. Prenatal US evaluation was performed at least once after diagnosis of infection with the following parameters measured: standard fetal biometric measurements, umbilical and middle cerebral artery Dopplers, placental thickness, amniotic fluid volume, and anatomic survey for infection-associated findings. The primary outcome was composite ANO, defined as one or more of the following: preterm birth, NICU admission, small for gestational age (SGA), respiratory distress, intrauterine fetal demise, neonatal demise, or other neonatal complications. Secondary outcomes were sonographic findings stratified by trimester of infection and severity of SARS-CoV-2 infection. Prenatal US findings were compared with neonatal outcomes, severity of infection, and trimester of infection. RESULTS: A total 103 SARS-CoV-2 affected mother-infant pairs with prenatal US evaluation were identified; 3 cases were excluded due to known major fetal anomalies. Of the 100 included cases, neonatal outcomes were available in 92 pregnancies (97 infants); of these, 28 (29%) had a composite ANO. Twenty-three (23%) had at least one abnormal prenatal US finding. The most common abnormalities seen on US were placentomegaly (11/23, 47.8%) and fetal growth restriction (FGR) (8/23, 34.8%). FGR was associated with a higher rate of a composite ANO (25% vs 1.5%; aOR: 22.67; 95% 95% CI, 2.63-194.91; p<0.001), even when SGA was removed from the composite ANO. Cochran-Mantel Haensel test controlling for possible FGR confounders continued to show this association (relative risk, 3.7; 95% confidence interval, 2.6-5.9; p<0.001). Median estimated fetal weight (EFW) and birthweight were lower in patients with a composite ANO (p<0.001). Infection in the third trimester was associated with lower median percentile of EFW (p=0.019). An association between placentomegaly and third trimester SARS CoV-2 infection was noted (p=0.045). CONCLUSION: In our study of SARS-CoV-2 affected maternal-infant pairs, rates of FGR were comparable to the general population. However, composite ANO rates were high. Pregnancies with FGR after SARS-CoV-2 infection were associated with an increased risk for ANO and may require close surveillance.

Critical factors in the successful expansion of Pneumococcal Conjugate Vaccine in India during the COVID-19 pandemic.

India had decided to roll out PCV in India in 2015, but successful implementation of any new vaccine introduction mandates an enormous effort. PCV was scaled up during the COVID-19 pandemic, which posed new, unprecedented challenges in the vaccine rollout. However, India successfully expanded PCV in the country in record time across all states and Union Territories. During the pandemic, supply-side restrictions, delayed vaccine shipments, staff shortages, and restrictions in conducting training negatively affected the roll-out of PCV across the country. However, despite the ongoing pandemic, India successfully rolled out PCV across the country in 7 months. In this review, the authors have conducted a narrative review to delineate the crucial factors that helped in the successful expansion of PCV.

Challenges in the treatment and prevention of monkeypox infection; A comprehensive review.

Human monkeypox (HMPX) is a zoonotic disease, literally meaning that it can be passed on from animals (non-primate) to human (primate). All the reported and recorded cases have been traced back either to international travel or import of African animals. In the Unites states, sporadic monkeypox cases have been reported in specific over the past 50 years, starting its first identification in the Democratic Republic of the Congo (D.R.C.) in 1970. Due to its extreme versatility, this disease poses threat as a serious public health issue that needs to be monitored, researched and prevented. Data indicate that prior immunization with the smallpox vaccine is beneficial and may provide protection against the monkeypox virus. JYNNEOSTM is a live viral vaccine that has been approved to improve clinical manifestations of the infection. On the other hand, public ignorance about safety precaution towards monkeypox post-COVID is another challenge that needs to be overcome in tackling HMPX as a possible re-emergent infection. This review is a collation of the epidemiology, etiology, transmission, clinical features and treatment of human monkeypox (HMPX).

Analysis of severe acute respiratory syndrome coronavirus 2 antibodies response in COVID-19 patients and health-care workers

Background: COVID-19 epidemic causes destructive consequences on human beings and on the global economy. Aim: The purpose of this study was to evaluate the severe acute respiratory syndrome coronavirus 2 antibodies response in COVID-19 patients and health-care providers to them in different categories and with respect to age, sex, and symptoms. Materials and Methods: Analysis of immunoglobulin (Ig) G and total COVID antibodies was done by chemiluminescent microparticle immunoassay (CMIA) and IgM antibodies by rapid card test method in 300 cases. Results: Out of 300 cases, asymptomatic were 29%, mild 26.66%, moderate 17.66%, and severe were 28.33%;percentage of males were higher than females in all. The most common age group involved was 30-40 years (20%). The most common symptom was fever (51.33%), followed by cough (38.66%), and the most common comorbidity was hypertension (16.33%). We observed that severe category had a higher percentage of symptoms as well as comorbidities. Out of 300 cases, 56.66% were IgG positive, and 89.6% were total COVID antibody positive. In rapid IgM antibodies, out of 50 cases, 13 were positive. We observed that IgM was positive mainly in severe cases compared to mild cases, while IgG level was lower in severe cases than those of mild cases. In our study, majority of cases (97 cases) are IgG positive approximately in 8-14 days after onset of symptoms. Conclusion: Quantitative analysis of antibodies is a simple, quick, and cheap method and could play major role in diagnosis and prognosis of COVID-19, and also used to pick up silent carriers (asymptomatic patients) who missed in false-negative reverse transcription polymerase chain reaction in such epidemic.

Evaluation of Cardiac, Autonomic Functions in Ambulant Patients with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder caused by dystrophin gene mutation resulting in muscle weakness, motor delays, difficulty in standing, and inability to walk by 12 years. As disease progresses, it leads to cardiac and respiratory failure. Evaluation of cardiac autonomic status and echocardiography in DMD patients at a young age can be a potential biomarker to assess disease progression. This study aimed to investigate the younger DMD population of 5-11years of age with mild to moderate cardiac involvement for early detection using non-invasive and cost-effective tools. Genetically confirmed male DMD patients, aged 5-11 years (n = 47), screened from the outpatient department of a tertiary neuroscience institution were subjected to heart rate variability and echocardiographic analysis, and values were correlated with their clinical variables. DMD patients showed a significantly higher difference in HR, interventricular septum, E m/s, and E-wave to A-wave (E/A) ratio than normal values (p < 0.001). Significantly higher HR indicates initial sinus tachycardia and decreased IVD (d), and increased E m/s and E/A ratio mark the onset of cardiac symptoms in DMD patients even though its chamber dimension remains normal and are associated with cardiac muscle fibrosis.

Bridging Access to Pediatric Pain Care: Telehealth Utilization.

OBJECTIVES: Retrospective naturalistic design was utilized to evaluate subsequent shifts to patient access of tertiary pain management care following shelter in place (SIP) and increased telehealth during the COVID-19 pandemic. METHODS: Data for this study were extracted from retrospective review of Pediatric-Collaborative Health Outcomes Information Registry (Peds-CHOIR) with additional demographic information collected via chart review. Participants were 906 youth who received an initial evaluation either in-person (n=472) within the 18 months before SIP or via telehealth (n=434) within the 18 months after SIP during the COVID-19 pandemic. Patient variables to assess access included geographic distance from the clinic, ethnic and racial diversity, and patient's insurance type. Descriptive characteristics for each group were analyzed using chi-squared test, percentage change, and t-test analyses. RESULTS: Results indicated that transitioning to telehealth resulted in maintained access rates between groups as measured by race and ethnic diversity as well as distance travelled from the clinic. A trend of increase in government-funded insurances was found, though no significant differences were identified between telehealth and in-person visits. Though the majority of participants (in-person: 52.75%; telehealth 55.81%) lived within 50 miles of the clinic, results indicated that telehealth allowed for a significant increase in evaluation access for families living further from clinic within a 50-mile radius. DISCUSSION: Overall, accessibility to pediatric pain management via telehealth during SIP was maintained despite significant declines in overall access to healthcare, with some trends in increased accessibility for patients with government insurance.

Outcome of patients with COVID pneumonia on high flow nasal oxygen therapy

Background & Aims: The coronavirus pandemic has caused a rapid surge in patients requiring intensive care unit (ICU) admission. The mainstay of treatment is supplemental oxygen therapy by an oxygen mask, nonrebreathing mask, high flow nasal oxygen therapy (HFNOT), non-invasive and invasive mechanical ventilation. HFNOT is a relatively newer, easy-to-use technique with better patient compliance. This study aimed to assess the outcome of HFNOT in Corona Virus disease (COVID) patients in ICU. Methods: This record based;retrospective study included 43 reverse transcriptase polymerase chain reaction (RTPCR) confirmed COVID patients whose respiratory support was initiated on HFNOT as per the inclusion criteria. The primary outcome of this study was to assess the number of patients requiring mechanical ventilation (HFNOT failure). The secondary outcome was to assess the association of HFNOT failure with age, co-morbidity index, and severity of illness. Results: Out of forty-three patients, twenty-five patients (58%) required conversion to mechanical ventilation. Eighteen patients (42%) were managed with HFNOT alone. HFNOT failure was more with increasing age and higher comorbidity score (p value<0.05). Conclusion: We concluded that HFNOT can be successfully used in COVID patients in ICU without the need for mechanical ventilation. However, it should be used cautiously in patients with higher 4C mortality scores.

Evaluation of T and B cell immunophenotyping and antibody response post Covid-19 vaccination.

PURPOSE: To evaluate T and B cell subsets and IgG antibodies in response to SARS-CoV-2 post COVID-19 vaccination. METHODS: A total of 50 healthy adults (18-60 years) receiving anti-SARS-CoV-2 vaccination (COVISHIELD) were recruited for the study. Blood samples were collected from participants at 3 time points; just before vaccination (Visit 0, V0), just before booster dose (Visit 1, V1) and 6th month after 1st dose (Visit 2, V2). Peripheral blood mononuclear cell isolation was done and evaluated for T and B cell subsets by Flow cytometry. Quantitative determination of IgG antibodies to SARS-CoV-2 was done by Chemiluminescence immunoassay in all samples. Final data for all three visits was available for 37 participants who remained healthy. Ethics approval was obtained from Medanta Institution of Ethics Committee vide MICR No. 1290/2021 dated 24th May 2021. RESULTS: Mean age of the participants was 34.6 â€‹± â€‹5.7 years (Range: 24-45 years). Highly significant improvement in SARS-CoV-2 IgG levels was observed after each visit {Mean IgG: (V0 v/s. V1: 133.8 â€‹± â€‹339.2AU/ml v/s. 434.5 â€‹± â€‹519.2AU/ml; p-value â€‹= â€‹0.003) and V0 v/s. V2: 133.8 â€‹± â€‹339.2AU/ml v/s. 420.9 â€‹± â€‹394.2AU/ml; p-value â€‹= â€‹0.002) Between visits 0 and 1, the mean value for CD4 Naïve T cells showed significant increase, while CD4 central memory (CM) T cells showed significant decrease. Between visits 0 and 2 the mean values for CD4 Naïve T cells, CD8 Naïve T cells and Pre germinal centre (Pre GC) B cells showed significant increase. During the same period the mean values for CD4CM, CD8 effector memory (EM) and CD8 CM T cells showed significant decrease. CONCLUSION: It is concluded that both, humoral and cellular immunity, play an important role in maintaining immunity against COVID-19 infection, following COVISHIELD vaccination. Moreover, in subjects with normalisation of antibody levels post vaccination, persistence of T cell subsets may still offer some immunity.

FAIMER Global Faculty Development: A Sustainable Partnership Model to Advance Health Professions Education.

The Foundation for Advancement of International Medical Education and Research (FAIMER), a member of Intealth, offers longitudinal faculty development programs (LFDPs) in health professions education (HPE) and leadership through its International FAIMER Institute (IFI) in the United States and FAIMER Regional Institutes (FRIs) globally. FAIMER fosters mutual collaboration and delineates shared responsibilities for FRI development in partnership with local institutions, using an adapted hub-and-spoke organizational design. This paper describes FAIMER's model, its sustainability, and its impacts at individual, institutional, and national levels. IFI was launched in 2001 in Philadelphia, Pennsylvania, as a 2-year part-time hybrid LFDP; with the COVID-19 pandemic onset, IFI transitioned to a fully online program. Since FAIMER's launch, 11 FRIs developed in Brazil, Chile, China, Egypt, India, Indonesia, and South Africa, each modeled on the IFI curriculum and adapted to local context. The more than 1,600 IFI and FRI graduates (fellows) from over 55 countries now form a global community of health professions educators who have shared exposure to HPE methods and assessment, leadership and management, educational scholarship and research, and project management and evaluation. Across all global locations and program formats, fellows self-reported a similar increase in knowledge and skills in HPE. All programs center on the fellows' institutional projects as experiential learning; these projects have focused primarily on educational methods and curriculum revisions. An increased quality of education was reported as the top impact resulting from fellows' projects. As a result of these programs, fellows have influenced education policy in their countries and established academic societies for HPE, thus contributing to recognition of the HPE academic specialty. FAIMER has successfully developed a sustainable model for advancing HPE globally, creating a vibrant network of health professions educators who have influenced country-specific educational policy and practice. FAIMER's model offers one approach to building global capacity in HPE.

A Proposed Grading System and Experience of COVID-19 Associated Rhino Orbito Cerebral Mucormycosis from an Indian Tertiary Care Center.

Mucormycosis is an opportunistic fungal infection. India faced an unprecedented increase in patients with post coronavirus disease 2019 (COVID-19) associated rhino-orbito-cerebral mucormycosis (ROCM). This study proposes a grading system which correlates the extent of the disease with the management plan. An observational study was conducted January 2021-June 2021. We identified 65 patients. Eleven patients had mild disease, 27 patients had moderate, 16 patients were severe and 11 patients were graded as very severe. The management was planned based on this grading system. Early diagnosis, aggressive surgical debridement and antifungal drug therapy is the key to improve survival in ROCM. Procedures such as endoscopic orbital clearance, sublabial maxillectomy, and modified endoscopic Denkers (MED) approach facilitate access and surgical debridement. The new grading system proposed assists in planning the approach and extent of surgical debridement.

Collateral Damage: Increasing Risks to Children in a Hostile Immigration Policy Environment.

Purpose of Review: To identify how recent immigration policies have affected the health of children in immigrant families (CIF). Recent Findings: As the number of children and families arriving to the US border has increased, so too have immigration policies directly targeting them. Summary: Anti-immigrant policies increase the dangers experienced by children migrating to the USA, while also limiting access to needed resources and medical care for CIF inside the country, including many who are US citizens. The resultant deprivation and toxic stress are associated with adverse consequences for children's physical and mental health.