COVID-19 VACCINATION-INFECTION STATUS AND IMMUNOLOGICAL PROFILE: IDENTIFICATION OF HIGH RISK POPULATION FOR TARGETED BOOSTER IMMUNIZATION IN INDIA (preprint)

Background: The COVID-19 pandemic's global impact was mitigated through rapid vaccine development, leading to a mix of natural and vaccination-derived immunity. Immunological profile in hybrid immunity remains less studies, especially in regions where non-mRNA vaccines were used. This study focuses on the immunological profiles and predictors of immune response in one such population. Methods: This was a cross-sectional study to assess their humoral and cellular immune responses based on vaccination and infection history. Immunological assays were performed to measure anti-spike protein and neutralizing antibodies as well as interferon-γ release assay. Multivariable linear regression model was used to estimate predictors of immune response. Results: The study revealed significant differences in immune response among participants based on their hybrid immunity status, vaccination, and infection history. Higher antibody titres and cellular responses were observed in individuals with hybrid immunity, especially those with dual pre-Omicron and Omicron infections (3326 BAU/ml, IQR: 770.25-5678.25 and 4.92 IU of IFN-γ/mL, IQR:3.74-16.98 respectively, p <0.001). Age and comorbidities such as diabetes and hypertension were associated with lower antibody levels and cellular response, while vaccination and hybrid immunity correlated with higher immune responses. Conclusion: The prevalence of hybrid immunity was high, yet a substantial portion of the population lacks it, indicating the necessity for targeted immunization strategies. The findings underscore the importance of prioritizing high-risk individuals, such as elderly and individuals with comorbidities, for booster vaccinations to enhance community-level protection against COVID-19.

FUNGAL OSTEOMYELITIS OF FRONTAL BONE FOLLOWING COVID ASSOCIATED MUCORMYCOSIS (preprint)

Introduction: - The second wave of COVID 19 lead to resurgence of opportunistic infections due to injudicious use of steroids. Sinonasal Mucormycosis was declared as an epidemic during the pandemic. The mucormycosis was managed effectively by surgical debridement along with systemic amphotericin B. Now, following the initial treatment of mucormycosis there is a resurgence, in the form of fungal osteomyelitis of the frontal bone. Methods – the prospective study included the cases from ten patients with fungal osteomyelitis of frontal bone due to mucormycosis, all the patients underwent surgical debridement of sequestrum and involucrum with systemic antifungals. Results - The average duration of the recurrence was 22 days following the initial treatment Range (10 days to 33 days). Extracranial bossing following outer frontal cortex erosion in 30% of cases, bicortical erosion in 30%, bifrontal involvement (20%), dural involvement (30%), brain parenchymal involvement and prefrontal cortex (20%) case. All cases underwent debridement of entire sequestrous bone and involucrum till normal bone was identified. The mean duration of admission was 4 weeks (3 to 6 weeks). All treated patients are currently alive without disease, confirmed by CECT. Conclusion - The successful treatment of fungal osteomyelitis due to mucormycosis requires four pronged approach (1) early detection (2) multidisciplinary management of comorbidities (3) surgical debridement of necrotic bone and (4) adequate systemic antifungal therapy. Long term outcomes of fungal osteomyelitis of frontal bone are yet to be established

Towards Real-Time Airborne Pathogen Sensing: Electrostatic Capture and On-Chip LAMP Based Detection of Airborne Viral Pathogens (preprint)

Considerable loss of life, economic slowdown, and public health risk associated with the transmission of airborne respiratory pathogens was underscored by the recent COVID-19 pandemic. Airborne transmission of zoonotic diseases such as the highly pathogenic avian influenza (HPAI) and porcine reproductive and respiratory syndrome virus (PRRSV) has caused major disruptions to domestic and global food security. Current ambient air pathogen monitoring systems involves the collection of air samples from indoor settings suspected of viral contamination, followed by subsequent processing of capture samples to determine the presence and species of airborne viral matter. Nucleic acid amplification techniques are considered the gold standard for pathogen diagnostics. Currently, the necessary extraction and purification of viral RNA from air collector systems prior to sample analysis is both time consuming and performed manually. A monitoring system with separate air sampling and biochemical detection procedures is prone to delay the response to emergent viral threats. In this paper, we present a pathogen monitoring system that overcomes these limitations related to extraction and purification of viral samples and lays the groundwork for a real-time monitor for airborne viral pathogens. We demonstrate a high flow electrostatic precipitator system, that uses small collection wells as counter electrodes for pathogen collection. Integrated reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) is used for detection of captured viral matter within wells. On-chip heating of collection wells is enabled by integrated planar heaters and small volumes of reagent (30 L) directly to the collection wells. We present the design of such a system and show experimental results that demonstrate the use of this device for detection of aerosolized SARS-CoV-2 virus like particles (VLPs), a model pathogen for SARV-CoV-2.

A Drug-Free Pathogen Capture and Neutralizing Nasal Spray to Prevent Emerging Respiratory Infections (preprint)

Respiratory infections pose a global health crisis. Vaccines are pathogen specific, and new vaccines are needed for mutants and emerging pathogens. Here, we report a drug free prophylactic platform - a Pathogen Capture and Neutralizing Spray (PCANS) that acts via a multi-pronged approach to prevent a broad spectrum of respiratory infections. PCANS forms a protective coating in the nasal cavity that enhances the capture of large respiratory droplets. The coating acts as a physical barrier against a broad spectrum of viruses and bacteria, and rapidly neutralizes them, reducing the pathogen load by >99.99%. In mice, PCANS showed nasal retention for at least 8 h and was safe for daily administration. A single prophylactic dose of PCANS protected mice against supra-lethal dosages of a mouse-adapted H1N1 Influenza virus (PR8), reduced lung viral titer by >99.99%, improved survival, and suppressed pathological manifestations. Together, our data suggest PCANS as a promising daily-use prophylactic approach against current and emerging respiratory infections.

p38-MAPK is prerequisite for the synthesis of SARS-CoV-2 protein (preprint)

The inhibition of p38 mitogen-activated protein kinase (p38-MAPK) by small molecule chemical inhibitors was previously shown to impair severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, however, mechanisms underlying antiviral activity remains unexplored. In this study, reduced growth of SARS-CoV-2 in p38- knockout Vero cells, together with enhanced viral yield in cells transfected with construct expressing p38, suggested that p38-MAPK is essential for the propagation of SARS-CoV-2. The SARS-CoV-2 was also shown to induce phosphorylation (activation) of p38, at time when transcription/translational activities are considered to be at the peak levels. Further, we demonstrated that p38 supports viral RNA/protein synthesis without affecting viral attachment, entry, and budding in the target cells. In addition, we demonstrated that long-term culture of SARS-CoV-2 in the presence of p38 inhibitor SB203580 does not easily select resistant viral mutants. In conclusion, we provide mechanistic insights on the regulation of SARS-CoV-2 replication by p38 MAPK.

A case of fever in a returning traveler.

ABSTRACT: After the lifting of COVID-19 restrictions, international travel has demonstrated recovery to prepandemic levels. Travel, particularly to tropical regions, can be associated with contracting various infectious diseases. For this reason, collecting a travel history is a necessity when assessing any patient with vague infectious symptoms, most notably fever. Early suspicion, identification, and treatment of tropical illnesses can be lifesaving. This case study concerns a patient who recently traveled to Africa and is under evaluation for fever in the emergency department. The proper approach to the febrile traveler and the pathophysiology, diagnosis, and treatment of malaria are reviewed.

Telemedicine for diabetes management during COVID-19: what we have learnt, what and how to implement.

The past two decades have witnessed telemedicine becoming a crucial part of health care as a method to facilitate doctor-patient interaction. Due to technological developments and the incremental acquisition of experience in its use, telemedicine's advantages and cost-effectiveness has led to it being recognised as specifically relevant to diabetology. However, the pandemic created new challenges for healthcare systems and the rate of development of digital services started to grow exponentially. It was soon discovered that COVID-19-infected patients with diabetes had an increased risk of both mortality and debilitating sequelae. In addition, it was observed that this higher risk could be attenuated primarily by maintaining optimal control of the patient's glucose metabolism. As opportunities for actual physical doctor-patient visits became restricted, telemedicine provided the most convenient opportunity to communicate with patients and maintain delivery of care. The wide range of experiences of health care provision during the pandemic has led to the development of several excellent strategies regarding the applicability of telemedicine across the whole spectrum of diabetes care. The continuation of these strategies is likely to benefit clinical practice even after the pandemic crisis is over.

The Fragile Patient: Considerations in the Management of Invasive Mould Infections (IMIs) in India.

Invasive mould infections (IMIs), which are mostly caused by Aspergillus spp. and Mucormycetes, are opportunistic infections that impose a substantial threat to patients who are considered to be 'fragile'. There is no fixed definition for fragile patients; however, patients with cancer or acquired immunodeficiency syndrome (AIDS), patients who have undergone organ transplants, and patients being treated in the intensive care units (ICUs) were considered fragile. Management of IMIs in fragile patients is challenging, owing to their compromised immune status. The diagnostic challenges associated with IMIs due to insufficient sensitivity and specificity of the current diagnostic tests lead to delayed treatment. A widening demographic of at-risk patients and a broadening spectrum of pathogenic fungi have added to the challenges to ascertain a definite diagnosis. A recent surge of mucormycosis associated with SARS-CoV-2 infections and the resultant steroid usage has been reported. Liposomal amphotericin B (L-AmB) is the mainstay for treating mucormycosis while voriconazole has displaced amphotericin B as the mainstay for treating Aspergillus infection due to its better response, improved survival, and fewer severe side effects. The selection of antifungal treatment has to be subjected to more scrutiny in fragile patients owing to their comorbidities, organ impairment, and multiple ongoing treatment modalities. Isavuconazole has been documented to have a better safety profile, stable pharmacokinetics, fewer drug-drug interactions, and a broad spectrum of coverage. Isavuconazole has thus found its place in the recommendations and can be considered a suitable option for treating fragile patients with IMIs. In this review, the authors have critically appraised the challenges in ascertaining an accurate diagnosis and current management considerations and suggested an evidence-based approach to managing IMIs in fragile patients.

Systematic Evaluation of Hematologic Parameters and Blood Smear Findings in Patients With SARS-CoV-2 vs Other Viral Respiratory Infections.

OBJECTIVES: We evaluated and compared the peripheral blood findings in patients with acute COVID-19 vs other viral respiratory infections. METHODS: We retrospectively reviewed peripheral blood counts and smear morphology in patients with a positive viral respiratory panel (VRP) or SARS-CoV-2 test. RESULTS: A total of 97 peripheral blood samples (COVID-19 infection, 53; VRP positive, 44) from 50 patients (mean [SD] age, 45.8 [20.8] years; females 52%) were reviewed. There were no statistically significant differences in the demographic characteristics between the 2 groups. The most common peripheral blood abnormalities were anemia, thrombocytopenia, absolute lymphopenia, and reactive lymphocytes. The following peripheral blood findings were significantly associated with other viral respiratory infections compared with COVID-19 infection: low red blood cell count, low hematocrit, high mean corpuscular volume, thrombocytopenia, low mean platelet volume, high red cell distribution width, band neutrophilia, and toxic granulation in neutrophils. CONCLUSIONS: Our study showed that there are several peripheral blood count and morphologic abnormalities seen in patients with COVID-19, but most of these findings lack specificity as they are also seen in the other viral respiratory infections.

How can lessons from the COVID-19 pandemic enhance antimicrobial resistance surveillance and stewardship?

COVID-19 demanded urgent and immediate global attention, during which other public health crises such as antimicrobial resistance (AMR) increased silently, undermining patient safety and the life-saving ability of several antimicrobials. In 2019, WHO declared AMR a top ten global public health threat facing humanity, with misuse and overuse of antimicrobials as the main drivers in the development of antimicrobial-resistant pathogens. AMR is steadily on the rise, especially in low-income and middle-income countries across south Asia, South America, and Africa. Extraordinary circumstances often demand an extraordinary response as did the COVID-19 pandemic, underscoring the fragility of health systems across the world and forcing governments and global agencies to think creatively. The key strategies that helped to contain the increasing SARS-CoV-2 infections included a focus on centralised governance with localised implementation, evidence-based risk communication and community engagement, use of technological methods for tracking and accountability, extensive expansion of access to diagnostics, and a global adult vaccination programme. The extensive and indiscriminate use of antimicrobials to treat patients, particularly in the early phase of the pandemic, have adversely affected AMR stewardship practices. However, there were important lessons learnt during the pandemic, which can be leveraged to strengthen surveillance and stewardship, and revitalise efforts to address the AMR crisis.

Acute Liver Failure in a Healthy Young Female With COVID-19.

Several well-described manifestations of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. Among them, a transient elevation of liver enzymes is the typical presentation of coronavirus disease 2019 (COVID-19) liver-related injury. The mechanism of liver involvement is likely a combination of viral injury and immune-mediated inflammation. In contrast, acute liver failure in the setting of COVID-19 has rarely been reported. Herein, we report a case of pediatric acute liver failure in a previously healthy female adolescent infected with SARS-CoV-2 with biopsy evidence of replicating virus in hepatocytes, which has not been previously reported.

Design and rationale of the CHILL phase II trial of hypothermia and neuromuscular blockade for acute respiratory distress syndrome.

The Cooling to Help Injured Lungs (CHILL) trial is an open label, two group, parallel design multicenter, randomized phase IIB clinical trial assessing the efficacy and safety of targeted temperature management with combined external cooling and neuromuscular blockade to block shivering in patients with early moderate-severe acute respiratory distress syndrome (ARDS). This report provides the background and rationale for the clinical trial and outlines the methods using the Consolidated Standards of Reporting Trials guidelines. Key design challenges include: [1] protocolizing important co-interventions; [2] incorporation of patients with COVID-19 as the cause of ARDS; [3] inability to blind the investigators; and [4] ability to obtain timely informed consent from patients or legally authorized representatives early in the disease process. Results of the Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) trial informed the decision to mandate sedation and neuromuscular blockade only in the group assigned to therapeutic hypothermia and proceed without this mandate in the control group assigned to a usual temperature management protocol. Previous trials conducted in National Heart, Lung, and Blood Institute ARDS Clinical Trials (ARDSNet) and Prevention and Early Treatment of Acute Lung Injury (PETAL) Networks informed ventilator management, ventilation liberation and fluid management protocols. Since ARDS due to COVID-19 is a common cause of ARDS during pandemic surges and shares many features with ARDS from other causes, patients with ARDS due to COVID-19 are included. Finally, a stepwise approach to obtaining informed consent prior to documenting critical hypoxemia was adopted to facilitate enrollment and reduce the number of candidates excluded because eligibility time window expiration.

Surveillance on Adverse Events Following COVISHIELD (ChAdOx1 nCoV-19) vaccination in Goa, India: An observational study.

BACKGROUND: COVISHIELD, ChAdOx1 nCoV- 19 Corona Virus Vaccine was granted emergency use authorization (EUA) as the first vaccine in India in January 2021. Knowing what to anticipate after vaccination will reduce vaccine hesitancy in the public. This study aimed to identify and measure the adverse events following COVID-19 vaccination. MATERIALS AND METHODS: A cross-sectional observational study was conducted at Goa Medical College, starting on February 21 till May 23, 2021. A total of 418 people were enrolled. We collected the data using the Microsoft Form and analyzed using Microsoft Excel and R-program. RESULTS: Of the 418 vaccine recipients, the incidence rate of AEFI (Adverse Events Following Immunization) was 54.31%. Fever, fatigue, and headache were the most commonly reported systemic AEFIs. Among these, 54.7% of AEFI were mild, 42.38% were of the moderate category, and only 2.96% were of grade 3 severity. None of the AEFIs were severe enough for hospitalization. Most of them developed symptoms within 24 hours of the first dose. Complete recovery from AEFIs took a median time of 24 hours. CONCLUSION: Most of our study findings were consistent with the phase 1, 2/3 trials findings of Oxford-AstraZeneca's ChAdOx1 vaccine. The AEFI symptoms were considered immune reactions to the vaccine. The AEFIs were more common among younger individuals and females. The chance of missing a serious adverse event like a thromboembolic phenomenon cannot be ruled out. We observed low AEFI rates with COVISHIELD in the Indian population compared to Oxford-AstraZeneca's ChAdOx1 vaccine in the UK-based population, which can be explained by pre-existing immunity against adenovirus in the Indian population. However, based on the study findings, we may interpret that the COVISHIELD, Serum Institute of India, carries a good safety profile overall.

Reverse Transcription Recombinase Polymerase Amplification integrated with CRISPR Technology and LFA for point-of-care detection of SARS-CoV-2 virus

The field-deployable point-of-care diagnostic test for rapid detection of SARS-COV-2 is needed for implementation of the control measures. In this direction, recently developed CRISPR technology combined with isothermal recombinase polymerase amplification assay is a versatile highly sensitive detection platform for rapid diagnosis of infectious diseases. Here we report the development of RT-RPA-CRISPR based LFA assay for detection of SARS-CoV-2 targeting conserved RdRp and E genes. Various sets of primers and gRNAs were designed targeting conserved regions of the RdRp and E genes of different lineages of SARS-CoV-2 viruses. The isothermal RT-RPA based amplification reactions were standardized using invitro transcribed RNAs of the target regions. The optimum amplification was observed at 42degreeC for 30 min as confirmed by visualization of the amplicons in agarose gel. Subsequently, CRISPRCAS12 reaction was implemented for specific detection of amplicons. Different sets of gRNAs targeting RdRp and E genes were designed and synthesized by in-vitro transcription. The CRISP/CAS12-gRNA complex and single stranded fluorescence probe were added to the RT-RPA amplicons for cleavage of fluorescence probe in positive reaction. Subsequently, the cleaved probes were detected in precoated LFA strips. Upon probe cleavage reaction, the product was mixed with buffer and loaded into LFA strips. In positive reaction, test line showed strong band in test line and light band in control line. The standardized RT-RPA-CRISPR-LFA assay was tested for detection of SARS-CoV-2 using previously isolated RNAs from clinical cases of human SARS-CoV-2 infections. The developed assay successfully detected the positive cases. In conclusion, the developed assay could serve as versatile POC platform for rapid detection of SARS-CoV-2 nucleic acids in human as well as animals.

A precise and timely graph‐based approach to identify SARS Covid19 infection from medical imaging data using IsoCovNet

More than 100 million individuals have been infected by the COVID19 virus since 2019. Even if the vaccination procedure has already begun, it will take time to attain an adequate supply. There have been several efforts by computer scientists to filter COVID19 from CXR or CT scans due to the disease's extensive prevalence. These patients' CT and CXR scans are utilized to identify COVID19 using IsoCovNet, a Graph‐Isomorphic‐Network, that is, GIN‐based model for detecting COVID19. A GIN‐based design dictates that our suggested model only takes data in the form of graphs. At the outset, the input image undergoes a conversion into an unordered network, that is, a graph that considers only the links between elements rather than the entire image. This approach significantly reduces the model's processing time. We verified the effectiveness of our proposed IsoCovNet network by using four datasets, which consist of both x‐ray and CT‐scan images, from five standard sources that are publicly available on platforms like Kaggle and GitHub. The network achieved an accuracy of 99.51% on binary datasets and a higher accuracy of 99.84% on the multi‐classification task of detecting Covid19. [ FROM AUTHOR] Copyright of International Journal of Imaging Systems & Technology is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

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.

SARS-CoV-2 Pandemic-Therapeutics in Warp Speed.

Ever since the coronavirus disease 2019 (COVID-19) pandemic struck, the challenges posed to the scientific community by its causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been countless, and still continue to emerge. Even though a host of repurposed and new therapeutic agents as well as vaccines have been, and are being assessed at a breakneck speed, this contagion continues to create havoc, returning back in waves, with appearance of newer viral variants which are associated with numerous challenges, which include greater transmissibility, increased virulence, immune escape, etc. In this study, we discuss the current status of various therapeutic agents which are being used, or in the various stages of preclinical/clinical trials for managing COVID-19.

Mental health support for and telehealth use by Australians living with borderline personality disorder during the onset of the COVID-19 pandemic: A national study.

Objective: To investigate mental health service use and telehealth experience of people living with BPD in Australia during the first year of the COVID-19 pandemic. Methods: An online survey was used to collect data from people who self-identified with a diagnosis of BPD. Results: One hundred and sixty-nine survey responses were included in the analysis. More than half of participants acknowledged receiving information from their health service about resources that they could use if they become distressed. More than 70% of participants used telehealth for receiving mental health services; the majority used telehealth to consult a psychologist or to obtain prescriptions. Telehealth sessions were conducted over the phone, via videoconferencing, or using a mix of the two. While using telehealth, some participants found it more difficult to control their impulses to self-harm, to express thoughts about self-harm and suicide, to control feelings of anger, and to establish and maintain agreed treatment boundaries. Thematic analysis of participants' experiences of telehealth identified five main themes: Communication challenges, Technology challenges, Privacy concerns, Benefits of telehealth, and Personal preferences. Conclusion: The study findings revealed a variety of positive and negative consumer experiences. While the majority of participants found telehealth somewhat benefitted their mental health, challenges were also reported which raise concerns about the broader utility and effectiveness of telehealth.