A hierarchical Bayesian model for estimating age-specific COVID-19 infection fatality rates in developing countries (preprint)

The COVID-19 infection fatality rate (IFR) is the proportion of individuals infected with SARS-CoV-2 who subsequently die. As COVID-19 disproportionately affects older individuals, age-specific IFR estimates are imperative to facilitate comparisons of the impact of COVID-19 between locations and prioritize distribution of scare resources. However, there lacks a coherent method to synthesize available data to create estimates of IFR and seroprevalence that vary continuously with age and adequately reflect uncertainties inherent in the underlying data. In this paper we introduce a novel Bayesian hierarchical model to estimate IFR as a continuous function of age that acknowledges heterogeneity in population age structure across locations and accounts for uncertainty in the estimates due to seroprevalence sampling variability and the imperfect serology test assays. Our approach simultaneously models test assay characteristic, serology, and death data, where the serology and death data are often available only for binned age groups. Information is shared across locations through hierarchical modeling to improve estimation of the parameters with limited data. Modeling data from 26 developing country locations during the first year of the COVID-19 pandemic, we found seroprevalence did not change dramatically with age, and the IFR at age 60 was above the high-income country benchmark for most locations.

Cross-Protection Induced by Highly Conserved Human B, CD4+, and CD8+ T Cell Epitopes-Based Coronavirus Vaccine Against Severe Infection, Disease, and Death Caused by Multiple SARS-CoV-2 Variants of Concern (preprint)

Background: The Coronavirus disease 2019 (COVID-19) pandemic has created one of the largest global health crises in almost a century. Although the current rate of SARS-CoV-2 infections has decreased significantly; the long-term outlook of COVID-19 remains a serious cause of high death worldwide; with the mortality rate still surpassing even the worst mortality rates recorded for the influenza viruses. The continuous emergence of SARS-CoV-2 variants of concern (VOCs), including multiple heavily mutated Omicron sub-variants, have prolonged the COVID-19 pandemic and outlines the urgent need for a next-generation vaccine that will protect from multiple SARS-CoV-2 VOCs. Methods: In the present study, we designed a multi-epitope-based Coronavirus vaccine that incorporated B, CD4+, and CD8+ T cell epitopes conserved among all known SARS-CoV-2 VOCs and selectively recognized by CD8+ and CD4+ T-cells from asymptomatic COVID-19 patients irrespective of VOC infection. The safety, immunogenicity, and cross-protective immunity of this pan-Coronavirus vaccine were studied against six VOCs using an innovative triple transgenic h-ACE-2-HLA-A2/DR mouse model. Results: The Pan-Coronavirus vaccine: (i) is safe; (ii) induces high frequencies of lung-resident functional CD8+ and CD4+ TEM and TRM cells; and (iii) provides robust protection against virus replication and COVID-19-related lung pathology and death caused by six SARS-CoV-2 VOCs: Alpha (B.1.1.7), Beta (B.1.351), Gamma or P1 (B.1.1.28.1), Delta (lineage B.1.617.2) and Omicron (B.1.1.529). Conclusions: A multi-epitope pan-Coronavirus vaccine bearing conserved human B and T cell epitopes from structural and non-structural SARS-CoV-2 antigens induced cross-protective immunity that cleared the virus, and reduced COVID-19-related lung pathology and death caused by multiple SARS-CoV-2 VOCs.

Examining the adoption of telehealth during public health emergencies based on technology organization environment framework

PurposeDisasters and pandemics pose challenges to health-care provision. Accordingly, the need for adopting innovative approach is required in providing care to patient. Therefore, the purpose of this study is to present telehealth as an innovative approach for providing care to patients and reducing spread of the infection and advocates for the adoption of telehealth for digitalized treatment of patients. Design/methodology/approachAn integrative review methodology of existing evidence was conducted to provide implications for integration of telehealth for digitalized treatment of patients. This paper draws on Technology Organization Environment (TOE) framework to develop a model and propositions to investigate the factors that influence telehealth adoption from the perspective of the supply side and the demand side of medical services. FindingsFindings from this study discuss applications adopted for telehealth and recommendations on how telehealth can be adopted for medical-care delivery. More importantly, the findings and propositions of this study can act as a roadmap to potential research opportunities within and beyond the pandemic. In addition, findings from this study help provide guidelines on how health practitioners can rapidly integrate telehealth into practice for public health emergencies. Originality/valueThis study identifies the social, technological and organizational factors that influence telehealth adoption, and opportunities of adopting telehealth during the public health emergencies. This study concludes that specific policy changes to improve integration of interoperable solutions;data security;better physical infrastructures;broadband access;better transition and workflow balance;availability of funding and remuneration;regulations and reimbursement;awareness;and training will improve telehealth adoption during public health emergencies.

Snakebite care through the first two waves of COVID-19 in West Bengal, India: a qualitative study.

Snakebite is a public health problem in many countries, with India having the highest number of deaths. Not much is known about the effect of the COVID-19 pandemic on snakebite care. We conducted 20 in-depth interviews with those bitten by venomous snakes through the two waves of COVID-19 (March-May 2020; May-November 2021), their caregivers, health care workers and social workers in two areas (Sundarbans and Hooghly) of West Bengal, India. We used a constructivist approach and conducted a thematic analysis. We identified the following themes: 1. Snakebite continued to be recognised as an acute emergency during successive waves of COVID-19; 2. COVID-19 magnified the financial woes of communities with high snakebite burden; 3. The choice of health care provider was driven by multiple factors and consideration of trade-offs, many of which leaned toward use of traditional providers during COVID-19; 4. Rurality, financial and social disadvantage and cultural safety, in and beyond the health system, affected snakebite care; 5. There is strong and shared felt need for multi-faceted community programs on snakebite. We mapped factors affecting snakebite care in the three-delay model (decision to seek care, reaching appropriate health facility, receiving appropriate care), originally developed for maternal mortality. The result of our study contextualises and brings forth evidence on impact of COVID-19 on snakebite care in West Bengal, India. Multi-faceted community programs, are needed for addressing factors affecting snakebite care, including during disease outbreaks - thus improving health systems resilience. Community programs for increasing formal health service usage, should be accompanied by health systems strengthening, instead of an exclusive focus on awareness against traditional providers.

Intra-Host Evolution Provides for the Continuous Emergence of SARS-CoV-2 Variants.

Variants of concern (VOC) in SARS-CoV-2 refer to viruses whose viral genomes differ from the ancestor virus by ≥3 single-nucleotide variants (SNVs) and that show the potential for higher transmissibility and/or worse clinical progression. VOC have the potential to disrupt ongoing public health measures and vaccine efforts. Still, too little is known regarding how frequently new viral variants emerge and under what circumstances. We report a study to determine the degree of SARS-CoV-2 sequence evolution in 94 patients and to estimate the frequency at which highly diverse variants emerge. Two cases accumulated ≥9 SNVs over a 2-week period and one case accumulated 23 SNVs over 3 weeks, including three nonsynonymous mutations in the spike protein (D138H, E554D, D614G). The remainder of the infected patients did not show signs of intra-host evolution. We estimate that in as much as 2% of hospitalized COVID-19 cases, variants with multiple mutations in the spike glycoprotein emerge in as little as 1 month of persistent intra-host virus replication. This suggests the continued local emergence of variants with multiple nonsynonymous SNVs, even in patients without overt immune deficiency. Surveillance by sequencing for (i) viremic COVID-19 patients, (ii) patients suspected of reinfection, and (iii) patients with diminished immune function may offer broad public health benefits. IMPORTANCE New SARS-CoV-2 variants can potentially disrupt ongoing public health measures and vaccine efforts. Still, little is known regarding how frequently new viral variants emerge and under what circumstances. Based on this study, we estimate that in hospitalized COVID-19 cases, variants with multiple mutations may emerge locally in as little as 1 month, even in patients without overt immune deficiency. Surveillance by sequencing for continuously shedding patients, patients suspected of reinfection, and patients with diminished immune function may offer broad public health benefits.

Scaling Biosafety Up During and Down After the COVID-19 Pandemic.

Purpose: The aim of this work was to review and analyze changes to the practice of biosafety imposed by pandemics. Methods: A narrative review of the COVID-19 pandemic that began in 2020 and prior pandemics from the perspective of a working virologist. Results: By definition, pandemics, outbreaks, and other emergencies are transient phenomena. They manifest as waves of events that induce unforeseen needs and present unknown challenges. After a pandemic, the return to normality is as crucial as the scale-up during the exponential growth phase. The COVID-19 pandemic presents an example to study operational biosafety and biocontainment issues during community transmission of infectious agents with established pandemic potential, the propensity to induce severe disease, and the ability to disrupt aspects of human society. Conclusions: Scaling down heightened biocontainment measures after a pandemic is as important as scaling up during a pandemic. The availability of preventive vaccines, and therapeutic drug regimens, should be considered in risk assessments for laboratory studies. There exists the need to preserve situational memory at the personal and institutional levels that can be served by professional societies.

Prevention and treatment of atherothrombosis: Potential impact of nanotechnology.

Complications with atherosclerosis can often lead to fatal clot formation and blood vessel occlusion - also known as atherothrombosis. A key component to the development of atherosclerosis and atherothrombosis is the endothelium and its ability to regulate the balance between prothrombotic and antithrombotic activities. Endothelial surface glycocalyx has a critical role in maintenance of vascular integrity. The endothelial glycocalyx, nitric oxide, prostacyclins, heparan sulfate, thrombomodulin, and tissue factor pathway inhibitor all prevent thrombosis, while P-selectin, among many other factors, favors thrombosis. However, endothelial dysfunction gives rise to the acceleration of thrombotic development and eventually the requirement of antithrombotic therapy. Most FDA-approved anticoagulant and antiplatelet therapies today carry a side effect profile of major bleed. Within the past five years, several preclinical studies using different endothelial targets and nanotechnology as a drug delivery method have emerged to target the endothelium and to enhance current antithrombosis without increasing bleed risk. While clinical studies are required, this review illustrates the proof-of-concept of nanotechnology in promoting a greater safety and efficacy profile through multiple in vitro and in vivo studies.

SARS-CoV-2 variants show temperature-dependent enhancedpolymerase activity in the upper respiratory tract and high transmissibility (preprint)

With the convergent global emergence of SARS-CoV-2 variants of concern (VOC), a precise comparison study of viral fitness and transmission characteristics is necessary for the prediction of dominant VOCs and the development of suitable countermeasures. While airway temperature plays important roles in the fitness and transmissibility of respiratory tract viruses, it has not been well studied with SARS-CoV-2. Here we demonstrate that natural temperature differences between the upper (33) and lower (37) respiratory tract have profound effects on SARS-CoV-2 replication and transmission. Specifically, SARS-COV-2 variants containing the P323L or P323L/G671S mutation in the NSP12 RNA-dependent RNA polymerase (RdRp) exhibited enhanced RdRp enzymatic activity at 33 compared to 37 and high transmissibility in ferrets. MicroScale Thermophoresis demonstrated that the NSP12 P323L or P323L/G671S mutation stabilized the NSP12-NSP7-NSP8 complex interaction. Furthermore, reverse genetics-derived SARS-CoV-2 variants containing the NSP12 P323L or P323L/G671S mutation displayed enhanced replication at 33, and high transmission in ferrets. This suggests that the evolutionarily forced NSP12 P323L and P323L/G671S mutations of recent SARS-CoV-2 VOC strains are associated with increases of the RdRp complex stability and enzymatic activity, promoting the high transmissibility.

Inhibition of a broad range of SARS-CoV-2 variants by antiviral phytochemicals in hACE2 mice.

Although several vaccines and antiviral drugs against SARS-CoV-2 are currently available, control and prevention of COVID-19 through these interventions is limited due to inaccessibility and economic issues in some regions and countries. Moreover, incomplete viral clearance by ineffective therapeutics may lead to rapid genetic evolution, resulting in the emergence of new SARS-CoV-2 variants that may escape the host immune system as well as currently available COVID-19 vaccines. Here, we report that phytochemicals extracted from Chlorella spp. and Psidium guajava possess broad-spectrum antiviral activity against a range of SARS-CoV-2 variants. Through chromatography-based screening, we identified four bioactive compounds and subsequently demonstrated their potential antiviral activities in vivo. Interestingly, in hACE2 mice, treatment with these compounds significantly attenuates SARS-CoV-2-induced proinflammatory responses, demonstrating their potential anti-inflammatory activity. Collectively, our study suggests that phytochemicals from edible plants may be readily available therapeutics and prophylactics against multiple SARS-CoV-2 strains and variants.

Assessing the burden of COVID-19 in developing countries: systematic review, meta-analysis and public policy implications.

INTRODUCTION: The infection fatality rate (IFR) of COVID-19 has been carefully measured and analysed in high-income countries, whereas there has been no systematic analysis of age-specific seroprevalence or IFR for developing countries. METHODS: We systematically reviewed the literature to identify all COVID-19 serology studies in developing countries that were conducted using representative samples collected by February 2021. For each of the antibody assays used in these serology studies, we identified data on assay characteristics, including the extent of seroreversion over time. We analysed the serology data using a Bayesian model that incorporates conventional sampling uncertainty as well as uncertainties about assay sensitivity and specificity. We then calculated IFRs using individual case reports or aggregated public health updates, including age-specific estimates whenever feasible. RESULTS: In most locations in developing countries, seroprevalence among older adults was similar to that of younger age cohorts, underscoring the limited capacity that these nations have to protect older age groups.Age-specific IFRs were roughly 2 times higher than in high-income countries. The median value of the population IFR was about 0.5%, similar to that of high-income countries, because disparities in healthcare access were roughly offset by differences in population age structure. CONCLUSION: The burden of COVID-19 is far higher in developing countries than in high-income countries, reflecting a combination of elevated transmission to middle-aged and older adults as well as limited access to adequate healthcare. These results underscore the critical need to ensure medical equity to populations in developing countries through provision of vaccine doses and effective medications.

Can Hong Kong exceptionalism last? Dilemmas of governance and public administration over five decades 1970s-2020

Purpose>The purpose of this book launch speech is to introduce the book I author, Can Hong Kong exceptionalism last? Dilemmas of governance and public administration over five decades 1970s-2020 (2021). The book critically reviews the governance and public administration from 1970s to 2020, identifying strengths and capabilities as well as constraints and dilemmas.Design/methodology/approach>The book is based on my decades of academic observations and personal political experience by interpreting and re-interpreting the Hong Kong journey, with reflections on past assumptions and raising new questions.Findings>This book identifies five exceptional aspects: (a) Under British rule Hong Kong was governed as an atypical colony;(b) It was one of the Four Little Dragons as part of the East Asian Miracle;(c) In the 1990s, it was one of the regional pioneers in public sector reform;(d) The unique constitutional status of post-1997 Hong Kong as a Special Administrative Region (SAR) of China;(e) After reunification, the SAR government, though only semi-democratic, is checked by balancing and monitoring mechanisms no less vigorous than some developed democracies. It also examines various governance problems faced in the post-1997 period.Originality/value>Hong Kong is again in times of uncertainty and volatility. The city has entered a ‘second transition’ after 2020, and it is undergoing a bigger test than in 1997. After reviewing the past, I opine in the book that Hong Kong has to identify its niche areas, not only in economics. It needs a paradigm shift in how it relates to the Mainland within ‘One Country’ and how it relates to the world as a global metropolis.

Validation of the Mental Health Checklist (MHCL) during COVID-19 lockdown.

The COVID-19 pandemic resulted in unprecedented disruption to everyday life, including widespread social distancing and self-quarantining aimed at reducing the virus spread. The Mental Health Checklist (MHCL) is a measure developed to assess psychological health during extended periods of isolation and confinement, and has shown strong psychometric properties in community samples and during Antarctic missions. This study validated the MHCL in a sample of 359 U.S. and U.K adults during the peak of the COVID-19 lockdown. Confirmatory factor analysis (CFA) tested model fit, and convergent validity analyses were conducted to compare the MHCL with validated measures of depression, anxiety and stress, as well as insomnia. The MHCL exhibited good model fit for most CFA indices, and showed strong convergent validity with other measures of psychological well-being. Findings suggest that the MHCL is useful for assessing mental health in a variety of environments and conditions.

Transmissibility and pathogenicity of SARS-CoV-2 variants in animal models.

As of February 2022, SARS-CoV-2 is still one of the most serious public health threats due to its high mortality rate and rapid spread of novel variants. Since the first outbreak in 2019, general understanding of SARS-CoV-2 has been improved through basic and clinical studies; however, knowledge gaps still exist in our understanding of the emerging novel SARSCoV-2 variants, which impacts the corresponding development of vaccines and therapeutics. Especially, accumulation of mutations in SARS-CoV-2 and rapid spread in populations with previous immunity has resulted in selection of variants that evade the host immune response. This phenomenon threatens to render current SARS-CoV-2 vaccines ineffective for controlling the pandemic. Proper animal models are essential for detailed investigations into the viral etiology, transmission and pathogenesis mechanisms, as well as evaluation of the efficacy of vaccine candidates against recent SARS-CoV-2 variants. Further, the choice of animal model for each research topic is important for researchers to gain better knowledge of recent SARS-CoV-2 variants. Here, we review the advantages and limitations of each animal model, including mice, hamsters, ferrets, and non-human primates, to elucidate variant SARS-CoV-2 etiology and transmission and to evaluate therapeutic and vaccine efficacy.

Coinfection with SARS-CoV-2 and Influenza A Virus Increases Disease Severity and Impairs Neutralizing Antibody and CD4+ T Cell Responses.

Given the current coronavirus disease 2019 (COVID-19) pandemic, coinfection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) is a major concern for public health. However, the immunopathogenic events occurring with coinfections of SARS-CoV-2 and IAV remain unclear. Here, we report the pathogenic and immunological consequences of SARS-CoV-2 and IAV H1N1 coinfection in the K18-hACE2 transgenic mouse model. Compared with a single infection with SARS-CoV-2 or IAV, coinfections not only prolonged the primary virus infection period but also increased immune cell infiltration and inflammatory cytokine levels in bronchoalveolar lavage fluid leading to severe pneumonia and lung damage. Moreover, coinfections caused severe lymphopenia in peripheral blood, resulting in reduced total IgG, neutralizing antibody titers, and CD4+ T cell responses against each virus. This study sheds light on the immunopathogenesis of SARS-CoV-2 and IAV coinfection, which may guide the development of effective therapeutic strategies for the treatment of patients coinfected with these viruses. IMPORTANCE The cocirculation of influenza virus merging with the COVID-19 pandemic raises a potentially severe threat to public health. Recently, increasing numbers of SARS-CoV-2 and influenza virus coinfection have been reported from many countries. It is a worrisome issue that SARS-CoV-2 coinfection with other pathogens may worsen the clinical outcome and severity of COVID-19 and increase fatality. Here, we evaluated SARS-CoV-2 and IAV coinfection using the K18-hACE2 mouse model. Coinfected mice exhibited increased mortality with prolonged IAV shedding. Furthermore, coinfected mice showed a higher level of cytokines and chemokines than a single infection condition. Interestingly, our data show that coinfected mice showed significantly fewer virus-specific and neutralizing antibodies than the mice with a single infection. Overall, this study suggests that coinfection aggravates viral pathology by impaired neutralizing antibody response.

Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets.

Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients.IMPORTANCE The SARS-CoV-2 pandemic continues to spread worldwide, with rapidly increasing numbers of mortalities, placing increasing strain on health care systems. Despite serious public health concerns, no effective vaccines or therapeutics have been approved by regulatory agencies. In this study, we tested the FDA-approved drugs lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir against SARS-CoV-2 infection in a highly susceptible ferret infection model. While most of the drug treatments marginally reduced clinical symptoms, they did not reduce virus titers, with the exception of emtricitabine-tenofovir treatment, which led to diminished virus titers in nasal washes at 8 dpi. Further, the azathioprine-treated immunosuppressed ferrets showed delayed virus clearance and low SN titers, resulting in a prolonged infection. As several FDA-approved or repurposed drugs are being tested as antiviral candidates at clinics without sufficient information, rapid preclinical animal studies should proceed to identify therapeutic drug candidates with strong antiviral potential and high safety prior to a human efficacy trial.

High Frequencies of PD-1+TIM3+TIGIT+CTLA4+ Functionally Exhausted SARS-CoV-2-Specific CD4+ and CD8+ T Cells Associated with Severe Disease in Critically ill COVID-19 Patients (preprint)

SARS-CoV-2-specific memory T cells that cross-react with common cold coronaviruses (CCCs) are present in both healthy donors and COVID-19 patients. However, whether these cross-reactive T cells play a role in COVID-19 pathogenesis versus protection remain to be fully elucidated. In this study, we characterized cross-reactive SARS-CoV-2-specific CD4+ and CD8+ T cells, targeting genome-wide conserved epitopes in a cohort of 147 non-vaccinated COVID-19 patients, divided into six groups based on the degrees of disease severity. We compared the frequency, phenotype, and function of these SARS-CoV-2-specific CD4+ and CD8+ T cells between severely ill and asymptomatic COVID-19 patients and correlated this with alpha-CCCs and beta-CCCs co-infection status. Compared with asymptomatic COVID-19 patients, the severely ill COVID-19 patients and patients with fatal outcomes: (i) Presented a broad leukocytosis and a broad CD4+ and CD8+ T cell lymphopenia; (ii) Developed low frequencies of functional IFN-gamma-producing CD134+CD138+CD4+ and CD134+CD138+CD8+ T cells directed toward conserved epitopes from structural, non-structural and regulatory SARS-CoV-2 proteins; (iii) Displayed high frequencies of SARS-CoV-2-specific functionally exhausted PD-1+TIM3+TIGIT+CTLA4+CD4+ and PD-1+TIM3+TIGIT+CTLA4+CD8+ T cells; and (iv) Displayed similar frequencies of co-infections with beta-CCCs strains but significantly fewer co-infections with alpha-CCCs strains. Interestingly, the cross-reactive SARS-CoV-2 epitopes that recalled the strongest CD4+ and CD8+ T cell responses in unexposed healthy donors (HD) were the most strongly associated with better disease outcome seen in asymptomatic COVID-19 patients. Our results demonstrate that, the critically ill COVID-19 patients displayed fewer co-infection with alpha-CCCs strain, presented broad T cell lymphopenia and higher frequencies of cross reactive exhausted SARS-CoV-2-specific CD4+ and CD8+ T cells. In contrast, the asymptomatic COVID-19 patients, appeared to present more co-infections with alpha-CCCs strains, associated with higher frequencies of functional cross-reactive SARS-CoV-2-specific CD4+ and CD8+ T cells. These findings support the development of broadly protective, T-cell-based, multi-antigen universal pan-Coronavirus vaccines.

Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets.

While the seroprevalence of SARS-CoV-2 in healthy people does not differ significantly among age groups, those aged 65 years or older exhibit strikingly higher COVID-19 mortality compared to younger individuals. To further understand differing COVID-19 manifestations in patients of different ages, three age groups of ferrets are infected with SARS-CoV-2. Although SARS-CoV-2 is isolated from all ferrets regardless of age, aged ferrets (≥3 years old) show higher viral loads, longer nasal virus shedding, and more severe lung inflammatory cell infiltration, and clinical symptoms compared to juvenile (≤6 months) and young adult (1-2 years) groups. Furthermore, direct contact ferrets co-housed with the virus-infected aged group shed more virus than direct-contact ferrets co-housed with virus-infected juvenile or young adult ferrets. Transcriptome analysis of aged ferret lungs reveals strong enrichment of gene sets related to type I interferon, activated T cells, and M1 macrophage responses, mimicking the gene expression profile of severe COVID-19 patients. Thus, SARS-CoV-2-infected aged ferrets highly recapitulate COVID-19 patients with severe symptoms and are useful for understanding age-associated infection, transmission, and pathogenesis of SARS-CoV-2.

Integrated Mid-IR photonics for gas and aerosol sensors

We propose an on-chip mid-infrared (MIR) photonic spectroscopy platform for aerosol and gas characterization to obtain highly discriminatory information on constituent chemistry. Sensing of aerosols (liquid or solid particles in the gas phase) is crucial for various environmental, climactic, and pulmonary healthcare applications. Further, there are several unintended exposures to bioaerosols, such as with viruses, bacteria, and fungi, for instance, the current pandemic of COVID-19 which is occurring across the world. Currently, chemical characterization of aerosols is performed using FTIR spectroscopy and Raman spectroscopy, both yielding chemical fingerprinting. But, these are bench-scale instruments, and no single spectrometer provides physical-chemical characterization of aerosol particles. Hence, we develop a miniaturized framework for performing in-situ physicochemical characterization. © 2020 OSA - The Optical Society. All rights reserved.

Low-Dose Whole Thorax Radiation Therapy for COVID-19 Pneumonia: Inpatient Onboarding Process for a Randomized Controlled Trial

Purpose/Objective(s): The mortality of the SARS-CoV-2 virus (COVID-19) has been associated with a pulmonary inflammatory response resulting in hypoxemia and rapid clinical decline. Recent work has indicated a potential therapeutic window for treatment to prevent ventilator-dependence thereby reducing mortality. PREVENT is an ongoing prospective multicenter Phase II randomized controlled trial where patients hospitalized with COVID-19 pneumonia are randomized to ultra-low dose radiation therapy (RT) versus control. This study is registered at clinicaltrials.gov, NCT04466683. The following is a description of the inpatient onboarding process of the center contributing the largest number of patients to this trial. Materials/Methods: COVID-19 hospital admissions from the previous day were attained by the clinical research manager each morning, screened for eligibility, and then sent to the designated radiation oncologist who further delineated from this list. Common exclusion criteria were: 1. Oxygen saturation > 96% on room air, 2. Age < 50, 3. > 9 days from initial COVID-19 symptomatology. From this list, HIPAA-compliant text message contact was made with infectious disease, critical care, and nursing staff with reciprocal discussion of the trial protocol and approval for consulting the patient. Subsequently, a virtual consult was made with the patient, with witnessed informed consent obtained via telephone and in person by our research associate. Patients randomized to RT were treated within 24 hours of consent. Simulation and treatment were performed on a linear accelerator with one personal protective equipment-protected therapist moving in and out of the treatment room, and a second therapist manning the console. On-site dose calculation was performed by physics, after which the radiation oncologist approved the fields prior to treatment delivery. Simulation and treatment were performed without a computer plan;therapists underwent several practice sessions prior to treating patients on trial. Results: Between August 28, 2020 and October 6, 2020, the first 10 enrolled patients on this multicenter trial were randomized and treated at our institution;no research staff member nor radiation oncology clinical team member contracted COVID-19 while employing this protocol. Conclusion: This represents the first published protocol to address efficient and safe recruitment of COVID-19 patients for a radiation oncology trial. Despite the procedural hurdles of conducting a trial in the midst of a pandemic, the combination of recruitment efficiency (> 2 patients/week) and safety to the research and clinical teams (no COVID-19 infections) of this protocol has allowed for the PREVENT trial to make substantial progress in meeting recruitment goals (n = 100). This onboarding process serves as a model in conducting recruitment of COVID-19 patients for clinical trials, and is worthy of emulation at additional centers.