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1.
Clin Infect Dis ; 2022 Feb 18.
Article in English | MEDLINE | ID: covidwho-1886373

ABSTRACT

BACKGROUND: The role of SARS-CoV-2 in the pathogenesis of testicular damage is uncertain. METHODS: We investigated the virological, pathological, and immunological changes in testes of hamsters challenged by SARS-CoV-2 wild-type and its variants by intranasal or direct testicular inoculation using influenza virus A(H1N1)pdm09 as control. RESULTS: Besides self-limiting respiratory tract infection, intranasal SARS-CoV-2 challenge caused acute decrease in sperm count, and serum testosterone and inhibin B at 4 to 7 days post-infection (dpi), and subsequently reduced testicular size and weight, and serum sex hormone level at 42 to 120 dpi. Acute histopathological damage with varying degree of testicular inflammation, haemorrhage, and necrosis, degeneration of seminiferous tubules and disruption of orderly spermatogenesis were seen with increasing virus inoculum. Degeneration and necrosis of Sertoli and Leydig cells were found. Though viral loads and SARS-CoV-2 nucleocapid (N) protein expression were markedly lower in testicular than lung tissues, direct intra-testicular injection showed N expressing interstitial cells and epididymal epithelial cells. Control intranasal or intra-testicular challenge by A(H1N1)pdm09 showed no testicular infection or damage. From 7 to 120 dpi, degeneration and apoptosis of seminiferous tubules, immune complex deposition and depletion of spermatogenic cell and spermatozoa persisted. Intranasal challenge with Omicron and Delta variants could also induce similar testicular changes. These testicular damages can be prevented by vaccination. CONCLUSIONS: SARS-CoV-2 can cause acute testicular damage with subsequent chronic asymmetric testicular atrophy and associated hormonal changes despite a self-limiting pneumonia in hamsters. Awareness of possible hypogonadism and subfertility is important in managing convalescent COVID-19 males.

2.
Am J Surg ; 2022 May 06.
Article in English | MEDLINE | ID: covidwho-1821107

ABSTRACT

BACKGROUND: Surgical education strongly involves the use of mentorship to improve the confidence and efficiency of trainees. Social distancing due to the COVID-19 pandemic may serve as a catalyst to promote the use of telementoring and other remote learning opportunities in medical education. METHODS: A comprehensive literature review was performed using the electronic databases PubMed, Embase, Web of Science, Scopus, and the Cochrane Library with respect to telementoring in the surgical field. RESULTS: The overall consensus of telementoring experience among all 25 studies was generally positive, citing "positive experience," "increased confidence," and "increased surgical skill." Using over 15 different technologies, a total of 12 simulations, 149 tasks, and 491 surgeries were conducted via telementoring. Eight mentor-mentee relationships were identified, with the most common relationship being surgeon-to-surgeon in 12 studies. CONCLUSIONS: The implementation of telementoring has been shown to be effective in improving surgical skills and learner experiences while overcoming financial and geographical barriers.

4.
Am J Ophthalmol Case Rep ; 26: 101538, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1797275

ABSTRACT

Purpose: To report a uveomeningeal syndrome with bilateral optic disc edema and a MEWDS-like presentation. Observations: A 17-year-old female experienced daily fevers for 3 days (ranging from 101.4 F to 102 F), then received the first dose of the Pfizer SARS-CoV-2 vaccine nearly three weeks later. Within two days she experienced severe headaches with severity scale of 8/10. Retinal imaging at the time showed optic disc edema in both eyes (OU) and multifocal well-circumscribed chorioretinal white lesions in the periphery OU. Neuroimaging and routine infectious and inflammatory laboratory testing were normal. Lumbar puncture showed elevated opening pressure and cerebrospinal pleocytosis consistent with an aseptic meningitis. At follow up, one month later the symptoms and retinal findings resolved. Conclusions: MEWDS is typically an idiopathic condition but can occur in the setting of viral illness. Although other white dot syndromes have been associated with uveomeningeal presentations, to our knowledge this is the first such case to be described in the English language ophthalmic literature.

5.
Circ Res ; 130(10): 1510-1530, 2022 May 13.
Article in English | MEDLINE | ID: covidwho-1794328

ABSTRACT

BACKGROUND: Coronary artery disease is an incurable, life-threatening disease that was once considered primarily a disorder of lipid deposition. Coronary artery disease is now also characterized by chronic inflammation' notable for the buildup of atherosclerotic plaques containing immune cells in various states of activation and differentiation. Understanding how these immune cells contribute to disease progression may lead to the development of novel therapeutic strategies. METHODS: We used single-cell technology and in vitro assays to interrogate the immune microenvironment of human coronary atherosclerotic plaque at different stages of maturity. RESULTS: In addition to macrophages, we found a high proportion of αß T cells in the coronary plaques. Most of these T cells lack high expression of CCR7 and L-selectin, indicating that they are primarily antigen-experienced memory cells. Notably, nearly one-third of these cells express the HLA-DRA surface marker, signifying activation through their TCRs (T-cell receptors). Consistent with this, TCR repertoire analysis confirmed the presence of activated αß T cells (CD4

Subject(s)
Coronary Artery Disease , Plaque, Atherosclerotic , T-Lymphocytes , Antigens , Clone Cells/immunology , Coronary Artery Disease/immunology , Endothelial Cells , Epitopes , HLA-DR alpha-Chains , Humans , Lymphocyte Activation , Plaque, Atherosclerotic/immunology , T-Lymphocytes/immunology
6.
Urban Studies ; : 00420980221081336, 2022.
Article in English | Sage | ID: covidwho-1775109

ABSTRACT

How best to integrate migrant workers in host societies has been a longstanding question in the study of migration and globalisation. Scholars have been conceptualising new modes of transnational mobilities that point to the politics of differential inclusion to address encounters between migrants and locals in Asian global cities. This article uses an instructive case study of temporary, low-wage male migrant workers in Singapore and the issue of their recreational spaces to show that the politics of inclusion/exclusion are layered onto the question of integration/segregation. We take integration to mean the incorporation of migrants into local society to give full access to social institutions of protection and care, and inclusion to refer to the acceptance of migrants into social relationships that define urban life. Segregation and exclusion are their respective corollaries. We focus on state-provisioned recreation centres sited near the dormitories, which were expanded to function as segregating spaces to keep migrant workers away from the city after the Little India riot in 2013. We show that they have instead become contact zones producing accidental diversities of urban encounters between migrants, locals and state-linked agents. We discuss how these contact zones have developed differently across the centres built before and after the riot, the transformation of the accidental diversities in the recreational centres by state-linked agents into a new migrant grassroots sector and the ongoing intensification of this during the COVID-19 pandemic. The new relationalities offer the promise of transcending the layered binaries of integration/segregation and inclusion/exclusion.

7.
J Neuroophthalmol ; 2021 Oct 22.
Article in English | MEDLINE | ID: covidwho-1769465
8.
PLoS Negl Trop Dis ; 16(3): e0010080, 2022 03.
Article in English | MEDLINE | ID: covidwho-1736486

ABSTRACT

BACKGROUND: Breast-feeding holds considerable potential to reduce infant mortality. Feeding choices, already complex, take on additional complexity against a backdrop of the risk of transmissible Ebola Virus. This review describes the factors that influence infant feeding and attitudes of pregnant women, mothers, family members and health practitioners, policy makers and providers (midwives) concerning infant feeding when there is a risk of Mother-to-Child (MTC) transmission of Ebola Virus Disease (EVD). METHODOLOGY: A systematic review of qualitative studies identified through rigorous searches of thirteen online databases and additional citation searches of included studies was undertaken. Search terms included breast-feeding, breast-feeding, infant feeding; Ebola; and qualitative, interview(s) and findings. Independent extraction of data by two reviewers using predefined extraction forms. Studies were assessed using the CASP Qualitative checklist. PRINCIPAL FINDINGS: 5219 references were screened. 38 references related specifically to Ebola, and five papers met the inclusion criteria with data gathered from two settings: Guinea and Sierra Leone. The EVD outbreak had a significant impact on beliefs, attitudes, and resources to support infant feeding practices negatively affecting the nutritional status of children. The evidence from these studies highlight the need for guidance and appropriate psychosocial support need to be available to mothers who display symptoms and become infected and to front-line staff who are giving advice. Communities need to be engaged because stigma and fear may hinder uptake of appropriate interventions. The EVD outbreak caused multi-level system disruption akin to that seen following a natural disaster, meaning that logistics and coordination are critical and need adequate resourcing. Food production and distribution, and malnutrition screening are also disrupted and thereby compounding compromised nutritional status. The limited number of relevant studies highlights the need for further primary research, particularly in translation of messages to local settings. CONCLUSIONS: An EVD outbreak causes multi-level disruption that negatively impacts infant feeding and child care practices. Negative impacts have multiple causes and successful planning for Ebola outbreaks requires that nutrition of infants and young children is a priority. Lessons from the Ebola pandemic have wider applicability to other pandemic contexts including Covid-19.


Subject(s)
COVID-19 , Ebolavirus , Hemorrhagic Fever, Ebola , Attitude , Child, Preschool , Disease Outbreaks , Female , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/prevention & control , Humans , Infant , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy , Sierra Leone/epidemiology
9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-314977

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted largely by respiratory droplets or airborne aerosols. Despite being frequently found in the immediate environment and faeces of patients, evidence supporting oral acquisition of SARS-CoV-2 is unavailable. Utilizing Syrian hamster model, we demonstrated that the severity of pneumonia induced by intranasal inhalation of SARS-CoV-2 increased with virus inoculum. SARS-CoV-2 retained its infectivity in vitro in simulated human fed-gastric and fasted-intestinal fluid after two hours. Oral inoculation with the highest intranasal inoculum (10 5 PFU) caused only mild pneumonia in 67% (4/6) of the animals with no clinical symptoms. The lung histopathology and viral load were significantly lower than those infected by the lowest intranasal inoculum (100 PFU). However, 83% oral infection (10/12 hamsters) had similar level of detectable viral shedding from oral swabs and faeces as intranasally infected hamsters. Our findings indicated oral acquisition of SARS-CoV-2 can establish asymptomatic respiratory infection with less efficiency.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325226

ABSTRACT

So far, effective antivirals have not been widely available for treating COVID-19. In this study, we identify a dual-functional cross-linking peptide 8P9R which can inhibit the two entry pathways (endocytic pathway and TMPRSS2-mediated surface pathway) of SARS-CoV-2 in cells. The endosomal acidification inhibitors (8P9R and chloroquine) can synergistically enhance the activity of arbidol, a spike-ACE2 fusion inhibitor, against SARS-CoV-2 and SARS-CoV in cells. In vivo studies indicate that 8P9R or the combination of repurposed drugs (arbidol, chloroquine and camostat which is a TMPRSS2 inhibitor), simultaneously interfering with the two entry pathways of coronavirus, can significantly suppress SARS-CoV-2 replication in hamsters and SARS-CoV in mice. Here, we use drug combination (arbidol, chloroquine, and camostat) and a dual-functional 8P9R to demonstrate that blocking the two entry pathways of coronavirus can be a promising and achievable approach for inhibiting SARS-CoV-2 replication in vivo. Cocktail therapy of these drug combinations should be considered in treatment trials for COVID-19.

11.
Cureus ; 13(12): e20651, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1614252

ABSTRACT

Multisystem inflammatory syndrome (MIS) is a rare entity that usually presents with a constellation of symptoms such as fever, hypotension, gastrointestinal symptoms, cardiac dysfunction, or dermatological involvement, representing an inflammatory state. During the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, several cases of multisystem inflammatory syndrome in children (MIS-C) have been described in the literature. The Centers for Disease Control and Prevention (CDC) has acknowledged the increasing incidence of the same entity in adults, referred to as multisystem inflammatory syndrome in adults (MIS-A). This case series describes four patients who presented to the Monmouth Medical Center in New Jersey with symptoms suggestive of MIS-A associated with SARS-CoV-2 infection and their clinical outcomes. All patients were within the age group of 20-40 years with no underlying medical condition. The period between SARS-CoV-2 infection and the development of MIS-A varied from 10 days through a month. Presentations ranged from a mild flu-like illness to shock requiring vasopressors. A positive SARS-CoV-2 antibody test was essential for the diagnosis. Inflammatory markers, such as ferritin, D-dimer, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and interleukin-6 (IL-6), were elevated on admission. The Use of immunomodulatory agents, namely steroids and intravenous immunoglobulin (IVIG), resulted in positive clinical outcomes. Inflammatory markers and imaging on admission did not appear to predict the disease course. A positive SARS-CoV-2 polymerase chain reaction (PCR) did not appear to influence the response to treatment. Given the high probability of MIS-A with negative viral testing, the use of both antibody and viral testing with the addition of inflammatory markers may be essential to diagnose this SARS-CoV-2-associated condition.

12.
Emerg Microbes Infect ; 11(1): 368-383, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1604258

ABSTRACT

Older individuals are at higher risk of SARS-CoV-2 infection and severe outcomes, but the underlying mechanisms are incompletely understood. In addition, how age modulates SARS-CoV-2 re-infection and vaccine breakthrough infections remain largely unexplored. Here, we investigated age-associated SARS-CoV-2 pathogenesis, immune responses, and the occurrence of re-infection and vaccine breakthrough infection utilizing a wild-type C57BL/6N mouse model. We demonstrated that interferon and adaptive antibody response upon SARS-CoV-2 challenge are significantly impaired in aged mice compared to young mice, which results in more effective virus replications and severe disease manifestations in the respiratory tract. Aged mice also showed increased susceptibility to re-infection due to insufficient immune protection acquired during the primary infection. Importantly, two-dose COVID-19 mRNA vaccination conferred limited adaptive immune response among the aged mice, making them susceptible to SARS-CoV-2 infection. Collectively, our findings call for tailored and optimized treatments and prevention strategies against SARS-CoV-2 among older individuals.


Subject(s)
Age Factors , COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Aging/immunology , Animals , Antibodies, Viral/immunology , COVID-19/pathology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Disease Models, Animal , Disease Susceptibility , Female , Humans , Immunity , Mice , Mice, Inbred C57BL , Respiratory System/immunology , Respiratory System/virology , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Vaccination , Virus Replication
14.
Surv Ophthalmol ; 67(1): 217-225, 2022.
Article in English | MEDLINE | ID: covidwho-1575690

ABSTRACT

Graduate medical education (GME) in ophthalmology has faced and overcome many challenges over the past years, and 2020 has been a game-changer. Although the severe acute respiratory syndrome coronavirus pandemic disrupted medical education globally, ophthalmic educators rapidly transformed their curricula to novel and effective virtual learning formats. Thus, while the COVID-19 outbreak has been one of the most significant challenges faced in the history of medical education, it has also provided an impetus to develop innovative teaching practices, bringing with it unprecedented success in allowing medical students to continue their education in ophthalmology despite these challenges. We review and appraise novel educational interventions implemented by various institutions in response to the COVID-19 pandemic, highlighting their effectiveness, challenges and proposing future directions beyond the pandemic. Many of these innovations will persist even after the end of the pandemic because they have proven that face-to-face learning is not required for all aspects of the ophthalmic GME curriculum. As ophthalmic educators harness the power of educational technology it is critical that their novel educational initiatives are incorporated into competency-based curricula with assessments mapped to the competencies. Future research should focus on evaluating the impact of this transformation to virtual learning environments on student performances as well as implementing longitudinal assessment strategies for clinical competence in workplace-based practice.


Subject(s)
COVID-19 , Education, Medical , Ophthalmology , Students, Medical , Curriculum , Humans , Ophthalmology/education , Pandemics , SARS-CoV-2
17.
Clin Infect Dis ; 2021 Sep 18.
Article in English | MEDLINE | ID: covidwho-1429186

ABSTRACT

BACKGROUND: The effect of low environmental temperature on viral shedding and disease severity of COVID-19 is uncertain. METHODS: We investigated the virological, clinical, pathological, and immunological changes in hamsters housed at room (21 oC), low (12-15 oC), and high (30-33 oC) temperature after challenge by 10 5 plaque-forming units of SARS-CoV-2. RESULTS: The nasal turbinate, trachea, and lung viral load and live virus titre were significantly higher (~0.5-log10 gene copies/ß-actin, p<0.05) in the low temperature group at 7 days post-infection (dpi). The low temperature group also demonstrated significantly higher level of TNF-α, IFN-γ, IL-1ß, and CCL3, and lower level of the antiviral IFN-α in lung tissues at 4dpi than the other two groups. Their lungs were grossly and diffusely haemorrhagic, with more severe and diffuse alveolar and peribronchiolar inflammatory infiltration, bronchial epithelial cell death, and significantly higher mean total lung histology scores. By 7dpi, the low temperature group still showed persistent and severe alveolar inflammation and haemorrhage, and little alveolar cell proliferative changes of recovery. The viral loads in the oral swabs of the low temperature group were significantly higher from 10-17dpi by about 0.5-1.0-log10 gene copies/ß-actin. The mean neutralizing antibody titre of the low temperature group was significantly (p<0.05) lower than that of the room temperature group at 7dpi and 30dpi. CONCLUSIONS: This study provided in-vivo evidence that low environmental temperature exacerbated the degree of virus shedding, disease severity, and tissue proinflammatory cytokines/chemokines expression, and suppressed the neutralizing antibody response of SARS-CoV-2-infected hamsters. Keeping warm in winter may reduce the severity of COVID-19.

18.
Nat Commun ; 12(1): 2790, 2021 05 13.
Article in English | MEDLINE | ID: covidwho-1387341

ABSTRACT

SARS-CoV-2 is of zoonotic origin and contains a PRRA polybasic cleavage motif which is considered critical for efficient infection and transmission in humans. We previously reported on a panel of attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction of the spike protein. Here, we characterize pathogenicity, immunogenicity, and protective ability of a further cell-adapted SARS-CoV-2 variant, Ca-DelMut, in in vitro and in vivo systems. Ca-DelMut replicates more efficiently than wild type or parental virus in Vero E6 cells, but causes no apparent disease in hamsters, despite replicating in respiratory tissues. Unlike wild type virus, Ca-DelMut causes no obvious pathological changes and does not induce elevation of proinflammatory cytokines, but still triggers a strong neutralizing antibody and T cell response in hamsters and mice. Ca-DelMut immunized hamsters challenged with wild type SARS-CoV-2 are fully protected, with little sign of virus replication in the upper or lower respiratory tract, demonstrating sterilizing immunity.


Subject(s)
COVID-19/diagnosis , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Virus Replication/genetics , Animals , COVID-19/immunology , COVID-19/virology , Cell Line, Tumor , Chlorocebus aethiops , Cricetinae , Cytokines/immunology , Cytokines/metabolism , Female , Host-Pathogen Interactions , Humans , Male , Mesocricetus , Mice, Inbred BALB C , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Vero Cells , Virulence/genetics , Virulence/immunology
19.
Clin Infect Dis ; 73(3): e719-e734, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1338687

ABSTRACT

BACKGROUND: Mass vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing amidst widespread transmission during the coronavirus disease-2019 (COVID-19) pandemic. Disease phenotypes of SARS-CoV-2 exposure occurring around the time of vaccine administration have not been described. METHODS: Two-dose (14 days apart) vaccination regimen with formalin-inactivated whole virion SARS-CoV-2 in golden Syrian hamster model was established. To investigate the disease phenotypes of a 1-dose regimen given 3 days prior (D-3), 1 (D1) or 2 (D2) days after, or on the day (D0) of virus challenge, we monitored the serial clinical severity, tissue histopathology, virus burden, and antibody response of the vaccinated hamsters. RESULTS: The 1-dose vaccinated hamsters had significantly lower clinical disease severity score, body weight loss, lung histology score, nucleocapsid protein expression in lung, infectious virus titers in the lung and nasal turbinate, inflammatory changes in intestines, and a higher serum neutralizing antibody or IgG titer against the spike receptor-binding domain or nucleocapsid protein when compared to unvaccinated controls. These improvements were particularly noticeable in D-3, but also in D0, D1, and even D2 vaccinated hamsters to varying degrees. No increased eosinophilic infiltration was found in the nasal turbinate, lung, and intestine after virus challenge. Significantly higher serum titer of fluorescent foci microneutralization inhibition antibody was detected in D1 and D2 vaccinated hamsters at day 4 post-challenge compared to controls despite undetectable neutralizing antibody titer. CONCLUSIONS: Vaccination just before or soon after exposure to SARS-CoV-2 does not worsen disease phenotypes and may even ameliorate infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , Antibodies, Viral , Cricetinae , Humans , Mesocricetus , Vaccines, Inactivated
20.
Clin Infect Dis ; 73(2): e503-e512, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1315661

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is primarily an acute respiratory tract infection. Distinctively, a substantial proportion of COVID-19 patients develop olfactory dysfunction. Especially in young patients, loss of smell can be the first or only symptom. The roles of inflammatory obstruction of the olfactory clefts, inflammatory cytokines affecting olfactory neuronal function, destruction of olfactory neurons or their supporting cells, and direct invasion of olfactory bulbs in causing olfactory dysfunction are uncertain. METHODS: We investigated the location for the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the olfactory epithelium (OE) to the olfactory bulb in golden Syrian hamsters. RESULTS: After intranasal inoculation with SARS-CoV-2, inflammatory cell infiltration and proinflammatory cytokine/chemokine responses were detected in the nasal turbinate tissues. The responses peaked between 2 and 4 days postinfection, with the highest viral load detected at day 2 postinfection. In addition to the pseudo-columnar ciliated respiratory epithelial cells, SARS-CoV-2 viral antigens were also detected in the mature olfactory sensory neurons labeled by olfactory marker protein, in the less mature olfactory neurons labeled by neuron-specific class III ß-tubulin at the more basal position, and in the sustentacular cells, resulting in apoptosis and severe destruction of the OE. During the entire course of infection, SARS-CoV-2 viral antigens were not detected in the olfactory bulb. CONCLUSIONS: In addition to acute inflammation at the OE, infection of mature and immature olfactory neurons and the supporting sustentacular cells by SARS-CoV-2 may contribute to the unique olfactory dysfunction related to COVID-19, which is not reported with SARS-CoV-2.


Subject(s)
COVID-19 , Olfactory Receptor Neurons , Animals , Cricetinae , Humans , Mesocricetus , Olfactory Mucosa , SARS-CoV-2
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