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1.
Pediatr Ann ; 50(12): e509-e514, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1566701

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has had profound effects on society and, in particular, on many aspects of medical care. Residency training programs are often integral parts of our medical community and consequently have experienced changes in structure, format, and content. The conversion to virtual or online learning has been nearly universal. Decreases in common pediatric diagnoses such as respiratory syncytial virus and asthma have led to less first-hand experience for residents. Limitations designed to minimize the spread of COVID-19, such as use of personal protective equipment and group size limits, have led to fewer clinic rotations, fewer clinic sessions, and fewer patient experiences. Infections of residents themselves have led to an increase in back-up call system usage and a strain on staffing. Mandatory limits on group gatherings have also impaired camaraderie and the overall well-being of trainees. [Pediatr Ann. 2021;50(12):e509-e514.].

2.
Front Immunol ; 12: 743924, 2021.
Article in English | MEDLINE | ID: covidwho-1441113

ABSTRACT

Antigen-specific vaccines developed for the COVID-19 pandemic demonstrate a remarkable achievement and are currently being used in high income countries with much success. However, new SARS-CoV-2 variants are threatening this success via mutations that lessen the efficacy of antigen-specific antibodies. One simple approach to assisting with this issue is focusing on strategies that build on the non-specific protection afforded by the innate immune response. The BCG vaccine has been shown to provide broad protection beyond tuberculosis disease, including against respiratory viruses, and ongoing studies are investigating its efficacy as a tool against SARS-CoV-2. Gamma delta (γδ) T cells, particularly the Vδ2 subtype, undergo rapid expansion after BCG vaccination due to MHC-independent mechanisms. Consequently, γδ T cells can produce diverse defenses against virally infected cells, including direct cytotoxicity, death receptor ligands, and pro-inflammatory cytokines. They can also assist in stimulating the adaptive immune system. BCG is affordable, commonplace and non-specific, and therefore could be a useful tool to initiate innate protection against new SARS-CoV-2 variants. However, considerations must also be made to BCG vaccine supply and the prioritization of countries where it is most needed to combat tuberculosis first and foremost.


Subject(s)
BCG Vaccine/therapeutic use , COVID-19/prevention & control , SARS-CoV-2 , T-Lymphocyte Subsets/drug effects , Animals , BCG Vaccine/economics , BCG Vaccine/pharmacology , Costs and Cost Analysis , Humans , T-Lymphocyte Subsets/immunology , Vaccination/economics
5.
Commun Biol ; 4(1): 915, 2021 07 26.
Article in English | MEDLINE | ID: covidwho-1327224

ABSTRACT

Vaccines against SARS-CoV-2 are urgently required, but early development of vaccines against SARS-CoV-1 resulted in enhanced disease after vaccination. Careful assessment of this phenomena is warranted for vaccine development against SARS CoV-2. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent high dose challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titre were boosted by a second dose. Data from these challenge models on the absence of enhanced disease and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.


Subject(s)
COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/immunology , Ferrets , Macaca mulatta
6.
Vaccine ; 39(34): 4885-4894, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1284599

ABSTRACT

Safe and effective vaccines will provide essential medical countermeasures to tackle the COVID-19 pandemic. Here, we assessed the safety, immunogenicity and efficacy of the intradermal delivery of INO-4800, a synthetic DNA vaccine candidate encoding the SARS-CoV-2 spike protein in the rhesus macaque model. Single and 2 dose vaccination regimens were evaluated. Vaccination induced both binding and neutralizing antibodies, along with IFN-γ-producing T cells against SARS-CoV-2. Upon administration of a high viral dose (5 × 106 pfu) via the intranasal and intratracheal routes we observed significantly reduced virus load in the lung and throat, in the vaccinated animals compared to controls. 2 doses of INO-4800 was associated with more robust vaccine-induced immune responses and improved viral protection. Importantly, histopathological examination of lung tissue provided no indication of vaccine-enhanced disease following SARS-CoV-2 challenge in INO-4800 immunized animals. This vaccine candidate is currently under clinical evaluation as a 2 dose regimen.


Subject(s)
COVID-19 , Vaccines, DNA , Viral Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Humans , Macaca mulatta , Pandemics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
8.
Cogn Behav Pract ; 28(4): 573-587, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1184866

ABSTRACT

Given the severity and suicide risk of patients typically treated by Dialectical Behavior Therapy (DBT) and the absence of guidelines regarding delivery of DBT via telehealth, it is crucial that the DBT treatment community gather and rapidly disseminate information about effective strategies for delivering DBT via telehealth. The current study surveyed DBT providers (N = 200) to understand challenges and lessons learned as they transitioned to conducting DBT via telehealth during the COVID-19 pandemic. Open-ended responses to challenges and lessons-learned were coded. Most frequently noted challenges were Therapy-Interfering Behaviors and elements related to the provision of Individual Therapy and Skills Training Group. The majority of providers offered advice for implementing group skills training, avoiding or overcoming therapist burnout, and emphasized continued adherence to treatment principles, even in the context of this new treatment modality. Overall, this qualitative study marks a starting point on identifying best practices delivering DBT via telehealth for which it is anticipated that clinical recommendations in this area will evolve, informed by clinician, researcher, and consumer input.

9.
Nat Commun ; 12(1): 1260, 2021 02 24.
Article in English | MEDLINE | ID: covidwho-1101645

ABSTRACT

A novel coronavirus, SARS-CoV-2, has been identified as the causative agent of the current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to assess the safety and efficacy of novel vaccines and therapeutics. Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques. Immune responses against SARS-CoV-2 are also similar in both species and equivalent to those reported in milder infections and convalescent human patients. This finding is reiterated by our transcriptional analysis of respiratory samples revealing the global response to infection. We describe a new method for lung histopathology scoring that will provide a metric to enable clearer decision making for this key endpoint. In contrast to prior publications, in which rhesus are accepted to be the preferred study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of interventions against SARS-CoV-2. Importantly, accessing cynomolgus macaques will greatly alleviate the pressures on current rhesus stocks.


Subject(s)
COVID-19/immunology , COVID-19/virology , Lung/pathology , Lung/virology , Animals , Disease Models, Animal , Female , Immunity, Cellular/physiology , Interferon-gamma/metabolism , Macaca fascicularis , Macaca mulatta , Male , Pandemics , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity
10.
Clin Ophthalmol ; 15: 341-346, 2021.
Article in English | MEDLINE | ID: covidwho-1067514

ABSTRACT

Purpose: To examine changing patterns of ophthalmic presentations to emergency departments (EDs) during the lockdowns associated with the first wave of the COVID-19 pandemic in Australia and the two months immediately following lockdown relaxation. Patients and Methods: This was a retrospective audit of triage coding and ICD-10-AM coding for all patient presentations to four Australian EDs from March 29 to May 31 in 2019 and 2020 (the COVID-19 lockdown period and the corresponding period in 2019), and from June 1 to July 31 in 2019 and 2020 (the post-lockdown period and the corresponding period in 2019). Number of ophthalmic presentations triaged per day and number of seven common and/or time-sensitive, vision threatening ophthalmic diagnoses were examined. Differences in mean daily presentation numbers were assessed with non-paired Student's t-test with Bonferroni correction. Results: Total ophthalmic presentations per day during COVID-19 lockdowns fell by 16% compared to the corresponding period in 2019 (13.0 ± 4.0 in 2019 vs 10.8 ± 3.3 in 2020, mean ± standard deviation; p=0.01). There was also a significant decrease in presentations of atraumatic retinal detachment, conjunctivitis, and eye pain. In the two months following easing of lockdown restrictions, total ophthalmic presentations per day returned to the same level as that of the corresponding period in 2019 (12.2 ± 4.3 in 2019 vs 12.3 ± 4.1 in 2020, p=0.97). Conclusion: Total ophthalmic presentations and presentations of atraumatic retinal detachment, conjunctivitis and, eye pain to EDs fell during the lockdowns associated with the first wave of COVID-19 in Australia. These may represent delays in patients seeking appropriate medical attention and may have implications on patient morbidity long after the COVID-19 pandemic.

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