Computed tomography Coronary angiography in rural referral hospitals: A single-Centre experience.

OBJECTIVE: To describe the first 9 months of a newly established computed tomography coronary angiogram (CTCA) over the period of the COVID-19 pandemic. METHODS: A retrospective analysis of the first 9 months of a CT-CA program. DESIGN: Data were collected for the period of June 2020 to March 2021. Information reviewed included demographics, risk factors, renal function, technical factors and outcomes including Calcium Score and Coronary Artery Disease Reporting and Data System (CAD-RADS). SETTING: A single Rural Referral Hospital in regional New South Wales. PARTICIPANTS: Ninety-six CTCAs were reviewed. Ages ranged from 29 to 81 years. 37 (39%) male, 59 (61%) female. 15 (15.6%) identified as Aboriginal and/or Torres Strait Islander. MAIN OBJECTIVE OUTCOMES: CTCA is a viable alternative to invasive coronary angiogram in appropriate populations for regional areas. RESULTS: Eighty-eight (91.6%) were considered technically satisfactory. Mean heart rate was 57 beats per minute with a range of 108. Cardiovascular risk factors included hypertension, dyslipidemia, smoking status, family history and diabetes mellitus. Of patients with CAD-RADS scores 3 or 4 who underwent subsequent invasive coronary angiogram (ICA), 80% were determined to have operator-defined significant stenosis. Significant cardiac and non-cardiac findings were extensive. CONCLUSIONS: CTCA is a safe and efficacious imaging modality for low- to moderate-risk chest pain patients. There was acceptable diagnostic accuracy and the investigation was safe.

PD-1 and ICOS counter-regulate tissue resident regulatory T cell development and IL-10 production during flu.

Regulatory T cells that express the transcription factor Foxp3 (Treg cells) are a highly heterogenous population of immunoregulatory cells critical for maintaining immune homeostasis and preventing immunopathology during infections. Tissue resident Treg (TR-Treg) cells are maintained within nonlymphoid tissues and have been shown to suppress proinflammatory tissue resident T cell responses and promote tissue repair. Human populations are repetitively exposed to influenza infections and lung tissue resident effector T cell responses are associated with flu-induced long-term pulmonary sequelae. The kinetics of TR-Treg cell development and molecular features of TR-Treg cells during repeated and/or long-term flu infections are unclear. Utilizing a Foxp3RFP/IL-10GFP dual reporter mouse model along with intravascular fluorescent in vivo labeling, we characterized the TR-Treg cell responses to repetitive heterosubtypic influenza infections. We found lung tissue resident Treg cells accumulated and expressed high levels of co-inhibitory and co-stimulatory receptors post primary and secondary infections. Blockade of PD-1 or ICOS signaling reveals that PD-1 and ICOS signaling pathways counter-regulate TR-Treg cell expansion and IL-10 production, during secondary influenza infection. Furthermore, the virus-specific TR-Treg cell response displayed distinct kinetics, when compared to conventional CD4+ tissue resident memory T cells, during secondary flu infection. Our results provide insight into the tissue resident Foxp3+ regulatory T cell response during repetitive flu infections, which may be applicable to other respiratory infectious diseases such as tuberculosis and COVID.

Overview of Literature Related to Post COVID-19 Rehabilitation

Objective(s) To examine current literature on the role of physical therapy (PT) in management of post COVID-19 related conditions and common symptomatology in adults, as well as potential guidelines for rehabilitation in the outpatient setting. Data Sources PubMed, CINAHL, Medline, Cochrane. Study Selection Searches were conducted to examine current data related to PT interventions and their effectiveness for treating post COVID-19 conditions. Articles were evaluated for relevance based on the following criteria: articles in English, original peer reviewed articles, adult population (over 18), relevant PT interventions for rehabilitation, post-acute infection of COVID-19. Consensus agreement confirmed approximately 25% of reviewed articles. Data Extraction Articles were analyzed for relevance to implications regarding post COVID-19 and potential PT rehabilitation interventions. Interventions were assessed in feasibility and applicability to an outpatient clinic setting. Independent data extraction followed by consensus discussion was applied. Articles were examined for content regarding the latest updates on disease criteria, manifestations, new classifications, and cohorts emerging as the pandemic progresses as well as management strategies applicable to PT practice. Data Synthesis After article analysis, the findings include a key theme that PT services helped improve overall functional mobility and symptom management in patients after an acute infection of COVID-19. An essential consideration is keeping the interventions specific to the patient and their goals while preventing exacerbations of symptoms that could lead to further setbacks. Conclusions

PD-1 and ICOS counter-regulate tissue resident regulatory T cell development and IL-10 production during flu

Regulatory T cells that express the transcription factor Foxp3 (Treg cells) are a highly heterogenous population of immunoregulatory cells critical for maintaining immune homeostasis and preventing immunopathology during infections. Tissue resident Treg (TR-Treg) cells are maintained within nonlymphoid tissues and have been shown to suppress proinflammatory tissue resident T cell responses and promote tissue repair. Human populations are repetitively exposed to influenza infections and lung tissue resident effector T cell responses are associated with flu-induced long-term pulmonary sequelae. The kinetics of TR-Treg cell development and molecular features of TR-Treg cells during repeated and/or long-term flu infections are unclear. Utilizing a Foxp3RFP/IL-10GFP dual reporter mouse model along with intravascular fluorescent in vivo labeling, we characterized the TR-Treg cell responses to repetitive heterosubtypic influenza infections. We found lung tissue resident Treg cells accumulated and expressed high levels of co-inhibitory and co-stimulatory receptors post primary and secondary infections. Blockade of PD-1 or ICOS signaling reveals that PD-1 and ICOS signaling pathways counter-regulate TR-Treg cell expansion and IL-10 production, during secondary influenza infection. Furthermore, the virus-specific TR-Treg cell response displayed distinct kinetics, when compared to conventional CD4+ tissue resident memory T cells, during secondary flu infection. Our results provide insight into the tissue resident Foxp3+ regulatory T cell response during repetitive flu infections, which may be applicable to other respiratory infectious diseases such as tuberculosis and COVID.

Mutations and Evolution of the SARS-CoV-2 Spike Protein.

The SARS-CoV-2 spike protein mediates target recognition, cellular entry, and ultimately the viral infection that leads to various levels of COVID-19 severities. Positive evolutionary selection of mutations within the spike protein has led to the genesis of new SARS-CoV-2 variants with greatly enhanced overall fitness. Given the trend of variants with increased fitness arising from spike protein alterations, it is critical that the scientific community understand the mechanisms by which these mutations alter viral functions. As of March 2022, five SARS-CoV-2 strains were labeled "variants of concern" by the World Health Organization: the Alpha, Beta, Gamma, Delta, and Omicron variants. This review summarizes the potential mechanisms by which the common mutations on the spike protein that occur within these strains enhance the overall fitness of their respective variants. In addressing these mutations within the context of the SARS-CoV-2 spike protein structure, spike/receptor binding interface, spike/antibody binding, and virus neutralization, we summarize the general paradigms that can be used to estimate the effects of future mutations along SARS-CoV-2 evolution.

BTK/ITK dual inhibitors: Modulating immunopathology and lymphopenia for COVID-19 therapy.

Bruton's tyrosine kinase (BTK) signaling is involved in innate immune responses and regulates the production of proinflammatory cytokines that can contribute to COVID-19 immunopathology. Clinical trials with BTK inhibitors in COVID-19 treatment have been proposed, and previous studies have attempted to investigate the therapeutic effects of ibrutinib and underlying mechanisms in treating viral pneumonia. These attempts, however, did not consider potential off target effect of BTK inhibitors on T cell differentiation, function, and survival, which may be beneficial in treatment for COVID-19. Here, we summarize the current knowledge of BTK/IL-2-inducible T-cell kinase (ITK) signaling in immunopathology and lymphopenia and discuss the potential of BTK/ITK dual inhibitors such as ibrutinib in modulating immunopathology and lymphopenia, for COVID-19 therapy.