Protective and Pathogenic Immune Responses to Cutaneous Leishmaniasis

Leishmania (Kinetoplastida: Trypanosomatidae) parasites are known to cause a broad spectrum of clinical diseases in humans, collectively known as the leishmaniases. Cutaneous leishmaniasis is the most common clinical presentation with varying degrees of severity largely driven by host immune responses, specifically the interplay between innate and adaptive immune response. The establishment of a T lymphocyte driven cell-mediated immune response, leading to activated phagocytic cells, leading to Leishmania parasite killing and control of infection. Alternatively, the Leishmania parasite manipulates the host immune system, enabling parasite proliferation and clinical disease. Here we review how the cumulative interactions of different aspects of the host immune response determines disease outcome, severity, and immunity to re-infection.

Very Early Cognitive Screening and Self-Reported Feeling of Fatigue Three Months After Stroke

Stroke is a major cause of disability and the second leading cause of death worldwide. Post-stroke fatigue has been reported as one of the most limiting symptoms after a stroke. Early identification of risk factors for developing post-stroke fatigue is important for providing timely rehabilitation. A correlation has been found between fatigue and cognitive impairment after stroke, but 2 months after stroke at the earliest. In the present study, we examined whether cognitive function screening using the Montreal Cognitive Assessment (MoCA) very early after stroke could explain fatigue 3 months after stroke. A total of 311 stroke patients admitted to a comprehensive stroke unit in Sweden between 2011 and 2016 were included in this longitudinal study. Cognition was screened within 2 days after admission to the stroke unit. Data on self-reported feeling of fatigue were retrieved from Riksstroke’s 3-month follow-up form. The data were analyzed using binary logistic regression. We found that the cognitive function in an acute phase after stroke could not explain self-reported feeling of fatigue in a later stage. The correlation between cognitive impairment and fatigue that has been reported may be detectable no earlier than the subacute phase of stroke. As previous studies have shown that functional outcome, severity of stroke, and sex also correlate with fatigue after stroke, we controlled for these variables in our analysis. In line with previous studies, we found that female patients had higher odds of experiencing fatigue. This is something that health care professionals should be aware of when working with stroke patients.

Low FT3 is an independent marker of disease severity in patients hospitalized for COVID-19

Aim: To study the prevalence of thyroid dysfunction and its association with disease severity in hospitalized patients of coronavirus disease-19 (COVID-19). Methods: In this retrospective cohort study, thyroid function tests (TFT) of 236 hospitalized patients of COVID-19, along with demographic, comorbid, clinical, biochemical, and disease severity records were analysed. Patients were divided into previous euthyroid or hypothyroid status to observe the effect of prior hypothyroidism on severity of COVID-19. Results: TFT abnormalities were common. Low free T3 (FT3), high thyroid stimulating hormone (TSH) and low TSH were seen in 56 (23.7%), 15 (6.4%) and 9 (3.8%) patients, respectively. The median levels of TSH (2.06 vs 1.26 mIU/mL, p=0.001) and FT3 (2.94 vs 2.47 pg/mL, p=0.000) were significantly lower in severe disease. Previous hypothyroid status (n=43) was associated with older age, higher frequency of comorbidities, higher FT4 and lower FT3. TFT did not correlate with markers of inflammation (except lactate dehydrogenase), however, FT3 and TSH negatively correlated with outcome severity score and duration of hospital stay. Cox-regression analysis showed that low FT3 was associated with severe COVID-19 (p=0.032, HR 0.302; CI 0.101-0.904), irrespective of prior hypothyroidism. Conclusions: Functional thyroid abnormalities (low FT3 and low TSH) are frequently seen in hospitalized patients of COVID-19. Although these abnormalities did not correlate with markers of inflammation, this study shows that low FT3 at admission independently predicts severity of COVID-19.

Risk Identification and Prediction for COVID-19 Mortality

This paper studies several key metrics for COVID-19 using a public surveillance system data set. It compares the difference between two case fatality rates: the naive case fatality rate, which has been frequently mentioned in media outlets, and one which is the sample estimate for the mortality rate. A logistic regression model is applied to modeling the daily mortality rate. The conclusion is that time, gender, age and some of their interactions, appear to have a significant impact on the mortality rate; the daily mortality rate has been decreasing since the outbreak; males older than 60 has been the most vulnerable group. The receiver operating characteristics curve and the curve under the area show that the proposed logistic model is capable of predicting the outcome of a reported case with accuracy as high as 89%. These findings are helpful in assessing the magnitude of the risk posed by the COVID-19 virus to certain groups, predicting outcome severity, and optimally allocating medical resources such as intensive care units and ventilators.

Single-dose mRNA vaccine effectiveness against SARS-CoV-2 in healthcare workers extending 16 weeks post-vaccination: a test-negative design from Quebec, Canada

Introduction In Canada, first and second doses of mRNA vaccines against SARS-CoV-2 were uniquely spaced 16 weeks apart, but the duration of single-dose protection remains uncertain. We estimated one- and two-dose mRNA vaccine effectiveness (VE) among healthcare workers (HCWs) in Quebec, Canada including protection against varying outcome severity, variants of concern (VOC), and the stability of single-dose protection out to 16 weeks post-vaccination. Methods A test-negative design compared vaccination among SARS-CoV-2 test-positive and weekly-matched (10:1), randomly-sampled, test-negative HCWs using linked surveillance and immunization databases. Vaccine status was defined by one dose ≥14 days or two doses ≥7 days before illness onset or specimen collection. Adjusted VE was estimated by conditional logistic regression. Results Primary analysis included 5,316 cases and 53,160 controls. Single-dose VE was 70% (95%CI: 68-73) against SARS-CoV-2 infection, 73% (95%CI: 71-75) against COVID-19 illness and 97% (95%CI: 92-99) against associated hospitalization. Two-dose VE was 86% (95%CI: 81-90) and 93% (95%CI: 89-95), respectively, with no associated hospitalizations. VE was higher for non-VOC than VOC (73% Alpha) among single-dose (77%, 95%CI: 73-81 versus 63%, 95%CI: 57-67) but not two-dose recipients (87%, 95%CI: 57-96 versus 94%, 95%CI: 89-96). Across 16 weeks, no decline in single-dose VE was observed with appropriate stratification based upon prioritized vaccination determined by higher versus lower likelihood of direct patient contact. Conclusion One mRNA vaccine dose provided substantial and sustained protection to HCWs extending at least four months post-vaccination. In circumstances of vaccine shortage, delaying the second dose may be a pertinent public health strategy to consider.

Implementation of a provincial acute stroke pathway and its impact on access to advanced stroke care in Saskatchewan

BackgroundFor ischaemic stroke, outcome severity is heavily time dependent. Systems of care need to be in place to ensure that patients with stroke are treated quickly and appropriately across entire health regions. Prior to this study, the province of Saskatchewan, Canada did not have a provincial stroke strategy in place.MethodsA quality improvement project was undertaken to create and evaluate a provincial stroke strategy. The Saskatchewan Acute Stroke Pathway was created using a multidisciplinary team of experts, piloted at five stroke centres and then implemented provincially. The number of stroke alerts, door-to-imaging, door-to-needle, door-to-groin puncture times and treatment rates were collected at all centres. Improvements over time were analysed using run charts and individuals control charts.ResultsThe number of stroke alerts province-wide trended upwards in the last 6 months of the study. There were no clear trends or shifts in the proportion of stroke alerts treated with alteplase or endovascular therapy. Across the province, the weighted mean door-to-imaging time decreased from 21 to 15 min, the weighted mean door-to-needle time decreased from 62 to 47 min and the mean door-to-groin puncture time decreased from 83 to 70 min. There was high variability in the degree of improvement from centre to centre.ConclusionsThe implementation of a province wide acute stroke pathway has led to improvement in stroke care on a provincial basis. Further work addressing intercentre variability is ongoing.

Single-dose mRNA vaccine effectiveness against SARS-CoV-2 in healthcare workers extending 16 weeks post-vaccination: a test-negative design from Quebec, Canada

Introduction: In Canada, first and second doses of mRNA vaccines against SARS-CoV-2 were uniquely spaced 16 weeks apart, but the duration of single-dose protection remains uncertain. We estimated one- and two-dose mRNA vaccine effectiveness (VE) among healthcare workers (HCWs) in Quebec, Canada including protection against varying outcome severity, variants of concern (VOC), and the stability of single-dose protection out to 16 weeks post-vaccination. Methods: A test-negative design compared vaccination among SARS-CoV-2 test-positive and weekly-matched (10:1), randomly-sampled, test-negative HCWs using linked surveillance and immunization databases. Vaccine status was defined by one dose ≥14 days or two doses ≥7 days before illness onset or specimen collection. Adjusted VE was estimated by conditional logistic regression. Results: Primary analysis included 5,316 cases and 53,160 controls. Single-dose VE was 70% (95%CI: 68-73) against SARS-CoV-2 infection, 73% (95%CI: 71-75) against COVID-19 illness and 97% (95%CI: 92-99) against associated hospitalization. Two-dose VE was 86% (95%CI: 81-90) and 93% (95%CI: 89-95), respectively, with no associated hospitalizations. VE was higher for non-VOC than VOC (73% Alpha) among single-dose (77%, 95%CI: 73-81 versus 63%, 95%CI: 57-67) but not two-dose recipients (87%, 95%CI: 57-96 versus 94%, 95%CI: 89-96). Across 16 weeks, no decline in single-dose VE was observed with appropriate stratification based upon prioritized vaccination determined by higher versus lower likelihood of direct patient contact. Conclusion: One mRNA vaccine dose provided substantial and sustained protection to HCWs extending at least four months post-vaccination. In circumstances of vaccine shortage, delaying the second dose may be a pertinent public health strategy to consider.