Chronic Pulmonary Manifestations of COVID-19 Infection: Imaging Evaluation.

This case presents a patient with severe COVID-19 pneumonia requiring intensive care unit admission and a prolonged hospital stay. The infection resulted in long-term morbidity, functional decline, and abnormal chest CT findings. The mechanisms for long-term lung injury after COVID-19 infection, imaging appearances, and the role of imaging in follow-up are discussed.

A randomized, double-blind, placebo-controlled trial of intravenous alpha-1 antitrypsin for ARDS secondary to COVID-19.

Background: Patients with severe coronavirus disease 2019 (COVID-19) develop a febrile pro-inflammatory cytokinemia with accelerated progression to acute respiratory distress syndrome (ARDS). Here we report the results of a phase 2, multicenter, randomized, double-blind, placebo-controlled trial of intravenous (IV) plasma-purified alpha-1 antitrypsin (AAT) for moderate to severe ARDS secondary to COVID-19 (EudraCT 2020-001391-15). Methods: Patients (n = 36) were randomized to receive weekly placebo, weekly AAT (Prolastin, Grifols, S.A.; 120 mg/kg), or AAT once followed by weekly placebo. The primary endpoint was the change in plasma interleukin (IL)-6 concentration at 1 week. In addition to assessing safety and tolerability, changes in plasma levels of IL-1ß, IL-8, IL-10, and soluble tumor necrosis factor receptor 1 (sTNFR1) and clinical outcomes were assessed as secondary endpoints. Findings: Treatment with IV AAT resulted in decreased inflammation and was safe and well tolerated. The study met its primary endpoint, with decreased circulating IL-6 concentrations at 1 week in the treatment group. This was in contrast to the placebo group, where IL-6 was increased. Similarly, plasma sTNFR1 was substantially decreased in the treatment group while remaining unchanged in patients receiving placebo. IV AAT did not definitively reduce levels of IL-1ß, IL-8, and IL-10. No difference in mortality or ventilator-free days was observed between groups, although a trend toward decreased time on ventilator was observed in AAT-treated patients. Conclusions: In patients with COVID-19 and moderate to severe ARDS, treatment with IV AAT was safe, feasible, and biochemically efficacious. The data support progression to a phase 3 trial and prompt further investigation of AAT as an anti-inflammatory therapeutic. Funding: ECSA-2020-009; Elaine Galwey Research Bursary.

Development of a simulation placement in a pre-registration nursing programme.

BACKGROUND: A 4-week simulation placement for first-year student nurses using an innovative blended approach was developed and delivered in one university. This was the first tariff-funded simulation placement in the UK for student nurses. AIMS: To describe how this flexible simulation placement was developed, operated and adapted due to COVID-19 while exploring the student nurses' experiences and preparedness for practice. METHODS: An anonymous online survey was undertaken and a placement evaluation was completed and compared with traditional clinical placement evaluations by previous students at the same point in their studies. RESULTS: Students were as satisfied with the simulation placement as students who had attended real practice placements: 92% of students were satisfied with their simulated placement experience and 92% felt prepared for practice. CONCLUSION: This simulated placement has been an acceptable replacement for traditional practice placements, particularly during the COVID-19 pandemic.

Attitudes Towards Vaccination for Coronavirus Disease 2019 in Patients with Severe Alpha-1 Antitrypsin Deficiency.

Patients with severe alpha-1 antitrypsin deficiency (AATD) are at increased risk for the development of chronic obstructive pulmonary disease (COPD), particularly if they smoke. This, coupled with their predilection for dysregulated inflammation and autoimmunity, makes affected individuals priority candidates for vaccination against coronavirus disease 2019 (COVID-19). To promote vaccine uptake effectively, an understanding of the factors motivating people to proceed with vaccination is essential. The attitudes of patients with AATD towards COVID-19 vaccination have yet to be described. We prospectively studied 170 Pi*ZZ genotype AATD patients, 150 patients with nonhereditary (Pi*MM genotype) COPD and 140 Pi*MM genotype individuals without lung disease receiving first-dose vaccination with ChAdOx1 nCoV-19 (AstraZeneca). Patient attitudes towards vaccination and motivations for getting vaccinated were assessed at the time of the vaccine being offered. Following completion of the 2-dose vaccine series, Pi*ZZ patients were then re-assessed regarding their attitudes towards booster vaccination. The most common primary motivation for accepting vaccination in Pi*ZZ participants ≥50 years old was a fear of illness or death from COVID-19. In contrast, Pi*ZZ patients <50 years most often cited a desire to socialize. The motivation pattern of younger Pi*ZZ AATD patients was similar to that of non-deficient individuals of comparable age, whereas older Pi*ZZ individuals were more closely aligned with Pi*MM COPD and differed from age-matched controls without lung disease. When considering booster vaccination, Pi*ZZ patients were increasingly motivated by a desire to reacquire social freedoms. A desire to reduce the risk of transmission was not a prominent consideration in any of the groups studied. The most commonly cited reason for booster hesitancy was a lack of incentive, given that no additional social freedoms were available to triple-vaccinated individuals compared to those who were double-vaccinated at the time. Taken together, these data may inform policymakers attempting to promote vaccine uptake among patients with AATD.

Protease-anti-protease compartmentalization in SARS-CoV-2 ARDS: Therapeutic implications.

BACKGROUND: Interleukin-6 (IL-6) is elevated in SARS-CoV-2 infection. IL-6 regulates acute-phase proteins, such as alpha-1 antitrypsin (AAT), a key lung anti-protease. We investigated the protease-anti-protease balance in the circulation and pulmonary compartments in SARS-CoV-2 acute respiratory distress syndrome (ARDS) compared to non-SARS-CoV-2 ARDS (nsARDS) and the effects of tocilizumab (IL-6 receptor antagonist) on anti-protease defence in SARS-CoV-2 infection. METHODS: Levels and activity of AAT and neutrophil elastase (NE) were measured in plasma, airway tissue and tracheal secretions (TA) of people with SARS-CoV-2 ARDS or nsARDS. AAT and IL-6 levels were evaluated in people with moderate SARS-CoV-2 infection who received standard of care +/- tocilizumab. FINDINGS: AAT plasma levels doubled in SARS-CoV-2 ARDS. In lung parenchyma AAT levels were increased, as was the percentage of neutrophils involved in NET formation. A protease-anti-protease imbalance was detected in TA with active NE and no active AAT. The airway anti-protease, secretory leukoprotease inhibitor was decreased in SARS-CoV-2-infected lungs and cleaved in TA. In nsARDS, plasma AAT levels were elevated but TA samples had less AAT cleavage, with no detectable active NE in most samples. Induction of AAT in ARDS occurred mainly through IL-6. Tocilizumab down-regulated AAT during SARS-CoV-2 infection. INTERPRETATION: There is a protease-anti-protease imbalance in the airways of SARS-CoV-2-ARDS patients. This imbalance is a target for anti-protease therapy. FUNDING: NIH Serological Sciences Network, National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases.

Patterns in the Pandemic Decline of Public School Enrollment

Early evidence indicates that the COVID-19 pandemic sharply reduced public school enrollment in many states. However, little is known about the underlying patterns of these declines. Using new district-level data from Massachusetts, we find that these declines were concentrated in traditional districts while charter, virtual, and vocational districts increased their enrollment. Though the enrollment declines in traditional districts were widespread, we also find that the percent declines were significantly larger in smaller districts and those serving higher concentrations of White and economically disadvantaged students. The implications for understanding the pandemic?s effects on learning opportunities and the anticipated fiscal stress on public schools are discussed.

Increased incidence of acute calculous cholecystitis observed during COVID-19 social restrictions.

PURPOSE: In response to the outbreak of COVID-19 in Ireland, the government implemented a nationwide stay-at-home order, with the closure of all non-essential businesses. During this period, there was a significant increase in supermarket expenditure. It has been shown that stress, anxiety and boredom are triggers for unhealthy eating habits. Fat consumption is a risk factor for both the development of gallstones and, additionally, the development of acute calculous cholecystitis. The aim of this study was to assess the incidence of acute calculous cholecystitis during the nationwide lockdown and compare it to the same period one year prior. METHODS: A retrospective review of all emergency abdominal imaging performed during the first 5 weeks of the lockdown was completed using the hospital PACS (picture archiving and communication system). All cases of acute calculous cholecystitis were identified and compared with the same period 1 year prior. RESULTS: Eighteen cases of acute calculous cholecystitis were identified from 24 March to 27 April 2020. Eleven cases were identified during the same period in 2019. This represented an increase of 63%. Non-COVID-19-related emergency presentations decreased during this period, and imaging of emergency presentations decreased by 24%. The rate of scans positive for acute cholecystitis more than doubled (p < 0.037). CONCLUSION: A statistically significant increase in cases of acute calculous cholecystitis was observed during a nationwide lockdown during the COVID-19 pandemic. It is hypothesised that this is due to increased consumption of fatty foods during this period due to stress, anxiety and boredom.

Acute severe respiratory syndrome coronavirus-2 treatment overview for pediatrics.

PURPOSE OF REVIEW: The novel severe respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has caused a world-wide pandemic with devastating effects. Fortunately, most children display only mild-to-moderate symptoms, but there are a subset that will have severe symptoms warranting treatment. This review evaluates the current evidence for antiviral and anti-inflammatory treatment of acute SARS-COV-2 infections, including coronavirus disease 2019 in pediatrics. RECENT FINDINGS: Treatment recommendations continue to evolve with emerging results from clinical trials. Initial therapies were tailored to repurposed medications, and have now transitioned toward more specific antiviral therapy. In addition to specific antiviral therapy, there is also support to modulate the immune system and reduce inflammatory damage seen in coronavirus disease 2019. Much of the data result from adult studies with subsequent extrapolation to pediatrics. SUMMARY: Recommended therapy will continue to adapt as results return from clinical trials. A continued commitment from the National Institutes of Health and research community to assist in determining optimal therapies for pediatric patients is essential. Until then, most recommendations will likely be informed from the results seen in adult populations.

Characterization of the Inflammatory Response to Severe COVID-19 Illness.

Rationale: Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood.Objectives: To define the cytokine profile of COVID-19 and to identify evidence of immunometabolic alterations in those with severe illness.Methods: Levels of IL-1ß, IL-6, IL-8, IL-10, and sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from healthy volunteers, hospitalized but stable patients with COVID-19 (COVIDstable patients), patients with COVID-19 requiring ICU admission (COVIDICU patients), and patients with severe community-acquired pneumonia requiring ICU support (CAPICU patients). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also evaluated.Measurements and Main Results: IL-1ß, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable patients, and demonstrated higher levels of IL-1ß, IL-6, and sTNFR1 but lower IL-10 than CAPICU patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P < 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution (P < 0.0001).Conclusions: The COVID-19 cytokinemia is distinct from that of other types of pneumonia, leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population.