A Data-Driven Context-Aware Health Inference System for Children during School Closures

Many countries have implemented school closures due to the outbreak of the COVID-19 pandemic, which has inevitably affected children's physical and mental health. It is vital for parents to pay special attention to their children's health status during school closures. However, it is difficult for parents to recognize the changes in their children's health, especially without visible symptoms, such as psychosocial functioning in mental health. Moreover, healthcare resources and understanding of the health and societal impact of COVID-19 are quite limited during the pandemic. Against this background, we collected real-world datasets from 1,172 children in Hong Kong during four time periods under different pandemic and school closure conditions from September 2019 to January 2022. Based on these data, we first perform exploratory data analysis to explore the impact of school closures on six health indicators, including physical activity intensity, physical functioning, self-rated health, psychosocial functioning, resilience, and connectedness. We further study the correlation between children's contextual characteristics (i.e., demographics, socioeconomic status, electronic device usage patterns, financial satisfaction, academic performance, sleep pattern, exercise habits, and dietary patterns) and the six health indicators. Subsequently, a health inference system is designed and developed to infer children's health status based on their contextual features to derive the risk factors of the six health indicators. The evaluation and case studies on real-world datasets show that this health inference system can help parents and authorities better understand key factors correlated with children's health status during school closures. © 2023 ACM.

COVID-19 neutrophils show elevated migration and NETosis, which is reduced by PI3K inhibition

Rational: Evidence of neutrophil dysfunction in COVID-19 is based on transcriptomics. Cell functions are interwoven pathways, so understanding the effect of COVID-19 across neutrophil function may identify therapeutic targets. We examined neutrophil phenotype and function in 41 hospitalised, non-ICU COVID-19 patients versus 23 age-matched controls (AMC) and 26 community acquired pneumonia (CAP) patients. Method(s): Isolated neutrophils underwent ex vivo analyses for migration, phagocytosis and NETosis, and the effect of PI3K inhibition. Circulating DNAse 1 activity and levels of cfDNA were measured. Result(s): Compared to AMC and CAP, COVID-19 neutrophils demonstrated elevated transmigration (p=0.0397, A) and NETosis (p=0.0366, B), but impaired phagocytosis (p=0.0236, C) associated with impaired ROS generation (p<0.0001). COVID-19 and CAP patients showed increased systemic markers of NETosis including increased cfDNA (p=0.0153) and impaired DNAse activity (p<0.0.001, D). Ex vivo inhibition of PI3K gamma and delta reduced NET release by COVID-19 neutrophils (p=0.0156). Conclusion(s): COVID-19 is associated with neutrophil dysfunction across all main effector functions, with elevated migration, impaired antimicrobial responses and elevated NETosis. These changes represent a clear mechanism for tissue damage and highlight that targeting neutrophil function via PI3k may help modulate COVID-19 severity. (Figure Presented).

Implementation of Key Risk Mitigation Strategies and Learnings Enabling Successful Efficient Execution in Malikai Phase 2 Project Mooring Campaigns

Malikai Tension Leg Platform (TLP) being the first TLP in Malaysian waters, was installed in 2016 at a water depth of 500m. The mooring system was designed with tender-assisted drilling (TAD) features to allow for station keeping activities during drilling operations. Malikai Phase 2 is brownfield project to develop six infill wells to be drill using existing well slots available on TLP. To drive project value of replication and standardization, similar TAD vessel was used as per Phase 1 campaign. The project execution strategy emphasizes on the reuse of Phase 1 mooring component to lower the CAPEX and re-certification of the mooring component were done to maintain the integrity of the hardware. Existence of porkmarks and large part of geo-hazard on the Malikai seafloor, remain one of the main challenges to safety pre-lay polyester on the selected routes. Furthermore, due to Covid-19 pandemic the shipment of the polyester ropes was delayed. Improvement was made in the offshore installation methodology with introduction of the direct hook-up methods to eliminate the risk of polyester damaging during pre-laid, eliminate the chain twists issue on ground chain section and that also help in preserving project schedule. The development of innovative contracting and supply chain management strategies such as competitive bidding exercise and leverage on contractor expertise to drive the efficient execution. Virtual working setting is a new way of working in marine assurances due to Covid-19 travel restrictions. This paper will provide a board overview of various aspects of Malikai Phase 2 brownfield development during pandemic condition while highlighting key success factors and lesson learned for future projects. Copyright © 2022, Offshore Technology Conference.

Dysfunctional neutrophil response in COVID-19 infection vary by subtype

S94 Figure 1Comparison of neutrophil effector functions between COVID-19 variants (alpha n=33, delta n=13, omicron n-14). A.% change in phagocytosis significantly increased between alpha and delta patients (p=0.0162). B. Fold change in cells migrated through a transwell pore to IL8 compared to vehicle control significantly reduced in omicron patients compared alpha and delta (vs alpha p=0.0018, vs delta p=0.0370). C. Neutrophil extracellular trap production after stimulation with PMA compared to vehicle control significantly reduced in omicron patients compared to alpha (p=0.0396)[Figure omitted. See PDF]DiscussionOur results showing changes in neutrophil „function and phenotype differ between variants of COVID-19 infection, potentially reflect viral evolution. This change in neutrophil function may contribute to the evolving clinical phenotype observed in patients. Our population of ward-based COVID-19 patients represents the majority of inpatient hospital burden where early intervention may prevent clinical deterioration. Targeting neutrophil function may be an effective way of improving infection outcome in the future.ReferenceBelchamber K, et al. Altered neutrophil phenotype and function in non-ICU hospitalised COVID-19 patients correlated with disease severity. medRxiv, 2021: p. 2021.06.08.21258535.

Impact of School Closure on Children'S Sleep Pattern During the COVID-19 Pandemic

Background: School closure is one of the main global health policies performed worldwide during the coronavir us di sease 2019 (COVID-19) outbreak. Despite all of the advantages, there may be some risks for children who are quarantined. This study aimed to objectively measure and compares the sleep patterns of Hong Kong school students before and during the COVID-19 outbreak. Methods: Baseline assessment was performed before the first wave of the COVID-19 outbreak in Hong Kong. The sleep pattern was recorded by a physical activity monitor (Actigraph wGT3X-BT, Pensacola, Florida, USA). The follow-up assessment was conducted in early 2020. Findings: In total, 718 students were collected in the baseline . Sub sequently 1 40 students joined t he reassessment between March and April 2020. Analysis of sleep timing shows that 98.0% primary students, 78.0% secondary students and 79.9% primary school students and 58.8% secondary school students go to bed before midnight before and after the outbreak, respectively (p<0.001). Mean sleep duration (hours) was 6.81 (0.62) and 8.09 (0.07) at baseline and during the outbreak, respectively. The differences in the mean sleep features for total sleep time, sleep fragmentation index and sleep fragmentation were 0.92 (1.64), 1.64 (6.95) and 2.49 (9.18), respectively. The overall sleep quality was poorer as evidenced by delays in bedtime and wake up time, increased duration in bed, longer sleep latency, increases in the movement and fragmentation indices. Conclusion: This exceptional longitudinal study reported objective data on the change in sleep patterns before and during the COVID-19 outbreak with school closures.

Blocking the human common beta subunit of the GM-CSF, IL-5 and IL-3 receptors markedly reduces hyperinflammation in ARDS models.

Acute respiratory distress syndrome (ARDS) is triggered by various aetiological factors such as trauma, sepsis and respiratory viruses including SARS-CoV-2 and influenza A virus. Immune profiling of severe COVID-19 patients has identified a complex pattern of cytokines including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-5, which are significant mediators of viral-induced hyperinflammation. This strong response has prompted the development of therapies that block GM-CSF and other cytokines individually to limit inflammation related pathology. The common cytokine binding site of the human common beta (ßc) receptor signals for three inflammatory cytokines: GM-CSF, IL-5 and IL-3. In this study, ßc was targeted with the monoclonal antibody (mAb) CSL311 in engineered mice devoid of mouse ßc and ßIL-3 and expressing human ßc (hßcTg mice). Direct pulmonary administration of lipopolysaccharide (LPS) caused ARDS-like lung injury, and CSL311 markedly reduced lung inflammation and oedema, resulting in improved oxygen saturation levels in hßcTg mice. In a separate model, influenza (HKx31) lung infection caused viral pneumonia associated with a large influx of myeloid cells into the lungs of hßcTg mice. The therapeutic application of CSL311 potently decreased accumulation of monocytes/macrophages, neutrophils, and eosinophils without altering lung viral loads. Furthermore, CSL311 treatment did not limit the viral-induced expansion of NK and NKT cells, or the tissue expression of type I/II/III interferons needed for efficient viral clearance. Simultaneously blocking GM-CSF, IL-5 and IL-3 signalling with CSL311 may represent an improved and clinically applicable strategy to reducing hyperinflammation in the ARDS setting.

Mental health & maltreatment risk of children with special educational needs during COVID-19.

BACKGROUND: Children with special educational needs (SEN) are more vulnerable during the COVID-19 pandemic with risk of poor mental wellbeing and child maltreatment. OBJECTIVE: To examine the impact of COVID-19 on the mental health of children with SEN and their maltreatment risk. PARTICIPANTS AND SETTING: 417 children with SEN studying at special schools and 25,427 children with typical development (TD) studying at mainstream schools completed an online survey in April 2020 in Hong Kong during school closures due to COVID-19. METHOD: Emotional/behavioural difficulties, quality of life and parental stress of children with SEN were compared with typically developed children using mixed effect model. Linear regression analyses were performed to explore factors associated with child emotional/behavioural difficulties and parental stress during the pandemic. Chi-square test was performed to detect the differences in maltreatment risk before and during COVID-19. RESULTS: Children with SEN had significantly poorer overall quality of life (68.05 vs 80.65, p < 0.01). 23.5% of children had at least one episode of severe physical assault and 1.9% experienced very severe physical assault during COVID-19. Rates of physical assault increased significantly (59.8% vs. 71.2% p < 0.001) while children with mental disorders had increased risk of severe physical assault comparing to those without mental disorders (RR = 1.58, ꭓ2 = 5.19 p = 0.023). CONCLUSION: Children with SEN had poorer mental health than typically developed children during the COVID-19 pandemic. Maltreatment risk for children with SEN is higher in comparison to pre-COVID-19 era. Surveillance of child maltreatment, continuity of medical and rehabilitation care to support children with SEN are essential during a disease pandemic.

Elevated NETosis and migration but impaired anti-microbial responses in neutrophils from non-ICU, hospitalized COVID-19 patients

RationalInfection with the SARS-CoV2 virus is associated with elevated neutrophil counts. Evidence of neutrophil dysfunction in COVID-19 is based predominantly on transcriptomics or single functional assays. Cell functions are interwoven pathways, and so understanding the effect of COVID-19 across the spectrum of neutrophil function may identify therapeutic targets to treat disease.ObjectivesExamine neutrophil phenotype and functional capacity in COVID-19 patients versus age-matched controls (AMC).MethodsIsolated neutrophils from 41 non-ICU COVID-19 patients and 23 AMC underwent ex vivo analyses for migration, phagocytosis of Streptococcus pneumoniae, reactive oxygen species (ROS) generation, neutrophil extracellular trap formation (NETosis) and cell surface receptor expression. Serum DNAse 1 activity was measured, alongside circulating levels of cell-free (cf)DNA, myeloperoxidase (MPO), VEGF, IL-6 and sTNFRI. All measurements were correlated to clinical outcome. Serial sampling on day 3–5 post hospitalisation were also measured.ResultsCompared to AMC, COVID-19 neutrophils demonstrated elevated transmigration (p=0.0397) and NETosis (p=0.0366), but impaired phagocytosis (p=0.0236) associated with impaired ROS generation (p<0.0001). Surface expression of CD54 (p<0.0001) and CD11c (p=0.0008) was significantly increased and CD11b significantly decreased (p=0.0229) on COVID-19 patient neutrophils. On day 3–5 follow-up, levels of senescent neutrophils increased compared to day 1 (indicated by decreased CXCR2 and elevated CXCR4 expression (p=0.0332)). COVID-19 patients showed increased systemic markers of NETosis including increased cfDNA (p=0.0153) and impaired DNAse activity (p<0.0.001). MPO, VEGF, sTNFRI, and IL-6 (p<0001) were elevated in COVID-19, which positively correlated with disease severity by 4C score.ConclusionCOVID-19 is associated with neutrophil dysfunction across all main effector functions, with altered phenotype, elevated migration, impaired antimicrobial responses and elevated NETosis. These changes represent a clear mechanism for tissue damage and highlight that targeting neutrophil function may help modulate COVID-19 severity.Please refer to page A189 for declarations of interest related to this abstract.

Respiratory disease, and treatment / thematic poster session impact of the uk lockdown on early copd

INTRODUCTION: Public health measures to reduce the transmission of COVID-19 have required various changes in life-style, including loss or risk to employment and social isolation. We wished to assess how these measured effected 30-45 year old smokers at risk of COPD participating in the BLF Early COPD cohort study METHODS: At enrolment, participants were aged 30-45 years, tobacco smokers with >10 pack-year smoking history, FEV1=>80% predicted and a BMI < 35kg/m2. Participants were seen face-to-face in clinic pre-COVID. During lock-down, they were posted questionnaires and contacted by telephone. The last clinic visit took place on the 12 March 2020, remote visits took place between 16 April and 28 Sep. 260 individuals at six sites (25 Belfast, 38 Birmingham, 25 Edinburgh, 101 London, 27 Manchester and 44 Nottingham) were asked about smoking habits. The MRC chronic bronchitis questionnaire, COPD Assessment test (CAT), Leicester cough questionnaire, Hospital Anxiety and Depression questionnaire were completed in writing by the participant and returned by post or photographed and returned by email. At enrolment, the post-BD FEV1 was 3.81 (SD 0.8) litres, 101% (11) of GLI predicted. Comparisons were made by paired t-tests and chi-squared tests. RESULTS: Level of anxiety increased from 6.74 (SD 4.4) to 7.37 (SD 4.7, n=233;p=0.010) during lock-down;depression scores increased from 4.30 (3.9) to 5.14 (SD 4.1;n=233;p<0.001). Anxiety increased in 78/233 and depression in 89/233 participants by 2 or more units, 2 units is considered the minimally important (MCID) in bronchiectasis, COPD and ILD (Wynne, 2020) Figure 1 shows that during lock-down, the proportion of participants not smoking increased from 31/259 (12.0%) to 62/259 (23.9%;p<0.001). In those who continued to smoke, cigarettes per day (p=0.59) and rolling tobacco consumption (g/week) (p=0.92) were unchanged. Participants reported less chronic bronchitis defined as “do you bring up phlegm like this on most days (or nights) as much as three months each year”, fell from 83/260 (31.9%) participants to 74/259 (28.6%;p<0.001). CAT scores fell from 10.5 (SD 6.4) to 9.6 (SD 6.3;n=233;p=0.007) and total cough score improved from 18.7 (SD 2.7) to 19.1 (2.6;n=204;p=0.007). CONCLUSIONS: Despite increased anxiety and depression, participants quit smoking and those that continued to smoke, did not smoke more. Respiratory symptoms of chronic bronchitis, cough and CAT scores improved. REFERENCES:Wynne SC, et al. Chron Respir Dis. 2020 Jan-Dec;17:1479973120933292. doi: 10.1177/1479973120933292. .