Pediatric Covid-19 Mortality: Twosided Challenges from Health Resource Disparity

BACKGROUND AND AIM: The COVID-19 pandemic impacted high (HICs) and low to high- middle income countries (LHMICs) disproportionately. We sought to investigate factors contributing to disparate pediatric COVID-19 mortality. METHOD(S): We used the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) COVID-19 database, and stratified country group defined by World Bank criteria. All hospitalized patients aged less than 19 years with suspected or confirmed COVID-19 diagnosis from January 2020 through April 2021 were included. RESULT(S): A total of 12,860 patients with 3,819 cases from HICs and 9,041 cases from LHMICs were included in this study. Of these, 8,961 (73.8%) patiens were confirmed cases and 2444 (20.1%) were suspected COVID19. Overall in-hospital mortality was 425 (3.3%) patients, with 4.0% mortality in LHMICs (361/9041), which was higher than 1.7% mortality in HICs (64/3819);adjusted HR (aHR) 4.74, 95%CI 3.16-7.10, p<0.001. There were significant differences between country income groups in the use of interventions, with higher use of antibiotics, corticosteroid, prone position, high flow nasal cannula, and invasive mechanical ventilation in HICs, and higher use of anticoagulants and non-invasive ventilation in LHMICs. Infectious comorbidities such as tuberculosis and HIV/AIDS were shown to be more prevalent in LHMICs [2 (0.0%) vs 171 (1.9 %), 1 (0.0%) vs. 149 (1.6%) patients, respectively]. Mortality rates in children who received mechanical ventilation in LHMICs were higher compared with children in HICs [89 (43.6%) vs. 17 (7.2%) patients, aHR 12.0, CI95% 7.2-19.9, p<0.001]. CONCLUSION(S): Various contributing factors to COVID-19 mortality identified in this study may reflect management differences in HICs and LHMICs. (Figure Presented).

COVID-19 pandemic: the impact on Canada's intensive care units

The COVID-19 pandemic has exposed the precarious demand-capacity balance in Canadian hospitals, including critical care where there is an urgent need for trained health care professionals to dramatically increase ICU capacity. The impact of the pandemic on ICUs varied significantly across the country with provinces that implemented public health measures later and relaxed them sooner being impacted more severely. Pediatric ICUs routinely admitted adult patients. Non-ICU areas were converted to ICUs and staff were redeployed from other essential service areas. Faced with a lack of critical care capacity, triage plans for ICU admission were developed and nearly implemented in some provinces. Twenty eight percent of patients in Canadian ICUs who required mechanical ventilation died. Surviving patients have required prolonged ICU admission, hospitalization and extensive ongoing rehabilitation. Family members of patients were not permitted to visit, resulting in additional psychological stresses to patients, families, and healthcare teams. ICU professionals also experienced extreme psychological stresses from caring for such large numbers of critically ill patients, often in sub-standard conditions. This resulted in large numbers of health workers leaving their professions. This pandemic is not yet over, and it is likely that new pandemics will follow. A review and recommendations for the future are provided. © 2022 Gibney et al.

Neurological impact of COVID-19: Sub-acute brain microstructural alterations in self-isolated individuals

Objective: This study investigates the effects of COVID-19 on brain microstructure among those recently recovering from COVID-19 through self isolation. Background: Microstructural differences have previously been detected in comparisons of COVID-19 patients with controls, particularly in regions related to the olfactory system. The olfactory system is connected with the caudate, putamen, thalamus, precuneus, and cingulate regions. Design/Methods: Here we report diffusion magnetic resonance imaging (3 T Siemens MRI) findings from 40 patients (mean age: 43.7, 68% female) who self-isolated after testing positive for COVID (COV+), and 14 COVID negative (COV-) subjects (mean age: 43, 64% female) who had flu-like symptoms. This is part of the Canadian-based NeuroCOVID-19 study. Fractional anisotropy (FA), mean diffusivity (MD), mode of anisotropy (MO), free water fraction (F), tissue-specific FA (FAt) and tissue-specific MD (MDt) were obtained using data with b=700 and 1400 (DIPY free-water model). Regions of interest in the grey matter and white matter were delineated using FreeSurfer. Differences between groups were assessed using an analysis of variance (ANOVA), the Kruskal-Wallis Test and the Mann-Whitney Test, corrected for false-discovery rate of 0.05. Effect size (Cohen's d) was also computed (d>0.45 deemed large effect). Results: In the COV+ group, all three tests revealed decreased FA and FAt in the insula, and increased MD in the parstriangularis cortex. Increased FA and FAt in the cuneus (along with decreased MD) was also found. MD was reduced in COV+ in the temporal and supramarginal areas. MO was lower in COV+ in the insula and amygdala regions. Conclusions: In patients, higher MD with lower FA and MO suggest increased extracellular fluids, while lower MD with decreased FA and MO may suggest necrotic debris built up following inflammation. The cuneus and insula are involved in visual and taste processing, respectively. This study highlights the need to study neurological effects of COVID-19.

“Long-hauler ” impact of COVID-19 on brain microstructure: a 3-month follow-up study

Objective: This study investigates the chronic effects of COVID-19 on brain microstructure. Background: Microstructural differences have previously been detected in comparisons of COVID-19 patients with controls, particularly in the insula, cuneus, inferior temporal and anterior cingulate regions. Design/Methods: Here we report diffusion magnetic resonance imaging (3 T Siemens MRI) findings from 20 participants (mean age: 45.3, 55% female), both immediately after recovery and at a 3-month follow-up. Fractional anisotropy (FA), mean diffusivity (MD), mode of diffusivity (MO), free water fraction (F), tissue-specific FA (FAt) and tissue-specific MD (MDt) were obtained using DTI data with b=700 and 1400 (DIPY free-water model). Regions of interest in the grey matter and white matter were delineated using FreeSurfer. To assess differences between baseline and follow-up, a paired t-test, the Wilcoxon Test and Friedman Test were performed, corrected for false-discovery rate of 0.05. Effect size (Cohen's d) was also computed (d>0.45 deemed large effect). Results: All three tests revealed decreased F in the hippocampus and decreased MD in the parahippocampal region of the WM at follow-up. In the GM, F was increased in the medial orbitofrontal region. In the WM, MD was increased in the paracentral region and MDt was increased in the parahippocampal and lateral orbitofrontal regions. Conclusions: These results suggest that microstructural abnormalities persist following recovery. Increased extracellular fluid (i.e. F and MD) in the frontal lobe suggest spreading of COVID-19 impact, while decreased F and MD in the hippocampal region suggest debris accumulation as part of the inflammatory process. None of the regions affected in sub-acute COVID-19 appear to fully recover within three months.

Challenges of Conducting Osteoarthritis Quality Improvement Project in an Integrative Clinic During COVID-19

Methods: Patients with OA were identified through EPIC. Those that had a treatment scheduled in the Comprehensive Pain Center at Oregon Health & Science University were contacted and baseline patient reported outcomes (PRO) were obtained. The PRO tools included the Hip dysfunction and Osteoarthritis Outcome Score (HOOS), Knee dysfunction and Osteoarthritis Outcome Score (KOOS), Brief Pain Inventory (BPI) and PROMIS Global 10. The PRO were gathered at return visits for one year. Common treatment pathways were assessed using change scores. The OHSU IRB determined that the project did not need IRB oversite due to its QI nature. Results: Due to COVID-19 related changes in treatment patterns and safety precautions-virtual visits for MDs and psychologists, interruptions for acupuncture, chiropractic, massage and Rolfing -PROtools could not be handed to patients prior to visits. A multipronged approach to data gathering was implemented, including telephone and iPad accessed questionnaires. iPads required QR-code generation for participant identification. As of 10/15/2021, 51 patients provide 160 questionnaires. Average age of participants was 62.1 (8.85). Initial PROMIS GLOBAL physical score was 8.7 (SD 0.9) and mental was 10.0 (SD 0.33). Our original proposal estimated that we would have 125 individuals at this point in the project. We will discuss changes in methodology in response to COVID-19. Background: Implementation of a quality improvement (QI) project to understand treatment pathways of osteoarthritis patients (OA) in an integrativemedicine clinic. As the majority of visits shifted to virtual, we had to pivot our project. Conclusion: While COVID-19 created significant barriers to health care, it also created new patterns of utilization in patients with OA. Due to these changes, the methodology of conducting a QI project also had to change. While there were significant obstacles, our QI project was able to continue and new treatment patterns have emerged.

Potential drug-drug interactions in hospitalized COVID-19 patients (CATCO-DDI)

Background: Therapies for managing COVID-19 disease may interact with other drugs, particularly in hospitalized patients with comorbidities. Objectives: Characterize the prevalence of drug-drug interactions (DDIs) between investigational/approved medications for managing COVID-19 (COVID-meds) and co-medications (co-meds) in hospitalized COVID-19 patients. Methods: Multicentre retrospective observational study of hospitalized COVID-19 patients screened for the CATCO trial between 1-Apr-20 and 15-Sep-20. Patients' co-meds were assessed for potential DDIs with the following COVID-meds: hydroxychloroquine (HQ), lopinavir/ritonavir (LPV), remdesivir (REM), dexamethasone (DEX), azithromycin (AZ), interferon beta-1B (IFN) and tocilizumab (TOC). The Liverpool-COVID DDI website and Lexicomp were used to identify and characterize DDI severity (red: do not co-administer, amber: potential interaction) and potential clinical impact. QT prolongation risk was assessed with the Tisdale risk score. The primary outcome was the prevalence of subjects with =1 potential clinically significant (red/amber) DDI between each COVID-med and co-med. Secondary outcomes included DDI severity and potential clinical impact. Descriptive statistics are presented as medians (range) or proportions. Results: Data from 51 patients are available: 61% male, age 74 (44-95) years, 6 (1-15) comorbidities, Tisdale risk score 6 (31.4% moderate risk, 11.8% high risk) and 10 (0-19) co-meds. LPV had the highest rate of potential DDIs (92.2%, 45% red, 3 DDIs per patient) with risk of increased co-med toxicity (most commonly psychotropics, anticoagulants/antiplatelets), while REM and IFN had the least (2% and 9.6%, respectively). Most patients (75%) had =1 DEX DDI (mostly amber, 1per patient) with risk of increased co-med toxicity. The most common DDIs with HQ and AZ involved increased risk of QTc prolongation. Over one-third (35%) of patients were deemed ineligible for CATCO at screening due to DDIs with LPV. Conclusions: Hospitalized COVID-19 patients are at high risk of DDIs with many investigational/approved COVID medications. Routine DDI screening is recommended, ideally using both general and COVID-specific DDI resources.

A quantitative study of particle dispersion due to respiratory support modalities in pre-hospital and in-hospital critical care environments

RATIONALE: Patients with COVID-19 may require supplemental oxygen and non-invasive respiratory support devices during pre-hospital aeromedical transport as well as in-hospital intensive care units. It is unclear whether these therapies increase the dispersion of potentially infectious bioaerosols and placing health workers at increased risk. METHODS: The studies were conducted in two environments: (1) fixed-wing air ambulance cruising at 25,000 ft;(2) a simulated critical care unit in hospital. A breathing patient simulator consisting of a medical mannequin exhaling nebulized particles from the lower respiratory tract was connected to a ventilator to simulate a patient with mild-moderate respiratory distress. Aerosolized saline and DNA bacteriophage φX174 were used to model aerosol dispersion in the aeromedical and simulated intensive care unit, respectively. Dispersion of 1.0 μm particles were measured in key locations, due to the three respiratory support modalities including;non-invasive bilevel positive pressure ventilation (BiPAP);high-flow nasal oxygen (HFNO);and nasal prongs. In the simulated intensive care unit study, viability of aerosolized bacteriophage φX174 was quantified using plaque assays (Fig. 1) RESULTS: In both environments, particle concentrations were highest close to the simulator's mouth and declined with distance from the mouth. In the aeromedical environment, nasal prongs (with a surgical mask) were associated with the highest particle concentrations and BiPAP the lowest. In that environment, at a location near the mouth, particle concentrations associated with HFNO with a surgical mask (5.5 × 104 particles/L of sampled air) and BiPAP (7.5 × 103 particles/L) were significantly lower when compared to nasal prongs with a surgical mask (1.2 × 105 particles/L) (each P < 0.05). In the simulated intensive care unit, HFNO was associated with the highest particle concentrations and BiPAP the lowest. In this environment, at a location near the mouth, particle concentrations as well as bacteriophage viability associated with nasal prongs (7.4 × 104 particles/L and 1.6 × 104 PFU/L) and BiPAP (1.1 × 104 particles/L and 1.9 × 102 PFU/L) were significantly lower when compared to HFNO (5.3 × 105 particles/L and 2.6 × 104 PFU/L) (each P < 0.05). CONCLUSIONS: These findings highlight the comparable risk of dispersing particles among respiratory support devices and the importance of appropriate infection prevention and control practices and personal protective equipment for healthcare workers when caring for patients with transmissible respiratory viral infections such as COVID-19. These findings also suggest a comparable risk associated with use of nasal prongs and HFNO in both environments.

Quantitative Assessment of Viral Dispersion Associated with Respiratory Support Devices in a Simulated Critical Care Environment

Rationale: Patients with severe coronavirus disease (COVID-19) require supplemental oxygen and ventilatory support. It is unclear whether some respiratory support devices may increase the dispersion of infectious bioaerosols and thereby place healthcare workers at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives: To quantitatively compare viral dispersion from invasive and noninvasive respiratory support modalities.