Time-related aortic inflammatory response, as assessed with 18F-FDG PET/CT, in patients hospitalized with severely or critical COVID-19

Aim: Arterial involvement has been implicated in the coronavirus disease of 2019 (COVID-19). Fluorine 18-fluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG PET/CT) imaging is a valuable tool for the assessment of aortic inflammation and is a predictor of outcome. We sought to prospectively assess the presence of aortic inflammation and its time-dependent trend in patients with COVID-19. Method(s): Between November 2020 and May 2021, in this pilot, casecontrol study, we recruited 20 patients with severe or critical COVID-19 (mean age of 59+/-12 years), while 10 age and sex-matched individuals served as the control group. Aortic inflammation was assessed by measuring 18F-FDG uptake in PET/CT performed 20-120 days post-admission. Global aortic target to background ratio (GLA-TBR) was calculated as the sum of TBRs of ascending and descending aorta, aortic arch, and abdominal aorta divided by 4. Index aortic segment TBR (IAS-TBR) was designated as the aortic segment with the highest TBR. Result(s): There was no significant difference in aortic 18F-FDG PET/CT uptake between patients and controls (GLA-TBR: 1.46 [1.40-1.57] vs. 1.43 [1.32-1.70], respectively, p=0.422 and IAS-TBR: 1.60 [1.50-1.67] vs. 1.50 [1.42-1.61], respectively, p=0.155). There was a moderate correlation between aortic TBR values (both GLA and IAS) and time distance from admission to 18F-FDG PET-CT scan (Spearman's rho=-0.528, p=0.017 and Spearman's rho=-0.480, p=0.032, respectively), Figure 1. Patients who were scanned less than or equal to 60 days from admission (n=11) had significantly higher GLA-TBR values compared to patients that were examined more than 60 days post-admission (GLA-TBR: 1.53 [1.42-1.60] vs. 1.40 [1.33-1.45], respectively, p=0.016 and IAS-TBR: 1.64 [1.51-1.74] vs. 1.52 [1.46-1.60], respectively, p=0.038). There was a significant difference in IAS-TBR between patients scanned <=60 days and controls (1.64 [1.51-1.74] vs. 1.50 [1.41-1.61], p=0.036), Figure 2. Conclusion(s): This is the first study suggesting that aortic inflammation, as assessed by 18F-FDG PET/CT imaging, is increased in the early post-COVID phase in patients with severe or critical COVID-19 and largely resolves over time. Our findings may have important implications for the understanding of the course of the disease and for improving our preventive and therapeutic strategies.

SARS-CoV-2 load in exhaled end-tidal breath fine aerosol condensates among acutely symptomatic COVID-19 cases

SARS-CoV-2 infectious virions have been reported in exhaled breath, but their source remains elusive: breath sampling systems used to date do not separate breath aerosols by size, fail to prevent salivary/fomite contamination, or aerosol size evolution before sample capture. We hypothesised that sampling end-tidal, oral exhaled breath condensate (EBC), after separating large droplets by inertial impaction 4cm from the lips, would quantify viral loads in distal lung-derived fine aerosols (FA). We used a collector (PBM-HALE ) that captures mechanically aerosolised viruses to sample adult participants for <30 min under informed consent;cases symptomatic for <5 days (n=30) or >5 days (n=12), positive by nasopharyngeal swab RT-PCR (Ct>=13.1), were sampled in clinical triage 'red zones', or COVID-19 wards with no mechanical ventilation or open windows. Salivary alpha amylase activity (Salimetrics LLC), or SARS-CoV-2 viral load (VIASURE SARS-CoV-2 (ORF1ab and N gene)) after QIAsymhpony DSP midi extraction, was quantified in 0.2mL FA EBC fractions. No salivary alpha amylase activity was detected in healthy participant FA EBC (>1:1,750 dilution of paired saliva vs assay detection limit (n=300)). No SARS-CoV-2 RNA was detected in FA EBC (1.18mL +/- 0.32 total volume) among any COVID-19 cases (Aug 2020-Jan 2022) at limits of detection of 120 genomes/mL FA EBC or 4.72 genomes/min exhalation. No pre-extraction spike-in control reaction inhibition was observed. No ambient contamination of the alveolar FA EBC was detected with this sampling device. The alveolar fraction of orally exhaled tidal breath lacks detectable SARS-CoV-2 viral load.

Rehabilitation facilitates the natural recovery of symptoms, mental health and quality of life outcomes post COVID-19

Aim: To investigate the effects of rehabilitation (Rehab) added to usual care (UC) versus UC on symptoms, mental health and quality of life (QoL) outcomes post COVID-19. Method(s): A supervised Rehab program was offered to 55 post COVID-19 patients who were hospitalized with severe/critical COVID-19 pneumonia and a Copd Assesment Test (CAT) score >= 10, post hospital discharge (6-8 weeks). Twenty-eight patients accepted to enroll to Rehab, whereas 27 refused to participate (UC). All patients were evaluated at baseline and after 2 months. Result(s): Groups were not different in mean age (56 years), gender (53% ), ICU admission (65%), intubation (47%), days of hospitalization (31), number of symptoms (9), and number of comorbidities (1.4). The baseline evaluation was conducted at 82+/-30 days after symptoms onset. Only Rehab was associated with improvements in respiratory symptoms, dyspnea, fatigue, depression/anxiety, cognitive impairment, and QoL. (Table 1) Conclusion(s): Rehabilitation facilitates recovery of symptoms and QoL post COVID-19 that otherwise would remain incomplete with usual care.

Additive effects of rehabilitation on natural recovery of functional capacity post COVID-19

Aim: To investigate the effects of rehabilitation (Rehab) added to usual care (UC) versus UC on functional capacity outcomes in patients with COVID-19 pneumonia. Method(s): A supervised Rehab program was offered to 55 post COVID patients who were hospitalized with severe/critical COVID-19 pneumonia and a COPD Assessment Test (CAT) score >= 10, post hospital discharge (6-8 weeks). Twenty-eight patients accepted to enroll to Rehab, whereas 27 refused to participate (UC). All patients were evaluated at baseline and after 2 months. Result(s): Groups were not different in mean age (56 years), gender (53% ), ICU admission (65%), intubation (47%), days of hospitalization (31), number of symptoms (9), and number of comorbidities (1.4). The baseline evaluation was conducted at 82+/-30 days after symptoms onset. Both Rehab and UC were associated with improvements in functional capacity;however, these were greater following Rehab (Table 1). Conclusion(s): Rehabilitation amplifies the functional recovery post COVID-19. (Figure Presented).

P.0797 Effects on mental health, sleep and quality of life in hospitalized patients with COVID-19 infection

Background: Experience from previous coronavirus outbreaks had shown that infected patients are at risk for developing psychiatric disorders, such as mood and sleep disturbances. Similarly, accumulating evidence suggests that patients with COVID-19 infection experience an excess of adverse psychological outcomes and neuropsychiatric complications [1,2]. The aim of this study was to investigate the impact of COVID-19 infection and hospitalization on the mental health, quality of life, and sleep of patients following hospital discharge. Methods: Patients were assessed during follow up visits in the outpatient clinic 1-2 months after hospital discharge from a large Covid-19 reference hospital in Athens, Greece (from May 8th 2020 till February 4th 2021) using validated screening tools for Depression and Anxiety (HADS), post-traumatic stress disorder (IES-R), sleeping difficulties (Athens Insomnia Scale, AIS), and Quality of Life (EQ-5D-5L). Sociodemographic information, smoking history, co-morbidities and severity of disease (hospitalization, ICU) were also collected. Results: A total of 131 eligible patients who provided informed consent were included. Overall, Covid-19 patients experienced considerable levels of mental health symptoms following hospital discharge. Moreover, rates were significantly higher for female compared to male patients despite having shorter duration of hospitalizations (14.89 vs 18.82 bed days) and/or ICU admissions (13.51 vs 14.92). This finding was consistent across all recorded psychological outcomes i.e. depression (p=0.004), anxiety (p=0.017), traumatic stress (p<0.001), fear (p<0.001) and insomnia (p=0.002). In addition, differences in prevalence rates between genders were particularly marked for moderate levels of depression and traumatic stress and for severe levels of anxiety. Smoking and comorbidities were not found to significantly correlate with the presence of affective symptoms or sleep dysfunction. However, an association was observed between severity and the existence of comorbidity with the proportion of patients with comorbidities increasing from 67.5% of the patients with minimal depression to 91.43% to those with mild and 80% with moderate depression (p-value=0.018). Finally, quality of life was worse for patients that have had an admission in the ICU (EQ-5D-5L: 15.82 ± 5.27) compared to those who were hospitalized but did not require ICU treatment (EQ-5D-5L: 8.39 ± 2.81) (p-value<0.001). Conclusion: COVID-19 disease can have a significant psychological impact on hospitalized patients and particularly women despite the relative less severe course of their illness. This finding is in line with a previous study, showing that, despite significantly lower levels of baseline inflammatory markers, female patients suffered more for both anxiety and depression at one-month follow-up following hospital admission (3). Regardless of potential sex differences, the prevalence of moderate and severe mental illness symptoms in COVID‐19 patients may be higher compared with the general population or other high risk groups such as different patient groups or healthcare workers [2-4]. Our results highlight the need for appropriate interventions to promote physical and mental wellbeing of COVID-19 survivors and cater for long-term needs. No conflict of interest

The present and future of inhalation therapy for the management of obstructive airway diseases: Emphasis on pressurized metered-dose inhalers

Inhalation therapy has an ancient history and has been recognized as the most effective and safe way of delivering pharmaceutical compounds directly to the airways for the treatment of respiratory diseases. Nowadays, a great variety of devices exist;nebulizers, soft mist inhalers (SMIs), pressurized Metered Dose Inhalers (pMDIs) and single- or multi-dose Dry Powder Inhalers (DPIs). The choice for the optimal device is patient-specific and depends on the advantages and disadvantages of each device category, and the patients' age and capacity to use them correctly. Factors that determine therapeutic success, apart from the previously mentioned, are: the physician-patient relationship, the patient's opinion, willingness, and preferences for certain medical devices, and proper training on device use. Various sources of evidence indicate that frequent change of devices is associated with treatment failure and should be avoided in order to achieve good therapeutic outcomes. The most frequently used types of inhalation devices for management of chronic and acute obstructive respiratory diseases are the pMDIs. Despite having some environmental footprint and requiring a good technique by the users to achieve reliable therapeutic effects, these devices are essential tools for primary care physicians and pulmonologists. In the COVID-19 era, and despite diametrically opposed opinions on the appropriateness of using nebulizers, most experts recommend against their use in order to reduce the potential risk of spreading the SARS-CoV-2 virus. If required, most experts recommend the use of pMDI via a spacer, except for life threatening exacerbations. The ongoing research, to improve the underlying technologies of these devices, introduce environmentally friendlier propellants and combine these devices with modern applications of telemedicine and artificial intelligence, creates new pathways for the continuous utilization of these inhalation devices in everyday clinical practice.