Integrated multiomics analysis to infer COVID-19 biological insights.

Three years after the pandemic, we still have an imprecise comprehension of the pathogen landscape and we are left with an urgent need for early detection methods and effective therapy for severe COVID-19 patients. The implications of infection go beyond pulmonary damage since the virus hijacks the host's cellular machinery and consumes its resources. Here, we profiled the plasma proteome and metabolome of a cohort of 57 control and severe COVID-19 cases using high-resolution mass spectrometry. We analyzed their proteome and metabolome profiles with multiple depths and methodologies as conventional single omics analysis and other multi-omics integrative methods to obtain the most comprehensive method that portrays an in-depth molecular landscape of the disease. Our findings revealed that integrating the knowledge-based and statistical-based techniques (knowledge-statistical network) outperformed other methods not only on the pathway detection level but even on the number of features detected within pathways. The versatile usage of this approach could provide us with a better understanding of the molecular mechanisms behind any biological system and provide multi-dimensional therapeutic solutions by simultaneously targeting more than one pathogenic factor.

Apnoea-hypopnoea-index comparing the 2007 and 2012 American Academy of Sleep Medicine criteria in chronic obstructive pulmonary disease/obstructive sleep apnoea overlap syndrome.

BACKGROUND: In 2007 and 2012, the American Academy of Sleep Medicine (AASM) updated their scoring criteria for nocturnal respiratory events. We hypothesised that this could have led to changes in the apnoea-hypopnoea index (AHI) of patients with chronic obstructive pulmonary disease (COPD)/obstructive sleep apnoea (OSA) overlap syndrome. METHODS: In a retrospective study, polysomnographic (PSG) recordings of 34 patients with COPD/OSA overlap syndrome were independently analysed using the AASM criteria from 2007 (AASM2007) and 2012 (AASM2012). The primary outcome was the difference in AHI, the secondary outcomes were frequency of hypopnoeas, diagnosis of overlap syndrome and differences between the AASM 2007 recommended (AASM2007Rec) and altered (AASM2007Alt) classifications. Data are presented as mean (standard deviation) if normally distributed, and as median (interquartile range) if non-normally distributed. RESULTS: The PSGs of 34 elderly [aged 67 (7.0) years] and predominantly male (m:f, 31:3) patients with COPD [FEV1%pred 48.4% (19.6%)] were analysed. The AHI using AASM2007Rec criteria was 5.9 (2.0, 15.1) events/hour vs. 20.4 (11.5, 28.0) events/hour using the 2012 criteria (P<0.001); with the AASM2007Alt criteria, the AHI was 15.0 (9.3, 26.3) events/hour (P<0.001). Using the 2012 classification, the number of scored hypopnoeas increased by +48% compared to the AASM2007Rec criteria (P<0.001), 92% of these events were associated with arousal. Although statistically non-significant, using the AASM2007Alt classification, 12% of our cohort would not have been diagnosed with COPD/OSA overlap syndrome (P=0.114), this was also the case for 47% of the cohort when the AASM2007Rec classification was used (P<0.01). CONCLUSIONS: The use of the AASM2012 scoring rules results in a significantly higher AHI compared to the AASM2007 criteria in patients with COPD/OSA overlap syndrome, mostly due to an increased number of arousal-associated hypopnoeas. These observations are important for the definition of the COPD/OSA overlap syndrome.

Ultrasound assessment of upper airway dilator muscle contraction during transcutaneous electrical stimulation in patients with obstructive sleep apnoea.

BACKGROUND: Electrical current can be used to stimulate upper airway dilator muscles to treat obstructive sleep apnoea (OSA). Ultrasound devices are widely available and may be used to detect contraction of the upper airway dilator muscles assessing the functionality of electrical stimulation (ES) used for this treatment. METHODS: In a physiological sub-study of a randomised controlled trial, patients with OSA underwent ultrasound examination to assess contraction of the upper airway dilator muscles in response to transcutaneous ES. Ultrasound scans were scored according to the picture quality (poor = '0', acceptable = '1' and good = '2'). Tongue base thickness was assessed in mid-sagittal and coronal planes with (D2, A2) and without ES (D1, A1), while awake and seated. The primary outcome was to determine the increase in tongue thickness during ES in both views (D2 - D1 = ΔD), as well as any increase in the cross-sectional area (CSA) in the coronal view (A2 - A1 = ΔA). Data were presented as mean and standard deviation (SD). RESULTS: Fourteen patients [eight male, age 57.5 (9.8) years, body mass index (BMI) 29.5 (2.8) kg/m2] with OSA [Apnea-Hypopnea Index (AHI) 19.5 (10.6) × hour-1] were studied. Quality of the ultrasound scans was acceptable or good with 1.5 (0.5) points. In the mid-sagittal plane, ΔD was +0.17 (0.07) cm in midline and +0.21 (0.09) cm in the widest diameter, a percentual change of 12.2% (4%) and 12.8% (5.2%) (P<0.001, respectively). In the coronal plane, ΔD was +0.17 (0.04) cm, an increase of 12.3% (4.6%) (P<0.001, respectively), ΔA in the CSA increased by +18.9% (3.0%) with stimulation (P<0.001). There was a negative correlation between age and ΔA (r= -0.6, P=0.03), but no significant associations were found with gender, BMI, neck circumference, Epworth Sleepiness Scale (ESS), AHI, skin and subcutaneous tissue in the submental area. CONCLUSIONS: Ultrasound can visualise upper airway dilator muscle contraction during transcutaneous ES in awake patients with OSA. Contraction is best detected in the CSA of the tongue base in the coronal plane.

Serum interleukin-6 in systemic sclerosis and its correlation with disease parameters and cardiopulmonary involvement.

OBJECTIVE: To assess serum interleukin-6 (IL-6)level in patients with systemic sclerosis (SSc) and its correlations with European Scleroderma Study Group activity score (EUSTAR), Scleroderma Assessment Questionnaire (SAQ), disability index and cardiopulmonary involvement. METHODS: Twenty SSc patients and 10 matched healthy controls were included. Serum IL-6 was measured in patients and controls. Disease activity, status,and disability were assessed.Cardiopulmonary involvement was evaluated by pulmonary function tests (PFTs), six minute walk test, echocardiography, and high resolution computed tomography (HRCT) of chest. RESULTS: Serum level of IL-6 was significantly higher in patients with SSc (6.3± 1.4pg/ml) versus healthy controls (3.2± 0.4pg/ml) (P=0.002). IL-6 level showed positive correlations with disease duration (r=0.49, P=0.03), EUSTAR score (r=0.64, P=0.002), Index of Respiratory Status "IRS" (r=0.46, P=0.001), Index of Musculoskeletal Status "IMSS" (r=0.45, P=0.049), Index of Vascular Status "IVS" (r=0.39, P=0.04), mean and peak of pulmonary artery pressure (r=0.44 & 0.55, P=0.02 & 0.002 respectively). Negative correlations of IL-6 level with DLCO% (r=-0.49, P=0.006),six minute walk distance (6MWD) (r=-0.52, P= 0.003) and right ventricle fraction area change (r=-0.48, P=0.03) were found, while there were strong positive correlations with HRCT-ground glass score (r=0.77, P=0.0001) and HRCT-fibrosis score (r=0.62, P=0.003). CONCLUSION: IL-6 level is increased in patients with SSc and significantly correlates with EUSTAR score, IRS, DLCO, 6MWD, HRCT scores, and echocardiographic abnormalities of the right side of the heart. These results support the role of IL-6 in the disease activity and in the development of cardiopulmonary manifestations in SSc patients.

High sensitivity C-reactive protein: its correlation with sputum cell counts in bronchial asthma.

BACKGROUND: Two major acute-phase proteins were identified in human, C-reactive protein and serum amyloid A. There are 3 types of C-reactive protein assays: conventional C-reactive protein, high sensitivity C-reactive protein and cardiac C-reactive protein. High sensitivity C-reactive protein assays can detect minor inflammatory changes that could be missed by other indices of inflammation. Induced sputum cell counts are relatively non-invasive, safe and reliable method for identifying the presence and type of airway inflammation in asthmatic patients. PURPOSE OF THE WORK: This study was designed to detect the role of serum levels of high sensitivity C-reactive protein in asthmatic patients with or without inhaled corticosteroids treatment. Also to determine the relationship of serum high sensitivity C-reactive protein levels to clinical indices of asthma and inflammatory cell counts in induced sputum. SUBJECTS & METHODS: Serum high sensitivity C-reactive protein level, pulmonary function tests, body mass index and induced sputum cell counts were estimated in 50 asthmatic patients (26 steroid inhaled and 24 steroid naïve). Fifteen healthy volunteers, who matched in age and sex with the other groups, were used as a control group. RESULTS: There was an increase of high sensitivity C-reactive protein in asthmatic patients among both steroid inhaled and steroid naïve patients compared to the healthy controls. Serum high sensitivity C-reactive protein correlated negatively with pulmonary function tests and positively with sputum eosinophil % in both inhaled steroid and steroid naïve groups. CONCLUSION: High sensitivity C-reactive protein is one of the markers of systemic inflammation that can be indirectly reflecting the degree of severity of airway inflammation in bronchial asthma.