Breath-holding physiology, radiological severity and adverse outcomes in COVID-19 patients: A prospective validation study.

BACKGROUND AND OBJECTIVE: COVID-19 remains a major cause of respiratory failure, and means to identify future deterioration is needed. We recently developed a prediction score based on breath-holding manoeuvres (desaturation and maximal duration) to predict incident adverse COVID-19 outcomes. Here we prospectively validated our breath-holding prediction score in COVID-19 patients, and assessed associations with radiological scores of pulmonary involvement. METHODS: Hospitalized COVID-19 patients (N = 110, three recruitment centres) performed breath-holds at admission to provide a prediction score (Messineo et al.) based on mean desaturation (20-s breath-holds) and maximal breath-hold duration, plus baseline saturation, body mass index and cardiovascular disease. Odds ratios for incident adverse outcomes (composite of bi-level ventilatory support, ICU admission and death) were described for patients with versus without elevated scores (>0). Regression examined associations with chest x-ray (Brixia score) and computed tomography (CT; 3D-software quantification). Additional comparisons were made with the previously-validated '4C-score'. RESULTS: Elevated prediction score was associated with adverse COVID-19 outcomes (N = 12/110), OR[95%CI] = 4.54[1.17-17.83], p = 0.030 (positive predictive value = 9/48, negative predictive value = 59/62). Results were diminished with removal of mean desaturation from the prediction score (OR = 3.30[0.93-11.72]). The prediction score rose linearly with Brixia score (ß[95%CI] = 0.13[0.02-0.23], p = 0.026, N = 103) and CT-based quantification (ß = 1.02[0.39-1.65], p = 0.002, N = 45). Mean desaturation was also associated with both radiological assessment. Elevated 4C-scores (≥high-risk category) had a weaker association with adverse outcomes (OR = 2.44[0.62-9.56]). CONCLUSION: An elevated breath-holding prediction score is associated with almost five-fold increased adverse COVID-19 outcome risk, and with pulmonary deficits observed in chest imaging. Breath-holding may identify COVID-19 patients at risk of future respiratory failure.

Renin Angiotensin System Blockers and Risk of Mortality in Hypertensive Patients Hospitalized for COVID-19: An Italian Registry.

BACKGROUND: It is uncertain whether exposure to renin-angiotensin system (RAS) modifiers affects the severity of the new coronavirus disease 2019 (COVID-19) because most of the available studies are retrospective. METHODS: We tested the prognostic value of exposure to RAS modifiers (either angiotensin-converting enzyme inhibitors [ACE-Is] or angiotensin receptor blockers [ARBs]) in a prospective study of hypertensive patients with COVID-19. We analyzed data from 566 patients (mean age 75 years, 54% males, 162 ACE-Is users, and 147 ARBs users) hospitalized in five Italian hospitals. The study used systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the primary outcome. RESULTS: Sixty-six patients died during hospitalization. Exposure to RAS modifiers was associated with a significant reduction in the risk of in-hospital mortality when compared to other BP-lowering strategies (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.32 to 0.90, p = 0.019). Exposure to ACE-Is was not significantly associated with a reduced risk of in-hospital mortality when compared with patients not treated with RAS modifiers (OR: 0.66, 95% CI: 0.36 to 1.20, p = 0.172). Conversely, ARBs users showed a 59% lower risk of death (OR: 0.41, 95% CI: 0.20 to 0.84, p = 0.016) even after allowance for several prognostic markers, including age, oxygen saturation, occurrence of severe hypotension during hospitalization, and lymphocyte count (adjusted OR: 0.37, 95% CI: 0.17 to 0.80, p = 0.012). The discontinuation of RAS modifiers during hospitalization did not exert a significant effect (p = 0.515). CONCLUSIONS: This prospective study indicates that exposure to ARBs reduces mortality in hospitalized patients with COVID-19.

The respiratory rehabilitation Maugeri network service reconfiguration after 1 year of COVID-19.

As part of the Italian Health Service the respiratory ICS Maugeri network were reconfigured and several in-hospital programs were suspended to be substituted by workforce and facilities reorganization for acute and post-acute COVID-19 care need. The present review shows the time course variation of respiratory ICS network in terms of admissions diagnosis and outcomes. A comparative review of the admissions and outcome measures data (anthropometric, admission diagnosis, provenience, comorbidities, disability, symptoms, effort tolerance, disease impact, length of stay and discharge destinations) over 1 year period (March 2020-March 2021) was undertaken and compared to retrospective data from a corresponding 1 year (March 2019-March 2020) period to determine the impact of the network relocation on the delivery of pulmonary specialist rehabilitation to patients with complex needs during the pandemic episode. One of the changes implemented at the respiratory Maugeri network was the relocation of the Pulmonary Rehabilitation units from its 351 beds base to a repurposed 247 beds and a reduction in total number of admitted patients (n=3912 in pre-COVID time; n=2089 in post COVID time). All respiratory diagnosis, except COVID sequelae, decreased (chronic respiratory failure-CRF, COPD, obstructive sleep apnoea syndrome-OSAS, interstitial lung disease-ILD, tracheostomized patients and other mixed diseases decreased of 734, 705, 157, 87, 79 and 326 units respectively). During the pandemic time, 265 post COVID sequelae with CRF were admitted for rehabilitation (12.62%), % of patients coming from acute hospital increased, LOS and NIV use remained stable while CPAP indication decreased. Disease impact, dyspnea and effort tolerance as their improvements after rehabilitation, were similar in the two periods.  Only baseline disability, expressed by Barthel index, seems higher in the 2° observation time as its improvement. Hospital deaths and transfers to acute hospitals were higher during pandemic crisis while home destination decreased. This review demonstrated impact of coronavirus pandemic situation, specifically the relocation of the respiratory inpatient rehabilitation wards in a huge Italian network.

Pre-sleep arousal and sleep quality during the COVID-19 lockdown in Italy.

OBJECTIVE: The COVID-19 pandemic has strongly affected daily habits and psychological wellbeing, and many studies point to large modifications in several sleep and sleep-related domains. Nevertheless, pre-sleep arousal during the pandemic has been substantially overlooked. Since hyperarousal represents one of the main factors for the development and the perpetuation of chronic insomnia disorder, the assessment of variables associated with high levels of pre-sleep arousal during the pandemic is clinically relevant. The study aimed to assess the prevalence and predictors of perceived sleep quality and pre-sleep arousal in an Italian sample during the COVID-19 lockdown. METHODS: We used an online survey to collect self-reported sociodemographic, environmental, clinical, sleep, and sleep-related data. Our final sample included 761 participants. RESULTS: Beyond a high frequency of poor sleep quality, depressive and stress symptoms, our results show that almost half of the sample suffered from clinically relevant levels of at least one component (ie, cognitive, somatic) of pre-sleep arousal. Subjects with greater pre-sleep arousal exhibited poorer sleep quality. Also, sleep quality was strongly associated with somatic and cognitive pre-sleep arousal. Regarding the predictors of sleep and sleep-related measures, depressive and event-related stress symptoms were the main factors associated with both poor sleep quality and pre-sleep arousal components. Moreover, specific sociodemographic and environmental variables were uniquely related to sleep quality, cognitive or somatic pre-sleep arousal. CONCLUSIONS: These findings suggest that the assessment of specific sleep-related factors (ie, pre-sleep arousal), together with more global measures of sleep quality, may be crucial to depict the complex impact of the pandemic on sleep, and to help prevent and counteract the spread of insomnia symptoms.

Persistence of the Effects of the COVID-19 Lockdown on Sleep: A Longitudinal Study.

The effects of the COVID-19 pandemic on sleep have been widely documented, but longitudinal evaluations during different phases of the "COVID-19 era" are needed to disentangle the specific consequences of the r145estrictive measures on sleep variables. The aim of this study was to assess the immediate effect of the lockdown's end on sleep and sleep-related dimensions in an Italian sample, also considering the stress and depressive symptoms. We used an online survey to longitudinally collect data on sociodemographic, environmental, clinical, sleep, and sleep-related variables in two time points: during and immediately after the lockdown. The final sample included 102 participants. The large prevalence of poor sleep quality, clinically relevant pre-sleep arousal, and depressive symptoms, as well as poor sleep quality and pre-sleep arousal score observed during the lockdown, remained stable after its end. On the other hand, the prevalence of moderate-to-severe event-related stress and intrusive symptom scores exhibited a drastic reduction after the end of home confinement. Both bedtime and rise time were anticipated after the lockdown, while sleep quality exhibited only a trend of post-lockdown sleep disturbance reduction. Our findings point to a reduced stress level (specific for the intrusive symptomatology) after the end of the lockdown and persistence of sleep problems, suggesting two non-mutually exclusive hypotheses: (a) the strict restrictive measures are not the main cause of sleep problems during the pandemic and (b) home confinement induces long-lasting effects on sleep observable after its end, and a longer period of time might be needed to observe an improvement.

Breath-holding as a novel approach to risk stratification in COVID-19.

BACKGROUND: Despite considerable progress, it remains unclear why some patients admitted for COVID-19 develop adverse outcomes while others recover spontaneously. Clues may lie with the predisposition to hypoxemia or unexpected absence of dyspnea ('silent hypoxemia') in some patients who later develop respiratory failure. Using a recently-validated breath-holding technique, we sought to test the hypothesis that gas exchange and ventilatory control deficits observed at admission are associated with subsequent adverse COVID-19 outcomes (composite primary outcome: non-invasive ventilatory support, intensive care admission, or death). METHODS: Patients with COVID-19 (N = 50) performed breath-holds to obtain measurements reflecting the predisposition to oxygen desaturation (mean desaturation after 20-s) and reduced chemosensitivity to hypoxic-hypercapnia (including maximal breath-hold duration). Associations with the primary composite outcome were modeled adjusting for baseline oxygen saturation, obesity, sex, age, and prior cardiovascular disease. Healthy controls (N = 23) provided a normative comparison. RESULTS: The adverse composite outcome (observed in N = 11/50) was associated with breath-holding measures at admission (likelihood ratio test, p = 0.020); specifically, greater mean desaturation (12-fold greater odds of adverse composite outcome with 4% compared with 2% desaturation, p = 0.002) and greater maximal breath-holding duration (2.7-fold greater odds per 10-s increase, p = 0.036). COVID-19 patients who did not develop the adverse composite outcome had similar mean desaturation to healthy controls. CONCLUSIONS: Breath-holding offers a novel method to identify patients with high risk of respiratory failure in COVID-19. Greater breath-hold induced desaturation (gas exchange deficit) and greater breath-holding tolerance (ventilatory control deficit) may be independent harbingers of progression to severe disease.

Joint effect of heart failure and coronary artery disease on the risk of death during hospitalization for COVID-19.

AIMS: heart failure (HF) and coronary artery disease (CAD) are independent predictors of death in patients with COVID-19. The adverse prognostic impact of the combination of HF and CAD in these patients is unclear. METHODS AND RESULTS: we analysed data from 954 consecutive patients hospitalized for SARS-CoV-2 in five Italian Hospitals from February 23 to May 22, 2020. The study was a systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the outcome measure. Mean duration of hospitalization was 33 days. Mortality was 11% in the total population and 7.4% in the group without evidence of HF or CAD (reference group). Mortality was 11.6% in the group with CAD and without HF (odds ratio [OR]: 1.6, p = 0.120), 15.5% in the group with HF and without CAD (OR: 2.3, p = 0.032), and 35.6% in the group with CAD and HF (OR: 6.9, p<0.0001). The risk of mortality in patients with CAD and HF combined was consistently higher than the sum of risks related to either disorder, resulting in a significant synergistic effect (p<0.0001) of the two conditions. Age-adjusted attributable proportion due to interaction was 64%. Adjusting for the simultaneous effects of age, hypotension, and lymphocyte count did not significantly lower attributable proportion which persisted statistically significant (p = 0.0360). CONCLUSION: The combination of HF and CAD exerts a marked detrimental impact on the risk of mortality in hospitalized patients with COVID-19, which is independent on other adverse prognostic markers.

Sleep laboratories reopening and COVID-19: a European perspective.

Clinical activities regarding sleep disordered breathing (SDB) have been sharply interrupted during the initial phase of the coronavirus disease 2019 (COVID-19) epidemic throughout Europe. In the past months, activities have gradually restarted, according to epidemiological phase of COVID-19 and national recommendations. The recent increase in cases throughout Europe demands a reconsideration of management strategies of SDB accordingly. Diagnosis of SDB and initiation of treatment pose some specific problems to be addressed to preserve the safety of patients and health personnel. This perspective document by a group of European sleep experts aims to summarise some different approaches followed in Europe and United States, which reflect national recommendations according to the epidemiological phase of the COVID-19 infection. Respiratory sleep medicine is likely to change in the near future, and use of telemedicine will grow to avoid unnecessary risks and continue to provide optimal care to patients. In addition, the document covers paediatric sleep studies and indications for titration of noninvasive ventilation, as well as precautions to be followed by patients who are already on positive airway pressure treatment. A single consensus document developed by the European Respiratory Society and national societies would be desirable to harmonise SDB management throughout Europe.