A retrospective observational study of face-to-face versus hybrid phase II cardiac rehabilitation program during COVID-19 pandemic

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): With the support of: Col.legi de Fisioterapeutes de Catalunya [R02/2018] Health Department of Generalitat de Catalunya. Instrumental action of intensification of nursing professionals (SLT017/20/000098) Introduction Cardiac rehabilitation (CR) is a class I level A recommendation. The COVID-19 pandemic forced us to halt face-to-face patient physical exercise programs during the lockdown. Due to it, it was necessary to redesign the cardiac rehabilitation program (CRP) modality to achieve the goals of CR. Purpose To assess the impact of the COVID-19 pandemic in the functional capacity of cardiac patients who finished phase II CRP and to determine the impact of the CRP modality performed during COVID-19 period. Methods We conducted a retrospective observational study with patients admitted to our CRP from October 2019 to June 2021. Eligible patients were diagnosed with myocardial infarction, unstable angina or chronic coronary syndrome, without cognitive deficit, with Barthel index >60 and providing signed informed consent. Patients attended to face-to-face CRP (pre-COVID-19) receiving supervised exercise training centre-based program consisting of 3 hours a week (spread over 3 alternate days) of supervised exercise training for 10 weeks. After COVID-19 lockdown (post-COVID-19), we designed a new hybrid model of CRP. It consisted in attending the supervised training centre-based sessions to ensure the correct learning of the physical exercise routine. Patients continued this practice for their own under telemonitoring by video call once a week. Face-to-face and hybrid models were offered according to the needs of participants. All patients performed an exercise stress test before and at the end of phase II (3 months). Results Ninety-one patients were included, 49 during pre-COVID-19 and 42 during post-COVID-19. Related to baseline characteristics, no statistically significant differences were observed between groups. Considering functional capacity, metabolic equivalent (MET) improved 0.8 (SD 1.7) and 1.3 (SD 1.6) (p=0.186) at 3 months in the pre- and post-COVID-19 period respectively. Related to the minutes of exercise, the increase was 0.8 (SD 1.6) and 1.3 (SD 1.6) (p=0.108) respectively. In the post-COVID-19 period, 18 patients took part in face-to-face model and 24 in hybrid version. In regard to baseline characteristics, patients in the hybrid model were younger than face-to-face version, 56.4 vs 61.1 years (p=0.096) and the low level of risk of CRP was higher in the hybrid model, 50.0% vs 16.7%;(p=0.239). Related to functional capacity, patients in the hybrid version had better baseline conditions, 8.0 (SD 2.3) vs 6.3 (SD 1.6) MET (p=0.011) and 8.2 (SD 2.3) vs 6.3 (SD 2.0) minutes (p=0.007). However, the improvements observed at 3 months were lower in the hybrid model, 0.9 (SD 1.6) vs 1.8 (SD 1.4) MET (p=0.072) and 0.9 (SD 1.5) vs 1.9 (SD 1.5) minutes (p=0.028). Conclusions COVID-19 pandemic did not affect the gains in functional capacity in phase II CRP. In the post-COVID-19 period, patients in both models increased their physical condition and the differences observed in the improvement were possibly due to the baseline risk level of CRP.

A crystallographic snapshot of SARS-CoV-2 main protease maturation process

SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral Mpro is responsible for the cleavage of the viral polyprotein in 11 sites, including its own N- and C-terminus. The lack of structural information for intermediary forms of Mpro is a setback for the understanding its self-maturation process. Herein, we used X-ray crystallography combined with biochemical data to characterize multiple forms of SARS-CoV-2 Mpro. For the immature form, we show that extra N-terminal residues caused conformational changes in the positioning of domainthree over the active site, hampering the dimerization and diminishing its activity. We propose that this form preludes the cis and trans-cleavage of N-terminal residues. Using fragment screening, we probe new cavities in this form which can be used to guide therapeutic development. Furthermore, we characterized a serine site-directed mutant of the Mpro bound to its endogenous Nand C-terminal residues during dimeric association stage of the maturation process. We suggest this form is a transitional state during the C-terminal trans-cleavage. This data sheds light in the structural modifications of the SARS-CoV-2 main protease during its self-maturation process.

Predicting CoViD-19 hospitalized patients' outcome with homocysteine

Background: Homocysteine (Hcy) has been reported as a potential predictive biomarker for CoViD-19 infection severity in many studies. Hyper-homocysteinemia is related to many virus infection outcomes, including HEV, HPV and HIV. Recent data confirmed the value of Hcy in predicting the risk of severe pneumonia. Materials and Methods: Our retrospective cohort study, including 313 CoViD-19 hospitalized patients (female 34.8%;mean age 62 years), also included a broad panel of clinical laboratory data collected. Of the enrolled patients, 10.9% died during hospitalization (3% were transferred to other hospitals and were lost to follow-up). Results: Hcy was found to be the strongest predictor of CoViD- 19 critical-progression leading to death. Univariate analysis demonstrated that age (OR 1.04), Hcy (OR 1.06), and neutrophil/lymphocyte count ratio (OR 1.03) were significant predictors of critical progression leading to death and RBC (OR 0.68) and lymphocytes count (OR 0.23) with benign outcome. ROC analysis indicated Hcy cut off of 16 μmol/L for predicting CoViD- 19 infection outcome (sensitivity 40% and specificity 84%);patients with Hcy levels >16 μmol/L had significantly increased risk of in-hospital mortality (p=0.002) both as a continuous and dichotomic value. Conclusions: Our results demonstrate that Hcy is an effective predictive biomarker for hospitalized CoViD-19 patients' outcome. Hcy may be a valuable biomarker to help clinicians to identify patients who are at higher risk for severe CoViD-19 infection.

Pneumomediastinum and pneumothorax in CoViD-19 patients: A case series

Background: Pneumomediastinum and pneumothorax are not rarely observed during the CoViD-19 pandemic especially among mechanically ventilated patients. We present a case series of six patients with pneumothorax and pneumomediastinum in CoViD- 19 pneumonia. Presentation of the case series: All patients were males with a mean age of 59.63 years. Two patients had spontaneous pneumomediastinum and pneumothorax.One of them denied tobacco or respiratory disease, while the other patient had an history of spontaneous pneumothorax.Four of the six patients received noninvasive ventilation and the average number of days between ventilation and subsequent barotrauma was 8,5 days. Positive end expiratory pressure (PEEP) was started at 10 cmH2 and then reduced to 8 cmH2.Three of patients had not significant comorbidities, while two of them had a medical history significant for hypertension, type 2 diabetes and ischemic heart disease. Five of six patients had a extensive bilateral interstitial pneumonia and no evidence of pulmonary embolism, three of them also had secondary bacterial pneumonia. Pneumomediastinum was treated conservatively in all patients. One patient with extensive pneumothorax required drainage. The probability of pneumomediastinum and pneumothorax increase with the combination of parenchymal injury from CoViD-19 infection and inflammatory response with additional positive pressure ventilation and likely super imposed bacterial infection. Conclusions: Pneumomediastinum and pneumothorax are important CPAP/NIV therapy complications in CoViD-19 and they should be considered if patients begin to deteriorate.

Olanzapine versus haloperidol in CoViD patients

Background and Aim: Haloperidol is the most widely used drug for the prevention and treatment of delirium in the Operating Units of Internal Medicine. New generation antipsychotics are a possible alternative often with fewer side effects. The objective of this study is the evaluation of a single-center observational retrospective study to compare the efficacy and tolerability of oral olanzapine versus haloperidol for the management of delirium in CoViD-19 patients. Materials and Methods: 97 patients were enrolled. The analysis of all data is retrospective as a single-center observational study approved by the ethics committee. Two groups were identified: the first of 49 patients treated with haloperidol, 48 patients treated with olanzapine. Results:We observed lower efficacy and safety of oral haloperidol than olanzapine in the management of delirium in elderly patients with CoViD-19-related pneumonia. In particular, we observed a reduction in the number of episodes of delirium, a reduction in hospitalization and greater compliance with ventilatory therapy with fewer adverse events in the group treated with olanzapine. Conclusions: Oral olanzapine therapy may be indicated as a better alternative for the management of delirium in the fragile high-risk geriatric patient.

The city turned off: Urban dynamics during the COVID-19 pandemic based on mobile phone data.

Due to the rapid expansion of the COVID-19 pandemic, many countries ordained lockdowns, establishing different restrictions on people's mobility. Exploring to what extent these measures have been effective is critical in order to better respond to similar future scenarios. This article uses anonymous mobile phone data to study the impact of the Spanish lockdown on the daily dynamics of the Madrid metropolitan area (Spain). The analysis has been carried out for a reference week prior to the lockdown and during several weeks of the lockdown in which different restrictions were in place. During these weeks, population distribution is compared during the day and at night and presence profiles are obtained throughout the day for each type of land use. In addition, a spatial multiple regression analysis is carried out to determine the impact of the different land uses on the local population. The results in the reference week, pre-COVID-19, show how the population in activity areas increases in each time slot on a specific day and how in residential areas it decreases. However, during the lockdown, activity areas cease to attract population during the day and the residential areas therefore no longer show a decrease. Only basic essential commercial activities, or others that require the presence of workers (industrial or logistics) maintain some activity during lockdown.

A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process.

SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral Mpro is responsible for the cleavage of the viral polyprotein in 11 sites, including its own N and C-terminus. The lack of structural information for intermediary forms of Mpro is a setback for the understanding its self-maturation process. Herein, we used X-ray crystallography combined with biochemical data to characterize multiple forms of SARS-CoV-2 Mpro. For the immature form, we show that extra N-terminal residues caused conformational changes in the positioning of domain-three over the active site, hampering the dimerization and diminishing its activity. We propose that this form preludes the cis and trans-cleavage of N-terminal residues. Using fragment screening, we probe new cavities in this form which can be used to guide therapeutic development. Furthermore, we characterized a serine site-directed mutant of the Mpro bound to its endogenous N and C-terminal residues during dimeric association stage of the maturation process. We suggest this form is a transitional state during the C-terminal trans-cleavage. This data sheds light in the structural modifications of the SARS-CoV-2 main protease during its self-maturation process.

Clinical application of lung ultrasound score on COVID-19 setting: a regional experience in Southern Italy.

OBJECTIVE: We aimed to assess the correlation between LUS Soldati proposed score and clinical presentation, course of disease and the possible need of ventilation support/intensive care. PATIENTS AND METHODS: All consecutive patients with laboratory confirmed SARS-CoV-2 infection and hospitalized in two COVID Centers were enrolled. All patients performed blood gas analysis and lung ultrasound (LUS) at admission. The LUS acquisition was based on standard sequence of 14 peculiar anatomic landmarks with a score between 0-3 based on impairment of LUS picture. Total score was computed with their sum with a total score ranging 0 to 42, according to Soldati LUS score. We evaluated the course of hospitalization until either discharge or death, the ventilatory support and the transition in intensive care if needed. RESULTS: One hundred and fifty-six patients were included in the final analysis. Most of patients presented moderate-to-severe respiratory failure (FiO2 <20%, PaO2 <60 mmHg) and consequent recommendation to invasive mechanic ventilation (CPAP/NIV/OTI). The median ultrasound thoracic score was 28 (IQR 18-36) and most of patients could be ascertained either in a score 2 (40%) or score 3 pictures (24.4%). The bivariate correlation analysis displayed statistically significant and high positive correlations between the LUS score and the following parameters: ventilation (rho=0.481, p<0.001), lactates (rho=0.464, p<0.001), dyspnea (rho=0.398, p=0.001) mortality (rho=0.410, p=0.001). Conversely, P/F (rho= -0.663, p<0.001), pH (rho = -0.363, p=0.003) and pO2 (rho = -0.400 p=0.001) displayed significant negative correlations. CONCLUSIONS: LUS score improve the workflow and provide an optimal management both in early diagnosis and prognosis of COVID-19 related lung pathology.

How to Reorganize the Radiology Departments to Face the 2019 Coronavirus Disease Outbreak

Radiology departments have been directly involved from the beginning of the novel coronavirus disease (COVID-19) emergency to provide imaging lung assessment of suspected and positive patients while ensuring the execution of other routine and emergency examinations for non-COVID-19 patients. To limit the risk of the infection spread, radiology departments should be reconfigured. We propose the example of the reorganization of the Radiology Department of our hospital, in the center of Milan, in Northern Italy, which consisted of the creation of 2 completely distinct pathways and distinct radiological machines for COVID-19 positive or suspected positive and for non-COVID-19 patients.

Prevalence of comorbidities in hospitalized populationwith COVID-19: Our experience

Background and Aim: Our objective was to evaluate the prevalenceof comorbidities in our hospitalized population with COVID-19.Materials and Methods: Forty-two patients (64.29% males,25.71% females;mean age of 70.75 ±13.73 yrs), admitted toour Hospital between March and June 2020, had been identifiedas having laboratory-confirmed 2019-SARS-CoV infection. Results: On admission 83.33% of patients presented with dyspnea, 80.95% with cough and 78.75% with fever. Diarrhea was uncommon (19.05%). Patients were classified according to their BMI(kg/m2) as lean (18.5-25) or affected by grade 1 obesity (25-29.9), grade II obesity (30-34.9) and grade III obesity (= 35). Obesity was present in 50% of cases;grade I 35.71%, gradeII and grade III 11.90% and 2.38%, respectively. Hypertension waspresent in 92.86% of patients, COPD in 54.76%, chronic kidneydisease in 45.24%, ischemic heart disease in 35.71%, diabetesin 33,33%, dementia in 30,95% and atrial fibrillation in 7.14%.On admission to the hospital lymphocytopenia was a frequent laboratory finding (97.62%). The coagulation profile revealed an elevation of fibrinogen (66.67%) and D-dimer (85.71%) levelsdespite a normal PT and APTT. The elevation of the pro BNP levelswas observed in 61.90% and troponin levels were at the sametime elevated in 13.16% of COVID-19 patients. Twelve patients(28.5%) died. Coronary artery disease was found in 70% of them. Conclusions: Comorbidities are common in patients with COVID-19. Although COVID 19 has been initially associated to a respiratory disease, it may involve the cardiovascular system with adramatic impact.