Subclinical Myocardial Injury in Patients Recovered from COVID-19 Pneumonia: Predictors and Longitudinal Assessment.

(1) Background: Emerging data regarding patients recovered from COVID-19 are reported in the literature, but cardiac sequelae have not yet been clarified. To quickly detect any cardiac involvement at follow-up, the aims of the research were to identify: elements at admission predisposing subclinical myocardial injury at follow up; the relationship between subclinical myocardial injury and multiparametric evaluation at follow-up; and subclinical myocardial injury longitudinal evolution. (2) Methods and Results: A total of 229 consecutive patients hospitalised for moderate to severe COVID-19 pneumonia were initially enrolled, of which 225 were available for follow-up. All patients underwent a first follow-up visit, which included a clinical evaluation, a laboratory test, echocardiography, a six-minute walking test (6MWT), and a pulmonary functional test. Of the 225 patients, 43 (19%) underwent a second follow-up visit. The median time to the first follow-up after discharge was 5 months, and the median time to the second follow-up after discharge was 12 months. Left ventricular global longitudinal strain (LVGLS) and right ventricular free wall strain (RVFWS) were reduced in 36% (n = 81) and 7.2% (n = 16) of the patients, respectively, at first the follow-up visit. LVGLS impairment showed correlations with patients of male gender (p 0.008, OR 2.32 (95% CI 1.24-4.42)), the presence of at least one cardiovascular risk factor (p < 0.001, OR 6.44 (95% CI 3.07-14.9)), and final oxygen saturation (p 0.002, OR 0.99 (95% CI 0.98-1)) for the 6MWTs. Subclinical myocardial dysfunction had not significantly improved at the 12-month follow-ups. (3) Conclusions: in patients recovered from COVID-19 pneumonia, left ventricular subclinical myocardial injury was related to cardiovascular risk factors and appeared stable during follow-up.

Understanding the Factors Affecting COVID-19 Mortality in Italy: Does a Relationship Exist With a Sharp Increase in Intensive Care Unit Admissions?

OBJECTIVE: The present study aims to explore whether a relationship exists between the immediate sharp increase in intensive care unit (ICU) admissions and the mortality rates in Italy. METHODS: Official epidemiological data on coronavirus disease (COVID-19) were employed. The forward lagged (0, 3, 7, 14 days) daily variations in the number of deaths according to the number of days after the outbreak started and the daily increases in ICU admissions were estimated. RESULTS: A direct relationship between the sharp increase of ICU admissions and mortality rates has been shown. Furthermore, the analysis of the forward lagged daily variations in the number of deaths showed that an increase in the daily number of ICU admissions resulted in significantly higher mortality after 3, 7, and 14 days. The most pronounced effect was detected after 7 days, with 250 deaths (95% CI: 108.1-392.8) for the highest increase in the ICU admissions, from 100 to 200. CONCLUSIONS: These results would serve as a warning for the scientific community and the health care decision-makers to prevent a quick and out-of-control saturation of the ICU beds in case of a relapse of the COVID-19 outbreak.

Ethics committees in the time of COVID-19.

BACKGROUND: ethics committees (ECs) protect the rights, safety, and well-being of research participants and ensure the scientific correctness of clinical research. COVID-19 pandemic and the lockdown from 9 March to 16 May 2020 have potentially influenced several activities, including ECs. OBJECTIVES: to assess the impact of COVID-19 outbreak on Italian ECs and their performance during the lockdown. DESIGN: cross-sectional survey. SETTING AND PARTICIPANTS: the survey was conducted in mid-June 2020 in Italy contacting all the 90 local ECs. MAIN OUTCOME MEASURES: amount and kind of activities performed during the lockdown, characteristics of submitted studies and adoption of standard protocols of evaluation of research applications during the pandemic. Chi-square test was used to estimate the differences between territories with higher incidence (HI) and lower incidence (LI) of COVID-19. RESULTS: 258 questionnaires were collected from 46 ECs that participated in the study. Ten were excluded due to missing substantial data. Responses were divided into two groups according to location of EC: the HI (125 responses) and the LI (123 responses). Seventy-five percent of the HI describe an increase in the number of studies submitted, while 53% of the LI does not (p=0.001). Due to the pandemic and its effects on research, the 15% of participants belonging to HI territories reported that consideration and respect of research-related and general ethical principles could have decreased, as well the adoption of standard protocols of evaluation of research applications. EC secretariats located in HI Regions moved to smart working more than in LI ones (75% vs 59%; p=0.001). Where the EC workload increased significantly, it was reported that it was impossible to perform an accurate analysis of the submitted documentation, with the effect of providing a favorable opinion to studies of not excellent quality, though always ensuring the respect of ethical principles and patients' safety. CONCLUSIONS: COVID-19 impact on ECs has been heavier in HI territories, but smart working has been effective in ensuring EC activities and the subsequent activation of clinical studies potentially useful to face the pandemic. Clear differences arise between ECs belonging to the Italian Regions that have recorded a HI of COVID-19 cases compared to those located in Regions with a LI of cases. In some EC members' perception, the high number of studies in the most affected Regions together with the emergency experienced during the lockdown may have exposed ECs to the risk of decreasing the adoption of ethical principles and standard protocols of evaluation of research applications.

The PROVENT-C19 registry: A study protocol for international multicenter SIAARTI registry on the use of prone positioning in mechanically ventilated patients with COVID-19 ARDS.

BACKGROUND: The worldwide use of prone position (PP) for invasively ventilated patients with COVID-19 is progressively increasing from the first pandemic wave in everyday clinical practice. Among the suggested treatments for the management of ARDS patients, PP was recommended in the Surviving Sepsis Campaign COVID-19 guidelines as an adjuvant therapy for improving ventilation. In patients with severe classical ARDS, some authors reported that early application of prolonged PP sessions significantly decreases 28-day and 90-day mortality. METHODS AND ANALYSIS: Since January 2021, the COVID19 Veneto ICU Network research group has developed and implemented nationally and internationally the "PROVENT-C19 Registry", endorsed by the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care…'(SIAARTI). The PROVENT-C19 Registry wishes to describe 1. The real clinical practice on the use of PP in COVID-19 patients during the pandemic at a National and International level; and 2. Potential baseline and clinical characteristics that identify subpopulations of invasively ventilated patients with COVID-19 that may improve daily from PP therapy. This web-based registry will provide relevant information on how the database research tools may improve our daily clinical practice. CONCLUSIONS: This multicenter, prospective registry is the first to identify and characterize the role of PP on clinical outcome in COVID-19 patients. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of a clinical intervention. Indeed observation-based registries could be effective tools aimed at identifying specific clusters of patients within a large study population with widely heterogeneous clinical characteristics. TRIAL REGISTRATION: The registry was registered (ClinicalTrial.Gov Trials Register NCT04905875) on May 28,2021.

Outcomes of COVID-19 Patients with Severe Hypoxemic Acute Respiratory Failure: Non-Invasive Ventilation vs. Straight Intubation-A Propensity Score-Matched Multicenter Cohort Study.

The best timing for endotracheal intubation in patients with coronavirus disease 2019 (COVID-19) hypoxemic acute respiratory failure (hARF) remains debated. Aim of this study is to compare the outcomes of COVID-19 patients with hARF receiving either a trial of non-invasive ventilation (NIV) or intubated with no prior attempt of NIV ("straight intubation"). All consecutive patients admitted to the 25 participating ICUs were included and divided in two groups: the "straight intubation" group and the "NIV" group. A propensity score matching was performed to correct for biases associated with the choice of the respiratory support. Primary outcome was in-hospital mortality. Secondary outcomes were length of mechanical ventilation, hospital stay and reintubation rate. A total of 704 COVID-19 patients were admitted to ICUs during the study period. After matching, 141 patients were included in each group. No clinically relevant difference at ICU admission was found between groups. In-hospital mortality was significantly lower in the NIV group (22.0% vs. 36.2%), with no significant difference in secondary endpoints. There was no significant mortality difference between patients who received straight intubation and those intubated after NIV failure. In COVID-19 patients with hARF it is worth and safe attempting a trial of NIV prior to intubation.

Impact of the COVID-19 lockdown on psychological health and nutritional habits in Italy: results from the #PRESTOinsieme study.

OBJECTIVES: The present work aims to present the results of the 'PRESTOinsieme' (which is 'we will be together soon' in English). The web-based survey (www.prestoinsieme.com) describes changes in lifestyle habits and symptoms of psychological discomfort in the Italian population during the COVID-19 lockdown. DESIGN: Cross-sectional online survey disseminated by messaging apps (ie, WhatsApp and Telegram) and social networks (ie, Instagram, Facebook and LinkedIn). SETTING: Italy. PARTICIPANTS: Italian population older than 16 years of age. EXPOSURE: COVID-19 lockdown. MAIN OUTCOMES AND MEASURES: Survey respondents filled out a set of validated questionnaires aimed at assessing lifestyle habits and psychological health, that is, the General Health Questionnaire (GHQ-12) to screen for psychological distress, the Impact of Event Scale-Revised (IES-R) to screen for post-traumatic stress and the Center for Epidemiologic Studies Depression Scale (CES-D). RESULTS: Survey respondents totalled 5008. Moderate or severe psychological distress was reported in 25.5% and 22% of survey respondents, respectively. Lower age, female gender, being unemployed (OR 1.57, 95% CI 1.22 to 2.02) or being a student (OR 1.73, 95% CI 1.31 to 2.28) were predictors of more severe depressive symptoms. CONCLUSIONS: The present study is one of the largest population-based surveys conducted in Italy during the first COVID-19 lockdown, providing valuable data about the Italian population's psychological health. Further studies should be conducted to understand whether psychological distress persists after the end of the lockdown.

Impact of the "atherosclerotic pabulum" on in-hospital mortality for SARS-CoV-2 infection. Is calcium score able to identify at-risk patients?

BACKGROUND: Although the primary cause of death in COVID-19 infection is respiratory failure, there is evidence that cardiac manifestations may contribute to overall mortality and can even be the primary cause of death. More importantly, it is recognized that COVID-19 is associated with a high incidence of thrombotic complications. HYPOTHESIS: Evaluate if the coronary artery calcium (CAC) score was useful to predict in-hospital (in-H) mortality in patients with COVID-19. Secondary end-points were needed for mechanical ventilation and intensive care unit admission. METHODS: Two-hundred eighty-four patients (63, 25 years, 67% male) with proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who had a noncontrast chest computed tomography were analyzed for CAC score. Clinical and radiological data were retrieved. RESULTS: Patients with CAC had a higher inflammatory burden at admission (d-dimer, p = .002; C-reactive protein, p = .002; procalcitonin, p = .016) and a higher high-sensitive cardiac troponin I (HScTnI, p = <.001) at admission and at peak. While there was no association with presence of lung consolidation and ground-glass opacities, patients with CAC had higher incidence of bilateral infiltration (p = .043) and higher in-H mortality (p = .048). On the other side, peak HScTnI >200 ng/dl was a better determinant of all outcomes in both univariate (p = <.001) and multivariate analysis (p = <.001). CONCLUSION: The main finding of our research is that CAC was positively related to in-H mortality, but it did not completely identify all the population at risk of events in the setting of COVID-19 patients. This raises the possibility that other factors, including the presence of soft, unstable plaques, may have a role in adverse outcomes in SARS-CoV-2 infection.

A Web-Based Application to Monitor and Inform about the COVID-19 Outbreak in Italy: The {COVID-19ita} Initiative.

The pandemic outbreak of COVID-19 has posed several questions about public health emergency risk communication. Due to the effort required for the population to adopt appropriate behaviors in response to the emergency, it is essential to inform the public of the epidemic situation with transparent data sources. The COVID-19ita project aimed to develop a public open-source tool to provide timely, updated information on the pandemic's evolution in Italy. It is a web-based application, the front end for the eponymously named R package freely available on GitHub, deployed both in English and Italian. The web application pulls the data from the official repository of the Italian COVID-19 outbreak at the national, regional, and provincial levels. The app allows the user to select information to visualize data in an interactive environment and compare epidemic situations over time and across different Italian regions. At the same time, it provides insights about the outbreak that are explained and commented upon to yield reasoned, focused, timely, and updated information about the outbreak evolution.

Thrombotic Events after COVID-19 Vaccination in the Over-50s: Results from a Population-Based Study in Italy.

Several European countries suspended or changed recommendations for the use of Vaxzevria (AstraZeneca) for suspected adverse effects due to atypical blood-clotting. This research aims to identify a reference point towards the number of thrombotic events expected in the Italian population over 50 years of age who received Vaxzevria from 22 January to 12 April 2021. The venous thromboembolism (VT) and immune thrombocytopenia (ITP) event rates were estimated from a population-based cohort. The overall VT rate was 1.15 (95% CI 0.93-1.42) per 1000 person-years, and the ITP rate was 2.7 (95% CI 0.7-11) per 100,000 person-years. These figures translate into 83 and two expected events of VT and ITP, respectively, in the 15 days following the first administration of Vaxzevria. The number of thrombotic events reported from the Italian Medicines Agency does not appear to have increased beyond that expected in individuals over 50 years of age.

Management of Liver Tumors during the COVID-19 Pandemic: The Added Value of Selective Internal Radiation Therapy (SIRT).

BACKGROUND: In the context of the coronavirus disease 2019 (COVID-19) pandemic, liver-directed therapies (LDTs) may offer minimally invasive integrative tools for tumor control. Among them, selective internal radiation therapy (SIRT) represents a safe, flexible and effective treatment. Purpose of this study is to present our experience with SIRT during the first wave of COVID-19 pandemic and provide an overview of the indications and challenges of SIRT in this scenario. METHODS: We retrospectively analyzed the number of patients evaluated by Multidisciplinary Liver Tumor Board (MLTB) and who were undergoing LDTs between March and July 2020 and compared it with 2019. For patients treated with SIRT, clinical data, treatment details and the best radiological response were collected. RESULTS: Compared to 2019, we observed a 27.5% reduction in the number of patients referred to MLTB and a 28.3% decrease in percutaneous ablations; transarterial chemoembolizations were stable, while SIRT increased by 64%. The majority of SIRT patients (75%) had primary tumors, mostly HCC. The best objective response and disease control rates were 56.7% and 72.2%, respectively. CONCLUSION: The first wave of the COVID-19 pandemic was characterized by an increased demand for SIRT, which represents a safe, flexible and effective treatment, whose manageability will further improve by simplifying the treatment workflow, developing user-friendly and reliable tools for personalized dosimetry and improving interdisciplinary communication.

COVID-19 ICU mortality prediction: a machine learning approach using SuperLearner algorithm.

BACKGROUND: Since the beginning of coronavirus disease 2019 (COVID-19), the development of predictive models has sparked relevant interest due to the initial lack of knowledge about diagnosis, treatment, and prognosis. The present study aimed at developing a model, through a machine learning approach, to predict intensive care unit (ICU) mortality in COVID-19 patients based on predefined clinical parameters. RESULTS: Observational multicenter cohort study. All COVID-19 adult patients admitted to 25 ICUs belonging to the VENETO ICU network (February 28th 2020-april 4th 2021) were enrolled. Patients admitted to the ICUs before 4th March 2021 were used for model training ("training set"), while patients admitted after the 5th of March 2021 were used for external validation ("test set 1"). A further group of patients ("test set 2"), admitted to the ICU of IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan, was used for external validation. A SuperLearner machine learning algorithm was applied for model development, and both internal and external validation was performed. Clinical variables available for the model were (i) age, gender, sequential organ failure assessment score, Charlson Comorbidity Index score (not adjusted for age), Palliative Performance Score; (ii) need of invasive mechanical ventilation, non-invasive mechanical ventilation, O2 therapy, vasoactive agents, extracorporeal membrane oxygenation, continuous venous-venous hemofiltration, tracheostomy, re-intubation, prone position during ICU stay; and (iii) re-admission in ICU. One thousand two hundred ninety-three (80%) patients were included in the "training set", while 124 (8%) and 199 (12%) patients were included in the "test set 1" and "test set 2," respectively. Three different predictive models were developed. Each model included different sets of clinical variables. The three models showed similar predictive performances, with a training balanced accuracy that ranged between 0.72 and 0.90, while the cross-validation performance ranged from 0.75 to 0.85. Age was the leading predictor for all the considered models. CONCLUSIONS: Our study provides a useful and reliable tool, through a machine learning approach, for predicting ICU mortality in COVID-19 patients. In all the estimated models, age was the variable showing the most important impact on mortality.

Static compliance and driving pressure are associated with ICU mortality in intubated COVID-19 ARDS.

BACKGROUND: Pathophysiological features of coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) were indicated to be somewhat different from those described in nonCOVID-19 ARDS, because of relatively preserved compliance of the respiratory system despite marked hypoxemia. We aim ascertaining whether respiratory system static compliance (Crs), driving pressure (DP), and tidal volume normalized for ideal body weight (VT/kg IBW) at the 1st day of controlled mechanical ventilation are associated with intensive care unit (ICU) mortality in COVID-19 ARDS. METHODS: Observational multicenter cohort study. All consecutive COVID-19 adult patients admitted to 25 ICUs belonging to the COVID-19 VENETO ICU network (February 28th-April 28th, 2020), who received controlled mechanical ventilation, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1st day of controlled mechanical ventilation were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients. RESULTS: A total of 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: (1) Crs was not linearly associated with ICU mortality (p value for nonlinearity = 0.01), with a greater risk of death for values < 48 ml/cmH2O; (2) the association between DP and ICU mortality was linear (p value for nonlinearity = 0.68), and increasing DP from 10 to 14 cmH2O caused significant higher odds of in-ICU death (OR 1.45, 95% CI 1.06-1.99); (3) VT/kg IBW was not associated with a significant increase of the risk of death (OR 0.92, 95% CI 0.55-1.52). Multivariable analysis confirmed these findings. CONCLUSIONS: Crs < 48 ml/cmH2O was associated with ICU mortality, while DP was linearly associated with mortality. DP should be kept as low as possible, even in the case of relatively preserved Crs, irrespective of VT/kg IBW, to reduce the risk of death.

Monitoring Patients Reported Outcomes after Valve Replacement Using Wearable Devices: Insights on Feasibility and Capability Study: Feasibility Results.

Wearable devices (WDs) can objectively assess patient-reported outcomes (PROMs) in clinical trials. In this study, the feasibility and acceptability of using commercial WDs in elderly patients undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) will be explored. This is a prospective observational study. Participants were trained to use a WD and a smartphone to collect data on their physical activity, rest heart rate and number of hours of sleep. Validated questionnaires were also used to evaluate these outcomes. A technology acceptance questionnaire was used at the end of the follow up. In our participants an overall good compliance in wearing the device (75.1% vs. 79.8%, SAVR vs. TAVR) was assessed. Half of the patients were willing to continue using the device. Perceived ease of use is one of the domains that scored higher in the technology acceptance questionnaire. In this study we observed that the use of a WD is accepted in our frail population for an extended period. Even though commercial WDs are not tailored for clinical research, they can produce useful information on patient behavior, especially when coordinated with intervention tailored to the single patient.

Psychological Effects of Lockdown Measures for the COVID-19 Outbreak in Patients with Systemic Lupus Erythematosus.

OBJECTIVE: To compare the psychological impact of the lockdown measures contrasting the COVID-19 outbreak between systemic lupus erythematosus (SLE) and general population. PATIENTS AND METHODS: From July 15th to August 15th 2020, a retrospective survey referring to the period March 9th to May 18th 2020 was administered to SLE patients and the results of the survey, called LEPRE (Lupus Erythematosus PREsto) study, were compared with those from the PRESTO (imPact of quaRantine mEasures againST cOvid19) project, the same survey provided to the general population. Consecutive patients >18 years old affected by SLE and regularly followed in a single rheumatologic centre were involved. Primary outcome was to compare the scores of the Impact of Events Scale-Revised (IES-R), the General Health Questionnaire 12 (GHQ-12) and the Center for Epidemiological Depression Scale (CES-D) between patients and general population. RESULTS: A total of 64 patients completed the survey. After a propensity score matching, they were compared to 128 people from PRESTO project. The median age among patients was 43 years (I-III interquartile range 35-54.5), 88% were female and 100% Caucasian. IES-R [(score>23: 57% (34) vs 49% (58)], GHQ-12 [(score>13: 85% (52) vs 88% (106)], and CES-D [(score>15: 45% (28) vs 40% (46)] scores were not statistically different between patients and controls (p>0.05). CONCLUSION: Restrictive measures for COVID-19 pandemic had no greater impact on patients with SLE than in the general population. Strategy for coping to the SLE might be useful during lockdown measures and may be helpful for other chronic conditions.

Using Social Networks to Estimate the Number of COVID-19 Cases: The Incident (Hidden COVID-19 Cases Network Estimation) Study Protocol.

Recent literature has reported a high percentage of asymptomatic or paucisymptomatic cases in subjects with COVID-19 infection. This proportion can be difficult to quantify; therefore, it constitutes a hidden population. This study aims to develop a proof-of-concept method for estimating the number of undocumented infections of COVID-19. This is the protocol for the INCIDENT (Hidden COVID-19 Cases Network Estimation) study, an online, cross-sectional survey with snowball sampling based on the network scale-up method (NSUM). The original personal network size estimation method was based on a fixed-effects maximum likelihood estimator. We propose an extension of previous Bayesian estimation methods to estimate the unknown network size using the Markov chain Monte Carlo algorithm. On 6 May 2020, 1963 questionnaires were collected, 1703 were completed except for the random questions, and 1652 were completed in all three sections. The algorithm was initialized at the first iteration and applied to the whole dataset. Knowing the number of asymptomatic COVID-19 cases is extremely important for reducing the spread of the virus. Our approach reduces the number of questions posed. This allows us to speed up the completion of the questionnaire with a subsequent reduction in the nonresponse rate.