Assessing the heterogeneity of the impact of COVID-19 incidence on all-cause excess mortality among healthcare districts in Lombardy, Italy, to evaluate the local response to the pandemic: an ecological study.

OBJECTIVES: The fragmentation of the response to the COVID-19 pandemic at national, regional and local levels is a possible source of variability in the impact of the pandemic on society. This study aims to assess how much of this variability affected the burden of COVID-19, measured in terms of all-cause 2020 excess mortality. DESIGN: Ecological retrospective study. SETTING: Lombardy region of Italy, 2015-2020. OUTCOME MEASURES: We evaluated the relationship between the intensity of the epidemics and excess mortality, assessing the heterogeneity of this relationship across the 91 districts after adjusting for relevant confounders. RESULTS: The epidemic intensity was quantified as the COVID-19 hospitalisations per 1000 inhabitants. Five confounders were identified through a directed acyclic graph: age distribution, population density, pro-capita gross domestic product, restriction policy and population mobility.Analyses were based on a negative binomial regression model with district-specific random effects. We found a strong, positive association between COVID-19 hospitalisations and 2020 excess mortality (p<0.001), estimating that an increase of one hospitalised COVID-19 patient per 1000 inhabitants resulted in a 15.5% increase in excess mortality. After adjusting for confounders, no district differed in terms of COVID-19-unrelated excess mortality from the average district. Minimal heterogeneity emerged in the district-specific relationships between COVID-19 hospitalisations and excess mortality (6 confidence intervals out of 91 did not cover the null value). CONCLUSIONS: The homogeneous effect of the COVID-19 spread on the excess mortality in the Lombardy districts suggests that, despite the unprecedented conditions, the pandemic reactions did not result in health disparities in the region.

Strategies to convert hospital beds for COVID-19 patients to minimize emergency department overcrowding.

Background: The shortage of hospital beds for COVID-19 patients has been one critical cause of Emergency Department (ED) overcrowding. Purpose: We aimed at elaborating a strategy of conversion of hospital beds, from non-COVID-19 to COVID-19 care, minimizing both ED overcrowding and the number of beds eventually converted. Research Design: Observational retrospective study. Study Sample: We considered the centralized database of all ED admissions in the Lombardy region of Italy during the second "COVID-19 wave" (October to December 2020). Data collection and Analysis: We analyzed all admissions to 82 EDs. We devised a family of Monte Carlo simulations to evaluate the performance of hospital beds' conversion strategies triggered by ED crowding of COVID-19 patients, determining a critical number of beds to be converted when passing an ED-specific crowding threshold. Results: Our results suggest that the maximum number of patients waiting for hospitalization could have been decreased by 70% with the proposed strategy. Such a reduction would have been achieved by converting 30% more hospital beds than the total number converted in the region. Conclusions: The disproportion between reduction in ED crowding and additionally converted beds suggests that a wide margin to improve the efficiency of the conversions exists. The proposed simulation apparatus can be easily generalized to study management policies synchronizing ED output and in-hospital bed availability.

Prognostic value of respiratory parameters for COVID-19 patients in the emergency department: results from the EC-COVID study.

While several studies have evaluated the prognostic weight of respiratory parameters in patients with COVID-19, few have focused on patients' clinical conditions at the first emergency department (ED) assessment. We analyzed a large cohort of ED patients recruited within the EC-COVID study over the year 2020, and assessed the association between key bedside respiratory parameters measured in room air (pO2, pCO2, pH, and respiratory rate [RR]) and hospital mortality, after adjusting for key confounding factors. Analyses were based on a multivariable logistic Generalized Additive Model (GAM). After excluding patients who did not perform a blood gas analysis (BGA) test in room air or with incomplete BGA results, a total of 2458 patients were considered in the analyses. Most patients were hospitalized on ED discharge (72.0%); hospital mortality was 14.3%. Strong, negative associations with hospital mortality emerged for pO2, pCO2 and pH (p-values: < 0.001, < 0.001 and 0.014), while a significant, positive association was observed for RR (p-value < 0.001). Associations were quantified with nonlinear functions, learned from the data. No cross-parameter interaction was significant (all p-values were larger than 0.10), suggesting a progressive, independent effect on the outcome as the value of each parameter departed from normality. Our results collide with the hypothesized existence of patterns of breathing parameters with specific prognostic weight in the early stages of the disease.

One-year mortality in COVID-19 is associated with patients' comorbidities rather than pneumonia severity.

BACKGROUND: In patients with pneumonia or acute respiratory distress syndrome who survived hospitalization, one-year mortality can affect up to one third of discharged patients. Therefore, significant long-term mortality after COVID-19 respiratory failure could be expected. The primary outcome of the present study was one-year all-cause mortality in hospitalized COVID-19 patients. METHODS: Observational study of COVID-19 patients hospitalized at Papa Giovanni XXIII Hospital (Bergamo, Italy), during the first pandemic wave. RESULTS: A total of 1326 COVID-19 patients were hospitalized. Overall one-year mortality was 33.6% (N 446/1326), with the majority of deaths occurring during hospitalization (N=412, 92.4%). Thirty-four patients amongst the 914 discharged (3.7%) subsequentely died within one year. A third of these patients died for advanced cancer, while death without a cause other than COVID-19 was uncommon (8.8% of the overall post-discharge mortality). In-hospital late mortality (i.e. after 28 days of admission) interested a population with a lower age, and fewer comorbidities, more frequentely admitted in ICU. Independent predictors of post-discharge mortality were age over 65 years (HR 3.19; 95% CI 1.28-7.96, p-value=0.013), presence of chronic obstructive pulmonary disease (COPD) (HR 2.52; 95% CI 1.09-5.83, p-value=0.031) or proxy of cardiovascular disease (HR 4.93; 95% CI 1.45-16.75, p-value=0.010), and presence of active cancer (HR 3.64; 95% CI 1.50-8.84, p-value=0.004), but not pneumonia severity. CONCLUSIONS: One-year post-discharge mortality depends on underlying patients' comorbidities rather than COVID-19 pneumonia severity per se. Awareness among physicians of predictors of post-discharge mortality might be helpful in structuring a follow-up program for discharged patients.

Acute myocarditis as first presentation of severe ulcerative colitis in a young man. Multidisciplinary management and long-term follow-up.

Myocarditis is a rare extra-intestinal complication of inflammatory bowel disease (IBD), in particular, ulcerative colitis.We report a case of acute myocarditis as first manifestation of severe ulcerative colitis. A 22-year-old man was admitted with fever, bloody diarrhea, and fatigue. He had suffered from frequent bloody diarrhea, abdominal pain, fatigue, and weight loss for one month. A 12-lead-electrocardiogram showed sinus rhythm with QRS fragmentation and T waves inversion. High sensitivity troponin-I was elevated and the echocardiogram showed a mild pericardial effusion and inferior hypokinesia with normal ejection fraction. Cardiac magnetic resonance disclosed late enhancement in the inferior wall, corroborating the hypothesis of myocarditis. One week later, a colonoscopy revealed severe ulcerative extensive colitis (Mayo subscore 3). 5-aminosalicylic acid (mesalazine) and systemic steroid were started with good clinical and biochemical response. The following days the patient developed mesalazine hepatic and pancreatic induced toxicity requiring drug discontinuation and strict multi-disciplinary follow-up. At 7 months follow-up intestinal symptoms were well controlled with complete normalization of liver and pancreatic enzymes. Transthoracic echocardiography showed normal biventricular function and pericardial effusion resolution.This case underscores the importance of a high suspicion for extra intestinal involvement in patients with IBD. These complications may be multifactorial and need multidisciplinary management. Learning objective: •When a patient was first-time diagnosed with a severe form of inflammatory bowel disease or has a disease relapse, bear in mind myocarditis as possible extra intestinal manifestation.•Multidisciplinary management is crucial to ensure the best level of care and follow-up in a such challenging and insidious clinical picture.

Characterization of compliance phenotypes in COVID-19 acute respiratory distress syndrome.

BACKGROUND: Coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) seems to differ from the "classic ARDS", showing initial significant hypoxemia in the face of relatively preserved compliance and evolving later in a scenario of poorly compliant lungs. We tested the hypothesis that in patients with COVID-19 ARDS, the initial value of static compliance of respiratory system (Crs) (1) depends on the previous duration of the disease (i.e., the fewer days of illness, the higher the Crs and vice versa) and (2) identifies different lung patterns of time evolution and response to prone positioning. METHODS: This was a single-center prospective observational study. We enrolled consecutive mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria, admitted to intensive care unit (ICU). Patients were divided in four groups based on quartiles of initial Crs. Relationship between Crs and the previous duration of the disease was evaluated. Respiratory parameters collected once a day and during prone positioning were compared between groups. RESULTS: We evaluated 110 mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria admitted to our ICUs. Patients were divided in groups based on quartiles of initial Crs. The median initial Crs was 41 (32-47) ml/cmH2O. No association was found between the previous duration of the disease and the initial Crs. The Crs did not change significantly over time within each quartile. Positive end-expiratory pressure (PEEP) and driving pressure were respectively lower and greater in patients with lower Crs. Prone positioning significantly improved PaO2/FiO2 in the 4 groups, however it increased the Crs significantly only in patients in lower quartile of Crs. CONCLUSIONS: In our cohort, the initial Crs is not dependent on the previous duration of COVID-19 disease. Prone positioning improves oxygenation irrespective to initial Crs, but it ameliorates respiratory mechanics only in patients with lower Crs.

SIMEU position paper on non-invasive respiratory support in COVID-19 pneumonia.

The rapid worldwide spread of the Coronavirus disease (COVID-19) crisis has put health systems under pressure to a level never experienced before, putting intensive care units in a position to fail to meet an exponentially growing demand. The main clinical feature of the disease is a progressive arterial hypoxemia which rapidly leads to ARDS which makes the use of intensive care and mechanical ventilation almost inevitable. The difficulty of health systems to guarantee a corresponding supply of resources in intensive care, together with the uncertain results reported in the literature with respect to patients who undergo early conventional ventilation, make the search for alternative methods of oxygenation and ventilation and potentially preventive of the need for tracheal intubation, such as non-invasive respiratory support techniques particularly valuable. In this context, the Emergency Department, located between the area outside the hospital and hospital ward and ICU, assumes the role of a crucial junction, due to the possibility of applying these techniques at a sufficiently early stage and being able to rapidly evaluate their effectiveness. This position paper describes the indications for the use of non-invasive respiratory support techniques in respiratory failure secondary to COVID-19-related pneumonia, formulated by the Non-invasive Ventilation Faculty of the Italian Society of Emergency Medicine (SIMEU) on the base of what is available in the literature and on the authors' direct experience. Rationale, literature, tips & tricks, resources, risks and expected results, and patient interaction will be discussed for each one of the escalating non-invasive respiratory techniques: standard oxygen, HFNCO, CPAP, NIPPV, and awake self-repositioning. The final chapter describes our suggested approach to the failing patient.

Early Diagnosis of Acute Myocarditis in the ED: Proposal of a New ECG-Based Protocol.

The diagnosis of acute myocarditis (AM) is based on a multi-parametric assessment including clinical presentation, ECG, imaging and biomarkers. Fragmented QRS (fQRS) might be an additional diagnostic sign in patients with proven AM. The main objective of this study was to assess the diagnostic yield of fQRS in patients with suspected AM presenting to the emergency department (ED). Patients admitted between January 2016 and March 2021 with a proven diagnosis of AM, according to clinical, cardiac magnetic resonance (CMR) and/or histologic criteria, were included in the analysis. In total, 51 patients were analyzed (41 men, 78%), with a median age of 36 (29-45) years. Thirty-three (65%) patients had prodromal flu-like symptoms. Patients presented to the ED mostly complaining of chest pain (68%) and palpitations (21%). Seven (14%) patients experienced cardiac arrest, one of whom died. At presentation, 40 patients (78%) displayed fQRS, and 10 (20%) presented ventricular arrhythmias. All the surviving patients underwent CMR and displayed late gadolinium enhancement (LGE). ECG leads showed that fQRS matched the LGE distribution in 38 patients (95%). The presence of fQRS is a simple clinical bedside tool to support the initial suspect of AM in the emergency department and to guide the most appropriate clinical workup.

Frequency, characteristics, and outcome of patients with COVID-19 pneumonia and "silent hypoxemia" at admission: a severity-matched analysis.

BACKGROUND: An aspect of COVID-19 baffling physicians is the presentation of patients with acute respiratory failure, but normal mental faculties and no perception of dyspnea (i.e. "silent hypoxemia"). The aim of this study was to investigate the frequency, characteristics, and outcome of COVID-19 patients with silent hypoxemic status and comparing them with a symptomatic severity-matched group. METHODS: This is a retrospective monocentric observational study involving all patients with PCR confirmed SARS-CoV-2 pneumonia, admitted at Papa Giovanni XXIII Hospital, Bergamo (Italy) from Emergency Department due to acute respiratory failure, during the first Italian pandemic peak (February-April 2020). RESULTS: Overall 28-day mortality in 1316 patients was 26.9%. Patients who did not report dyspnea at admission (N 469, 35.6%) had a lower 28-day mortality (22.6 vs. 29.3%, P=0.009). The severity matching analysis (i.e. PaO2/FiO2 and imaging) led to the identification of two groups of 254 patients that did not differ for sex prevalence, age, BMI, smoking history, comorbidities, and PaCO2 at admission. The use of CPAP during the first 24 hours, such as the need of endotracheal intubation (ETI) during the overall admission were significantly lower in matched patients with silent hypoxemia, whereas 28-day mortality resulted similar (P=0.21). CONCLUSIONS: Lack of dyspnea is common in patients suffering from severe COVID-19 pneumonia leading to respiratory failure, since up to a third of them could be asymptomatic on admission. Dyspnea per se correlates with pneumonia severity, and prognosis. However, dyspnea loses its predictive relevance once other findings to evaluate pneumonia severity are available such as PaO2/FiO2 and imaging. Silent hypoxemic patients are less likely to receive CPAP during the first 24 hours and ETI during the hospitalization, in spite of a comparable mortality to the dyspneic ones.

Usefulness of CURB-65, pneumonia severity index and MuLBSTA in predicting COVID-19 mortality.

The aim of our study is to evaluate the accuracy of CURB-65 and Pneumonia Severity Index (PSI), the most widely used scores for community acquired pneumonia, and MuLBSTA, a viral pneumonia score, in predicting 28-day mortality in Coronavirus Disease 2019 (COVID-19) pneumonia.We retrospectively collected clinical data of consecutive patients with laboratory-confirmed COVID-19 pneumonia admitted at Papa Giovanni XXIII Hospital from February 23rd to March 14th, 2020. We calculated at Emergency Department (ED) presentation CURB-65, PSI and MuLBSTA and we compared their performances in discriminating between survivors and non-survivors at 28 days. Among 431 hospitalized patients, the majority presented with hypoxic respiratory failure: median (interquartile range, IQR) PaO2/FiO2 ratio at admission was 228.6 (142.0-278.1). In the first 24 hours, 111 (27%) patients were administered low-flow oxygen cannula, 50 (12%) Venturi Mask, 95 (23%) non-rebreather mask, 106 (26%) non-invasive ventilation, 12 (3%) mechanical ventilation and 41 (9%) were not administered oxygen therapy. Mortality rate at 28-day was 35% (150/431). Between survivors and non-survivors, median (IQR) scores were, respectively, 1.0 (1.0-2.0) and 2.0 (2.0-3.0) for CURB-65 (p<0.001); 90.5 (76.0-105.5) and 115.0 (100.0-129.0) for PSI (p<0.001); 7.0 (5.0-10.0) and 11.0 (9.0-13.0) for MuLBSTA (p<0.001). Areas under the receiver operating characteristic curve (AUCs) for each score were, respectively, 0.725 (0.662-0.787), 0.776 (0.693-0.859) and 0.743 (0.680-0.806) (p>0,05). PSI and MuLBSTA did not show a better performance when compared to CURB-65. Although CURB-65, PSI and MuLBSTA scores are useful tools to discriminate between survivors and non-survivors in COVID-19 pneumonia, their diagnostic accuracy in discriminating 28-day mortality in COVID-19 pneumonia is moderate, as confirmed by AUCs <0.80, and there is a potential underestimation of disease severity in the low-risk classes. For this reason, they should not be recommended in ED to decide between inpatient and outpatient management in patients affected by COVID-19 pneumonia.

Noninvasive respiratory support outside the intensive care unit for acute respiratory failure related to coronavirus-19 disease: a systematic review and meta-analysis.

BACKGROUND: Noninvasive respiratory support (NIRS) has been diffusely employed outside the intensive care unit (ICU) to face the high request of ventilatory support due to the massive influx of patients with acute respiratory failure (ARF) caused by coronavirus-19 disease (COVID-19). We sought to summarize the evidence on clinically relevant outcomes in COVID-19 patients supported by NIV outside the ICU. METHODS: We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials register, along with medRxiv and bioRxiv repositories for pre-prints, for observational studies and randomized controlled trials, from inception to the end of February 2021. Two authors independently selected the investigations according to the following criteria: (1) observational study or randomized clinical trials enrolling ≥ 50 hospitalized patients undergoing NIRS outside the ICU, (2) laboratory-confirmed COVID-19, and (3) at least the intra-hospital mortality reported. Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed. Data extraction was independently performed by two authors to assess: investigation features, demographics and clinical characteristics, treatments employed, NIRS regulations, and clinical outcomes. Methodological index for nonrandomized studies tool was applied to determine the quality of the enrolled studies. The primary outcome was to assess the overall intra-hospital mortality of patients under NIRS outside the ICU. The secondary outcomes included the proportions intra-hospital mortalities of patients who underwent invasive mechanical ventilation following NIRS failure and of those with 'do-not-intubate' (DNI) orders. RESULTS: Seventeen investigations (14 peer-reviewed and 3 pre-prints) were included with a low risk of bias and a high heterogeneity, for a total of 3377 patients. The overall intra-hospital mortality of patients receiving NIRS outside the ICU was 36% [30-41%]. 26% [21-30%] of the patients failed NIRS and required intubation, with an intra-hospital mortality rising to 45% [36-54%]. 23% [15-32%] of the patients received DNI orders with an intra-hospital mortality of 72% [65-78%]. Oxygenation on admission was the main source of between-study heterogeneity. CONCLUSIONS: During COVID-19 outbreak, delivering NIRS outside the ICU revealed as a feasible strategy to cope with the massive demand of ventilatory assistance. REGISTRATION: PROSPERO, https://www.crd.york.ac.uk/prospero/ , CRD42020224788, December 11, 2020.

Covid-19 and gender: lower rate but same mortality of severe disease in women-an observational study.

BACKGROUND: Gender-related factors might affect vulnerability to Covid-19. The aim of this study was to describe the role of gender on clinical features and 28-day mortality in Covid-19 patients. METHODS: Observational study of Covid-19 patients hospitalized in Bergamo, Italy, during the first three weeks of the outbreak. Medical records, clinical, radiological and laboratory findings upon admission and treatment have been collected. Primary outcome was 28-day mortality since hospitalization. RESULTS: 431 consecutive adult patients were admitted. Female patients were 119 (27.6%) with a mean age of 67.0 ± 14.5 years (vs 67.8 ± 12.5 for males, p = 0.54). Previous history of myocardial infarction, vasculopathy and former smoking habits were more common for males. At the time of admission PaO2/FiO2 was similar between men and women (228 [IQR, 134-273] vs 238 mmHg [150-281], p = 0.28). Continuous Positive Airway Pressure (CPAP) assistance was needed in the first 24 h more frequently in male patients (25.7% vs 13.0%; p = 0.006). Overall 28-day mortality was 26.1% in women and 38.1% in men (p = 0.018). Gender did not result an independent predictor of death once the parameters related to disease severity at presentation were included in the multivariable analysis (p = 0.898). Accordingly, the Kaplan-Meier survival analysis in female and male patients requiring CPAP or non-invasive ventilation in the first 24 h did not find a significant difference (p = 0.687). CONCLUSION: Hospitalized women are less likely to die from Covid-19; however, once severe disease occurs, the risk of dying is similar to men. Further studies are needed to better investigate the role of gender in clinical course and outcome of Covid-19.

Bergamo and Covid-19: How the Dark Can Turn to Light.

The novel coronavirus, SARS-CoV-2, continues to spread rapidly. Here we discuss the dramatic situation created by COVID-19 in Italy, particularly in the province of Bergamo (the most severely affected in the first wave), as an example of how, in the face of an unprecedented tragedy, acting (albeit belatedly)-including imposing a very strict lockdown-can largely resolve the situation within approximately 2 months. The measures taken here ensured that Bergamo hospital, which was confronted with rapidly rising numbers of severely ill COVID-19 patients requiring hospitalization, was able to meet the initial challenges of the pandemic. We also report that local organization and, more important, the large natural immunity against SARS-CoV-2 of the Bergamo population developed during the first wave of the epidemic, can explain the limited number of new COVID-19 cases during the more recent second wave compared to the numbers in other areas of Lombardy. Furthermore, we highlight the importance of coordinating the easing of containment measures to avoid what is currently observed in other countries, especially in the United States, Latin American and India, where this approach has not been adopted, and a dramatic resurgence of COVID-19 cases and an increase in the number of hospitalisations and deaths have been reported.