BACKGROUND:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to widespread post-acute sequelae of COVID-19 (PASC), affecting multiple body systems. Despite its prevalence, PASC's pathogenesis remains unclear, with hypotheses suggesting viral persistence, immune activation, and autoimmune responses among the pathogenetic mechanism. This study aimed to evaluate T cell memory response in PASC patients, one year post-hospital discharge and correlate it with clinical parameters to identify a potential PASC-associated fingerprint. METHODS:Peripheral blood mononuclear cells (PBMCs) from PASC patients and healthy controls (HC) were stimulated with a pool of spike peptides. CD4+ and CD8+ T cell responses were evaluated by flow cytometry using the activation-induced markers assay (AIM). RESULTS:Findings showed significant activation of the CD4+ T cell compartment, with a higher proportion of responders among PASC patients. Central memory (CM) T cells expressing pro-inflammatory cytokines were more prevalent in responders. Clinical correlations revealed higher SARS-CoV-2-specific T cell responses in patients with reduced diffuse lung capacity for carbon monoxide (DLCO) and residual symptoms. CONCLUSION:These immune changes, especially in CM T cells, could play a pivotal role in PASC's development and persistence, impacting patients' daily lives.

Background: Pulmonary function assessment is mandatory before oncological lung resection surgery. To do so, subjects undergo a pulmonary function test (PFT) and the calculation of predicted postoperative (PPO) values to estimate the residual lung function after surgery. The aim of this study is to evaluate the use of anatomical formulae in estimating postoperative pulmonary function in patients undergoing minimally invasive surgery (MIS). Methods: This is a retrospective study. Patients affected by lung cancer who underwent pulmonary lobectomy or segmentectomy with MIS or thoracotomy approach at our center from June 2020 to May 2021 were considered. Exclusion criteria were: subjects who underwent atypical pulmonary resection surgery or pneumonectomy; and patients who underwent adjuvant therapy (chemotherapy or immunotherapy). PFT data measured before and 1 year after surgery were collected. In particular, postoperative PFT data, especially forced expiratory volume in the first second (FEV1) and diffusing capacity for carbon monoxide (DLCO), and PPO values calculated by the anatomical formulae were compared. Secondary endpoints were: analysis of the postoperative pulmonary function in patients who underwent lung resection with the standard approach (thoracotomy) and evaluation of the anatomical formulae accuracy in subjects operated through thoracotomy. Results: The sample consisted of 48 patients operated on MIS (video-assisted thoracoscopic surgery and robotic-assisted thoracoscopic surgery) and 20 subjects who underwent thoracotomy for stage I-IIA and I-IIB lung cancer in both groups. The anatomical formula seemed to underestimate the postoperative FEV1% by 8.65% [interquartile range (IQR), 0.5-17.28%; P<0.001]. Furthermore, when comparing postoperative PPODLCO% and post-operative DLCO%, a significant difference was shown with an underestimation of the actual postoperative value of 2.78% (IQR, -3.63% to 10.47%; P=0.045). Conclusions: Our results confirmed that the anatomical formulae currently used to predict postoperative pulmonary function are reliable in the case of the standard approach (thoracotomy), while they tend to overestimate the loss of FEV1 and DLCO in the postoperative period in patients who were operated on MIS, thus excluding some subjects from the operation.

Pulmonary Peripheral Lesions (PPLs) diagnosis is usually performed using a guidance system in combination with bronchoscopes and diagnostic tools. We report two cases of PPLs sampling procedures combining the use of the single-use bronchoscope Ambu aScope 5 Broncho and CIOS 3D Spin Mobile (Siemens Healthineers) fluoroscopy system. A 69-year-old-female was found to have a lesion located in right B6 segment and a 73-year-old-male with a mass in the upper right lobe. We used for both cases a single-use bronchoscope to reach the correct area and the fluoroscopy system to guide peripheral transbronchial aspiration needle (TBNA) sampling. After the confirmation of the correct location of the TBNA tool, the sampling was performed. Rapid onsite evaluation (ROSE) confirmed the adequacy of the sample for molecular analysis and the final diagnosis. Thus, the use of ever-new disposable bronchoscopes for sampling peripheral lesions is a viable alternative to reusable bronchoscopes for advanced bronchoscopy procedures.

Background: Pleural infection represents a significant burden of disease to patients and healthcare system, due to substantial morbidity and mortality worldwide, without a definite consensus on the optimal treatment approach and relative outcomes Objectives: To assess type and timing of first-line interventions and clinical outcomes of patients with pleural infection Methods: Patients hospitalized with a diagnosis of pleural infection from 2015 to 2020 are included in this, ongoing, multi-center retrospective study, involving tertiary hospitals across Italy. The following data are collected: clinical features, including effusion aspect, type and timing of first-line treatment (aspiration, drainage and size; medical thoracoscopy-MT; surgery), surgery referral, length of hospital stay, 30-day mortality Results: To date, data from 182 patients (4 centres) have been collected. MT was most frequent first-line approach (41%), followed by chest drain (16%; prevalence of large bore tube), thoracentesis (9%) and surgery (9%). Two thirds (69%) of interventions were performed within the first 48 hours. A subsequent surgery referral was needed in 10% of patients and was most frequent in chest drain subgroup as compared to MT one. Hospital stay was 11.7, 11.4 and 22.5 days in patients who never underwent surgery, who underwent surgery at onset and who underwent second-line surgery, respectively (p<0.01). Mortality at 30-day was 2% Conclusions: Our preliminary data showed that MT was the most common approach to pleural infections, although first-line management was heterogenic. Short-term clinical outcomes were overall favourable, but likely influenced by timely intervention and high level expertise of centres

BACKGROUND:Greenhouse gases (GHGs) are significant contributors to climate change, and CO2 equivalent (CO2-e) is measured to compare emissions from GHGs. The healthcare sector contributes 4.4% of global CO2-e emissions, mainly with energy consumption and, in lesser extent, waste production. In this regard, bronchoscopy procedures produce a large amount of waste and are responsible for a significant consumption of energy.OBJECTIVE:We aimed at quantifying the impact on waste mass production, energy consumption, and recyclability of bronchoscopic procedures.METHODS:We conducted a prospective single-centre observational study; for each type of procedure (performed with either reusable or single-use instruments), the number of items used, their weight, and recyclability were evaluated, as well as the material of which recyclable waste was made of. We then calculated the total amount of waste produced, its recyclability, energy consumption, and CO2-e produced over 10 days of activity in our Interventional Pulmonology Unit.RESULTS:Sixty procedures generated 61,928 g of waste, of which only 15.8% was potentially recyclable. Single-use instruments generated nearly twofold more recyclable waste than reusable ones, 80% during the procedure phase. Reusable instruments generated 45% of waste during the reprocessing phase, of which 50% was recyclable. The recyclable material was totally composed of paper and plastic. During 10 days of activity, we consumed 64 kWh and produced more than 67 kg of CO2-e due to non-recyclable waste and energy consumption.CONCLUSIONS:Our results confirm the compelling need to recycle as many materials as possible, even if the amount of recyclable waste is limited. In this respect, official documents issued by international societies are urgently needed to align our activity with climate requirements and improve the sustainability of our work.

Post-acute conditions after coronavirus disease 2019 (COVID-19) are quite common, although the underlying pathogenetic mechanisms leading to these conditions are not yet completely understood. In this prospective observational study, we aimed to test the hypothesis that Growth Arrest-Specific 6 (Gas6) and its soluble receptors, Axl (sAxl) and MerTK (sMer), might be implicated. A total of 263 subjects underwent a structured clinical evaluation one year after their hospital discharge for COVID-19, and they consented to donate a blood sample to measure their circulating Gas6, sAxl, and sMer levels. A total of 98 (37.3%) post-COVID-19 subjects complained of at least one residual physical symptom one year after their hospital discharge. Univariate analysis revealed that sAxl was marginally associated with residual symptoms, but at the level of logistic regression analysis, only the diffusing capacity of the lungs for carbon monoxide (DLCO) (OR 0.98, CI 95%: 0.96–0.99; p = 0.007) and the female sex (OR 2.49, CI 95%: 1.45–4.28; p = 0.001) were independently associated with long-lasting symptoms. A total of 69 (26.2%) subjects had hair loss. At the level of univariate analysis, Gas6, sAxl, DLCO, and the female gender were associated with its development. In a logistic regression analysis model, Gas6 (OR 0.96, CI 95%: 0.92–0.99; p = 0.015) and sAxl (OR 0.98, CI 95%; 0.97–1.0; p = 0.014), along with the female sex (OR 6.58, CI 95%: 3.39–12.78; p = 0.0001), were independent predictors of hair loss. Decreased levels of Gas6 and sAxl were associated with a history of hair loss following COVID-19. This was resolved spontaneously in most patients, although 23.7% complained of persistent hair loss one year after hospital discharge.

Background: Dielectric properties of biological tissues are biophysical parameters; in lung they change with amount of air, blood and parenchyma. Remote Dielectric Sensing (ReDS (TM)) technology measures dielectric properties of lung tissues quantifying the content of fluids inside the scan volume. We aimed to evaluate the reliability of ReDS (TM) measure in Idiopathic Pulmonary Fibrosis (IPF) patients and in healthy volunteers, and to investigate the correlation of ReDS (TM) score with clinical, radiological and functional parameters. Methods: We conducted a prospective observational study, including 52 patients with diagnosis of IPF and 17 healthy volunteers; for each patient we recorded: complete functional evaluation, dyspnoea score (mMRC scale), Usual Interstitial Pneumonia (UIP) Computed Tomography (CT) pattern (UIP definite or probable) and ReDS (TM) measure (expressed in %). Results: ReDS (TM) measure was reported as correct both in patients and controls, the firsts with higher scores (33.8% vs 29.1%, p = 0.003). In IPF patients we observed a significant inverse correlation with ReDS (TM) score and Forced Vital Capacity (FVC), Vital Capacity (VC) and Total Lung Capacity (TLC) measures and, when we considered only patients with UIP definite CT pattern, the correlation was inverse with FVC, VC, TLC, DLCO. In IPF patients the higher was mMRC dyspnoea index, the higher was ReDS (TM) score. No significant correlations were observed between ReDS (TM) score and functional parameters in healthy controls. Discussion: We demonstrated a correlation of ReDS (TM) scores with some functional (mainly indicative or diagnostic for restriction) and clinical parameters in IPF patients; the score was correlated with density of tissues possibly quantifying tissue fibrosis in IPF patients.

Rationale Factors associated with long-term sequelae emerging after the acute phase of COVID-19 (so called “long COVID”) are unclear. Here, we aimed to identify risk factors for the development of COVID-19 sequelae in a prospective cohort of subjects hospitalized for SARS-CoV-2 infection and followed up one year after discharge. Methods A total of 324 subjects underwent a comprehensive and multidisciplinary evaluation one year after hospital discharge for COVID-19. A subgroup of 247/324 who consented to donate a blood sample were tested for a panel of circulating cytokines. Results In 122 patients (37.8%) there was evidence of at least one persisting physical symptom. After correcting for comorbidities and COVID-19 severity, the risk of developing long COVID was lower in the 109 subjects admitted to the hospital in the third wave of the pandemic than in the 215 admitted during the first wave, (OR 0.69, 95%CI 0.51-0.93, p=0.01). Univariable analysis revealed female sex, diffusing capacity of the lungs for carbon monoxide (DLCO) value, body mass index, anxiety and depressive symptoms to be positively associated with COVID-19 sequelae at 1 year. Following logistic regression analysis, DLCO was the only independent predictor of residual symptoms (OR 0.98 CI 95% (0.96-0.99), p=0.01). In the subgroup of subjects with normal DLCO (> 80%), for whom residual lung damage was an unlikely explanation for long COVID, the presence of anxiety and depressive symptoms was significantly associated to persistent symptoms, together with increased levels of a set of pro-inflammatory cytokines: interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-12, IL-1β, IL-17. In logistic regression analysis, depressive symptoms (p=0.02, OR 4.57 [1.21-17.21]) and IL-12 levels (p=0.03, OR 1.06 [1.00-1.11]) 1-year after hospital discharge were independently associated with persistence of symptoms. Conclusions Long COVID appears mainly related to respiratory sequelae, prevalently observed during the first pandemic wave. Among patients with little or no residual lung damage, a cytokine pattern consistent with systemic inflammation is in place.

Background:Mental health-related symptoms can persist over time beyond the most common respiratory clinical features of COVID-19. A recent meta-analysis underlined that mental health sequalae may be relevant for COVID-19 survivors and reported the following prevalence rates: 20% for post-traumatic stress disorder, 22% for anxiety, 36% for psychological distress, and 21% for depression. In the context of a multi-disciplinary follow-up project, we already investigated the mid-term (4 months) psychiatric outcomes in a sample of COVID-19 survivors. Patients were re-assessed after 1-year since hospital discharge.Methods:Follow-up conducted after 1 year involved 196 individuals recovered from COVID-19. Patients were assessed with a multi-disciplinary approach; including both a clinical interview performed by an experienced psychiatrist, trained in the use of the Mini-International Neuropsychiatric Interview (MINI) to assess the presence of anxiety, stress, and depressive symptoms and the following self-administered questionnaires: Beck Anxiety Inventory, Beck Depression Inventory-II, Resilience Scale for Adults, Impact of Event Scale, and COVID-19 Peritraumatic Distress Index (CPDI).Results:Anxiety (p < 0.0001) and depressive (p < 0.0003) symptoms registered at the clinical interview showed a significant improvement from the 4 to 12-months follow-up. Logistic regression model showed that female gender (p = 0.006), arterial hypertension (p = 0.01), obesity (0.04), anxiety (p < 0.0001), and depressive (p = 0.02) symptoms at 4-months follow-up were associated with persistence of anxiety symptoms at 12 months. At logistic regression analysis female gender (p = 0.02) and depressive symptoms at 4-months follow-up (p = 0.01) were associated with depressive symptoms after 12 months.Conclusion:Severity of the disease in the acute phase, in this study, was not a determining factor in identifying subjects at risk of developing clinically relevant anxiety and depression as a consequence of COVID-19 disease. Findings from the logistic regressions suggest that the factors most affecting depression and anxiety in COVID survivors after 12 months were female gender, the presence of anxiety and depression after 4 months and some physical symptoms, not necessarily COVID-related. Impact of infection and consequent hospitalization for COVID-19 did no longer represent a relevant issue for depressive symptoms, compared to other general factors.

The evidence that severe coronavirus disease 2019 (COVID-19) is a risk factor for development of mycotic respiratory infection with an increased mortality is rising. Immunosuppressed are among the most susceptible patients andAspergillusspecies is the most feared superinfection. In this study we evaluated mycotic isolation prevalence on bronchoalveolar lavage (BAL) of patients who underwent bronchoscopy in search of severe acute respiratory coronavirus 2 (SARS-CoV-2) RNA. Moreover, we described the clinical characteristics and main outcomes of these patients. We included 118 patients, 35.9% of them were immunosuppressed for different reasons: in 23.7% we isolated SARS-CoV-2 RNA, in 33.1% we identified at least one mycotic agent and both in 15.4%. On BAL we observed in three casesAspergillusspp, in six casesPneumocystisand in 32Candidaspp. The prevalence of significant mold infection was 29.3% and 70.7% of cases were false positive or clinically irrelevant infections. In-hospital mortality of patients with fungal infection was 15.3%. The most frequent computed tomography (CT) pattern, evaluated with the Radiological Society of North America consensus statement, among patients with a mycotic pulmonary infection was the atypical one (p< 0.0001). Mycotic isolation on BAL may be interpreted as an innocent bystander, but its identification could influence the prognosis of patients, especially in those who need invasive investigations during the COVID-19 pandemic; BAL plays a fundamental role in resolving clinical complex cases, especially in immunosuppressed patients independently from radiological features, without limiting its role in ruling out SARS-CoV-2 infection.

This cohort study examines prevalence and risk factors associated with lung function or physical impairment or posttraumatic stress symptoms among survivors of severe coronavirus disease 2019 (COVID-19). Importance Although plenty of data exist regarding clinical manifestations, course, case fatality rate, and risk factors associated with mortality in severe coronavirus disease 2019 (COVID-19), long-term respiratory and functional sequelae in survivors of COVID-19 are unknown. Objective To evaluate the prevalence of lung function anomalies, exercise function impairment, and psychological sequelae among patients hospitalized for COVID-19, 4 months after discharge. Design, Setting, and Participants This prospective cohort study at an academic hospital in Northern Italy was conducted among a consecutive series of patients aged 18 years and older (or their caregivers) who had received a confirmed diagnosis of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection severe enough to require hospital admission from March 1 to June 29, 2020. SARS-CoV-2 infection was confirmed via reverse transcription-polymerase chain reaction testing, bronchial swab, serological testing, or suggestive computed tomography results. Exposure Severe COVID-19 requiring hospitalization. Main Outcomes and Measures The primary outcome of the study was to describe the proportion of patients with a diffusing lung capacity for carbon monoxide (D-lco) less than 80% of expected value. Secondary outcomes included proportion of patients with severe lung function impairment (defined as D-lco <60% expected value); proportion of patients with posttraumatic stress symptoms (measured using the Impact of Event Scale-Revised total score); proportion of patients with functional impairment (assessed using the Short Physical Performance Battery [SPPB] score and 2-minute walking test); and identification of factors associated with D-lco reduction and psychological or functional sequelae. Results Among 767 patients hospitalized for severe COVID-19, 494 (64.4%) refused to participate, and 35 (4.6%) died during follow-up. A total of 238 patients (31.0%) (median [interquartile range] age, 61 [50-71] years; 142 [59.7%] men; median [interquartile range] comorbidities, 2 [1-3]) consented to participate to the study. Of these, 219 patients were able to complete both pulmonary function tests and D-lco measurement. D-lco was reduced to less than 80% of the estimated value in 113 patients (51.6%) and less than 60% in 34 patients (15.5%). The SPPB score was suggested limited mobility (score <11) in 53 patients (22.3%). Patients with SPPB scores within reference range underwent a 2-minute walk test, which was outside reference ranges of expected performance for age and sex in 75 patients (40.5%); thus, a total of 128 patients (53.8%) had functional impairment. Posttraumatic stress symptoms were reported in a total of 41 patients (17.2%). Conclusions and Relevance These findings suggest that at 4 months after discharge, respiratory, physical, and psychological sequelae were common among patients who had been hospitalized for COVID-19. Question What respiratory, functional, and psychological sequalae are associated with recovery from coronavirus disease 2019 (COVID-19)? Findings In this cohort study of 238 patients with COVID-19 hospitalized in an academic hospital in Northern Italy, more than half of participants had a significant reduction of diffusing lung capacity for carbon monoxide or measurable functional impairment and approximately one-fifth of patients had symptoms of posttraumatic stress 4 months after discharge. Meaning These findings suggest that despite virological recovery, a sizable proportion of patients with COVID-19 experienced respiratory, functional, or psychological sequelae months after hospital discharge.

Purpose The use of Electromagnetic navigation bronchoscopy (ENB) for the diagnosis of pulmonary peripheral lesions is still debated due to its variable diagnostic yield; a new 4D ENB system, acquiring inspiratory and expiratory computed tomography (CT) scans, overcomes respiratory motion and uses tracked sampling instruments, reaching higher diagnostic yields. We aimed at evaluating diagnostic yield and accuracy of a 4D ENB system in sampling pulmonary lesions and at describing their influencing factors. Methods We conducted a three-year retrospective observational study including all patients with pulmonary lesions who underwent 4D ENB with diagnostic purposes; all the factors potentially influencing diagnosis were recorded. Results 103 ENB procedures were included; diagnostic yield and accuracy were, respectively, 55.3% and 66.3%. We reported a navigation success rate of 80.6% and a diagnosis with ENB was achieved in 68.3% of cases; sensitivity for malignancy was 61.8%. The majority of lesions had a bronchus sign on CT, but only the size of lesions influenced ENB diagnosis (p < 0.05). Transbronchial needle aspiration biopsy was the most used tool (93.2% of times) with the higher diagnostic rate (70.2%). We reported only one case of pneumothorax. Conclusion The diagnostic performance of a 4D ENB system is lower than other previous navigation systems used in research settings. Several factors still influence the reachability of the lesion and therefore diagnostic yield. Patient selection, as well as the multimodality approach of the lesion, is strongly recommended to obtain higher diagnostic yield and accuracy, with a low rate of complications.

Background: Bronchoscopy with bronchoalveolar lavage (BAL) during the SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) pandemic should be reserved to a limited number of clinical indications. The yield of BAL for the diagnosis of suspected or confirmed pulmonary SARS-CoV-2 infection is still unknown. Objectives: We aimed to evaluate the diagnostic ratio of BAL in detecting SARS-CoV-2 pulmonary infection in patients undergoing bronchoscopy for different indications as well as describe the clinical, radiological, and endoscopic characteristics of patients with SARS-CoV-2 on BAL. Method: We conducted a multicenter retrospective study including all patients who underwent bronchoscopy for the detection of SARS-CoV-2 on BAL. Clinical, computed tomography (CT), endoscopic, and microbiologic data were gathered from March 16th to May 27th, 2020. Results: 131 patients were included. Bronchoscopy was performed for suspected SARS-CoV-2 infection (65.5%), alternative diagnosis (12.9%), suspected superinfections (19.8%), and lung atelectasis (1.5%). SARS-CoV-2 was isolated on BAL 43 times (32.8%) and the highest isolation rate was in patients with suspected SARS-CoV-2 infection (74.4%); 76% of positive patients had a double-negative nasopharyngeal swab. Peripheral, posterior and multilobar CT opacities were more frequent in SARS-CoV-2 patients, and the number of CT findings was higher in positive patients, particularly those with suspected SARS-CoV-2 infection. We recorded a progressive reduction of SARS-CoV-2 isolation during the observation period. Conclusions: In our centers, the rate of detection of SARS-CoV-2 on BAL in patients with suspected infection was 37.2%. The agreement of BAL with nasopharyngeal swabs was high; CT alterations could predict the pretest probability of SARS-CoV-2 infection, but suspicion of viral infection should be always considered.

Infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe respiratory tract damage and acute lung injury. Therefore, it is crucial to study breath-associated biofluids not only to investigate the breath’s biochemical changes caused by SARS-CoV-2 infection, but also to discover potential biomarkers for the development of new diagnostic tools. In the present study, we performed an untargeted metabolomics approach using a bidimensional gas chromatography mass spectrometer (GCxGC-TOFMS) on exhaled breath condensate (EBC) from COVID-19 patients and negative healthy subjects to identify new potential biomarkers for the noninvasive diagnosis and monitoring of the COVID-19 disease. The EBC analysis was further performed in patients with acute or acute-on-chronic cardiopulmonary edema (CPE) to assess the reliability of the identified biomarkers. Our findings demonstrated that an abundance of EBC fatty acids can be used to discriminate COVID-19 patients and that they may have a protective effect, thus suggesting their potential use as a preventive strategy against the infection.

Background: Although the usual primary clinical manifestation of Coronavirus disease (COVID-19) is respiratory, several non-respiratory symptoms have been described, including neuropsychiatric ones. The aim of this study was to investigate the mid-term mental health outcomes in patients recovered from COVID-19, 3–4 months after discharge from the University Hospital Maggiore della Carità, Novara, Italy. Furthermore, we investigated the possible association of the mid-term mental health consequences of the COVID-19 infection with patients' clinical current status, persistent physical impairment and severity of acute phase of the disease.Methods: Prospective study involving 238 individuals recovered from COVID-19. In the context of a multi-disciplinary approach, patients' assessment included both a clinical interview performed by an experienced psychiatrist, trained in the use of the Mini-International Neuropsychiatric Interview to assess the presence of anxiety and depressive symptoms and self-administered questionnaires: Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), Resilience Scale for Adults (RSA), Impact of Event Scale (IES).Results: At the psychiatric assessment 32.9 and 29.5% of participants showed anxiety and depressive symptoms, respectively. Changes in appetite and sleep patterns emerged for 15.6 and 31.2% of patients. According to the self-administered questionnaires, 7.1% of participants had moderate-severe anxiety levels (BAI), while 10.5% had mild to severe depression (BDI-II). Twenty-six (11%) participants were referred to further psychiatric consultation. Psychiatric symptoms showed no correlation with acute COVID-19 severity; in our sample patients with depressive symptoms at the clinical interview, as well as those with mild to severe levels of depression according to BDI-II scores, had lower forced expiratory volume in the 1st second (FEV1) values than those without and greater odds for persistent, poor tolerance for physical efforts.Conclusions: As could be expected, an approach including both a psychiatric interview and the use of self-administered questionnaires is likely to capture the psychiatric outcome of patients recovered from COVID-19 better than questionnaires alone. Anxiety and depressive symptoms at follow-up had no correlation with the severity of COVID acute manifestations, but rather with ongoing and persistent physical symptoms. Further studies and longer follow-up duration will allow a better understanding of the complex relationship between residual physical symptoms, quality of life and psychological health.

Many coronavirus disease 2019 (Covid-19) survivors show symptoms months after acute illness. The aim of this work is to describe the clinical evolution of Covid-19, one year after discharge. We performed a prospective cohort study on 238 patients previously hospitalized for Covid-19 pneumonia in 2020 who already underwent clinical follow-up 4 months post-Covid-19. 200 consented to participate to a 12-months clinical assessment, including: pulmonary function tests with diffusing lung capacity for carbon monoxide (DLCO); post-traumatic stress (PTS) symptoms evaluation by the Impact of Event Scale (IES); motor function evaluation (by Short Physical Performance Battery and 2 min walking test); chest Computed Tomography (CT). After 366 [363–369] days, 79 patients (39.5%) reported at least one symptom. A DLCO < 80% was observed in 96 patients (49.0%). Severe DLCO impairment (< 60%) was reported in 20 patients (10.2%), related to extent of CT scan abnormalities. Some degree of motor impairment was observed in 25.8% of subjects. 37/200 patients (18.5%) showed moderate-to-severe PTS symptoms. In the time elapsed from 4 to 12 months after hospital discharge, motor function improves, while respiratory function does not, being accompanied by evidence of lung structural damage. Symptoms remain highly prevalent one year after acute illness.

Introduction. The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions. Materials and Methods. In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients ( F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded. Results. At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) ( χ 2 10.4; p < 0.001 ), neutrophil-to-lymphocyte (NL) ratio ( χ 2 7.6; p = 0.006 ), and platelet count ( χ 2 5.39; p = 0.02 ), along with age ( χ 2 87.6; p < 0.001 ) and gender ( χ 2 17.3; p < 0.001 ), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4.68 was characterized by an odds ratio for in-hospital mortality OR = 3.40 (2.40-4.82), while the OR for a RDW > 13.7 % was 4.09 (2.87-5.83); a platelet count > 166,000 /μL was, conversely, protective (OR: 0.45 (0.32-0.63)). Conclusion. Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment.

After the first autochthonous case described on February 19, also in Italy the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection rapidly circulated, mainly in the Northern regions of the country. The earliest reports on Coronavirus disease-19 (COVID-19) have described worldwide a high prevalence of severe respiratory illness [[1]Zhou F. Yu T. Du R. et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.The Lancet. 2020; 395: 1054-1062Abstract Full Text Full Text PDF PubMed Scopus (18524) Google Scholar]. A suggestive feature of COVID-19 has been a rapid progression of the respiratory impairment, leading to acute respiratory distress syndrome (ARDS) and often requiring ventilation support [[2]Wang D. Hu B. Hu C. et al.Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China.JAMA. 2020; 323: 1061https://doi.org/10.1001/jama.2020.1585Crossref PubMed Scopus (16034) Google Scholar]. To date, whether clinical features at hospital presentation and outcome of COVID-19 have changed over the outbreak course is unknown. We explored this issue in a multicenter cohort of patients hospitalized for COVID-19 in Northern Italy. We retrospectively revised the clinical records of all consecutive patients admitted for SARS-CoV-2 infection between March 1 and May 12, 2020 in three hospitals of the Piedmont region: "Maggiore della Carità Hospital" in Novara, "Sant'Andrea" Hospital, in Vercelli, "Santi Antonio e Biagio e Cesare Arrigo" Hospital, in Alessandria. These hospitals are the referral of a large homogenous territory in Eastern Piedmont, one of the most hit by the SARS-CoV-2 pandemic [[3]Italian Civil Protection Department. Coronavirus Emergency. Accessed athttp://opendatadpc.maps.arcgis.com/apps/opsdashboard/index.html#/b0c68bce2cce478eaac82fe38d4138b1.Google Scholar]. The study protocol was approved by the institutional ethical committee of Novara (IRB code CE 97/20). For the purpose of the analysis, we divided the whole study duration in two time spans: period 1 (from March 1 to April 13, i.e. during the maximal diffusion of SARS-CoV-2 infection) and period 2 (from April 14 to May 12, during the declining infection). The starting of period 2 was set on April 14 as this date represented the turning point when the increase in the daily number of individuals positive for SARS-CoV-2 infection in Piedmont has ceased [[3]Italian Civil Protection Department. Coronavirus Emergency. Accessed athttp://opendatadpc.maps.arcgis.com/apps/opsdashboard/index.html#/b0c68bce2cce478eaac82fe38d4138b1.Google Scholar]. Informed consent was waived due to the retrospective nature of the study and use of pseudonymized data. The following endpoints were compared between patients admitted in the two abovementioned periods:1.Incidence of patients requiring mechanical ventilation on the day of admission.2.Incidence of patients with severe ARDS on the day of admission. Severe ARDS was defined according to the Berlin definition [[4]ARDS Definition Task ForceAcute respiratory distress syndrome: the Berlin Definition.JAMA. 2012; 307: 2526-2533Crossref PubMed Scopus (7582) Google Scholar].3.A score indicative of critical COVID-19 on the day of admission. Patients were stratified according to the Shang's score, which represents a clinical classification of COVID-19 severity, as per recent description in a cohort of patients diagnosed with SARS-CoV-2 infection in Wuhan (China) [[5]Shang W. Dong J. Ren Y. et al.The value of clinical parameters in predicting the severity of COVID‐19.J Med Virol. 2020; (May 21)https://doi.org/10.1002/jmv.26031Crossref Scopus (157) Google Scholar]. Patients with score of critical disease were identified as those with respiratory failure requiring mechanical ventilation or with shock or other organ failure requiring Intensive Care Unit monitoring and treatment. The daily percentage of patients with mechanical ventilation, severe ARDS and a score of critical disease on admission was obtained from the daily number of each outcome measure on admission and the total number of patients hospitalized in the same day. This was recorded for all 44 days of period 1 and 29 days of period 2. Incidence rate ratios (IRR) comparing period 1 and period 2 were calculated using Poisson regression. The weekly number of events per 100 patients was represented in a plot together with a Local polynomial regression smoothing curve. A span smoothing control of 0.75 with 2 degrees of the polynomials has been considered for the computation. The R2 model fitting statistics was also computed. A total of 522 patients were overall included in this analysis, 416 admitted from March 1 to April 13 (period 1) and 106 from April 14 to May 12 (period 2). Main characteristics of the two groups are indicated in Table 1. Patients hospitalized in the later phase of the SARS-CoV-2 outbreak were older and had a lower prevalence of male gender and diabetes mellitus. In period 2, cough, dyspnea and sputum production were less represented as clinical features upon Emergency Department presentation, body temperature was lower, and levels of C-reactive protein tended to be reduced. In the later phase patients were less frequently treated with hydroxychloroquine, lopinavir/ritonavir and tocilizumab.Table 1Main characteristics of patients admitted in the two time periods of the SARS-CoV-2 infection.Period 1 (March 1 to April 13) N=416Period 2 (April 14 to May 12) N=106p valueAge (years)67.5±1573.1±16.70.001Male gender255 (61.3)51 (48.5)0.015Obesity*87 (31.4)16 (20.3)0.07Arterial hypertension241 (57.9%)56 (52.8)0.38Diabetes mellitus125 (30)16 (15)0.002Cardiomyopathy107 (25.7)23 (21.7)0.45Chronic obstructive pulmonary disease70 (16.8)14 (13.2)0.38Chronic renal failure66 (15.9)24 (22.6)0.10History of cancer110 (26.4)27 (25.4)0.90Chronic liver disease12 (2.9)6 (5.7)0.23Autoimmune diseases33 (7.9)6 (5.7)0.54Symptoms upon presentationCough or dyspnea232 (55.8)43 (40.6)0.006Sputum production49 (11.8)2 (1.9)0.002Chest pain53 (12.7)5 (4.7)0.023Syncope21 (5.1)4 (3.7)0.63Clinical signs upon presentationSystolic blood pressure (mmHg)127±21130±240.20Body temperature (°C)37.5±1.037.1±1.10.001Heart rate (bpm)86±1787±220.68C-reactive protein (mg/dL)8.6±7.57.3±6.10.12In-hospital therapyHydroxychloroquine*325 (89.0)73 (80.2)0.034Lopinavir/ritonavir70 (16.8)5 (4.7)0.002Remdesivir8 (1.9)00.22Tocilizumab45 (10.8)1 (0.9)0.002Low molecular weight heparin*286 (78.4)84 (85.7)0.12Data are expressed as n (%) or mean±standard deviation. * Data were missing for obesity in 166 patients (139 in period 1 and 27 in period 2), for hydroxychloroquine in 66 patients (51 in period 1 and 15 in period 2) and for low molecular weight heparin in 59 patients (51 in period 1 and 8 in period 2). Open table in a new tab Data are expressed as n (%) or mean±standard deviation. * Data were missing for obesity in 166 patients (139 in period 1 and 27 in period 2), for hydroxychloroquine in 66 patients (51 in period 1 and 15 in period 2) and for low molecular weight heparin in 59 patients (51 in period 1 and 8 in period 2). Mean IR of mechanical ventilation on admission was 5.0 per 100 patient-days in period 1 and 0.6 per 100 patient-days in period 2; IR of severe ARDS on admission was 12.9 per 100 patient-days and 2.3 per 100 patient-days, respectively. For both these outcome measures, the rates in period 2 were significantly lower compared to period 1 (IRR of mechanical ventilation 0.11, 95% CI 0.07-0.19; p=0.0001; IRR of severe ARDS 0.18, 95% CI 0.14-0.23; p=0.0001) (Fig. 1). The occurrence of a score on the day of admission indicating a critical COVID-19 was 11.1 per 100 patient-days in period 1 and 2.6 per 100 patient-days in period 2, with a significant 65% relative reduction in the latter time span (IRR 0.35, 95% CI 0.26-0.48; p=0.0001) (Fig. 1). As patients admitted in the later phase were older, we performed a sensitivity analysis in the subgroup with age ≥70 years, where consistent results on the event rates upon hospitalization were observed in period 2 vs 1: mechanical ventilation: OR 0.27, 95% CI 0.03-2.10; severe ARDS: OR 0.39, 95% CI 0.20-0.79; score of severe disease: OR 0.24, 95% CI 0.05-1.02. Fig. 2 depicts the weekly course of total number of hospitalizations, percentage of mechanical ventilations, percentage of severe ARDS and percentage of patients with a score of severe disease across the two periods.Fig. 2Local Polynomial Regression smoothing (LOESS) plots.Show full captionPanel A: Total hospitalizations; a LOESS smoothing method has been considered for the analysis with a degree of non-linear approximation (span) of 0.75. R2=0.88. Panel B: Weekly number of patients with mechanical ventilation over number of hospitalizations; a LOESS smoothing method has been considered for the analysis with a degree of non-linear approximation (span) of 0.75. R2=0.75. Panel C: Weekly number of patients with severe ARDS over number of hospitalizations; a LOESS smoothing method has been considered for the analysis with a degree of non-linear approximation (span) of 0.75. R2=0.8. Panel D: Weekly number of patients with a clinical score of severe COVID-19 over number of hospitalizations; a LOESS smoothing method has been considered for the analysis with a degree of non-linear approximation (span) of 0.75. R2=0.6.ARDS= Acute Respiratory Distress SyndromeView Large Image Figure ViewerDownload Hi-res image Download (PPT) Panel A: Total hospitalizations; a LOESS smoothing method has been considered for the analysis with a degree of non-linear approximation (span) of 0.75. R2=0.88. Panel B: Weekly number of patients with mechanical ventilation over number of hospitalizations; a LOESS smoothing method has been considered for the analysis with a degree of non-linear approximation (span) of 0.75. R2=0.75. Panel C: Weekly number of patients with severe ARDS over number of hospitalizations; a LOESS smoothing method has been considered for the analysis with a degree of non-linear approximation (span) of 0.75. R2=0.8. Panel D: Weekly number of patients with a clinical score of severe COVID-19 over number of hospitalizations; a LOESS smoothing method has been considered for the analysis with a degree of non-linear approximation (span) of 0.75. R2=0.6. ARDS= Acute Respiratory Distress Syndrome In this observational, retrospective, multicenter investigation on consecutive patients admitted for COVID-19 we found that with decreasing viral diffusion the severity of the respiratory tract involvement and the inflammatory status at hospital presentation were less pronounced, as demonstrated by a fewer prevalence of cough, dyspnea and sputum production, as well as by a lower body temperature and a trend towards reduced C-reactive protein levels. As a consequence, in the later phase we observed an 89% relative reduction in the incidence rate of mechanical ventilation on admission and an 82% relative reduction of early severe ARDS. A clinical score on admission indicating a critical COVID-19 was also less frequently observed in period 2, with a 65% relative reduction. During the SARS-CoV-2 outbreak we report a linear decrease over time of severe ARDS and mechanical ventilation use (Fig. 2). In fact, the incidence of both these parameters was highest in the first 3 weeks of period 1, i.e. when the total number of cases and hospitalizations was still low, and continued to decrease in the subsequent 3 weeks of period 1, while the total number of cases and hospitalizations was increasing. Nevertheless, the percentage of patients with a score of critical disease tended to increase in the first weeks of period 1, concomitantly with the increase in the number of hospitalizations; this apparent inconsistency may be due to the hospital overcrowding and limited bed capacity in the intensive care units that occurred at the beginning of the epidemic in Northern Italy, when severe cases with less life expectancy were not intubated. Notably, period 1 almost entirely refers to the time of national lock-down, decreed on March 8th, characterized by strict social containing measures and limitation of several economic activities. The present study has strengths and limitations. It was performed comparing clinical features upon hospital presentation and outcome of COVID-19 over two subsequent periods in consecutive patients from the same area, receiving consistent in-hospital protocols of diagnosis or care and managed by the same care-workers. Our investigation has limitations inherent to observational and retrospective studies, mainly the risk of residual confounding. Individual data were accurately collected with a strict source verification for the event adjudication; however, the retrospective design and the conduction of the study during a National Emergency contributed to the lack of some, although limited, data, which were not available. Furthermore, data on COVID-19 patients who died before the Emergency Department presentation were not available. A selection bias may exist, as it is reasonable that the wider diffusion of the outbreak in the earlier period led to admit to the hospital only those patients with more critical clinical pictures. Finally, whether our results may also apply to regions with lower viral circulation or different health-care systems it is unknown. Actually, the exponential increase of COVID-19 cases at the beginning of the epidemic heavily affected the sustainability of hospital acceptance capacity, limiting hospitalization to more severe cases. In conclusion, this investigation indicates a progressive decreasing severity of COVID-19 at hospital presentation over the pandemic period in Northern Italy. In particular, the percentage of patients with early severe ARDS or requiring early mechanical ventilation was significantly reduced. We believe these findings may be relevant, as large areas in the world are fully involved in the SARS-CoV-2 pandemic yet and may represent the basis for further evaluations by epidemiologists and virologists. It is reasonable that the wider diffusion of the outbreak in the earlier period led to admit to the hospital only those patients with critical clinical pictures. However, our findings might support that, during the intense virus circulation, expositions to a higher viral load or re-expositions have caused more severe disease presentations [[6]Liu Y. Yan L.M. Wan L. et al.Viral Dynamics in Mild and Severe Cases of COVID-19.Lancet Infect Dis. 2020; 20: 656-657Abstract Full Text Full Text PDF PubMed Scopus (1178) Google Scholar]; indeed, the relationship between viral load and COVID-19 severity is controversial, with recent data showing no significant difference in the viral load of symptomatic versus asymptomatic patients with SARS-CoV-2 infection [[7]Lavezzo E. Franchin E. Ciavarella C. et al.Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo'.Nature. 2020; 584: 425-429Crossref PubMed Scopus (636) Google Scholar]. Specific studies are needed to investigate this latter issue, as well as to explore whether our results can be also due to a decrease over time in the virulence of SARS-CoV-2, linked to intrinsic (i.e. virus mutations) and/or extrinsic (i.e. environmental) mechanisms. GP conceived the study; GP and MM designed the study; ES, EH, AR, LG, CC and VL performed data collection; GP, MM and DA performed statistical analysis; GP wrote the manuscript; all authors contributed to data interpretation; critical revision of the paper for important intellectual content was done by all authors. None

JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 18, Issue 2 p. 153-156 Case for Diagnosis Disseminated ulcers with sporotrichoid distribution Federica Veronese, Corresponding Author Federica Veronese federica.veronese@med.uniupo.it Dermatologic Clinic, AOU Maggiore della Carità Hospital, Novara, Italy Correspondence to Federica Veronese, MD Dermatologic Clinic AOU Maggiore della Carità Hospital 28100 Novara E-mail: federica.veronese@med.uniupo.itSearch for more papers by this authorRossella Molinari, Rossella Molinari Medical Department, Division of Respiratory Medicine, University of Eastern Piedmont, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorStefano Astolfi, Stefano Astolfi Dermatologic Clinic, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorLuigia Saini, Luigia Saini Medical Department, Division of Respiratory Medicine, University of Eastern Piedmont, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorRoberta Nicali, Roberta Nicali Medical Department, Division of Respiratory Medicine, University of Eastern Piedmont, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorAnna Camaggi, Anna Camaggi Microbiology and Virology Laboratory, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorStefano Andreoni, Stefano Andreoni Microbiology and Virology Laboratory, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorPiero Emilio Balbo, Piero Emilio Balbo Medical Department, Division of Respiratory Medicine, University of Eastern Piedmont, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorPaola Savoia, Paola Savoia Dermatologic Clinic, Department of Health Science University of Eastern Piedmont, Novara, ItalySearch for more papers by this author Federica Veronese, Corresponding Author Federica Veronese federica.veronese@med.uniupo.it Dermatologic Clinic, AOU Maggiore della Carità Hospital, Novara, Italy Correspondence to Federica Veronese, MD Dermatologic Clinic AOU Maggiore della Carità Hospital 28100 Novara E-mail: federica.veronese@med.uniupo.itSearch for more papers by this authorRossella Molinari, Rossella Molinari Medical Department, Division of Respiratory Medicine, University of Eastern Piedmont, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorStefano Astolfi, Stefano Astolfi Dermatologic Clinic, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorLuigia Saini, Luigia Saini Medical Department, Division of Respiratory Medicine, University of Eastern Piedmont, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorRoberta Nicali, Roberta Nicali Medical Department, Division of Respiratory Medicine, University of Eastern Piedmont, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorAnna Camaggi, Anna Camaggi Microbiology and Virology Laboratory, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorStefano Andreoni, Stefano Andreoni Microbiology and Virology Laboratory, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorPiero Emilio Balbo, Piero Emilio Balbo Medical Department, Division of Respiratory Medicine, University of Eastern Piedmont, AOU Maggiore della Carità Hospital, Novara, ItalySearch for more papers by this authorPaola Savoia, Paola Savoia Dermatologic Clinic, Department of Health Science University of Eastern Piedmont, Novara, ItalySearch for more papers by this author First published: 06 February 2020 https://doi.org/10.1111/ddg.14028AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume18, Issue2February 2020Pages 153-156 RelatedInformation

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO(2) ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk.