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2.
Int J Environ Res Public Health ; 19(3)2022 01 21.
Article in English | MEDLINE | ID: covidwho-1686721

ABSTRACT

Physical activity (PA) is a major health factor and studies suggest workplaces could promote PA by modifying office design, motivational strategies and technology. The present study aims to evaluate the efficiency of UP150, a multifactorial workplace intervention for the improvement and maintenance of the level of physical fitness (PF) and wellbeing. Forty-five employees were randomly divided into the experimental (EG) and control (CG) groups. The PF was assessed pre-post intervention using the cubo fitness test (CFT), the amount of PA was evaluated using the IPAQ questionnaire and accelerometers while the workload was assessed using the NASA-TLX questionnaire and psycho-physical health by using the SF-12 questionnaire. The EG worked in UP150 offices while the CG worked in their usual offices for 8 weeks. The EG and CG came back 4 weeks after the intervention for CFT retention. The EG improved CFT motor efficiency and the amount of moderate PA, while it reduced mental load. The EG retained reached motor efficiency levels 4 weeks after the intervention. No differences were found in IPAQ. The UP150 demonstrated to be a proactive environment and to be efficient in the promotion of PA, improving PF and mental health while decreasing mental load.


Subject(s)
Health Promotion , Mental Health , Exercise/psychology , Female , Humans , Male , Surveys and Questionnaires , Workplace
3.
Nat Immunol ; 23(2): 275-286, 2022 02.
Article in English | MEDLINE | ID: covidwho-1661973

ABSTRACT

The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in coronavirus disease 2019 (COVID-19). The present study was designed to conduct a systematic investigation of the interaction of human humoral fluid-phase pattern recognition molecules (PRMs) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of 12 PRMs tested, the long pentraxin 3 (PTX3) and mannose-binding lectin (MBL) bound the viral nucleocapsid and spike proteins, respectively. MBL bound trimeric spike protein, including that of variants of concern (VoC), in a glycan-dependent manner and inhibited SARS-CoV-2 in three in vitro models. Moreover, after binding to spike protein, MBL activated the lectin pathway of complement activation. Based on retention of glycosylation sites and modeling, MBL was predicted to recognize the Omicron VoC. Genetic polymorphisms at the MBL2 locus were associated with disease severity. These results suggest that selected humoral fluid-phase PRMs can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications.


Subject(s)
COVID-19/immunology , Immunity, Humoral , Receptors, Pattern Recognition/immunology , SARS-CoV-2/immunology , Animals , C-Reactive Protein/immunology , C-Reactive Protein/metabolism , COVID-19/metabolism , COVID-19/virology , Case-Control Studies , Chlorocebus aethiops , Complement Activation , Coronavirus Nucleocapsid Proteins/genetics , Coronavirus Nucleocapsid Proteins/immunology , Coronavirus Nucleocapsid Proteins/metabolism , Female , Glycosylation , HEK293 Cells , Host-Pathogen Interactions , Humans , Male , Mannose-Binding Lectin/genetics , Mannose-Binding Lectin/immunology , Mannose-Binding Lectin/metabolism , Phosphoproteins/genetics , Phosphoproteins/immunology , Phosphoproteins/metabolism , Polymorphism, Genetic , Protein Binding , Receptors, Pattern Recognition/genetics , Receptors, Pattern Recognition/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Serum Amyloid P-Component/immunology , Serum Amyloid P-Component/metabolism , Signal Transduction , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells
4.
J Pers Med ; 11(11)2021 Nov 09.
Article in English | MEDLINE | ID: covidwho-1512451

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the coronavirus disease 2019 (COVID-19) pandemic. Besides virus intrinsic characteristics, the host genetic makeup is predicted to account for the extreme clinical heterogeneity of the disease, which is characterized, among other manifestations, by a derangement of hemostasis associated with thromboembolic events. To date, large-scale studies confirmed that genetic predisposition plays a role in COVID-19 severity, pinpointing several susceptibility genes, often characterized by immunologic functions. With these premises, we performed an association study of common variants in 32 hemostatic genes with COVID-19 severity. We investigated 49,845 single-nucleotide polymorphism in a cohort of 332 Italian severe COVID-19 patients and 1668 controls from the general population. The study was conducted engaging a class of students attending the second year of the MEDTEC school (a six-year program, held in collaboration between Humanitas University and the Politecnico of Milan, allowing students to gain an MD in Medicine and a Bachelor's Degree in Biomedical Engineering). Thanks to their willingness to participate in the fight against the pandemic, we evidenced several suggestive hits (p < 0.001), involving the PROC, MTHFR, MTR, ADAMTS13, and THBS2 genes (top signal in PROC: chr2:127192625:G:A, OR = 2.23, 95%CI = 1.50-3.34, p = 8.77 × 10-5). The top signals in PROC, MTHFR, MTR, ADAMTS13 were instrumental for the construction of a polygenic risk score, whose distribution was significantly different between cases and controls (p = 1.62 × 10-8 for difference in median levels). Finally, a meta-analysis performed using data from the Regeneron database confirmed the contribution of the MTHFR variant chr1:11753033:G:A to the predisposition to severe COVID-19 (pooled OR = 1.21, 95%CI = 1.09-1.33, p = 4.34 × 10-14 in the weighted analysis).

5.
World J Gastroenterol ; 27(33): 5520-5535, 2021 Sep 07.
Article in English | MEDLINE | ID: covidwho-1403895

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); since its first description in December 2019, it has rapidly spread to a global pandemic. Specific concerns have been raised concerning patients with inflammatory bowel diseases (IBD), which are chronic autoimmune inflammatory disorders of the gut that frequently require immunosuppressive and biological therapies to control their activity. Accumulating evidence has so far demonstrated that patients with IBD are not at increased risk of contracting severe acute respiratory syndrome coronavirus 2 infection. As for the general population, the identified risk factors for severe COVID-19 course among IBD patients have been established to be advanced age and the presence of comorbidities. Treatment with high-dose corticosteroids has also been associated with an increased risk of death in IBD patients with COVID-19. Information on COVID-19 is constantly evolving, with data growing at a rapid pace. This will guarantee better knowledge and stronger evidence to help physicians in the choice of the best therapeutic approach for each patient, concurrently controlling for the risk of IBD disease under treatment and the risk of COVID-19 adverse outcomes and balancing the two. Moreover, the impact of the enormous number of severe respiratory patients on healthcare systems and facilities has led to an unprecedented redeployment of healthcare resources, significantly impacting the care of patients with chronic diseases. In this newly changed environment, the primary aim is to avoid harm whilst still providing adequate management. Telemedicine has been applied and is strongly encouraged for patients without the necessity of infusion therapy and whose conditions are stable. The severe acute respiratory syndrome coronavirus 2 pandemic has already revolutionized the management of patients with chronic immune-mediated diseases such as IBD. Direct and indirect effects of the COVID-19 pandemic will be present for some time. This is the reason why continuous research, rapid solutions and constantly updated guidelines are of utmost importance. The aim of the present review is, therefore, to point out what has been learned so far as well as to pinpoint the unanswered questions and perspectives for the future.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Telemedicine , Humans , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/epidemiology , Pandemics , SARS-CoV-2
6.
World J Gastrointest Surg ; 13(7): 702-716, 2021 Jul 27.
Article in English | MEDLINE | ID: covidwho-1346630

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19), an infectious condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread worldwide since its first description in Wuhan in December 2019. Even though respiratory manifestations are the most prevalent and responsible for disease morbidity and mortality, extrapulmonary involvement has progressively gained relevance. In particular, gastrointestinal (GI) signs and symptoms, reported in up to two-thirds of patients with COVID-19, might represent the first and, in some cases, the only disease presentation. Their presence has been associated in some studies with an increased risk of a severe disease course. Proposed pathogenic mechanisms explaining GI tract involvement are either direct viral access to intestinal cells via angiotensin-converting enzyme 2 or indirect damage of the intestinal wall through mesenteric ischemia induced by the hypercoagulable state associated with COVID-19 infection. Although not typical of SARS-CoV-2 infection, several small bowel manifestations have been described in infected patients who underwent any form of abdominal imaging. The radiological findings were mainly reported in patients with abdominal symptoms, among which abdominal pain was the most common. AIM: To discuss small bowel radiological manifestations of SARS-CoV-2 infection in abdominal imaging studies. METHODS: Bibliographical searches were performed in PubMed, using the following keywords: "COVID-19" AND "imaging" AND "gastrointestinal" OR "abdominal" OR "small bowel". RESULTS: Of 62 patients with described radiologic small bowel alterations, mesenteric ischemia was diagnosed in 31 cases (50%), small bowel wall thickening in 10 cases (16%), pneumatosis in nine cases (15%), intussusception in eight cases (13%), pneumoperitoneum in two cases (3%) and paralytic ileus in two cases (3%). We also reported mesenteric adipose tissue hypertrophy and lymph nodes enlargement in a young woman. CONCLUSION: So far it is difficult to establish whether these manifestations are the direct consequence of SARS-CoV-2 infection or collateral findings in infected patients, but their recognition would be pivotal to set a closer follow-up and to reduce missed diagnoses.

7.
Hepatology ; 73(6): 2099-2109, 2021 06.
Article in English | MEDLINE | ID: covidwho-1274695

ABSTRACT

BACKGROUND AND AIMS: Data regarding outcome of COVID-19 in patients with autoimmune hepatitis (AIH) are lacking. APPROACH AND RESULTS: We performed a retrospective study on patients with AIH and COVID-19 from 34 centers in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes, defined as the need for mechanical ventilation, intensive care admission, and/or death. The outcomes of patients with AIH were compared to a propensity score-matched cohort of patients without AIH but with chronic liver diseases (CLD) and COVID-19. The frequency and clinical significance of new-onset liver injury (alanine aminotransferase > 2 × the upper limit of normal) during COVID-19 was also evaluated. We included 110 patients with AIH (80% female) with a median age of 49 (range, 18-85) years at COVID-19 diagnosis. New-onset liver injury was observed in 37.1% (33/89) of the patients. Use of antivirals was associated with liver injury (P = 0.041; OR, 3.36; 95% CI, 1.05-10.78), while continued immunosuppression during COVID-19 was associated with a lower rate of liver injury (P = 0.009; OR, 0.26; 95% CI, 0.09-0.71). The rates of severe COVID-19 (15.5% versus 20.2%, P = 0.231) and all-cause mortality (10% versus 11.5%, P = 0.852) were not different between AIH and non-AIH CLD. Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (P < 0.001; OR, 17.46; 95% CI, 4.22-72.13). Continuation of immunosuppression or presence of liver injury during COVID-19 was not associated with severe COVID-19. CONCLUSIONS: This international, multicenter study reveals that patients with AIH were not at risk for worse outcomes with COVID-19 than other causes of CLD. Cirrhosis was the strongest predictor for severe COVID-19 in patients with AIH. Maintenance of immunosuppression during COVID-19 was not associated with increased risk for severe COVID-19 but did lower the risk for new-onset liver injury during COVID-19.


Subject(s)
COVID-19 , Hepatitis, Autoimmune , Adolescent , Adult , Aged , Aged, 80 and over , Americas , COVID-19/complications , COVID-19/epidemiology , Europe , Female , Hepatitis, Autoimmune/complications , Hepatitis, Autoimmune/epidemiology , Humans , Male , Middle Aged , Propensity Score , Retrospective Studies , Young Adult
8.
Hepatology ; 73(6): 2099-2109, 2021 06.
Article in English | MEDLINE | ID: covidwho-1130497

ABSTRACT

BACKGROUND AND AIMS: Data regarding outcome of COVID-19 in patients with autoimmune hepatitis (AIH) are lacking. APPROACH AND RESULTS: We performed a retrospective study on patients with AIH and COVID-19 from 34 centers in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes, defined as the need for mechanical ventilation, intensive care admission, and/or death. The outcomes of patients with AIH were compared to a propensity score-matched cohort of patients without AIH but with chronic liver diseases (CLD) and COVID-19. The frequency and clinical significance of new-onset liver injury (alanine aminotransferase > 2 × the upper limit of normal) during COVID-19 was also evaluated. We included 110 patients with AIH (80% female) with a median age of 49 (range, 18-85) years at COVID-19 diagnosis. New-onset liver injury was observed in 37.1% (33/89) of the patients. Use of antivirals was associated with liver injury (P = 0.041; OR, 3.36; 95% CI, 1.05-10.78), while continued immunosuppression during COVID-19 was associated with a lower rate of liver injury (P = 0.009; OR, 0.26; 95% CI, 0.09-0.71). The rates of severe COVID-19 (15.5% versus 20.2%, P = 0.231) and all-cause mortality (10% versus 11.5%, P = 0.852) were not different between AIH and non-AIH CLD. Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (P < 0.001; OR, 17.46; 95% CI, 4.22-72.13). Continuation of immunosuppression or presence of liver injury during COVID-19 was not associated with severe COVID-19. CONCLUSIONS: This international, multicenter study reveals that patients with AIH were not at risk for worse outcomes with COVID-19 than other causes of CLD. Cirrhosis was the strongest predictor for severe COVID-19 in patients with AIH. Maintenance of immunosuppression during COVID-19 was not associated with increased risk for severe COVID-19 but did lower the risk for new-onset liver injury during COVID-19.


Subject(s)
COVID-19 , Hepatitis, Autoimmune , Adolescent , Adult , Aged , Aged, 80 and over , Americas , COVID-19/complications , COVID-19/epidemiology , Europe , Female , Hepatitis, Autoimmune/complications , Hepatitis, Autoimmune/epidemiology , Humans , Male , Middle Aged , Propensity Score , Retrospective Studies , Young Adult
9.
Hepatol Commun ; 2020 Jun 09.
Article in English | MEDLINE | ID: covidwho-1005756

ABSTRACT

BACKGROUND & AIMS: Chronic immunosuppression is associated with increased and more severe viral infections. However, little is known about the association between immunosuppression and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our aim was to describe the clinical course of immunosuppressed autoimmune hepatitis (AIH) patients during coronavirus disease 2019 (COVID-19) infection in Italy. METHODS: Our study is a case series of AIH patients treated with immunosuppression, who tested positive for SARS-CoV-2 in March 2020 during outbreak of COVID-19. RESULTS: Ten patients from six different hospitals in Italy were diagnosed with COVID-19 during the outbreak of SARS-CoV-2 in March 2020. Seven subjects were female (70%) and age ranged from 27 to 73 years. Before the onset of SARS-CoV-2 infection, all patients were taking immunosuppressive therapy for AIH, and eight of them were on biochemical remission. Two other patients had recent acute onset of their AIH, and were consequently started high-dose steroids, as per induction protocol. All patients had a respiratory syndrome and had a positive nasal swab for SARS-CoV-2. Five patients developed a CT-confirmed COVID-19 pneumonia. Six subjects received a combination of antiretroviral and antimalarial drugs. In seven patients the dosage of immunosuppressive medication was changed. Liver enzymes were repeated during SARS-CoV-2 infection in all hospitalized cases; they remained within the normal range in all cases, and improved in the two acute cases treated with high-dose steroids. The clinical outcome was comparable to the reported cases occurring in non-immunosuppressed subjects. CONCLUSION: Patients under immunosuppressive therapy for AIH developing COVID-19 show a disease course presumptively similar to that reported in non-immunosuppressed population. These data might help medical decision when dealing with SARS-CoV-2 infection in immunocompromised patients.

11.
N Engl J Med ; 383(16): 1522-1534, 2020 10 15.
Article in English | MEDLINE | ID: covidwho-606974

ABSTRACT

BACKGROUND: There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19. METHODS: We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case-control panels. RESULTS: We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10-8) in the meta-analysis of the two case-control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P = 1.15×10-10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P = 4.95×10-8, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group-specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P = 1.48×10-4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P = 1.06×10-5). CONCLUSIONS: We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.).


Subject(s)
ABO Blood-Group System/genetics , Betacoronavirus , Chromosomes, Human, Pair 3/genetics , Coronavirus Infections/genetics , Genetic Predisposition to Disease , Pneumonia, Viral/genetics , Polymorphism, Single Nucleotide , Respiratory Insufficiency/genetics , Aged , COVID-19 , Case-Control Studies , Chromosomes, Human, Pair 9/genetics , Coronavirus Infections/complications , Female , Genetic Loci , Genome-Wide Association Study , Humans , Italy , Male , Middle Aged , Multigene Family , Pandemics , Pneumonia, Viral/complications , Respiratory Insufficiency/etiology , SARS-CoV-2 , Spain
12.
J Hepatol ; 73(5): 1063-1071, 2020 11.
Article in English | MEDLINE | ID: covidwho-591707

ABSTRACT

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) poses a major health threat to healthy individuals and those with comorbidities, but its impact on patients with cirrhosis is currently unknown. Herein, we aimed to evaluate the impact of COVID-19 on the clinical outcome of patients with cirrhosis. METHODS: In this multicentre retrospective study, patients with cirrhosis and a confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were enrolled between 1st and 31th March 2020. Clinical and biochemical data at diagnosis of COVID-19 and at the last outpatient visit were obtained through review of medical records. RESULTS: Fifty patients with cirrhosis and confirmed SARS-CoV-2 infection were enrolled (age 67 years, 70% men, 38% virus-related, 52% previously compensated cirrhosis). At diagnosis, 64% of patients presented fever, 42% shortness of breath/polypnea, 22% encephalopathy, 96% needed hospitalization or a prolonged stay if already in hospital. Respiratory support was necessary in 71%, 52% received antivirals, 80% heparin. Serum albumin significantly decreased, while bilirubin, creatinine and prothrombin time significantly increased at COVID-19 diagnosis compared to last available data. The proportion of patients with a model for end-stage liver disease (MELD) score ≥15 increased from 13% to 26% (p = 0.037), acute-on-chronic liver failure and de novo acute liver injury occurred in 14 (28%) and 10 patients, respectively. Seventeen patients died after a median of 10 (4-13) days from COVID-19 diagnosis, with a 30-day-mortality rate of 34%. The severity of lung and liver (according to CLIF-C, CLIF-OF and MELD scores) diseases independently predicted mortality. In patients with cirrhosis, mortality was significantly higher in those with COVID-19 than in those hospitalized for bacterial infections. CONCLUSION: COVID-19 is associated with liver function deterioration and elevated mortality in patients with cirrhosis. LAY SUMMARY: Coronavirus disease 2019 (COVID-19) poses a major health threat to healthy individuals and those with comorbidities. Herein, we assessed its impact on patients with cirrhosis. Infection with COVID-19 was associated with liver function deterioration and elevated mortality in patients with cirrhosis.


Subject(s)
Coronavirus Infections , Liver Cirrhosis , Liver Function Tests , Pandemics , Pneumonia, Viral , Aged , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/methods , Comorbidity , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Female , Humans , Italy/epidemiology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Liver Cirrhosis/physiopathology , Liver Function Tests/methods , Liver Function Tests/statistics & numerical data , Male , Mortality , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Retrospective Studies , Risk Factors , SARS-CoV-2
13.
Clin Gastroenterol Hepatol ; 18(10): 2375-2377, 2020 09.
Article in English | MEDLINE | ID: covidwho-437178

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a major worldwide threat caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly spreading to a global pandemic. As of May 11, 2020, 4,176,346 cases have been reported worldwide, 219,814 in Italy, and of them, 81,871 occurred in the Lombardy region.1 Although the respiratory manifestations of COVID-19 have been widely described, the impact on the gastrointestinal (GI) system remains less clear. The reported prevalence of digestive symptoms ranges from 3% to 79%, depending on the setting,2-5 but data on GI endoscopic and histologic findings in COVID-19 patients are lacking. Therefore, the aim of this study is to describe the GI endoscopic and histologic findings in COVID-19 patients.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Digestive System Diseases/diagnosis , Endoscopy, Gastrointestinal/methods , Pneumonia, Viral/diagnosis , Aged , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Digestive System Diseases/etiology , Female , Humans , Italy/epidemiology , Male , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Retrospective Studies , SARS-CoV-2
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