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Introduction: Since 2020 COVID-19 pandemic has spread throughout the world and became an ongoing global health crisis due to SARS-CoV-2 virus. Elderly and pre-existing disorders including hypertension, heart problems, diabetes, cancer, autoimmune diseases and IBD are found associated with an increased risk of COVID-19. Although COVID-19 leads to mild flu-like symptoms in the majority of patients, the disease may cause severe complications and death. To date, a few clinical studies suggested that IBD and/or immunomodulation may reduce the susceptibility to COVID-19;however, the mechanisms through which this is happening is largely unknown. Aims & Methods: Aim of this study is to investigate the effects of IBD and different therapies on the risk of SARS-CoV-2 infection and COVID-19 severity through serum proteomics and metabolomics. Between April 2020 and April 2022, 238 IBD patients (N=145 Crohn disease, N=93 Ulcerative colitis) and 45 healthy controls (HC) of the North Italy area were enrolled and serum samples were collected. To evaluate the exposure to SARSCoV- 2, both clinical data were collected and seroprevalence of anti-SARSCoV- 2 Ab were analyzed by means of multiplex technology, the BioPlex 2200 Sars-Cov-2 IgG Panel (biorad, Italy). Serum samples underwent untargeted metabolomics analysis and the frequency of a serum metabolomics signature associated with protection were evaluated in IBD compared to HC and also between anti-TNF and Vedolizumab biological therapies for IBD patients. Result(s): The seroprevalence of anti-SARS-CoV-2 Ab in IBD cohort (22/238) indicates an overall lower incidence of COVID-19 in comparison with the general population of Lombardy. Our data indicated that IBD patients in treated with biologic drugs as anti-TNF (10,5%) and Vedolizumab (7,5%) have a lower incidence than IBD patients treated with conventional therapies (28,0%). Accordingly, we observed that serum metabolomics signature associated with protection was more frequent in IBD patients treated with anti-TNF (N=50, 70%), and with Vedolizumab (N=57, 85%) than healthy controls (N=45, 50%). The metabolomic protective profile is characterized by the presence of fat-soluble Tocopherols family members and Cholecalciferol and also of omega-3 and omega-6 polyunsaturated fatty acid. Conclusion(s): Our study indicates that IBD population treated with biologics has an overall lower risk to contract SARS-CoV-2 infection and a serum proteomic/metabolomic protection profile. The increased presence in IBD patients of radical scavengers such as tocopherols which are incorporated into cell membranes and protect against oxidative damage and anti-inflammatory and immunomodulating fatty acids suggest a better response to SARS-CoV-2 infection. Also increased levels of omega;-3 interfere with the entry of the virus by modulating the Lipid Rafts where ACE2 and TMPRSS2 are mainly expressed and PUFAs inhibit the attachment of SARS-CoV-2 virions to the human ACE2 receptor by interacting directly with the RBD sequence. Mechanistically understanding how this protection profile exerts its effects on COVID-19 severity might shed light on potential targets to increase resistance in higher risk subgroups of patients.
ABSTRACT
Introduction: The current pandemia is due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that was originally identified in China in 2019, when numerous cases of atypical pneumonia were reported. Elderly and pre-existing disorders including hypertension, heart problems, diabetes, cancer, autoimmune diseases and IBD are found associated with an increased risk of COVID-19. A few clinical studies suggested that IBD and immunomodulation may reduce the susceptibility to COVID-19;however, the molecular mechanisms are not fully revealed. Aims & Methods: In this study, we attempted to identify a transcriptomic signature as candidate of the effects of IBD and different therapies on the risk of SARS-CoV-2 infection and COVID-19 severity through colonic tissue gene expression. In 2020-2022, 192 IBD patients, 115 Crohn disease (CD), 77 Ulcerative colitis (UC) and 36 Healthy Controls (HC) of the North Italy area were enrolled. Colon biopsies from inflamed and non-inflamed mucosa were collected from IBD patients and healthy mucosa samples were collected from HC. To evaluate the exposure to SARS-CoV-2, clinical data were collected and seroprevalence of anti-SARS-CoV-2 Ab were analyzed by means of multiplex technology with BioPlex 2200 Sars-Cov-2 IgG Panel (biorad, Italy). Gene expression analysis of ACE2, TMPRSS2, TMPRSS4, ADAM17 were performed by qPCR in biopsies of the three experimental groups. Result(s): In IBD patients cohort the seroprevalence of anti-SARS-CoV-2 antibodies indicates an overall lower incidence of COVID-19 in comparison with the general population of Lombardy, and also a lower incidence in IBD patients in biological therapies vs. conventional ones. Gene expression analysis of the proteins involved in SARS-CoV-2 entry indicated that IBD patients treated with anti-TNF (N=72) had a lower mucosal level of SARS-CoV-2 receptor ACE2 and its sheddase ADAM17 than non-IBD subjects along with higher expression of the proteases TMPRSS2 and TMPRSS4. Moreover, vedolizumab-treated patients (N=40) showed a significant lower expression of ACE2, TMPRSS2 and TMPRSS4 than controls, whereas ADAM17 levels were similar. Conclusion(s): Data presented in our study suggest that the biologic-treated IBD population has an overall lower risk of contracting SARS-CoV-2 infection. Colonic expression of proteins involved in SARS-CoV-2 virus entry suggested an additional protective mechanism. Understanding the association of this protection profile with COVID-19 severity and the mechanisms of virus entry into the colon could reveal resistance pathways in higher-risk patient subgroups.
ABSTRACT
Background: The current novel coronavirus (SARS-CoV-2) pandemic is an ongoing global health crisis, which represents an important challenge for the whole society and mankind. Patients with inflammatory bowel disease (IBD) are treated with immunosuppressive drugs that are usually associated with more severe viral infections. However, the effects of the different therapies on the risk of SARS-CoV-2 infection and Covid-19 severity in IBD patients are still under investigation. Methods: Between April 2020 and April 2021, 238 IBD patients (N=145 with Crohn disease and N=93 with Ulcerative colitis) of the North Italy area have been enrolled. Both serum samples (N=238 IBD patients and N=45 healthy donors) and colon biopsies from inflamed and non-inflamed mucosa (N=88 IBD patients N=20 non-IBD control) have been collected. To evaluate the exposure to SARS-CoV-2, both clinical data and seroprevalence of anti-SARS-CoV-2 Ab have been analyzed. Serum samples were analyzed by untargeted metabolomics analysis and the frequency of a serum metabolomics signature associated with protection were evaluated in IBD versus healthy donors. Moreover, gene expression analysis of key proteins for virus entry (ACE2, TMPRSS2, TMPRSS4, ADAM17) were analyzed by qPCR in the gut mucosa biopsies of IBD patients. Results: The seroprevalence of anti-SARS-CoV-2 Ab in our cohort of IBD patients (10/238) indicates an overall lower incidence of COVID-19 in comparison with the general population of Lombardy. Accordingly, we observed that the serum metabolomics signature associated with protection was more frequent in IBD patients treated with anti-TNF (N=50, 70%), than healthy controls (N=45, 50%). Gene expression analysis of the proteins involved in SARS-CoV-2 entry also indicated that IBD patients treated with anti-TNF (N=14) had a lower mucosal level of SARS-CoV-2 receptor ACE2 and its sheddase ADAM17 than non-IBD subjects along with higher expression of the proteases TMPRSS2 and TMPRSS4. Moreover, vedolizumab-treated patients (N=7) showed a significant lower expression of ACE2, TMPRSS2 and TMPRSS4 than controls, whereas ADAM17 levels were similar. Conclusion: Our study indicates that IBD population treated with biologics has an overall lower risk to contract SARS-CoV-2 infection. Future studies to gather the mechanisms underpinning the effects of biologics on the expression of the proteins involved in SARS-CoV-2 viral entry in association with the specific metabolomics signature of viral susceptibility might shed light on potential targets to increase resistance in higher risk subgroups of patients.
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Background: The COVID-19 pandemic has dramatically changed lifestyles and quality of life (QoL) of the global population. Little is known regarding the psychological impact of the COVID-19 outbreak on patients with gastroenteropancreatic (GEP) or bronchopulmonary (BP) neuroendocrine tumors (NETs). Methods: We prospectively evaluated seven specific constructs (depression, anxiety, stress, QoL, NET-related QoL, patient-physician relationship, psychological distress) by using validated screening instruments including the Depression anxiety stress scale-21 (DASS-21), the EORTC QLQ-C30, the EORTC QLQ GI.NET21, the patient doctor relationship questionnaire 9 (PDRQ9) and the Impact of event scale-revised (IES-R). Mental symptoms and concerns of patients with any stage, well-differentiated GEP or BP-NET were surveyed twice, during the plateau phase of the first (W1) and second epidemic waves (W2) in Italy. Results: We enrolled 197 patients (98 males) with a median age of 62 years (G1/G2: 96%;pancreas: 29%;small bowel: 25%;active treatment: 38%). At W1, the prevalence of depression, anxiety and stress was 32%, 36% and 26% respectively. The frequency of depression and anxiety increased to 38% and 41% at W2, with no modifications in the frequency of stress. By ordinal logistic regression analysis, female patients showed more severe forms of stress at W1 (OR=0.45±0.14;p=0.01), while the educational status was associated with the levels of anxiety at both W1 (OR=1.33±0.22;p=0.07) and W2 (OR=1.45±0.26;p=0.03). An improvement of the physical (p=0.03) and emotional functioning domains (p=0.001) was observed over time. Both nausea/vomiting (p=0.0002), appetite (p=0.02), treatment related symptoms (p=0.005), disease-related worries (p=0.0006) and sexual function (p=0.02) improved between W1 and W2, suggesting that NET patients were able to cope with the perturbations caused by the pandemic. No difference was seen between W1 and W2 in the mean score (>4/5) of the PDRQ9. By IES-R, post-traumatic stress disorder was observed in 53% of patients at W2. Conclusions: The implementation of psychological interventions within NET clinics might favor the emergence of functional coping strategies, attenuating the psychological distress caused by the COVID-19 pandemic.
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Background: A great disparity in CRCS adherence exists between the various Regions of Italy, ranging from 98% (North) to 44% (South). The AIRTUM report in 2019 counted almost 2900 new CRC diagnosis for the Apulian Region, while CRCS adherence was inferior to 5%. To counterbalance this trend, an ORSS has been started since September 2019, consisting in an invitation to faecal occult blood tests for people aged 50-70 years. The effects of this strategy have not yet been quantified, while SARS-COV2 pandemic interference is unknown. The aim of our study was to evaluate the percentage of patients with recent CRC diagnosis by screening in a period across the start of the ORSS and unravel the reasons for patient refusal. Material and methods: Patients aged >50 years and residing in Apulia with CRC diagnosis made at the Division of Medical Oncology in “A.O.U. Consorziale Policlinico di Bari” between May 2018 and April 2021 were interviewed by phone. Hereditary or IBD related CRC were both considered exclusion criteria. We collected data about the cause of diagnosis, knowledge of CRCS, how the subjects were informed about screening and reasons for non-adhesion. Close relatives were also asked if had joined or intended to take part in CRCS since they were considered a very sensitized population. Results: We enrolled 130 patients, including 60 diagnosed before and 70 after September 2019. Overall, 10% of patients had received a diagnosis of CRC by screening. Of these, 1% was diagnosed before the start of the ORSS and 9% after. Only 23% of participants were sufficiently learned of CRCS across the study period, while invitation was received from ORSS in 14% and from general practitioners (GP) in 6%. The major reasons for CRCS denial were “diffidence” (65%) and “futility” (35%). Among close relatives of people with recent CRC history, a 24% of CRCS adherence was observed, while another 50% of them said that intended to take the test. Conclusions: We found an inadequate adherence to CRCS mainly due to poor consciousness of CRC disease and prevention, while it significantly increased in sensitized people. Moreover, the higher percentage of CRC diagnoses made by CRCS since 2019 may represent a direct effect of the ORSS, although the number of persons invited is still not enough. These data confirm the gap of the Apulia from other Italian Regions regarding the reluctance to carry out CRCS and suggest greater investments in awareness campaigns for the population and GP.
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Background: The outbreak of the COVID-19 pandemic led to a rapid reorganization of health care system in Italy. Therefore, CS slowed down during the two lockdown periods including for BC primary prevention such as mammography and breast ultrasound. Hence, the aim of our retrospective analysis was to evaluate the impact of the discontinuation of CS and subsequent delay in surgical treatment during COVID-19 on BC diagnosis. Patients and methods: All patients who underwent breast surgery after BC diagnosis from March 8, 2019 to March 8, 2021 were included in the study. Our population was then divided into two groups: group A, pre-Pandemic group, considered women who underwent surgical procedures from March 2019 to March 2020. Group B, Pandemic group, included patients who underwent breast surgery from March 9, 2020 to March 8, 2021. Results: A total of 524 newly diagnosed patients were evaluated;n=239 and n=285 in the pre-Pandemic and Pandemic, respectively. We observe an increase of patients with lymph-node involvement (35% vs 29% p= 0.14) and with a higher cancer stage (Stage III-IV 20% vs 15% p=0.13), but not statistically significative in the Pandemic Group compared to the pre-Pandemic group. Conclusions: In our analysis, the slowdown of CS for BC did not have a significant impact on BC diagnosis even though our data reveal a slight increase of advanced BC stage in pandemic group. Hence, a potential explanation could be identified in our efforts to keep diagnosis and treating oncological patients. Nevertheless, new data about post covid BC diagnosis are not still available. Reasonable, our findings are most likely going to be re-debeated in few years to clarify if this trend could be confirmed.
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Background: The COVID-19 pandemic has dramatically changed lifestyles and quality of life (QoL) of the global population. Little is known regarding the psychological impact of the COVID-19 outbreak on patients with gastroenteropancreatic (GEP) or bronchopulmonary (BP) neuroendocrine tumors (NETs). Methods: We prospectively evaluated seven specific constructs (depression, anxiety, stress, QoL, NET-related QoL, patient-physician relationship, psychological distress) by using validated screening instruments including the Depression anxiety stress scale-21 (DASS-21), the EORTC QLQ-C30, the EORTC QLQ GI.NET21, the patient doctor relationship questionnaire 9 (PDRQ9) and the Impact of event scale-revised (IES-R). Mental symptoms and concerns of patients with any stage, well-differentiated GEP or BP-NET were surveyed twice, during the plateau phase of the first (W1) and second epidemic waves (W2) in Italy. Results: We enrolled 197 patients (98 males) with a median age of 62 years (G1/G2: 96%;pancreas: 29%;small bowel: 25%;active treatment: 38%). At W1, the prevalence of depression, anxiety and stress was 32%, 36% and 26% respectively. The frequency of depression and anxiety increased to 38% and 41% at W2, with no modifications in the frequency of stress. By ordinal logistic regression analysis, female patients showed more severe forms of stress at W1 (OR=0.45±0.14;p=0.01), while the educational status was associated with the levels of anxiety at both W1 (OR=1.33±0.22;p=0.07) and W2 (OR=1.45±0.26;p=0.03). An improvement of the physical (p=0.03) and emotional functioning domains (p=0.001) was observed over time. Both nausea/vomiting (p=0.0002), appetite (p=0.02), treatment-related symptoms (p=0.005), disease-related worries (p=0.0006) and sexual function (p=0.02) improved between W1 and W2, suggesting that NET patients were able to cope with the perturbations caused by the pandemic. No difference was seen between W1 and W2 in the mean score (>4/5) of the PDRQ9. By IES-R, post-traumatic stress disorder was observed in 53% of patients at W2. Conclusions: The implementation of psychological interventions within NET clinics might favor functional coping strategies, attenuating the psychological distress caused by the COVID-19 pandemic. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
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BACKGROUND: The SARS-CoV-2 pandemic still has a huge impact on the management of many chronic diseases such as cancer. Few data are presently available reagarding how the management of renal cell carcinoma (RCC) has changed due to this unprecedented situation. OBJECTIVE: To discuss the challenges and issues of the diagnosis and treatment of RCC in the COVID-19 era, and to provide recommendations based on the collected literature and our personal experience. METHODS: Systematic review of the available Literature regarding the management of RCC during the SARS-CoV-2 pandemic. RESULTS: Our review showed a prevalence of narrative publications, raising the issue of the real relevance of the evidence retrieved. Indeed, the only original data about RCC and COVID-19 found were a small retrospective case series and two surveys, providing either patients' or physicians' viewpoints. CONCLUSIONS: The expected delayed diagnosis of RCC could lead to an increase of advanced/metastatic cases;thus, proper therapeutic choices for patients with small renal masses should be carefully evaluated case by case, in order to avoid negative effects on long-term survival rates. The controversial interaction between immune checkpoint blockade and COVID-19 pathogenesis is more hypothetical than evidence-based, and thus immunotherapy should not be denied, whenever appropriate. To avoid treatments which won't have an impact on patients' survival, a honest and accurate evaluation of the cost/benefit ratio of each treatment option should be always performed. Finally, SARS-CoV-2 swab positivity should not prevent the continuation of ongoing active treatments in asymptomatic cases, or or after symptoms' resolution.
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Background: Although myocarditis can be a severe cardiac complication of COVID-19 patients, few data are available in the literature about the incidence and clinical significance in patientsaffected by SARS-CoV-2Methods: This study aims to investigate the incidence and theclinical-laboratory features of myocarditis in a cohort of patientshospitalized for COVID-19. We retrospectively evaluated all theconsecutive patients admitted for COVID-19 in our Medicine Department between March 4 to May 20, 2020. Age, sex, in-hospitaldeath, length of stay, comorbidities, serum cardiac markers, interleukin-6, electrocardiogram, echocardiogram and therapy wererecorded. Results: 1169 patients with COVID-19 were included in the studyperiod;no one was excluded. 12 patients (1%) had acute myocarditis;5 (41.7%) were men, mean age was 76 (SD 11.34);length of stay was 38 days on average (SD 8);3 (25%) patientsdied. 8 (66.7%) had a history of cardiac disease;7 (58.33%) patients had other comorbidities like diabetes, chronic obstructivepulmonary disease, or renal insufficiency.Conclusions: COVID-19 patients who experimented myocarditiswere older, had a higher frequency of previous cardiac diseaseand significantly more prolonged hospitalization and a lower valueof interleukin-6 than myocarditis patients without comorbidities.This is suggesting different myocarditis related pathogenetic mechanisms. Further studies, specifically designed on this issue, arewarranted.
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Background: COVID-19, the disease caused by SARS-CoV-2, ischaracterized by multiple lung infiltrates and extensive venous andarterial thromboembolism. Little is known about the natural historyof the disease, so we plan an outpatient clinic to follow COVID-19patients.Materials and Methods: All patients discharged alive who hasdeveloped respiratory insufficiency (i.e., arterial pO2 less than 60mmHg), or have needed mechanical ventilation for at least 72hours, or had lung infiltrates >40% of pulmonary parenchyma waseligible for the study. All those patients were re-evaluated at 1 and3 months after discharge with high-resolution CT (HRCT) of thechest, blood gases, blood chemistry, and Doppler color flow of theinvolved vessels.Results: Between February and May 2020, seventy-one COVID-19 patients were re-evaluated. Of these, with HRCT study, 12(17.14%) had pulmonary fibrosis, 19 (27,14%) had ground-glassopacities and 25 (35%) had multiple lesions;15 (21,43%) wasnormal;52 (73%) had persistent hypocapnia (mean pCO2 35.9;SD 3.26);14 had to start steroid therapy again;all patients hadcomplete vein recanalization at CUS. Conclusions: Our preliminary report showed that an outpatientclinic for patients convalescent from COVID-19 is highly advisableand may result in better knowledge of the natural history of thedisease and may help to clarify which patients will need in prolonged treatment and interventions. Furthermore, we speculatedthat a high incidence of persistent hypocapnia may result frompulmonary venous vessel microthrombosis.