Impact of SARS-CoV-2 infection in patients with hereditary hemorrhagic telangiectasia: epidemiological and clinical data from the comprehensive Italian retrospective multicenter study.

Rare Disease patients manifested high concern regarding the possible increased risk of severe outcomes and worsening of disease-specific clinical manifestation due to the impact of COVID-19. Our aim was to assess the prevalence, outcomes, and impact of COVID-19 in patients with a rare disease such as Hereditary Hemorrhagic Telangiectasia (HHT) in Italian population. A nationwide, multicentric, cross-sectional observational study was conducted on patients with HHT from five Italian HHT centers by online survey. The association between COVID-19-related signs and symptoms and nosebleeds worsening, the impact of personal protective equipment on nosebleeds pattern, and the relationship between the presence of visceral AVMs and severe outcomes were analyzed. Out of 605 total survey responses and eligible for analysis, 107 cases of COVID-19 were reported. A mild-course COVID-19 disease, not requiring hospitalization, was observed in 90.7% of patients, while the remaining eight cases needed hospitalization, two of them requiring intensive-care access. No fatal outcome was recorded and 79.3% of patients reported a complete recovery. No difference in infection risk and outcome between HHT patients and general population was evidenced. No significative interference of COVID-19 on HHT-related bleeding was found. The majority of patients received COVID-19 vaccination, with relevant impact on symptoms and need for hospitalization in case of infection. COVID-19 in HHT patients had an infection profile similar to the general population. COVID-19 course and outcome were independent from any specific HHT-related clinical features. Moreover, COVID-19 and anti-SARS-CoV-2 measures did not seem to affect significantly HHT-related bleeding profile.

Advanced Echocardiographic Analysis in Medium-Term Follow-Up of Children with Previous Multisystem Inflammatory Syndrome.

Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory disease related to SARS-CoV2 infection, with frequent cardiovascular involvement in the acute setting. The aim of the study was to evaluate the cardiac function at 6 months. Thirty-two patients diagnosed with MIS-C were enrolled and underwent advanced echocardiogram at discharge and at 6 months. According to the left ventricular ejection fraction (LVEF) at admission, the patients were divided into group A (LVEF < 45%) and group B (LVEF ≥ 45%) and the follow-up results were compared. At discharge, all patients had normal LV and RV systolic function (LVEF 61 ± 4.4%, LV global longitudinal strain -22.1%, TAPSE 20.1mm, s' wave 0.13m/s, RV free wall longitudinal strain -27.8%) with normal LV diastolic function (E/A 1.5, E/e' 5.7, and left atrial strain 46.5%) and no significant differences at 6 months. Compared to group B, the group A patients showed a reduced, even if normal, LV global longitudinal strain at discharge (-21.1% vs. -22.6%, p-value 0.02), but the difference was no longer significant at the follow-up. Patients with MIS-C can present with depressed cardiac function, but if treated, the cardiac function recovered without late onset of cardiac disease. This favorable result was independent of the severity of acute LV dysfunction.

New International Guidelines and Consensus on the Use of Lung Ultrasound.

Following the innovations and new discoveries of the last 10 years in the field of lung ultrasound (LUS), a multidisciplinary panel of international LUS experts from six countries and from different fields (clinical and technical) reviewed and updated the original international consensus for point-of-care LUS, dated 2012. As a result, a total of 20 statements have been produced. Each statement is complemented by guidelines and future developments proposals. The statements are furthermore classified based on their nature as technical (5), clinical (11), educational (3), and safety (1) statements.

Functional assessment and rehabilitation protocol in acute patients affected by SARS-CoV-2 infection hospitalized in the Intensive Care Unit and in the Medical Care Unit.

BACKGROUND: Coronavirus disease (COVID-19) is characterized by different clinical pictures that may require prolonged hospitalization and produce disabilities challenging the recovery of previous independence. AIM: The aim is to evaluate the impact of an early assisted rehabilitation program on the functional status of an acutely hospitalized population affected by COVID-19. DESIGN: Single-institution retrospective longitudinal study. SETTING: Inpatient intensive care units (ICU) and medical care units (MCU). POPULATION: Acute COVID-19 patients. METHODS: General information was collected; age-adjusted Charlson Comorbidity Index was used for comorbidities. Duration of hospital stay, the length of stay in ICU and/or MCU, the length of the rehabilitative treatment, and the destination at the discharge were collected. Evaluation was performed when patients were clinically stable (T0), and at hospital discharge (T1); for subjects enrolled in ICU functional status was assessed at the time of transfer to the MCU. Muscle strength of the four limbs was measured with the Medical Research Council (MRC) sum-score. Functional status was assessed using the 3-item Barthel Index (BI-3) and the General Physical Mobility Score (GPMS). Early assisted-tailored rehabilitation protocol was applied in ICU and in MCU: the aims were the maintenance (or recovery) of the range of motion and of the strength and the recovery of sitting/standing position and gait. RESULTS: We evaluated 116 patients (mean age 65, SD 11) (65% male), 68 in ICU (mean age 60, SD 10), 48 in MCU (mean age 73, SD 9). At discharge, BI-3 and GPMS significantly improved in both ICU (P<0.001) and MCU (P<0.001) subgroups of patients. MRC sum-score significantly improved in ICU patients (P<0.001). Patients hospitalized in ICU had a significantly longer hospital stay. At discharge, patients admitted to the ICU reach a functional state that is close to that of patients admitted to the MCU. CONCLUSIONS: The results suggest that an early assisted rehabilitation program may be helpful in improving the short-term functional status of an acutely hospitalized population affected by COVID-19, with discharge at home of 48% CLINICAL REHABILITATION IMPACT: this study focuses on a functional assessment method to be used to identify the rehabilitation needs and verify the results of an early rehabilitation protocol applied to the acute COVID-19 patient admitted to ICU and MCU.

Serum and breastmilk SARS-CoV-2 specific antibodies following BNT162b2 vaccine: prolonged protection from SARS-CoV-2 in newborns and older children.

OBJECTIVES: Vaccination is the best strategy against COVID-19. We aimed to determine antibodies against SARS-CoV-2 in breastmilk and serum of mothers vaccinated with the mRNA vaccine. METHODS: This prospective study included 18 lactating women vaccinated with the BNT162b2 vaccine. Serum and breastmilk were collected before the first dose (T0), at the second dose (T1), 3 weeks after the second dose (T2), and 6 months after the first dose (T3). Serum anti-SARS-CoV-2 Spike (S) Immunoglobulin G (IgG) and Immunoglobulin A (IgA) were measured using a semi-quantitative enzyme-linked immunosorbent assay (ELISA) and secretory antibody (s) IgG and IgA in breastmilk using quantitative analysis. RESULTS: We detected serum anti-S IgG and IgA in all women after vaccination. Specific IgG and IgA were higher at T1, T2, and T3 compared with T0 (P <0.0001). Higher antibody levels were observed at T2 and lower values at T3 versus T2 (P = 0.007). After 6 months, all patients had serum IgG, but three of 18 (16%) had serum IgA. In breastmilk, sIgA was present at T1 and T2 and decreased after 6 months at T3 (P = 0.002). Breastmilk sIgG levels increased at T1 and T2 and peaked at T3 (P = 0.008). CONCLUSION: Secretory antibodies were transmitted through breastmilk until 6 months after anti-COVID-19 mRNA vaccination. Protection of the newborn through breastfeeding needs to be addressed.

Advanced Echocardiographic Analysis in Medium-Term Follow-Up of Children with Previous Multisystem Inflammatory Syndrome

Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory disease related to SARS-CoV2 infection, with frequent cardiovascular involvement in the acute setting. The aim of the study was to evaluate the cardiac function at 6 months. Thirty-two patients diagnosed with MIS-C were enrolled and underwent advanced echocardiogram at discharge and at 6 months. According to the left ventricular ejection fraction (LVEF) at admission, the patients were divided into group A (LVEF < 45%) and group B (LVEF ≥45%) and the follow-up results were compared. At discharge, all patients had normal LV and RV systolic function (LVEF 61 ±4.4%, LV global longitudinal strain −22.1%, TAPSE 20.1mm, s' wave 0.13m/s, RV free wall longitudinal strain −27.8%) with normal LV diastolic function (E/A 1.5, E/e' 5.7, and left atrial strain 46.5%) and no significant differences at 6 months. Compared to group B, the group A patients showed a reduced, even if normal, LV global longitudinal strain at discharge (−21.1% vs. −22.6%, p-value 0.02), but the difference was no longer significant at the follow-up. Patients with MIS-C can present with depressed cardiac function, but if treated, the cardiac function recovered without late onset of cardiac disease. This favorable result was independent of the severity of acute LV dysfunction.

Very High Negative Concordance Rate of RT-PCR for SARS-CoV-2 in Nasopharyngeal Swab and Tracheo-Bronchial Aspirate in Children

Reliable testing methods for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children are essential to allow normal activities. Diagnosis of SARS-CoV-2 infection is currently based on real-time reverse transcriptase-polymerase chain reaction (RT-PCR) performed on nasopharyngeal (NP) swabs;concerns have been raised regarding NP swab accuracy in children to detect the virus because of potential lack of cooperation of the patients or due to general uncertainties about concordance between high and low respiratory tract specimens in children. The aim of the study (IRB approval: ST/2020/405) is to prospectively compare RT-PCR results on NP and tracheo-bronchial aspirate (TA) in children admitted to the hospital for surgery or admitted to the Pediatric Intensive Care Unit (PICU) of a tertiary children hospital in Milano, Italy, during a peak of COVID-19 infections in the city. A total of 385 patients were enrolled in the study: 364 from surgical theater and 21 from PICU. Two patients (0.5%) tested positive on TA and were negative on NP;both cases occurred in November 2020, during a peak of infection in the city. Specificity of NP swab was.995 (95% CI: 0.980–0.999). Two patients with positive NP swabs tested negative on TA. Conclusion Our study shows that the specificity of SARS-CoV-2 RT-PCR on TA swab, compared to results of SARS-CoV-2 RT-PCR on NP, was very high for negative cases in our pediatric cohort during a period of high epidemiological pressure.

ECHOPAEDIA: Echography in Paediatric Patients in the Age of Coronavirus Disease 2019: Utility of Lung Ultrasound and Chest X-Ray in Diagnosis of Community-Acquired Pneumonia and Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia.

Background: In recent years, lung ultrasound (LUS) has spread to emergency departments and clinical practise gaining great support, especially in time of pandemic, but only a few studies have been done on children. The aim of the present study is to compare the diagnostic accuracy of LUS (using Soldati LUS score) and that of chest X-ray (CXR) in CAP and COVID-19 pneumonia in paediatric patients. Secondary objective of the study is to examine the association between LUS score and disease severity. Finally, we describe the local epidemiology of paediatric CAP during the study period in the era of COVID-19 by comparing it with the previous 2 years. Methods: This is an observational retrospective single-centre study carried out on patients aged 18 or younger and over the month of age admitted to the Paediatric Unit of our Foundation for suspected community-acquired pneumonia or SARS-CoV-2 pneumonia during the third pandemic wave of COVID-19. Quantitative variables were elaborated with Shapiro-Wilks test or median and interquartile range (IQR). Student's t-test was used for independent data. Association between quantitative data was evaluated with Pearson correlation. ROC curve analysis was used to calculate best cut-off of LUS score in paediatric patients. Area under the ROC curve (AUC), sensibility, and specificity are also reported with 95% confidence interval (CI). Results: The diagnostic accuracy of the LUS score in pneumonia, the area underlying the ROC curve (AUC) was 0.67 (95% CI: 0.27-1) thus showing a discrete discriminatory power, with a sensitivity of 89.66% and specificity 50% setting a LUS score greater than or equal to 1 as the best cut-off. Nine patients required oxygen support and a significant statistical correlation (p = 0.0033) emerged between LUS score and oxygen therapy. The mean LUS score in patients requiring oxygen therapy was 12. RCP was positively correlated to the patient's LUS score (p = 0.0024). Conclusions: Our study has shown that LUS is a valid alternative to CXR. Our results show how LUS score can be applied effectively for the diagnosis and stratification of paediatric pneumonia.

SARS-CoV-2 in inflammatory bowel disease population: Antibodies, disease and correlation with therapy.

BACKGROUND: Guidelines recommend to cease inflammatory bowel disease (IBD) biologic therapy during coronavirus disease 2019 (COVID-19). AIM: To investigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody positivity in an IBD cohort, COVID-19 disease severity and to evaluate the correlation with clinical/therapeutic variables. METHODS: Prospective observational cohort study. IBD patients were tested for SARS-CoV-2 IgG. Data on COVID-19 disease, demographics/therapeutics and clinical features of the IBD population were collected. IgG ≥ 7 was set for SARS-CoV-2 antibody positivity. Throat swab was performed in cases of IgG positivity. Correlations between antibody positivity or COVID-19 symptoms and therapeutic/clinical data were assessed. RESULTS: In total, 103 IBD patients were enrolled. Among them, 18.4% had IgG ≥ 7. Multivariate analysis of antibody positivity correlated only with IBD treatment. For IgG ≥ 7, the odds ratio was 1.44 and 0.16 for azathioprine and mesalazine, respectively, vs biologic drugs (P = 0.0157 between them). COVID-19 related symptoms were reported in 63% of patients with IgG positivity. All but one patient with COVID-19 symptoms did not require ceasing IBD treatment or hospitalization. IBD treatment and body mass index correlated with COVID-19 disease development with symptoms. CONCLUSION: The IBD population does not have a higher risk of severe COVID-19. The relative risk of having SARS-CoV-2 antibodies and symptoms was higher for patients taking azathioprine, then biologic therapy and lastly mesalazine. None of the patients under biologic therapy developed severe COVID-19.

Characterization of epidemiological distribution and outcome of COVID-19 in patients with hereditary hemorrhagic telangiectasia: a nationwide retrospective multi-centre study during first wave in Italy.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) continues to have a devastating impact across the world. A number of pre-existing common clinical conditions were reported to represent risk factors for more severe COVID-19 outcomes. Hereditary Hemorrhagic Telangiectasia (HHT) is a rare vascular heritable disorders, characterized by complications secondary to visceral Arterio-Venous Malformations. The impact of HHT, as well as for many Rare Diseases (RDs) on infection susceptibility profile and clinical adverse outcome risk is an unresolved issue. OBJECTIVES: The main objectives were: to assess the clinical features and outcomes of HHT patients infected with COVID-19; to compare the relative infection risk in these patients with the Italian general population throughout the first pandemic wave; to investigate the factors potentially associated with severe COVID-19 outcome in HHT patients, and the possible impact of COVID-19 infection on HHT-related symptoms/complications. Finally, we aimed to estimate how the lockdown-associated wearing of personal protective equipment/individual protection devices could affect HHT-related telangiectasia bleeding frequency. METHODS: The study is a nation-wide questionnaire-based survey, with a multi-Center retrospective cross-sectional design, addressed to the whole Italian HHT population. COVID-19 cases, occurring throughout the first pandemic wave, were collected by a questionnaire-based semi-structured interview. Only the cases ascertained by laboratory confirmation (molecular/serological) were included for epidemiological estimates. Information concerning eventual SarS-Cov-2 infection, as well as regarding HHT-related manifestations and HHT-unrelated co-morbidities were collected by the questionnaire. Prevalence data were compared to Italian general population in the same period. RESULTS: The survey disclosed 9/296 (3.04%) COVID-19 cases, 8/9 of them being resident in Lombardy, the main epidemic epicenter. Pneumonia was reported by 4/9 patients, which prompted hospital admission and intensive care management in 2 cases. No fatal outcome was recorded. After careful refinement of epidemiological analysis, the survey evidenced overlapping infection risk in HHT compared to general population. CONCLUSIONS: COVID-19 infection profile parallels geographical distribution of epidemic foci. COVID-19 in HHT patients can lead to highly variable clinical profile, likely overlapping with that of general population. The HHT disease does not seem to involve a different approach in terms of hospital admission and access to intensive care with respect to general population.

Emergency accesses in Dermatology Department during the Covid-19 pandemic in a referral third level center in the north of Italy.

During the lockdown period, most planned visits have been postponed and the number of accesses to emergency department (ED) has dramatically reduced. The aim of our study is to analyze the impact of the lockdown on the number, type, and severity of Dermatological ED diagnosis. We performed a retrospective review of all dermatological consultations in the ED of IRCSS San Matteo during the lockdown period in Italy (February 22-May 3 2020) and compared them with those from the same period in 2019. We noticed a sharply reduction in the number of dermatological consultations requested in the ED: from 164 patients in 2019 to 33 in 2020. Some diagnostic categories showed a significant difference with a higher incidence of vasculopathic lesions (0.6% vs 12.1%, P < .0001), urticarial rashes (8.5% vs 21.2%, P = .03), and scabies (3% vs 12.1%, P = .023). We observed an increase in the proportion of patients starting medications, before coming to the ED 26.2% in 2019 vs 66.7% in 2020 (P < .001). Furthermore, we noticed a significant increase in the average complexity of cases presenting to the ED in 2020, as proven by the increased need for biopsies and systemic therapy.

The impact of covid-19 pandemic on urgent endoscopy in Italy: a nation-wide multicenter study.

Objective: COVID-19 pandemic has seriously affected Italy. Radical changes occurred in the Italian NHS and thus in GI departments, as only urgent endoscopies were guaranteed. The study aimed to report how the demand for urgent endoscopy changed during the COVID-19 pandemic in Italy and to evaluate the appropriateness of urgent referrals in the Endoscopy Unit.Material and methods: Nation-wide, cross-sectional survey study in 54 Italian GI Units. Data were collected regarding urgent endoscopies (EGD, CS, ERCP) in two different time periods: March 2019 and March 2020.Results: Thirty-five (64.8%) GI endoscopy Units responded to the survey. The entity of reduction of overall urgent EGDs and CSs performed in March 2020 versus March 2019 was statistically significant: 541 versus 974 (-80%), p < .001 for EGD and 171 versus 265 (-55%), p < .008, for CS, respectively. No statistically significant reduction of urgent ERCP performed in March 2020 versus March 2019 was found. The increase in overall diagnostic yield for urgent EGD in March 2020 versus March 2019 was 7.3% (CI [0.028-0.117], p = .001). No statistically significant difference in diagnostic yield for CS between 2019 and 2020 was found.Conclusion: The study showed a statistically significant reduction of urgent EGD and CS performed during the SARS-CoV-2 pandemic, in March 2020, compared to March 2019. The diagnostic yield of urgent EGD performed in March 2020 was significantly higher than that of March 2019. No statistically significant difference was found in terms of diagnostic yield of urgent CS between March 2020 and March 2019.

Plasma from donors recovered from the new Coronavirus 2019 as therapy for critical patients with COVID-19 (COVID-19 plasma study): a multicentre study protocol.

Since the end of 2019, a new coronavirus strain has been reported in the Chinese province of Wuhan, indicated as 2019-nCoV or SARS-CoV-2. In February 2020, the first case of transmission on Italian soil was reported. On March 09, 2020, at the time of protocol design, the Italian Ministry of Health reported 10,149 people who had contracted the virus; of these, 8514 were positive, of which 5038 were hospitalized with symptoms (59.2%) and 877 in intensive care (10.3%), while the remaining 2599 were in home isolation; 631 were deceased (6.2%) and 1004 healed (9.9%). To date there are no studies in the literature that demonstrate its feasibility and efficacy in the context of the worldwide SARS-CoV-2 epidemic. Based upon the little existing evidence, we planned to assess the efficacy of the infusion of hyperimmune plasma in COVID-19 patients in a one-arm proof-of-concept clinical trial. The primary objective of our study is to evaluate the efficacy of the administration of plasma taken from convalescent donors of COVID-19 to critically ill patients with COVID-19 in terms of their survival. Death from any cause will be considered. The main limit of this study is its one-arm proof-of-concept design with only 43 patients enrolled. However, in the absence of previous evidence, larger and/or randomized trials did not appear to be ethically acceptable. Moreover, the results from this study, if encouraging, will allow us to plan further informed large clinical trials. Trial registration: NCT04321421 March 23, 2020.