Single-center study on SARS-CoV-2 infection in patients affected by CML: Vaccination status and bosutinib therapy as possible protective factors for hospitalization.

INTRODUCTION: COVID-19 pandemic had a considerable impact among haematological patients. On the other hand, the effect of this disease on patients (pts) affected by Chronic Myeloid Leukemia (CML) is not clearly defined. OBJECTIVES: The primary objective of this study was to evaluate mortality-hospitalization rates and possible protective factors for hospitalization in CML pts affected by COVID. METHODS: We collected data from CML patients followed at our institution whotested positive for SARS-CoV-2 infection. The following variables were assessed: demographical data, type of TKI therapy, vaccination status, presence of cardiovascular disease (CVD), period of infection, COVID-19 presenting symptoms, severity and mortality. Data were collected retrospectively and then analysed in univariate and multivariate analysis. RESULTS: Out of a total of 325 CML pts treated at our institution, we recorded 72 SARS-CoV-2pts (22%) who tested positive with a SARS-CoV-2 PCR assay. Twenty two were infected in 2020 (30%), 16 patients in 2021 (22%) and 34 in 2022 (46%); with a hospitalization rate of 27%, 25% and 3% respectively. Of the 72 confirmed infections, 13 pts (18%; (CI) 10-28) were asymptomatic and 48 (66%; CI: 55-76) had mild symptoms. A total of 11 pts were admitted to hospital and 3 of these required ICU admission. No deaths were recorded. The probability of hospitalization was significantly reduced if patients were vaccinated (odds ratio OR 0.037 with CI: 0-0.33 p 0.002) or treated with Bosutinib (OR 0.06 with CI: 0-0.5 p 0.008). CONCLUSION: In the present study, no significant increase in mortality was noted among patients with CML as compared to the general population inItaly. Vaccination and treatment with bosutinib were identified as baseline characteristics that were associated with a decreased risk of hospitalitazion resulting from COVID-19 infection.

Humoral and cellular immune response in patients with hematological disorders after two doses of BNT162b2 mRNA COVID‐19 vaccine: A single‐center prospective observational study (NCT05074706)

Hematological patients at higher risk of severe COVID‐19 were excluded from the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine trials. In this single‐center observational prospective study (NCT05074706), we evaluate immune response in the hematological patients followed at the Hematological Division of San Gerardo Hospital, Monza (Italy) deemed to be severely immunosuppressed after vaccination with two doses of the BNT162b2 vaccine. Anti‐SARS‐CoV‐2 immunoglobulin G titers above the cutoff value of 33.8 BAU/ml were detected in 303 (80.2%) out of the 378 patients enrolled. Patients with lymphoproliferative disorders had a significant lower probability of immunization (43.2% vs. 88.4%, p < 0.001). Patients treated with anti‐CD20 showed a significantly lower probability of immunization compared to all other treatments (21.4%, p < 0.0001). Among 69 patients who failed seroconversion, 15 patients (22.7%) showed a positive T‐cell response. Patients previously treated with anti‐CD20 were 2.4 times more likely to test positive for T‐cell responses (p = 0.014). Within a follow‐up of 9 months from the second COVID‐19 vaccination, symptomatic SARS‐CoV‐2 infections were reported by 20 patients (5.3%) and four of them required hospitalization. Successful serological or T‐cell‐mediated immunization conferred protection from symptomatic COVID‐19. Patients treated with anti‐CD20 who were not seroconverted after vaccination might still be protected from COVID‐19 due to the T‐cell immune response.

Enoxaparin for thromboprophylaxis in hospitalized COVID-19 patients: The X-COVID-19 Randomized Trial.

BACKGROUND: It is uncertain whether higher doses of anticoagulants than recommended for thromboprophylaxis are necessary in COVID-19 patients hospitalized in general wards METHODS: This is a multicentre, open-label, randomized trial performed in 9 Italian centres, comparing 40 mg b.i.d. versus 40 mg o.d. enoxaparin in COVID-19 patients, between April 30 2020 and April 25 2021. Primary efficacy outcome was in-hospital incidence of venous thromboembolism (VTE): asymptomatic or symptomatic proximal deep vein thrombosis (DVT) diagnosed by serial compression ultrasonography (CUS), and/or symptomatic pulmonary embolism (PE) diagnosed by computed tomography angiography (CTA). Secondary endpoints included each individual component of the primary efficacy outcome and a composite of death, VTE, mechanical ventilation, stroke, myocardial infarction, admission to ICU. Safety outcomes included major bleeding. RESULTS: The study was interrupted prematurely due to slow recruitment. We included 183 (96%) of the 189 enrolled patients in the primary analysis (91 in b.i.d., 92 in o.d.). Primary efficacy outcome occurred in 6 patients (6.5%, 0 DVT, 6 PE) in the o.d. group and 0 in the b.id. group (ARR 6.5, 95% CI: 1.5-11.6). The absence of concomitant DVT and imaging characteristics suggests that most pulmonary artery occlusions were actually caused by local thrombi rather than PE. Statistically nonsignificant differences in secondary and safety endpoints were observed, with two major bleeding events in each arm. CONCLUSIONS: No DVT developed in COVID-19 patients hospitalized in general wards, independently of enoxaparin dosing used for thromboprophylaxis. Pulmonary artery occlusions developed only in the o.d. group. Our trial is underpowered and with few events.

Childbirth experience and practice changing during COVID-19 pandemic: A cross-sectional study.

AIM: To evaluate mothers' satisfaction with childbirth experience in a cohort of women who delivered during COVID pandemia and to compare them to a pre-COVID cohort. DESIGN: We performed a cross-sectional study in a low-risk Maternity Unit. METHODS: Women who delivered during COVID-19 pandemic were compared to a pre-COVID cohort recruited in 2018 in the same setting. Italian version of the Birth Satisfaction Scale-Revised (I-BSS-R) was used. RESULTS: Three hundred and seventy-seven women were included (277 pre-COVID and 100 during COVID pandemic). No differences in terms of satisfaction at birth were reported (I-BSS-R mean 27.0, SD 5.3 versus mean 27.6, SD 6.1, p 0.34), despite an increased rate of active intrapartum interventions. Intrapartum variables that significantly reduced satisfaction were the same in the two groups: epidural analgesia (p < .0001 in both groups), prolonged active phases (p < .0001 in both), oxytocin administration (p < .0001 in both) and operative delivery (p 0.0009 versus p 0.0019).

Noninvasive Ventilatory Support of Patients with COVID-19 outside the Intensive Care Units (WARd-COVID).

Rationale: Treatment with noninvasive ventilation (NIV) in coronavirus disease (COVID-19) is frequent. Shortage of intensive care unit (ICU) beds led clinicians to deliver NIV also outside ICUs. Data about the use of NIV in COVID-19 is limited.Objectives: To describe the prevalence and clinical characteristics of patients with COVID-19 treated with NIV outside the ICUs. To investigate the factors associated with NIV failure (need for intubation or death).Methods: In this prospective, single-day observational study, we enrolled adult patients with COVID-19 who were treated with NIV outside the ICU from 31 hospitals in Lombardy, Italy.Results: We collected data on demographic and clinical characteristics, ventilatory management, and patient outcomes. Of 8,753 patients with COVID-19 present in the hospitals on the study day, 909 (10%) were receiving NIV outside the ICU. A majority of patients (778/909; 85%) patients were treated with continuous positive airway pressure (CPAP), which was delivered by helmet in 617 (68%) patients. NIV failed in 300 patients (37.6%), whereas 498 (62.4%) patients were discharged alive without intubation. Overall mortality was 25%. NIV failure occurred in 152/284 (53%) patients with an arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2) ratio <150 mm Hg. Higher C-reactive protein and lower PaO2/FiO2 and platelet counts were independently associated with increased risk of NIV failure.Conclusions: The use of NIV outside the ICUs was common in COVID-19, with a predominant use of helmet CPAP, with a rate of success >60% and close to 75% in full-treatment patients. C-reactive protein, PaO2/FiO2, and platelet counts were independently associated with increased risk of NIV failure.Clinical trial registered with ClinicalTrials.gov (NCT04382235).

SARS-CoV-2 pandemia in Lombardy: the impact on family Paediatricians.

As health care workers (HCWs) who care for children, who usually demonstrate milder symptoms than adults, family paediatricians have an increased risk of exposure to coronavirus. In April 2020, the Sindacato Medici Pediatri di Famiglia (SIMPeF), provided its members with rapid tests to detect antibodies against SARS-CoV-2; 1240 individuals, including 377 paediatricians, 108 staff members of pediatric clinics, and 755 cohabitant relatives of paediatricians, were tested in Lombardy, the most affected Italian region. The global prevalence of IgG antibodies in these individuals was 20.7%, which is higher than that of the general population and other HCWs. More than 70% of subjects with IgG antibodies presented symptoms, and 4.9% needed hospitalization. In addition, 64.2% of the study participants reported close contacts with a suspected case of COVID-19, while 72.9% of the family paediatricians reported occupational exposure to the disease. The initiative of the SIMPeF has been useful in assessing the impact of the COVID-19 pandemic on paediatric settings, as well as in raising paediatricians' awareness of the spreading of coronavirus.

Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study.

BACKGROUND: The COVID-19 pandemic is challenging advanced health systems, which are dealing with an overwhelming number of patients in need of intensive care for respiratory failure, often requiring intubation. Prone positioning in intubated patients is known to reduce mortality in moderate-to-severe acute respiratory distress syndrome. We aimed to investigate feasibility and effect on gas exchange of prone positioning in awake, non-intubated patients with COVID-19-related pneumonia. METHODS: In this prospective, feasibility, cohort study, patients aged 18-75 years with a confirmed diagnosis of COVID-19-related pneumonia receiving supplemental oxygen or non-invasive continuous positive airway pressure were recruited from San Gerardo Hospital, Monza, Italy. We collected baseline data on demographics, anthropometrics, arterial blood gas, and ventilation parameters. After baseline data collection, patients were helped into the prone position, which was maintained for a minimum duration of 3 h. Clinical data were re-collected 10 min after prone positioning and 1 h after returning to the supine position. The main study outcome was the variation in oxygenation (partial pressure of oxygen [PaO2]/fractional concentration of oxygen in inspired air [FiO2]) between baseline and resupination, as an index of pulmonary recruitment. This study is registered on ClinicalTrials.gov, NCT04365959, and is now complete. FINDINGS: Between March 20 and April 9, 2020, we enrolled 56 patients, of whom 44 (79%) were male; the mean age was 57·4 years (SD 7·4) and the mean BMI was 27·5 kg/m2 (3·7). Prone positioning was feasible (ie, maintained for at least 3 h) in 47 patients (83·9% [95% CI 71·7 to 92·4]). Oxygenation substantially improved from supine to prone positioning (PaO2/FiO2 ratio 180·5 mm Hg [SD 76·6] in supine position vs 285·5 mm Hg [112·9] in prone position; p<0·0001). After resupination, improved oxygenation was maintained in 23 patients (50·0% [95% CI 34·9-65·1]; ie, responders); however, this improvement was on average not significant compared with before prone positioning (PaO2/FiO2 ratio 192·9 mm Hg [100·9] 1 h after resupination; p=0·29). Patients who maintained increased oxygenation had increased levels of inflammatory markers (C-reactive protein: 12·7 mg/L [SD 6·9] in responders vs 8·4 mg/L [6·2] in non-responders; and platelets: 241·1 × 103/µL [101·9] vs 319·8 × 103/µL [120·6]) and shorter time between admission to hospital and prone positioning (2·7 days [SD 2·1] in responders vs 4·6 days [3·7] in non-responders) than did those for whom improved oxygenation was not maintained. 13 (28%) of 46 patients were eventually intubated, seven (30%) of 23 responders and six (26%) of 23 non-responders (p=0·74). Five patients died during follow-up due to underlying disease, unrelated to study procedure. INTERPRETATION: Prone positioning was feasible and effective in rapidly ameliorating blood oxygenation in awake patients with COVID-19-related pneumonia requiring oxygen supplementation. The effect was maintained after resupination in half of the patients. Further studies are warranted to ascertain the potential benefit of this technique in improving final respiratory and global outcomes. FUNDING: University of Milan-Bicocca.