Outcomes of non-invasive ventilation as the ceiling of treatment in patients with COVID-19.

BACKGROUND: Non-invasive mechanical ventilation (NIV) is effective for symptom relief and respiratory support in patients with respiratory insufficiency, severe comorbidities and no indication to intubation. Experience with NIV as the ceiling of treatment in severely compromised novel coronavirus disease (COVID-19) patients is lacking. METHODS: We evaluated 159 patients with COVID-19-related acute respiratory syndrome (ARDS), 38 of whom with NIV as the ceiling of treatment, admitted to an ordinary ward and treated with continuous positive airway pressure (CPAP) and respiratory physiotherapy. Treatment failure and death were correlated with clinical and laboratory parameters in the whole cohort and in patients with NIV as the ceiling of treatment. RESULTS: Patients who had NIV as the ceiling of treatment were elderly, with a low BMI and a high burden of comorbidities, showed clinical and laboratory signs of multi-organ insufficiency on admission and of rapidly deteriorating vital signs during the first week of treatment. NIV failure occurred overall in 77 (48%) patients, and 27/38 patients with NIV as the ceiling of treatment died. Congestive heart failure, chronic benign haematological diseases and inability/refusal to receive respiratory physiotherapy were independently associated to NIV failure and mortality. Need for increased positive end-expiratory pressures and low platelets were associated with NIV failure. Death was associated to cerebrovascular disease, need for CPAP cycles longer than 12h and, in the subgroup of patients with NIV as the ceiling of treatment, was heralded by vital sign deterioration within 48 h. CONCLUSIONS: NIV and physiotherapy are a viable treatment option for patients with severe COVID-19 and severe comorbidities.

Continuous positive airway pressure and pronation outside the Intensive Care Unit in COVID-19 acute respiratory distress syndrome.

BACKGROUND: The efficacy and safety of continuous positive airway pressure and respiratory physiotherapy outside the Intensive Care Unit during a pandemic. METHODS: In this cohort study performed in February-May 2020 in a large teaching hospital in Milan, COVID-19 patients with adult respiratory distress syndrome receiving continuous positive airway pressure (positive end-expiratory pressure =10 cm H2O, FiO2=0.6, daily treatment duration: 4×3h-cycles) and respiratory physiotherapy including pronation outside the Intensive Care Unit were followed-up. RESULTS: Of 90 acute respiratory distress syndrome (ARDS) patients treated with continuous positive airway pressure (45/90, 50% pronated at least once) outside the Intensive Care Unit and with a median (interquartile) follow-up of 37 (11-46) days, 45 (50%) were discharged at home, 28 (31%) were still hospitalized, and 17 (19%) died. Continuous positive airway pressure failure was recorded for 35 (39%) patients. Patient mobilization was associated with reduced failure rates (P=0.033). No safety issues were observed. CONCLUSIONS: Continuous positive airway pressure with patient mobilization (including pronation) was effective and safe in patients with ARDS due to COVID-19 managed outside the Intensive Care Unit setting during the pandemic.

Third cranial nerve palsy in an 88-year-old man after SARS-CoV-2 mRNA vaccination: change of injection site and type of vaccine resulted in an uneventful second dose with humoral immune response.

Vaccines for SARS-CoV-2 currently authorised by the European Medicine Agency are effective, safe and well tolerated in practice. Awareness of rare potential vaccine-related adverse effects (AEs) is important to improve their recognition, management and reporting. An 88-year-old man attended the emergency department with incomplete palsy of the right third cranial nerve 3 days after the first administration of Moderna mRNA-1273 SARS-CoV-2 vaccine. Imaging ruled out a vascular accident and a vaccine AE was hypothesised. Two weeks of oral steroids led to the patient's recovery, but without evidence of humoral immune response to vaccine. Thus, full immunisation with a dose of Pfizer mRNA-BNT162b2 SARS-CoV-2 vaccine in a different site was attempted. This was uneventful and followed by a robust antibody response. Empirical change of site and vaccine brand may represent a tailored option to obtain full immune protection in selected patients, after vaccine AEs.

COVID-19 second wave: appropriateness of admissions to the Emergency Department of a main metropolitan hospital in Milan.

BACKGROUND: In Europe, Italy and Lombardy, in autumn 2020, there was a steep increase in reported cases due to the second epidemic wave of SARS-Cov-2 infection. We aimed to evaluate the appropriateness of COVID-19 patients' admissions to the ED of the San Raffaele Hospital. METHODS: We compared data between the inter-wave period (IWP, from 1st to 30th September) and the second wave period (WP, 1st October to 15th November) focusing on the ED presentation, discharge priority colour code and outcomes. RESULTS: Out of 977 admissions with a SARS-Cov-2 positive swab, 6% were in the IWP and 94% in the WP. Red, yellow and white code increased (these latter from 1.8% to 5.4%) as well as self-presented in yellow and white code. Discharges home increased from 1.8% to 5.4%, while hospitalizations decreased from 63% to 51%. DISCUSSION: We found a rise in white codes (among self-presented patients), indicating inappropriateness of admissions. The increase in discharges suggests that several patients did not require hospitalization. CONCLUSIONS: The pandemic brought out the fundamental role of primary care to manage patients with low-intensity needs. The important increase in ED admissions of COVID-19 patients caused a reduction of NO-COVID-19 patients, with possible inadequate treatment.

Mild SARS-CoV-2 Infection After Gene Therapy in a Child With Wiskott-Aldrich Syndrome: A Case Report.

In this work we present the case of SARS-CoV-2 infection in a 1.5-year-old boy affected by severe Wiskott-Aldrich Syndrome with previous history of autoinflammatory disease, occurring 5 months after treatment with gene therapy. Before SARS-CoV-2 infection, the patient had obtained engraftment of gene corrected cells, resulting in WASP expression restoration and early immune reconstitution. The patient produced specific immunoglobulins to SARS-CoV-2 at high titer with neutralizing capacity and experienced a mild course of infection, with limited inflammatory complications, despite pre-gene therapy clinical phenotype.

Prevalence, Characteristics, Risk Factors, and Outcomes of Invasively Ventilated COVID-19 Patients with Acute Kidney Injury and Renal Replacement Therapy.

BACKGROUND: There is no information on acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) among invasively ventilated coronavirus disease 2019 (COVID-19) patients in Western healthcare systems. OBJECTIVE: To study the prevalence, characteristics, risk factors and outcome of AKI and CRRT among invasively ventilated COVID-19 patients. METHODS: Observational study in a tertiary care hospital in Milan, Italy. RESULTS: Among 99 patients, 72 (75.0%) developed AKI and 17 (17.7%) received CRRT. Most of the patients developed stage 1 AKI (33 [45.8%]), while 15 (20.8%) developed stage 2 AKI and 24 (33.4%) a stage 3 AKI. Patients who developed AKI or needed CRRT at latest follow-up were older, and among CRRT treated patients a greater proportion had preexisting CKD. Hospital mortality was 38.9% for AKI and 52.9% for CRRT patients. CONCLUSIONS: Among invasively ventilated COVID-19 patients, AKI is very common and CRRT use is common. Both carry a high risk of in-hospital mortality.

Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy.

OBJECTIVE: Describe characteristics, daily care and outcomes of patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). DESIGN: Case series of 73 patients. SETTING: Large tertiary hospital in Milan. PARTICIPANTS: Mechanically ventilated patients with confirmed COVID-19 admitted to the intensive care unit (ICU) between 20 February and 2 April 2020. MAIN OUTCOME MEASURES: Demographic and daily clinical data were collected to identify predictors of early mortality. RESULTS: Of the 73 patients included in the study, most were male (83.6%), the median age was 61 years (interquartile range [IQR], 54-69 years), and hypertension affected 52.9% of patients. Lymphocytopenia (median, 0.77 x 103 per mm3 ; IQR, 0.58-1.00 x 103 per mm3), hyperinflammation with C-reactive protein (median, 184.5 mg/dL; IQR, 108.2-269.1 mg/dL) and pro-coagulant status with D-dimer (median, 10.1 µg/m; IQR, 5.0-23.8 µg/m) were present. Median tidal volume was 6.7 mL/kg (IQR, 6.0-7.5 mL/kg), and median positive end-expiratory pressure was 12 cmH2O (IQR, 10-14 cmH2O). In the first 3 days, prone positioning (12-16 h) was used in 63.8% of patients and extracorporeal membrane oxygenation in five patients (6.8%). After a median follow-up of 19.0 days (IQR, 15.0-27.0 days), 17 patients (23.3%) had died, 23 (31.5%) had been discharged from the ICU, and 33 (45.2%) were receiving invasive mechanical ventilation in the ICU. Older age (odds ratio [OR], 1.12; 95% CI, 1.04-1.22; P = 0.004) and hypertension (OR, 6.15; 95% CI, 1.75-29.11; P = 0.009) were associated with mortality, while early improvement in arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio was associated with being discharged alive from the ICU (P = 0.002 for interaction). CONCLUSIONS: Despite multiple advanced critical care interventions, COVID-19 ARDS was associated with prolonged ventilation and high short term mortality. Older age and pre-admission hypertension were key mortality risk factors. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04318366.