Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19.

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage.

Pulmonary embolism in patients with COVID-19 pneumonia on adequate oral anticoagulation.

Thrombotic complications are common in patients with severe COVID-19 pneumonia with important consequences on the diagnostic and therapeutic management. We report a consecutive series of five patients on long-term oral anticoagulation therapy who presented to our hospital for severe COVID-19 pneumonia associated with segmental acute pulmonary embolism despite adherence to therapy and with an adequate anticoagulant range at the time of the event. Four patients were receiving a direct oral anticoagulant (two with edoxaban, one with rivaroxaban and one with apixaban) and one patient a vitamin K antagonist. No significant thrombotic risk factors, active cancer, or detectable venous thromboembolism were present. In all cases, elevated d-dimer and fibrinogen levels with a parallel rise in markers of inflammation were documented. The combination of these findings seems to support the hypothesis that considers the local vascular damage determined by severe viral infection as the main trigger of thrombi detected in the lungs, rather than emboli from peripheral veins.

COVID-19: high-resolution computed tomography findings in the first 64 patients admitted to the Hospital of Cremona, the epicentre of the pandemic in Europe.

PURPOSE: In December 2019, a new coronavirus (SARS-CoV-2) was identified as being responsible for the pulmonary infection called COVID-19. On 21 February 2020, the first autochthonous case of COVID-19 was detected in Italy. Our goal is to report the most common chest computed tomography (CT) findings identified in 64 patients, in the initial phase of COVID-19. METHODS: Sixty-four chest high-resolution computed tomography (HRCT) examinations performed at the Radiology Unit of the Hospital of Cremona, from 22 to 29 February 2020, of 64 patients during first week of hospitalization for COVID-19 were retrospectively evaluated. All cases were confirmed by real-time RT-PCR for SARS-CoV-2. Image analysis was independently conducted by 2 radiologists with 10 years and 1 year of experience in chest imaging. The inter-observer agreement was obtained by applying a Cohen's κ test. RESULTS: The average age of patients was 67.1 years (± 12.2); men 42 (66%). HRCT was performed on the 5th (± 1.5) day of hospitalization. More frequently, the initial CT changes of the lung show more or less extensive areas of ground-glass, as single pattern or with parenchymal consolidations. Coronavirus lung involvement appears very frequently multi-lobar, bilateral, and it concerns both subpleural and central regions. An excellent agreement (κ: 0.88-1, CI: 0.79-1.01, p < 0.05) concerning CT findings between the 2 operators was reached. CONCLUSIONS: Our data suggest that detection of the most frequent pulmonary CT-scan changes, in the early stages of COVID-19, can be performed, with excellent agreement, among readers with different experience, and consequently attribute their exact diagnostic value, in an appropriate clinical and environmental exposure setting.

Early Percutaneous Tracheostomy in Coronavirus Disease 2019: Association With Hospital Mortality and Factors Associated With Removal of Tracheostomy Tube at ICU Discharge. A Cohort Study on 121 Patients.

OBJECTIVES: Early tracheotomy, defined as a procedure performed within 10 days from intubation, is associated with more ventilator free days, shorter ICU stay, and lower mortality than late tracheotomy. During the coronavirus disease 2019 pandemic, it was especially important to save operating room resources and to have a shorter ICU stay for patients, when ICUs had insufficient beds. In this context of limited resources, early percutaneous tracheostomy could be an effective way to manage mechanically ventilated patients. Nevertheless, current recommendations suggest delaying or avoiding the tracheotomy in coronavirus disease 2019 patients. Aim of the study was to analyze the hospital mortality of coronavirus disease 2019 patients who had received early percutaneous tracheostomy and factors associated with removal of tracheostomy cannula at ICU discharge. DESIGN: Cohort study. SETTING: Coronavirus disease 2019 ICU. PATIENTS: Adult patients with coronavirus disease 2019 3 days after ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three days after ICU admission, 164 patients were present in ICU and included in the analysis. One-hundred and twenty-one patients (74%) were tracheostomized, whereas the other 43 (26%) were managed with translaryngeal intubation only. In multivariable analysis, early percutaneous tracheostomy was associated with lower hospital mortality. Sixty-six of tracheostomized patients (55%) were discharged alive from the hospital. Age and male sex were the only characteristics that were independently associated with mortality in the tracheostomized patients (45.5% and 62.8% in tracheostomized and nontracheostomized patients, respectively; p = 0.009). Tracheostomy tube was removed in 47 of the tracheostomized patients (71%). The only variable independently associated with weaning from tracheostomy at ICU discharge was a faster start of spontaneous breathing after tracheotomy was performed. CONCLUSIONS: Early percutaneous tracheostomy was safe and effective in coronavirus disease 2019 patients, giving a good chance of survival and of weaning from tracheostomy cannula at ICU discharge.

Spontaneous pneumomediastinum in COVID-19 pneumonia.

Spontaneous pneumomediastinum is a benign entity but can worsen the underlying condition with which it is associated. We evaluated the incidence and the clinical relevance of spontaneous pneumomediastinum in a consecutive series of 102 patients with COVID-19 pneumonia. Six cases of pneumomediastinum were identified by high-resolution chest CT-scan. Three patients required early intubation, and one of them died, while in in the remaining subjects the clinical course was benign. The presence of pneumomediastinum required some changes in the management of mechanical ventilation. In conclusion, spontaneous pneumomediastinum is a possible complication of severe COVID-19 pneumonia that can affect patient management and clinical outcomes.

First detection of Mycoplasma wenyonii in France: Identification, evaluation of the clinical impact and development of a new specific detection assay.

Mycoplasma wenyonii, a hemoplasma infecting cattle, was never detected in France. In 2014, evocative inclusions were observed in erythrocytes from cattle presenting milk drops, anemia, and edema in Brittany (France). A survey was then initiated to investigate the epidemiological situation and correlate mycoplasma detection with clinical signs. For this purpose, a new PCR assay targeting polC gene was designed. Comparative results with published PCR assays place this new one as more specific, allowing a one-step diagnosis without further sequencing. A total of 181 cows were included in this study and 4.97% (n = 9) were positive, resulting in the first molecular identification of M. wenyonii in France. All positive animals presented anemia, edema and milk drop. When selecting animals presenting evocative clinical signs, the prevalence of M. wenyonii in Brittany was estimated to 25.6%. Further studies are needed to evaluate the importance of the infection, the implication of arthropods and the existence of asymptomatic carriers.

Small airway dysfunction by impulse oscillometry in asthmatic patients with normal forced expiratory volume in the 1st second values.

Small airways are relevant to the pathophysiology of asthma. We investigated whether in asthmatic patients with normal forced expiratory volume in the 1st second (FEV(1)) values, impulse oscillometry system (IOS), as a measure of small airway function, contributed additional information to spirometry either at baseline or after bronchodilator, and whether it was related to the disease control. The fall in resistance from 5 to 20 Hz (R5-R20) and reactance at 5 Hz (X5) by IOS and spirometry measures of small airway function (forced expiratory flow at 25-75% [FEF(25-75)] and forced vital capacity/slow inspiratory vital capacity [FVC/SVC]) at baseline and after 400 micrograms of salbutamol were prospectively measured in 33 asthmatic patients (18 women; age range, 18-66 years). Disease control was assessed by the Asthma Control Test (ACT). R5-R20 but not X5 values were significantly related to FEF(25-75) and FVC/SVC values (p < 0.05 for both correlations). When the bronchodilator response was assessed, no correlation was found among IOS and spirometry changes. ACT scores were related to R5-R20, FEF(25-75), and FVC/SVC values (p < 0.01 for all correlations). In asthmatic patients with normal FEV(1) values, R5-R20 values were related to spirometry measures of small airway function. However, when the bronchodilator response was assessed, IOS and spirometry provided quite different results. Moreover, small airway dysfunction, as assessed by IOS and spirometry, was associated with poor disease control and history of asthma exacerbations. The results of this study confirm the value of IOS, as an investigative tool, and suggest that in asthmatic patients with normal FEV(1) values and poor disease control, small airway function should be investigated.

NEUROM: a ROM based RNS digital neuron.

In this work, a fast digital device is defined, which is customized to implement an artificial neuron. Its high computational speed is obtained by mapping data from floating point to integer residue representation, and by computing neuron functions through residue arithmetic operations, with the use of table look-up techniques. Specifically, the logic design of a residue neuron is described and complexity figures of area occupancy and time consumption of the proposed device are derived. The approach was applied to the logic design of a residue neuron with 12 inputs and with a Residue Number System defined in such a way as to attain an accuracy better than or equal to the accuracy of a 20-bit floating point system. The proposed design (NEUROM) exploits the RNS carry independence property to speed up computations, in addition it is very suitable for using look-up tables. The response time of our device is about 8 x T(ACC), where T(ACC) is the ROM access time. With a value of T(ACC) close to the 10 ns allowed by the current ROM technology, the proposed neuron responds within 80 ns, NEUROM is therefore the neuron device proposed in the literature which allows for maximum throughput. Moreover, when a pipeline mode of operation is adopted, the pipeline delay can assume a value as low as about 14 ns. In the case study considered, the total amount of ROM is about 5.55 Mbits. Thus, using current technology, it is possible to integrate several residue neurons into a single VLSI chip, thereby enhancing chip throughput. The paper also discusses how this amount of memory could be reduced, at the expense of the response time.