Introduction: Several recent case reports have described common early chest imaging findings of lung pathology caused by 2019 novel Coronavirus (SARS-COV2) which appear to be similar to those seen previously in SARS-CoV and MERS-CoV infected patients. Objective: We present some remarkable imaging findings of the first two patients identified in Italy with COVID-19 infection travelling from Wuhan, China. The follow-up with chest X-Rays and CT scans was also included, showing a progressive adult respiratory distress syndrome (ARDS). Results: Moderate to severe progression of the lung infiltrates, with increasing percentage of high-density infiltrates sustained by a bilateral and multi-segmental extension of lung opacities, were seen. During the follow-up, apart from pleural effusions, a tubular and enlarged appearance of pulmonary vessels with a sudden caliber reduction was seen, mainly found in the dichotomic tracts, where the center of a new insurgent pulmonary lesion was seen. It could be an early alert radiological sign to predict initial lung deterioration. Another uncommon element was the presence of mediastinal lymphadenopathy with short-axis oval nodes. Conclusions: Although only two patients have been studied, these findings are consistent with the radiological pattern described in literature. Finally, the pulmonary vessels enlargement in areas where new lung infiltrates develop in the follow-up CT scan, could describe an early predictor radiological sign of lung impairment.

Abstract Background Remdesivir is a prodrug of the nucleoside analogue GS-441524 and is under evaluation for treatment of SARS-CoV-2-infected patients. Objectives To evaluate the pharmacokinetics of remdesivir and GS-441524 in plasma, bronchoalveolar aspirate (BAS) and CSF in two critically ill COVID-19 patients. Methods Remdesivir was administered at 200 mg loading dose on the first day followed by 12 days of 100 mg in two critically ill patients. Blood samples were collected immediately after (C0) and at 1 (C1) and 24 h (C24) after intravenous administration on day 3 until day 9. BAS samples were collected on Days 4, 7 and 9 from both patients while one CSF on Day 7 was obtained in one patient. Remdesivir and GS-441524 concentrations were measured in these samples using a validated UHPLC-MS/MS method. Results We observed higher concentrations of remdesivir at C0 (6- to 7-fold higher than EC50 from in vitro studies) and a notable decay at C1. GS-441524 plasma concentrations reached a peak at C1 and persisted until the next administration. Higher concentrations of GS-441524 were observed in the patient with mild renal dysfunction. Mean BAS/plasma concentration ratios of GS-441524 were 2.3% and 6.4% in Patient 1 and Patient 2, respectively. The CSF concentration found in Patient 2 was 25.7% with respect to plasma. GS-441524 levels in lung and CNS suggest compartmental differences in drug exposure. Conclusions We report the first pharmacokinetic evaluation of remdesivir and GS-441524 in recovered COVID-19 patients. Further study of the pharmacokinetic profile of remdesivir, GS-441524 and the intracellular triphosphate form are required.

Background Few data about predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS) are available. Methods Retrospective study including all patients admitted with COVID-19 in an Italian reference hospital for infectious diseases between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between duration of VS and probability of clinical outcomes was evaluated through inverse probability weighted Cox model. Results 536 subjects were included. Median duration of VS from symptoms onset was 18 days (IQR 12-26). The estimated 30-day probability of VC was 70.2% (95%CI:65-75). At multivariable analysis, patients with comorbidities (aIRR = 0.88, p = 0.004), lymphopenia at hospital admission (aIRR = 0.75, p = 0.032) and with moderate/severe respiratory disease (aIRR = 0.42, p < 0.001) had a lower chance of achieving VC. The development of moderate/severe respiratory failure (aOR = 2.65, p = 0.003), a delayed hospital admission after symptoms onset (aOR = 1.18, p < 0.001), having baseline comorbidities (aOR = 1.25, p = 0.019) and D-dimer >1000 ng/mL at admission (aOR = 1.76, p = 0.035) independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery (aHR = 2.17, p < 0.001) and reduced the probability of death/mechanical ventilation (aHR = 0.36, p = 0.002). Conclusions In this study, severity of respiratory disease, comorbidities, delayed hospital admission and inflammatory markers negatively predicted the achievement of VC, which resulted to be associated to better clinical outcomes. These findings highlight the importance of prompt hospitalization of symptomatic patients, especially in presence of signs of severity or comorbidities.

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Background The pathogenesis of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unclear. We report the detection of viral RNA from different anatomical districts and the antibody profile in the first two COVID-19 cases diagnosed in Italy Methods We tested for SARS-CoV-2 RNA clinical samples, either respiratory and non-respiratory (i.e. saliva, serum, urine, vomit, rectal, ocular, cutaneous, and cervico-vaginal swabs), longitudinally collected from both patients throughout the hospitalization. Serological analysis was carried out on serial serum samples to evaluate IgM, IgA, IgG and neutralizing antibodies levels Results SARS-CoV-2 RNA was detected since the early phase of illness lasting over two weeks in both upper and lower respiratory tract samples. Virus isolate was obtained from acute respiratory sample, while no infectious virus was rescued from late respiratory samples with low viral RNA load, collected when serum antibodies had been developed. Several other specimens resulted positive including saliva, vomit, rectal, cutaneous, cervico-vaginal, and ocular swabs. Specific IgM, IgA and IgG were detected within the first week since diagnosis, with IgG appearing earlier and at higher titres. Neutralizing antibodies developed during the second week, reaching high titres 32 days since diagnosis Conclusions Our longitudinally analysis showed that SARS-CoV-2 RNA can be detected in different body samples which may be associated with broad tropism and different spectra of clinical manifestations and modes of transmission. Profiling antibody response and neutralizing activity can assist laboratory diagnosis and surveillance actions