Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia. Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia. Design, Setting, and Participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible. Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations. Main Outcomes and Measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization. Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04). Conclusions and Relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04716556.

C-C motive chemokine ligand 2 and thromboinflammation in COVID-19-associated pneumonia: A retrospective study.

PURPOSE: A derangement of the coagulation process and thromboinflammatory events has emerged as pathologic characteristics of severe COVID-19, characterized by severe respiratory failure. CC motive chemokine ligand 2 (CCL2), a chemokine originally described as a chemotactic agent for monocytes, is involved in inflammation, coagulation activation and neoangiogenesis. We investigated the association of CCL2 levels with coagulation derangement and respiratory impairment in patients with COVID-19. METHODS: We retrospectively evaluated 281 patients admitted to two hospitals in Italy with COVID-19. Among them, CCL2 values were compared in different groups (identified according to D-dimer levels and the lowest PaO2/FiO2 recorded during hospital stay, P/Fnadir) by Jonckheere-Terpstra tests; linear regression analysis was used to analyse the relationship between CCL2 and P/Fnadir. We performed Mann-Whitney test and Kaplan-Meier curves to investigate the role of CCL2 according to different clinical outcomes (survival and endotracheal intubation [ETI]). RESULTS: CCL2 levels were progressively higher in patients with increasing D-dimer levels and with worse gas exchange impairment; there was a statistically significant linear correlation between log CCL2 and log P/Fnadir. CCL2 levels were significantly higher in patients with unfavourable clinical outcomes; Kaplan-Meier curves for the composite outcome death and/or need for ETI showed a significantly worse prognosis for patients with higher (> median) CCL2 levels. CONCLUSIONS: CCL2 correlates with both indices of activation of the coagulation cascade and respiratory impairment severity, which are likely closely related in COVID-19 pathology, thus suggesting that CCL2 could be involved in the thromboinflammatory events characterizing this disease.

Imported dengue fever in Tuscany, Italy, in the period 2006 to 2012.

This report focuses on epidemiological and clinical features of dengue fever (DF) in Tuscany (Italy) between 2006 and 2012. Sixty-one DF cases were diagnosed, 32 of which were in the period of Aedes albopictus activity. Some clinical (arthralgia/myalgia, nausea/vomiting, and skin rash), laboratory (leukopenia and thrombocytopenia), and epidemiological characteristics (travel in a continent other than Africa) significantly distinguished DF cases from other febrile illnesses. Our data stress the importance of increasing awareness on dengue in Italy among clinicians in order to reach an early diagnosis in returning travelers and to implement appropriate clinical and public health interventions.

Use of the BacT/Alert MB mycobacterial blood culture system for detection of mycobacteria in sterile body fluids other than blood.

The definitive diagnosis of extrapulmonary tuberculosis is made by a positive body fluid culture result. Conventional culture methods require centrifugation or filtration of body fluid (peritoneal, pleural, synovial, or pericardial fluid) in order to improve the sensitivity. The aim of the present study was to evaluate the feasibility of the direct inoculation, at the patient's bedside, of up to 5 ml of uncentrifuged fluid onto BacT/Alert MB culture bottles (bioMérieux, Durham, NC).

[Acute hepatitis C infection: epidemiological and clinical aspects, and efficacy of interferon therapy]. / Epatite acuta C: aspetti epidemiologici, clinici e impatto della terapia interferonica.

Acute hepatitis C virus infection becomes chronic in 50-80% of patients; in recent years a number of studies on acute hepatitis C have shown that interferon treatment can solve more than 80% of cases. In this study we evaluated all cases of acute hepatitis C referred to our unit from 1998 to 2005 to study the epidemiological and clinical features and the efficacy of interferon therapy during the course of the disease. Forty-three patients (28 males, 15 females) were monitored: 22 were drug-addicts, 6 patients referred from recent surgery, in 3 cases a percutaneous exposure was described, 2 patients had had a colonoscopy, 4 were partners of subjects with chronic hepatitis C and in the remaining cases the transmission route was uncertain. All subjects were symptomatic, jaundice was evident in 20 out of 43 patients and in all cases hepatic protein synthesis was unaltered. Of the 21 patients who consented to interferon therapy, in 19 cases a sustained virological response was achieved while in 2 cases the follow-up period was too short for evaluation. Four of the 22 non-treated patients had a spontaneous resolution of the infection, in 13 cases the infection became chronic, and in 4 cases the follow-up was too short for an analysis. In our study all patients were young, in 58% of subjects a parenteral exposure was described and most patients were drug-addicts. All the treated patients obtained a sustained response, while in the majority of non-treated cases the infection became chronic.