Convalescent or standard plasma versus standard of care in the treatment of COVID-19 patients with respiratory impairment: short and long-term effects. A three-arm randomized controlled clinical trial.

BACKGROUND: The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies. METHODS: To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle. RESULTS: 180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57-73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61-2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63-2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively. CONCLUSIONS: Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020.

Clinical and epidemiological characteristics associated with pneumonia at disease onset in patients admitted for COVID-19 to the Emergency Department of a large Hospital in Piedmont (North-Western Italy).

OBJECTIVES: to explore clinical and epidemiological characteristics associated with an imaging feature of COVID-19 pneumonia at disease onset, in order to identify factors that may be evaluable by general practitioners at patient's home, and which may lead to identify a more severe disease, needing hospitalization. DESIGN: this is a retrospective/prospective observational hospital cohort. SETTING AND PARTICIPANTS: the study population includes all patients consecutively admitted to the emergency department of Città della salute e della scienza University Hospital from 01.03 to 31.05.2020 with a confirmed diagnosis of SARS-CoV-2 infection. MAIN OUTCOME MEASURES: patients were classified in two groups according to the findings of X-ray imaging, lung ultrasound and chest computer tomography, as pneumonia or not pneumonia patients. RESULTS: in multivariable analysis, factors most strongly associated with emergency department admission with pneumonia were age, oxygen saturation <90% (adj OR 4.16 ;95%CI 1.44-12.07), respiratory rate >24 breaths/min (adj OR 6.50; 95%CI 2.36-17.87), fever ≥38° (adj OR 3.05; 95%CI 1.53-6.08) and the presence of gastroenteric symptoms (vomiting and diarrhea). A delay (> 7 days) between the appearance of the initial lung symptoms (cough and dyspnea) and the admission to the emergency department was also related to a higher probability of receiving a positive imaging report (OR 4.99; 95%CI 2,02-12,34). CONCLUSIONS: in order to reorganize the management of COVID-19 patients in Italy, in view of the risk of a second wave of epidemic or of local outbreaks, it would be desirable to relocate the triage, and possibly the patient's care, from hospital to home. In this scenario it is important to identify all symptoms and signs associated with COVID-19 pneumonia that would facilitate the decision-making process of GPs leading to patients hospitalization.

[Covid-19 and clinical-epidemiological research in Italy: proposal of a research agenda on priority topics by the Italian association of epidemiology]. / Covid-19 e ricerca clinico-epidemiologica in Italia: proposta di un'agenda di ricerca su temi prioritari da parte dell'Associazione italiana di epidemiologia.

BACKGROUND: the Covid-19 pandemic has provoked a huge of clinical and epidemiological research initiatives, especially in the most involved countries. However, this very large effort was characterized by several methodological weaknesses, both in the field of discovering effective treatments (with too many small and uncontrolled trials) and in the field of identifying preventable risks and prognostic factors (with too few large, representative and well-designed cohorts or case-control studies). OBJECTIVES: in response to the fragmented and uncoordinated research production on Covid-19, the   italian Association of Epidemiology (AIE) stimulated the formation of a working group (WG) with the aims of identifying the most important gaps in knowledge and to propose a structured research agenda of clinical and epidemiological studies considered at high priority on Covid-19, including recommendations on the preferable methodology. METHODS: the WG was composed by 25 subjects, mainly epidemiologists, statisticians, and other experts in specific fields, who have voluntarily agreed to the proposal. The agreement on a list of main research questions and on the structure of the specific documents to be produced were defined through few meetings and cycles of document exchanges. RESULTS: twelve main research questions on Covid-19 were identified, covering aetiology, prognosis, interventions, follow-up and impact on general and specific populations (children, pregnant women). For each of them, a two-page form was developed, structured in: background, main topics, methods (with recommendations on preferred study design and warnings for bias prevention) and an essential bibliography. CONCLUSIONS: this research agenda represents an initial contribution to direct clinical and epidemiological research efforts on high priority topics with a focus on methodological aspects. Further development and refinements of this agenda by Public Health Authorities are encouraged.

[Audit and Feedback approach in the CoViD-19 emergency: adaptation of the EASY-NET project in the AOU Città della Salute e della Scienza of Turin.] / Audit e Feedback nell'emergenza CoViD-19: adattamento del progetto EASY-NET nell'AOU Città della Salute e della Scienza di Torino.

CoViD-19 pandemic heavily impacted most on-going research activities, causing delays and need of re-programming. EASY-NET (NET-2016-02364191) is a network project, started in April 2019, co-funded by the Italian Ministry of Health and the participating regions. Within the general project, centred on the evaluation of Audit and Feedback (A&F) strategies in improving quality and equity in different health care contexts, the Piedmont region is responsible of the work package 3 (WP3) on specific oncology pathways and procedures. After a thorough evaluation of the impact of the CoViD-19 emergency on the WP3 activities, at the beginning of March 2020, the decision was to continue, with some adaptations, the audits already started, and to delay those in the early planning phase. The provisional availability of part of the time-persons involved in EASY-NET on one side, and the urgency of acquiring data on the management of the large number of CoViD-19 patients admitted to the study coordinator hospital on the other side, determined the personnel responsible of the WP3, in accordance with the hospital management, to invest these resources in monitoring the CoViD-19 hospitalized patients with both A&F activity and research objectives. Besides periodic reports, a web site, with restricted access to the involved health care personnel, was developed to allow a direct and timely consultation of graphics describing the flow of the patients, their management, and outcomes. This experience was made possible thanks to a favourable combination of different factors: the presence within the hospital of a group of experienced epidemiologists in A&F, the availability of extra resources, the strong support and collaboration by the hospital management and the readiness for authorisation by the Ethics Committee. We underline the need to provide a certain degree of flexibility in the long-term projects funded by the Ministry of Health, the extraordinary adaptability of the A&F approach also to emergency situations and the possibility of combining audit activities and research objectives in the same project.