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Additional file 1. Scoping review protocol. Working method and tools used by the domain groups. Table S1. Selected articles catalogued by domain. Table S2. Tables of evidence. A) Virus characterization and viral entry: B) Host signature: C) Pathways: D. Phenotypes. Table S3. B) Conceptual table: SARS-CoV-2 entry. Tabla S4. Immune response to SARS-CoV-2 infection in lung and other tissues (A), peripheral blood (B) and specific cell types in blood immune cells (C). Pathways, host signature (differentially expressed genes and proteins) and body districts, subset per specific omics data: host proteomics, bulk RNAseq and scRNAseq. Table S5. Pathogenic mechanisms in COVID-19 phenotype: SARS-CoV-2���host interactions in the lung. (A), DEG and DEP analysis in other organs and tissues (B) Hub genes and pathway of innate immune response (C), Comorbidities COVID-19 associated not sharing COVID-19 pathogenesis (D), Comorbidities associated and related to COVID-19 pathway (E). Omics and pathway involved were split by different phenotypes: severe, mild/asymptomatic and other Infections. Annexes: Annex 1���Report from Working Group 1: Molecular characterisation of the virus; Annex 2���Report from Working Group 2���Pathways; Annex 3���Report from Working Group 3- Host signatures; Annex 4���Report from Working Group 4���Phenotype. Glossary.

Aims and background Multiple myeloma is the second most common hematological cancer. Although it accounts for only a relatively small percentage of all cancer types, the costs associated with managing multiple myeloma are considerable. Available studies are mainly focused on health care costs. The Costo del Mieloma Multiplo (Cost of MM, CoMiM) study investigated the cost of illness of multiple myeloma in Italy during one year of disease management. Methods CoMiM is a retrospective, prevalence-based, multi-center, cross-sectional study based on a stratified sample of patients seen during normal clinical practice (asymptomatic; symptomatic on drugs; symptomatic receiving autologous stem cell transplantation; plateau/remission). Demographics, clinical history, health care and non-health care resource consumption data were collected. Costs were evaluated from the societal viewpoint and expressed in Euro 2008. Results Data on 236 patients were analyzed (39 asymptomatic, 17%; 29 symptomatic receiving autologous stem-cell transplantation, 12%; 105 symptomatic receiving drugs, 44%; 63 plateau/remission, 27%). The total cost of illness reached € 19,267.1 ± 25,078.6 (asymptomatic, € 959.3 ± 1091.6; symptomatic receiving drugs, € 21,707.8 ± 21,785.3; symptomatic receiving autologous stem-cell transplantation, € 59,243.7 ± 24,214.0; plateau/remission, € 8130.7 ± 15,092.5). The main cost drivers of total cost of illness were drugs and hospital admissions (46.1% and 29.4%, respectively). Antineoplastics and immunomodulators drove the cost of drugs (21.6% and 21.1% of the total cost of illness). Cost of antineoplastics was led by bortezomib (97.4%), whereas the cost driver for immunomodulators was lenalidomide (99.4%). Cost of hospitalization funded by the Italian National Health Service was strongly influenced by transplantation (94.6%), whereas chemotherapy and skeletal fractures did not exceed 1% and 2%, respectively. Conclusions Despite some limitations, the CoMiM study provides Italian health care decision-makers with an insight into the stratified cost of illness of multiple myeloma patients.

Background: MDR-TB is emerging as a major challenge for tuberculosis control programs.In Italy the proportion of MDR-TB reported during 2013 was 3.3%; unfortunately, treatment outcomes in MDR-TB patients are poorly documented. Aim: To evaluate the outcomes of MDR-TB patients treated at the National Institute of Infectious Disease (INMI), a referral hospital for Infectious Diseases in Italy. Methods: 74 MDR-TB patients diagnosed between 2008 and 2015 were consecutively enrolled in an observational retrospective cohort study. All patients were treated according WHO guidelines. Results: The patients (median age 35.8 yr) were mainly male (63.5%) and foreign born (87.2%). Among 74 patients, 2 were extensively drug-resistant (XDR) cases, 2 patients were HIV-coinfected,and 45 (61.0%) were newly diagnosed. Fifty-eight (78.4%) cases were pulmonary sputum smear-positive. 51% of patients were transferred in from units of other regions of central and southern Italy. Among 57 patients who completed treatment in the study period, 68.4 % achieved treatment success, 22.8% were lost to follow up, 3% were transferred out and 1.8% died. Conclusion: Monitoring the treatment outcome of MDR-TB is essential to evaluate the effectiveness of interventions and to identify potential barriers for TB control. In our cohort MDR-TB is mainly related to the immigration of patients from countries with a high TB prevalence with a high proportion of new cases. Data show that, in a referral center for the treatment of MDR-TB, success rates close to the target defined by WHO can be achieved, even if actions are required to reduce the high proportion of patients lost to follow-up.

Person and institution involved in the organization and management of the patient.

Laboratory methods.

Summary Background Joint replacement surgery has been on the increase in recent decades and prosthesis infection remains the most critical complication. Many aspects of the primary prevention and clinical management of such prosthesis infections still need to be clarified. Controversial issues The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group – a panel of multidisciplinary experts – was to define recommendations for the following controversial issues: (1) Is a conservative surgical approach for the management of prosthetic joint infections effective? (2) Is the one-stage or the two-stage revision for the management of prosthetic joint infections more effective? (3) What is the most effective treatment for the management of prosthetic joint infections due to methicillin-resistant staphylococci? Results are presented and discussed in detail. Methods A systematic literature search using the MEDLINE database for the period 1988 to 2008 of randomized controlled trials and/or non-randomized studies was performed. A matrix was created to extract evidence from original studies using the CONSORT method to evaluate randomized clinical trials and the Newcastle–Ottawa Quality Assessment Scale for case–control studies, longitudinal cohorts, and retrospective studies. The GRADE method for grading quality of evidence and strength of recommendation was applied.

The first patient with influenza A/H1N1-related pneumonia was admitted to an Italian ICU at the end of August 2009. Until then, despite the international alarm, the level of awareness was low and very few Italian hospitals were equipped with ECMOs. Moreover the PCR test for A H1N1 virus was sporadically available and the emergency departments of even the largest institutions could rely only on the rapid test for the urgent screening of patients with pneumonia and respiratory failure. On September 5th, a young and “apparently” previously healthy man, was admitted to our ICU because of a severe ARDS caused by influenza A H1N1 virus. As there was no ECMO available, he was treated with prolonged cycles of prone positioning ventilation. Antiviral treatment was started with Oseltamivir, but as enteral absorption was impaired by paralytic ileus and tube feeding intolerance, Oseltamivir had to be discontinued. Intravenous Zanamivir 1200 mg/day for ten days was therefore prescribed as “off label” antiviral therapy. A bone marrow biopsy allowed the diagnosis of an initial stage of “hairy cells leukaemia.” ARDS related to A/H1N1 influenza was the first sign of the disease in our patient. He did well with complete clearance of the infection from the BAL after 10 days of Zanamivir, although the nasopharyngeal swabs remained positive for ten more days. Prone positioning ventilation may be a life-saver strategy in patients with severe ARDS when ECMO is not immediately available. However, prone positioning ventilation is often associated with severe impairment of the absorption of drugs that require enteral administration via the nasogastric tube. In these cases, intravenous Zanamivir may be an effective alternative strategy.

Hairy cell leukemia is an uncommon hematologic malignancy characterized by pancytopenia and marked susceptibility to infection. Tremendous progress in the management of patients with this disease has resulted in high response rates and improved survival, yet relapse and an appropriate approach to re-treatment present continuing areas for research. The disease and its effective treatment are associated with immunosuppression. Because more patients are being treated with alternative programs, comparison of results will require general agreement on definitions of response, relapse, and methods of determining minimal residual disease. The development of internationally accepted, reproducible criteria is of paramount importance in evaluating and comparing clinical trials to provide optimal care. Despite the success achieved in managing these patients, continued participation in available clinical trials in the first-line and particularly in the relapse setting is highly recommended. The Hairy Cell Leukemia Foundation convened an international conference to provide common definitions and structure to guide current management. There is substantial opportunity for continued research in this disease. In addition to the importance of optimizing the prevention and management of the serious risk of infection, organized evaluations of minimal residual disease and treatment at relapse offer ample opportunities for clinical research. Finally, a scholarly evaluation of quality of life in the increasing number of survivors of this now manageable chronic illness merits further study. The development of consensus guidelines for this disease offers a framework for continued enhancement of the outcome for patients.