Efficacy and Safety of Anticoagulant Therapy in COVID-19-Related Pulmonary Embolism with Different Extension.

Pulmonary embolism (PE) has been associated with SARS-CoV-2 infection, and its incidence is highly variable. The aim of our study was to describe the radiological and clinical presentations, as well as the therapeutic management, of PEs that occurred during SARS-CoV-2 infection in a cohort of hospitalized patients. In this observational study, we enrolled patients with moderate COVID-19 who developed PE during hospitalization. Clinical, laboratory, and radiological features were recorded. PE was diagnosed on clinical suspicion and/or CT angiography. According to CT angiography results, two groups of patients were further distinguished: those with proximal or central pulmonary embolism (cPE) and those with distal or micro-pulmonary embolism (mPE). A total of 56 patients with a mean age of 78 ± 15 years were included. Overall, PE occurred after a median of 2 days from hospitalization (range 0-47 days) and, interestingly, the majority of them (89%) within the first 10 days of hospitalization, without differences between the groups. Patients with cPE were younger (p = 0.02), with a lower creatinine clearance (p = 0.04), and tended to have a higher body weight (p = 0.059) and higher D-Dimer values (p = 0.059) than patients with mPE. In all patients, low-weight molecular heparin (LWMH) at anticoagulant dosage was promptly started as soon as PE was diagnosed. After a mean of 16 ± 9 days, 94% of patients with cPE were switched to oral anticoagulant (OAC) therapy, which was a direct oral anticoagulant (DOAC) in 86% of cases. In contrast, only in 68% of patients with mPE, the prosecution with OAC was indicated. The duration of treatment was at least 3 months from PE diagnosis in all patients who started OAC. At the 3-month follow-up, no persistence or recurrence of PE as well as no clinically relevant bleedings were found in both groups. In conclusion, pulmonary embolism in patients with SARS-CoV-2 may have different extensions. Used with clinical judgment, oral anticoagulant therapy with DOAC was effective and safe.

A Cholera Case Imported from Bangladesh to Italy: Clinico-Epidemiological Management and Molecular Characterization in a Non-Endemic Country.

Despite the number of cholera outbreaks reported worldwide, only a few cases are recorded among returning European travellers. We describe the case of a 41-year-old male, returning to Italy after a stay in Bangladesh, his origin country, who presented with watery diarrhoea. Vibrio cholerae and norovirus were detected in the patient's stools via multiplex PCR methods. Direct microscopy, Gram staining, culture and antibiotic susceptibility tests were performed. The isolates were tested using end-point PCR for the detection of potentially enteropathogenic V. cholera. Serotype and cholera toxins identification were carried out. Whole genome sequencing and bioinformatics analysis were performed, and antimicrobial resistance genes identified. A phylogenetic tree with the most similar genomes of databases previously described was built. Sample of the food brought back by the patient were also collected and analysed. The patient was diagnosed with V. cholerae O1, serotype Inaba, norovirus and SARS-CoV-2 concomitant infection. The isolated V. cholerae strain was found to belong to ST69, encoding for cholera toxin, ctxB7 type and was phylogenetically related to the 2018 outbreak in Dhaka, Bangladesh. Adopting a multidisciplinary approach in a cholera non-endemic country ensured rapid and accurate diagnosis, timely clinical management, and epidemiological investigation at national and international level.

Dynamic Evolution of Humoral and T-Cell Specific Immune Response to COVID-19 mRNA Vaccine in Patients with Multiple Sclerosis Followed until the Booster Dose.

This study characterizes antibody and T-cell immune responses over time until the booster dose of COronaVIrus Disease 2019 (COVID-19) vaccines in patients with multiple sclerosis (PwMS) undergoing different disease-modifying treatments (DMTs). We prospectively enrolled 134 PwMS and 99 health care workers (HCWs) having completed the two-dose schedule of a COVID-19 mRNA vaccine within the last 2-4 weeks (T0) and followed them 24 weeks after the first dose (T1) and 4-6 weeks after the booster (T2). PwMS presented a significant reduction in the seroconversion rate and anti-receptor-binding domain (RBD)-Immunoglobulin (IgG) titers from T0 to T1 (p < 0.0001) and a significant increase from T1 to T2 (p < 0.0001). The booster dose in PwMS showed a good improvement in the serologic response, even greater than HCWs, as it promoted a significant five-fold increase of anti-RBD-IgG titers compared with T0 (p < 0.0001). Similarly, the T-cell response showed a significant 1.5- and 3.8-fold increase in PwMS at T2 compared with T0 (p = 0.013) and T1 (p < 0.0001), respectively, without significant modulation in the number of responders. Regardless of the time elapsed since vaccination, most ocrelizumab- (77.3%) and fingolimod-treated patients (93.3%) showed only a T-cell-specific or humoral-specific response, respectively. The booster dose reinforces humoral- and cell-mediated-specific immune responses and highlights specific DMT-induced immune frailties, suggesting the need for specifically tailored strategies for immune-compromised patients to provide primary prophylaxis, early SARS-CoV-2 detection and the timely management of COVID-19 antiviral treatments.

Evolution of SARS-CoV-2 variants of concern over a period of Delta and Omicron cocirculation, among patients hospitalized for COVID-19 in an Italian reference hospital: Impact on clinical outcomes.

Despite the higher transmissibility of Omicron Variant of Concern (VOC), several reports have suggested lower risk for hospitalization and severe outcomes compared to previous variants of SARS-CoV-2. This study, enrolling all COVID-19 adults admitted to a reference hospital who underwent both the S-gene-target-failure test and VOC identification by Sanger sequencing, aimed to describe the evolving prevalence of Delta and Omicron variants and to compare the main in-hospital outcomes of severity, during a trimester (December 2021 to March 2022) of VOCs' cocirculation. Factors associated with clinical progression to noninvasive ventilation (NIV)/mechanical ventilation (MV)/death within 10 days and to MV/admission to intensive care unit (ICU)/death within 28 days, were investigated through multivariable logistic regressions. Overall, VOCs were: Delta n = 130/428, Omicron n = 298/428 (sublineages BA.1 n = 275 and BA.2 n = 23). Until mid-February, Delta predominance shifted to BA.1, which was gradually displaced by BA.2 until mid-March. Participants with Omicron VOC were more likely to be older, fully vaccinated, with multiple comorbidities and to have a shorter time from symptoms' onset, and less likely to have systemic symptoms and respiratory complications. Although the need of NIV within 10 days and MV within 28 days from hospitalization and the admission to ICU were less frequent for patients with Omicron compared to those with Delta infections, mortality was similar between the two VOCs. In the adjusted analysis, multiple comorbidities and a longer time from symptoms' onset predicted 10-day clinical progression, while complete vaccination halved the risk. Multimorbidity was the only risk factor associated with 28-day clinical progression. In our population, in the first trimester of 2022, Omicron rapidly displaced Delta in COVID-19 hospitalized adults. Clinical profile and presentation differed between the two VOCs and, although Omicron infections showed a less severe clinical picture, no substantial differences for clinical progression were found. This finding suggests that any hospitalization, especially in more vulnerable individuals, may be at risk for severe progression, which is more related to the underlying frailty of patients than to the intrinsic severity of the viral variant.

Evaluation of the immunomodulatory effects of interleukin-10 on peripheral blood immune cells of COVID-19 patients: Implication for COVID-19 therapy.

Objective: Several therapies with immune-modulatory functions have been proposed to reduce the overwhelmed inflammation associated with COVID-19. Here we investigated the impact of IL-10 in COVID-19, through the ex-vivo assessment of the effects of exogenous IL-10 on SARS-CoV-2-specific-response using a whole-blood platform. Methods: Two cohorts were evaluated: in "study population A", plasma levels of 27 immune factors were measured by a multiplex (Luminex) assay in 39 hospitalized "COVID-19 patients" and 29 "NO COVID-19 controls" all unvaccinated. In "study population B", 29 COVID-19 patients and 30 NO COVID-19-Vaccinated Controls (NO COVID-19-VCs) were prospectively enrolled for the IL-10 study. Whole-blood was stimulated overnight with SARS-COV-2 antigens and then treated with IL-10. Plasma was collected and used for ELISA and multiplex assay. In parallel, whole-blood was stimulated and used for flow cytometry analysis. Results: Baseline levels of several immune factors, including IL-10, were significantly elevated in COVID-19 patients compared with NO COVID-19 subjects in "study population A". Among them, IL-2, FGF, IFN-γ, and MCP-1 reached their highest levels within the second week of infection and then decreased. To note that, MCP-1 levels remained significantly elevated compared with controls. IL-10, GM-CSF, and IL-6 increased later and showed an increasing trend over time. Moreover, exogenous addition of IL-10 significantly downregulated IFN-γ response and several other immune factors in both COVID-19 patients and NO COVID-19-VCs evaluated by ELISA and a multiplex analysis (Luminex) in "study population B". Importantly, IL-10 did not affect cell survival, but decreased the frequencies of T-cells producing IFN-γ, TNF-α, and IL-2 (p<0.05) and down-modulated HLA-DR expression on CD8+ and NK cells. Conclusion: This study provides important insights into immune modulating effects of IL-10 in COVID-19 and may provide valuable information regarding the further in vivo investigations.

Comparison of SARS-CoV-2 Detection in Nasopharyngeal Swab and Saliva Samples from Patients Infected with Omicron Variant

To compare the detection of the SARS-CoV-2 Omicron variant in nasopharyngeal-swab (NPS) and oral saliva samples. 255 samples were obtained from 85 Omicron-infected patients. SARS-CoV-2 load was measured in the NPS and saliva samples by using Simplexa™ COVID-19 direct and Alinity m SARS-CoV-2 AMP assays. Results obtained with the two diagnostic platforms showed very good inter-assay concordance (91.4 and 82.4% for saliva and NPS samples, respectively) and a significant correlation among cycle threshold (Ct) values. Both platforms revealed a highly significant correlation among Ct obtained in the two matrices. Although the median Ct value was lower in NPS than in saliva samples, the Ct drop was comparable in size for both types of samples after 7 days of antiviral treatment of the Omicron-infected patients. Our result demonstrates that the detection of the SARS-CoV-2 Omicron variant is not influenced by the type of sample used for PCR analysis, and that saliva can be used as an alternative specimen for detection and follow-up of Omicron-infected patients.

The Third Dose of BNT162b2 COVID-19 Vaccine Does Not "Boost" Disease Flares and Adverse Events in Patients with Rheumatoid Arthritis.

Data on the risk of adverse events (AEs) and disease flares in autoimmune rheumatic diseases (ARDs) after the third dose of COVID-19 vaccine are scarce. The aim of this multicenter, prospective study is to analyze the clinical and immunological safety of BNT162b2 vaccine in a cohort of rheumatoid arthritis (RA) patients followed-up from the first vaccine cycle to the third dose. The vaccine showed an overall good safety profile with no patient reporting serious AEs, and a low percentage of total AEs at both doses (40/78 (51.3%) and 13/47 (27.7%) patients after the second and third dose, respectively (p < 0.002). Flares were observed in 10.3% of patients after the end of the vaccination cycle and 12.8% after the third dose. Being vaccinated for influenza was inversely associated with the onset of AEs after the second dose, at both univariable (p = 0.013) and multivariable analysis (p = 0.027). This result could allow identification of a predictive factor of vaccine tolerance, if confirmed in larger patient populations. A higher disease activity at baseline was not associated with a higher incidence of AEs or disease flares. Effectiveness was excellent after the second dose, with only 1/78 (1.3%) mild breakthrough infection (BI) and worsened after the third dose, with 9/47 (19.2%) BI (p < 0.002), as a probable expression of the higher capacity of the Omicron variants to escape vaccine recognition.

Sarilumab plus standard of care vs standard of care for the treatment of severe COVID-19: a phase 3, randomized, open-labeled, multi-center study (ESCAPE study).

Background: Among interleukin-6 inhibitors suggested for use in COVID-19, there are few robust evidences for the efficacy of sarilumab. Herein, we evaluated the efficacy and safety of sarilumab in severe COVID-19. Methods: In this phase 3, open-labeled, randomized clinical trial, conducted at 5 Italian hospitals, adults with severe COVID-19 pneumonia (excluding mechanically ventilated) were randomized 2:1 to receive intravenous sarilumab (400 mg, repeatable after 12 h) plus standard of care (SOC) (arm A) or to continue SOC (arm B). Randomization was web-based. As post-hoc analyses, the participants were stratified according to baseline inflammatory parameters. The primary endpoint was analysed on the modified Intention-To-Treat population, including all the randomized patients who received any study treatment (sarilumab or SOC). It was time to clinical improvement of 2 points on a 7-points ordinal scale, from baseline to day 30. We used Kaplan Meier method and log-rank test to compare the primary outcome between two arms, and Cox regression stratified by clinical center and adjusted for severity of illness, to estimate the hazard ratio (HR). The trial was registered with EudraCT (2020-001390-76). Findings: Between May 2020 and May 2021, 191 patients were assessed for eligibility, of whom, excluding nine dropouts, 176 were assigned to arm A (121) and B (55). At day 30, no significant differences in the primary endpoint were found (88% [95% CI 81-94] in arm A vs 85% [74-93], HR 1.07 [0.8-1.5] in arm B; log-rank p = 0.50). After stratifying for inflammatory parameters, arm A showed higher probability of improvement than B without statistical significance in the strata with C reactive protein (CRP) < 7 mg/dL (88% [77-96] vs 79% [63-91], HR 1.55 [0.9-2.6]; log-rank p = 0.049) and in the strata with lymphocytes <870/mmc (90% [79-96]) vs (73% [55-89], HR 1.53 [0.9-2.7]; log-rank p = 0.058). Overall, 39/121 (32%) AEs were reported in arm A and 14/55 (23%) in B (p = 0.195), while serious AEs were 22/121 (18%) and 7/55 (11%), respectively (p = 0.244). There were no treatment-related deaths. Interpretation: The efficacy of sarilumab in severe COVID-19 was not demonstrated both in the overall and in the stratified for severity analysis population. Exploratory analyses suggested that subsets of patients with lower CRP values or lower lymphocyte counts might have had benefit with sarilumab treatment, but this finding would require replication in other studies. The relatively low rate of concomitant corticosteroid use, could partially explain our results. Funding: This study was supported by INMI "Lazzaro Spallanzani" Ricerca Corrente Linea 1 on emerging and reemerging infections, funded by Italian Ministry of Health.

Comparison of SARS-CoV-2 Detection in Nasopharyngeal Swab and Saliva Samples from Patients Infected with Omicron Variant.

To compare the detection of the SARS-CoV-2 Omicron variant in nasopharyngeal-swab (NPS) and oral saliva samples. 255 samples were obtained from 85 Omicron-infected patients. SARS-CoV-2 load was measured in the NPS and saliva samples by using Simplexa™ COVID-19 direct and Alinity m SARS-CoV-2 AMP assays. Results obtained with the two diagnostic platforms showed very good inter-assay concordance (91.4 and 82.4% for saliva and NPS samples, respectively) and a significant correlation among cycle threshold (Ct) values. Both platforms revealed a highly significant correlation among Ct obtained in the two matrices. Although the median Ct value was lower in NPS than in saliva samples, the Ct drop was comparable in size for both types of samples after 7 days of antiviral treatment of the Omicron-infected patients. Our result demonstrates that the detection of the SARS-CoV-2 Omicron variant is not influenced by the type of sample used for PCR analysis, and that saliva can be used as an alternative specimen for detection and follow-up of Omicron-infected patients.

The unmet need for COVID-19 treatment in immunocompromised patients.

BACKGROUND: Immunocompromised (IC) patients are at increased risk of severe and/or prolonged COVID-19. MAIN TEXT: The recent study by Scaglione et al., addresses the issue of IC outpatients with SARS-CoV-2 infection. Authors describe the real-life use of SARS-CoV-2 antivirals and/or monoclonal antibodies and the clinical benefit in high-risk COVID-19 patients. The study supports the use of early combination therapy in a subgroup of extremely high risk patients, and considers the combined strategy as a gold standard regimen to both increase the effectiveness of early treatment, especially in IC individuals, and, reduce the emergence of SARS-CoV-2 escape mutants. CONCLUSION: A tailored and standardised therapeutic approach in case of IC out and inpatients with SARS-CoV-2 infection is needed.

Longitudinal characterisation of B and T-cell immune responses after the booster dose of COVID-19 mRNA-vaccine in people with multiple sclerosis using different disease-modifying therapies.

BACKGROUND: The decline of humoral response to COVID-19 vaccine led to authorise a booster dose. Here, we characterised the kinetics of B-cell and T-cell immune responses in patients with multiple sclerosis (PwMS) after the booster dose. METHODS: We enrolled 22 PwMS and 40 healthcare workers (HCWs) after 4-6 weeks from the booster dose (T3). Thirty HCWs and 19 PwMS were also recruited 6 months (T2) after the first dose. Antibody response was measured by anti-receptor-binding domain (RBD)-IgG detection, cell-mediated response by an interferon (IFN)-γ release assay (IGRA), Th1 cytokines and T-cell memory profile by flow cytometry. RESULTS: Booster dose increased anti-RBD-IgG titers in fingolimod-treated, cladribine-treated and IFN-ß-treated patients, but not in ocrelizumab-treated patients, although antibody titres were lower than HCWs. A higher number of fingolimod-treated patients seroconverted at T3. Differently, T-cell response evaluated by IGRA remained stable in PwMS independently of therapy. Spike-specific Th1-cytokine response was mainly CD4+ T-cell-mediated, and in PwMS was significantly reduced (p<0.0001) with impaired IL-2 production compared with HCWs at T3. In PwMS, total Th1 and IFN-γ CD4+ T-cell responders to spike protein were increased from T2 to T3.Compared with HCWs, PwMS presented a higher frequency of CD4+ and CD8+ terminally differentiated effector memory cells and of CD4+ effector memory (TEM) cells, independently of the stimulus suggesting the association of this phenotype with MS status. CD4+ and CD8+ TEM cell frequency was further increased at T3 compared with T2. CONCLUSIONS: COVID-19 vaccine booster strengthens humoral and Th1-cell responses and increases TEM cells in PwMS.

Aero-Medical Evacuation during SARS-CoV-2 Pandemic: Extraordinary Measure or Emerging Treatment Option?

Aero-medical evacuation has been considered as a feasible and safe treatment option during COVID pandemic, particularly when the needs of affected patients exceed what local clinics and hospitals are supposed to provide. In this article, we analyzed the clinical course of 17 patients medically evacuated to the "L. Spallanzani" Institute in Rome, Italy from foreign countries, mainly Africa and Eastern Europe, who had COVID-19 pneumonia with, or without, coinfections such as malaria, HIV, tuberculosis and microbiologically confirmed sepsis syndrome. The aero-medical evacuation of patients with infectious diseases has become one of the greatest medical achievements we have reached during this pandemic; in fact, only two patients with life threatening coinfections have died. Although logistically difficult and cost consuming, medical evacuation should be considered as a treatment option more than a single extraordinary measure, especially among complex cases that require specific technical and human resources.

Management of patients with lymphoma and COVID-19: Narrative review and evidence-based practical recommendations.

Patients with hematologic malignancies can be immunocompromized because of their disease, anti-cancer therapy, and concomitant immunosuppressive treatment. Furthermore, these patients are usually older than 60 years and have comorbidities. For all these reasons they are highly vulnerable to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and have an increased risk of developing severe/critical Coronavirus disease 2019 (COVID-19) compared to the general population. Although COVID-19 vaccination has proven effective in reducing the incidence of severe/critical disease, vaccinated patients with lymphoma may not be protected as they often fail to develop a sufficient antiviral immune response. There is therefore an urgent need to address the management of patients with lymphoma and COVID-19 in the setting of the ongoing pandemic. Passive immunization with monoclonal antibodies against SARS-CoV-2 is a currently available complementary drug strategy to active vaccination for lymphoma patients, while monoclonal antibodies and antiviral drugs (remdesivir, ritonavir-boosted nirmatrelvir, and molnupiravir) have proven effective in preventing the progression to severe/critical COVID-19. In this narrative review we present the most recent data documenting the characteristics and outcomes of patients with concomitant lymphoma and COVID-19. Our ultimate goal is to provide practice-oriented guidance in the management of these vulnerable patients from diagnosis to treatment and follow-up of lymphoma. To this purpose, we will first provide an overview of the main data concerning prognostic factors and fatality rate of lymphoma patients who develop COVID-19; the outcomes of COVID-19 vaccination will also be addressed. We will then discuss current COVID-19 prophylaxis and treatment options for lymphoma patients. Finally, based on the literature and our multidisciplinary experience, we will summarize a set of indications on how to manage patients with lymphoma according to COVID-19 exposure, level of disease severity and former history of infection, as typically encountered in clinical practice.

Viral load decrease in SARS-CoV-2 BA.1 and BA.2 Omicron sublineages infection after treatment with monoclonal antibodies and direct antiviral agents.

The efficacy on the Omicron variant of the approved early coronavirus disease-2019 (COVID-19) therapies, especially monoclonal antibodies, has been challenged by in vitro neutralization data, while data on in vivo antiviral activity are lacking. We assessed potential decrease from Day 1 to Day 7 viral load (VL) in nasopharyngeal swabs of outpatients receiving Sotrovimab, Molnupiravir, Remdesivir, or Nirmatrelvir/ritonavir for mild-to-moderate COVID-19 due to sublineages BA.1 or BA.2, and average treatment effect by weighted marginal linear regression models. A total of 521 patients (378 BA.1 [73%], 143 [27%] BA.2) received treatments (Sotrovimab 202, Molnupiravir 117, Nirmatrelvir/ritonavir 84, and Remdesivir 118): median age 66 years, 90% vaccinated, median time from symptoms onset 3 days. Day 1 mean VL was 4.12 log2 (4.16 for BA.1 and 4.01 for BA.2). The adjusted analysis showed that Nirmatrelvir/ritonavir significantly reduced VL compared to all the other drugs, except versus Molnupiravir in BA.2. Molnupiravir was superior to Remdesivir in both BA.1 and BA.2, and to Sotrovimab in BA.2. Sotrovimab had better activity than Remdesivir only against BA.1. Nirmatrelvir/ritonavir showed the greatest antiviral activity against Omicron variant, comparable to Molnupiravir only in the BA.2 subgroup. VL decrease could be a valuable surrogate of drug activity in the context of the high prevalence of vaccinated people and low probability of hospital admission.

Efficacy and safety of early soluble urokinase plasminogen receptor plasma-guided anakinra treatment of COVID-19 pneumonia: A subgroup analysis of the SAVE-MORE randomised trial.

Background: The SAVE-MORE trial demonstrated that anakinra treatment in COVID-19 pneumonia with plasma soluble urokinase plasminogen activator (suPAR) levels of 6 ng/mL or more was associated with 0.36 odds for a worse outcome compared to placebo when expressed by the WHO-Clinical Progression Scale (CPS) at day 28. Herein, we report the results of subgroup analyses and long-term outcomes. Methods: This prospective, double-blind, randomised clinical trial, recruited patients with a confirmed SARS-CoV-2 infection, in need of hospitalisation, lower respiratory tract infection and plasma suPAR ≥6 ng/mL from 37 academic and community hospitals in Greece and Italy. Patients were 1:2 randomised to subcutaneous treatment with placebo or anakinra (100 mg) once daily for 10 days. Pre-defined subgroups of Charlson's comorbidity index (CCI), sex, age, level of suPAR, and time from symptom onset were analysed for the primary endpoint (overall comparison of distribution of frequencies of the scores from the WHO-CPS between treatments on day 28), by multivariable ordinal regression analysis in the intention to treat (ITT) population. This trial is registered with the EU Clinical Trials Register (2020-005828-11) and ClinicalTrials.gov (NCT04680949). Findings: Patients were enrolled between 23 December 2020 and 31 March 2021; 189 patients in the placebo arm and 405 patients in the anakinra arm were the ITT population. Multivariable analysis showed that anakinra treatment was accompanied by significantly lower odds for worse outcome compared to placebo at day 28 for all studied subgroups (CCI ≥ 2, OR: 0.34, 95% confidence intervals [CI] 0.22-0.50; CCI < 2, OR: 0.38, 95% CI 0.21-0.68; suPAR > 9 ng/mL, OR: 0.35, 95% CI 0.19-0.66; suPAR 6-9 ng/mL, OR: 0.35, 95% CI 0.24-0.52; patients ≥65 years, OR: 0.41, 95% CI 0.25-0.66; and patients <65 years, OR: 0.29, 95% CI 0.19-0.45). The benefit was uniform, irrespective of the time from start of symptoms until the start of the study drug. At days 60 and 90, anakinra treatment had odds of 0.40 (95% CI 0.28-0.57) and 0.46 (95% CI 0.32-0.67) respectively, for a worse outcome compared to placebo. The costs of general ward stay, ICU stay, and drugs were lower with anakinra treatment. Interpretation: Anakinra represents an important therapeutic tool in the management of COVID-19 that may be administered in all subgroups of patients; benefits are maintained until day 90. Funding: Hellenic Institute for the Study of Sepsis; Swedish Orphan Biovitrum AB.

Telemedicine During COVID-19 Pandemic: Lesson Learned from the Lazio Region Infectious Diseases and Emergency Department Network.

Telemedicine and teleconsultation can be powerful and useful tools for patients to hamper the physical barriers to access to health care services during COVID-19 pandemic. We describe the teleconsultation (TC) model in the Lazio Region. It uses a hub-and-spoke network system on geographic regional basis using a web based digital platform, termed ADVICE with the aim to connect regional Emergency Departments (EDs) and Infectious Diseases (ID) acute and critical care settings for patients with acute ID syndrome. Between January 2020 and June 2021, the ADVICE platform received 18.686 TCs: of them, 10838 requests (58%) were for ID TCs in 7996 patients, followed by 2555(13%) requests for trauma, 2286(12%) for acute complex syndrome and 1681 (8%) for Stroke TCs. Three quarter of ID TCs were requested for SARS-COV-2 infection, followed by sepsis management in 7% and tuberculosis in 6%. In 5416 TCs, 68%, diagnostic investigations and therapeutic prescriptions were recommended before admission, in 1941 TCs, 24%, the recommendation was patient admission and in 608 TCs, 7%, was to discharge patient at home. Telemedicine have ensured high-profile consultations for ID patients and during COVID-19 the use of this resource optimized clinical patient management.

Interferon gamma-induced protein 10 (IP-10) for the early prognosis of the risk for severe respiratory failure and death in COVID-19 pneumonia.

OBJECTIVES: Elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict progression to severe respiratory failure (SRF) or death among patients with COVID-19 pneumonia and guide early anakinra treatment. As suPAR testing may not be routinely available in every health-care setting, alternative biomarkers are needed. We investigated the performance of C-reactive protein (CRP), interferon gamma-induced protein-10 (IP-10) and TNF-related apoptosis-inducing ligand (TRAIL) for predicting SRF or death in COVID-19. METHODS: Two cohorts were studied; one discovery cohort with 534 patients from the SAVE-MORE clinical trial; and one validation cohort with 364 patients from the SAVE trial including also 145 comparators. CRP, IP-10 and TRAIL were measured by the MeMed Key® platform in order to select the biomarker with the best prognostic performance for the early prediction of progression into SRF or death. RESULTS: IP-10 had the best prognostic performance: baseline concentrations 2000 pg/ml or higher predicted equally well to suPAR (sensitivity 85.0 %; negative predictive value 96.6 %). Odds ratio for poor outcome among anakinra-treated participants of the SAVE-MORE trial was 0.35 compared to placebo when IP-10 was 2,000 pg/ml or more. IP-10 could divide different strata of severity for SRF/death by day 14 in the validation cohort. Anakinra treatment decreased this risk irrespective the IP-10 concentrations. CONCLUSIONS: IP-10 concentrations of 2,000 pg/ml or higher are a valid alternative to suPAR for the early prediction of progression into SRF or death the first 14 days from hospital admission for COVID-19 and they may guide anakinra treatment. CLINICALTRIALS: gov, NCT04680949 and NCT04357366.