GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose- and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3 weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific T cell response peaks after the first dose and is characterized by high frequencies of CD8s. T cells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for genetic vaccine development, especially when robust CD8 response is needed.

The shed P2X7 receptor is an index of adverse clinical outcome in COVID-19 patients.

Introduction: The pathophysiology of the Corona Virus Disease 2019 (COVID-19) is incompletely known. A robust inflammatory response caused by viral replication is a main cause of the acute lung and multiorgan injury observed in critical patients. Inflammasomes are likely players in COVID-19 pathogenesis. The P2X7 receptor (P2X7R), a plasma membrane ATP-gated ion channel, is a main activator of the NLRP3 inflammasome, of the ensuing release of inflammatory cytokines and of cell death by pyroptosis. The P2X7R has been implicated in COVID-19-dependent hyperinflammation and in the associated multiorgan damage. Shed P2X7R (sP2X7R) and shed NLRP3 (sNLRP3) have been detected in plasma and other body fluids, especially during infection and inflammation. Methods: Blood samples from 96 patients with confirmed SARS-CoV-2 infection with various degrees of disease severity were tested at the time of diagnosis at hospital admission. Standard haematological parameters and IL-6, IL-10, IL-1ß, sP2X7R and sNLRP3 levels were measured, compared to reference values, statistically validated, and correlated to clinical outcome. Results: Most COVID-19 patients included in this study had lymphopenia, eosinopenia, neutrophilia, increased inflammatory and coagulation indexes, and augmented sNLRP3, IL-6 and IL-10 levels. Blood concentration of sP2X7R was also increased, and significantly positively correlated with lymphopenia, procalcitonin (PCT), IL-10, and alanine transaminase (ALT). Patients with increased sP2X7R levels at diagnosis also showed fever and respiratory symptoms, were more often transferred to Pneumology division, required mechanical ventilation, and had a higher likelihood to die during hospitalization. Conclusion: Blood sP2X7R was elevated in the early phases of COVID-19 and predicted an adverse clinical outcome. It is suggested that sP2X7R might be a useful marker of disease progression.

Epidemiology, aetiology and treatment of skin and soft tissue infections: final report of a prospective multicentre national registry.

Skin and soft tissue infections (SSTIs) represent a heterogenous group of pathological conditions involving the skin or the underlying subcutaneous tissues, fascia and muscle, characterised by a considerable variety of clinical presentations, severity and possible aetiological pathogens. Although previous analyses on restricted types of SSTIs and population have already been published, we conducted a large nationwide surveillance program on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients and their management. Twenty-nine Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. We included in our database all cases managed by ID specialists participating to the study, independently from their severity or the setting of consultation. Here, we integrated previous preliminary results analysing and reporting data referring to a 3-year period (October 2016-October 2019). During this period, the study population included 478 adult patients with diagnosis of SSTI. The type of infection diagnosed, the aetiological agent involved and some notes on antimicrobial susceptibilities were collected and reported herein. We also analysed the most common co-morbidities, the type and duration of therapy executed, before and after ID intervention and the length of stay. The results of our study provide information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy.

Oral Microbiome Dysbiosis Is Associated With Symptoms Severity and Local Immune/Inflammatory Response in COVID-19 Patients: A Cross-Sectional Study.

The human oral microbiome (HOM) is the second largest microbial community after the gut and can impact the onset and progression of several localized and systemic diseases, including those of viral origin, especially for viruses entering the body via the oropharynx. However, this important aspect has not been clarified for the new pandemic human coronavirus SARS-CoV-2, causing COVID-19 disease, despite it being one of the many respiratory viruses having the oropharynx as the primary site of replication. In particular, no data are available about the non-bacterial components of the HOM (fungi, viruses), which instead has been shown to be crucial for other diseases. Consistent with this, this study aimed to define the HOM in COVID-19 patients, to evidence any association between its profile and the clinical disease. Seventy-five oral rinse samples were analyzed by Whole Genome Sequencing (WGS) to simultaneously identify oral bacteria, fungi, and viruses. To correlate the HOM profile with local virus replication, the SARS-CoV-2 amount in the oral cavity was quantified by digital droplet PCR. Moreover, local inflammation and secretory immune response were also assessed, respectively by measuring the local release of pro-inflammatory cytokines (L-6, IL-17, TNFα, and GM-CSF) and the production of secretory immunoglobulins A (sIgA). The results showed the presence of oral dysbiosis in COVID-19 patients compared to matched controls, with significantly decreased alpha-diversity value and lower species richness in COVID-19 subjects. Notably, oral dysbiosis correlated with symptom severity (p = 0.006), and increased local inflammation (p < 0.01). In parallel, a decreased mucosal sIgA response was observed in more severely symptomatic patients (p = 0.02), suggesting that local immune response is important in the early control of virus infection and that its correct development is influenced by the HOM profile. In conclusion, the data presented here suggest that the HOM profile may be important in defining the individual susceptibility to SARS-CoV-2 infection, facilitating inflammation and virus replication, or rather, inducing a protective IgA response. Although it is not possible to determine whether the alteration in the microbial community is the cause or effect of the SARS-CoV-2 replication, these parameters may be considered as markers for personalized therapy and vaccine development.

The Association among Pyoderma Gangrenosum, Ulcerative Colitis, and Hidradenitis Suppurativa and the Syndromic Hidradenitis Suppurativa Network: A Case Report.

Hidradenitis suppurativa (HS), together with other inflammatory diseases, is involved in a syndromic network where different combinations of signs and symptoms characterize the definition. The observation of the concurrent occurrence of HS, pyoderma gangrenosum (PG), and inflammatory bowel disease (IBD), in detail ulcerative colitis (UC), led the authors to describe a new association. The patient, a 36-year-old woman, who saw IBD as the first appearing condition, shortly followed by HS and PG, was referred because of a clinical situation quickly worsening. A severe aggravation of both GI symptoms and general systemic situation total led to total colectomy. Surprisingly, shortly after the radical surgical treatment of UC, the cutaneous manifestations of HS and PG with no specific treatment almost completely disappeared suggesting the existence of a common etiopathogenetic mechanism and possibly an inductor role of UC on the other disorders. The presentation of this case offers the opportunity to deal with the fact that the resolution of one of the associated conditions may lead to the clearance of one or more of the others. It confirms a pathogenetic link between them and the pivotal role of one of them, in this case colitis.

Co-Infections in Critically Ill Patients with or without COVID-19: A Comparison of Clinical Microbial Culture Findings.

Co-infections in critically ill patients hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have an important impact on the outcome of coronavirus disease 2019 (COVID-19). We compared the microbial isolations found in COVID-19 patients hospitalized in an intensive care unit (ICU) with those in a non-COVID-19 ICU from 22 February to 30 April 2020 and in the same period of 2019. We considered blood, urine or respiratory specimens obtained with bronchoalveolar lavage (BAL) or bronchial aspirate (BASP), collected from all patients admitted in ICUs with or without COVID-19 infection. We found a higher frequency of infections due to methicillin-resistant (MR) staphylococci, vancomycin-resistant Enterococcus faecium, carbapenem-resistant Acinetobacter baumannii and Candida parapsilosis in COVID-19-positive patients admitted in ICUs compared to those who were COVID-19 negative. Carbapenem-resistant Pseudomonas aeruginosa was more frequently isolated from patients admitted in non-COVID-19 ICUs. Several conditions favor the increased frequency of these infections by antibiotic-resistant microorganisms. Among all, the severity of the respiratory tracts was definitely decisive, which required assisted ventilation with invasive procedures. The turnover in the ICU of a large number of patients in a very short time requiring urgent invasive interventions has favored the not always suitable execution of assistance procedures. No less important is the increased exposure to infectious risk from bacteria and fungi in patients with severe impairment due to ventilation. The highest costs for antifungal drugs were shown in the ICU-COVID group.

Ceftolozane/Tazobactam and Ceftazidime/Avibactam for Multidrug-Resistant Gram-Negative Infections in Immunocompetent Patients: A Single-Center Retrospective Study.

Complicated infections from multidrug-resistant Gram-negative bacteria (MDR-GNB) represent a serious problem presenting many challenges. Resistance to many classes of antibiotics reduces the probability of an adequate empirical treatment, with unfavorable consequences, increasing morbidity and mortality. Readily available patient medical history and updated information about the local microbiological epidemiology remain critical for defining the baseline risk of MDR-GNB infections and guiding empirical treatment choices, with the aim of avoiding both undertreatment and overtreatment. There are few literature data that report real-life experiences in the use of ceftolozane/tazobactam and ceftazidime/avibactam, with particular reference to microbiological cure. Some studies reported experiences for the treatment of MDR-GNB infections in patients with hematological malignancies or specifically in Pseudomonas aeruginosa infections. We report our clinical single-center experience regarding the real-life use of ceftolozane/tazobactam and ceftazidime/avibactam to treat serious and complicated infections due to MDR-GNB and carbapenem-resistant Enterobacterales (CRE), with particular regard given to intra-abdominal and urinary tract infections and sepsis.

Epidemiology and Microbiology of Skin and Soft Tissue Infections: Preliminary Results of a National Registry.

Skin and soft tissue infections (SSTIs) represent a wide range of clinical conditions characterized by a considerable variety of clinical presentations and severity. Their aetiology can also vary, with numerous possible causative pathogens. While other authors previously published analyses on several types of SSTI and on restricted types of patients, we conducted a large nationwide surveillance programme on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients. Twenty-five Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. All the cases included in our database, independently from their severity, have been managed by ID specialists joining the study while SSTIs from other wards/clinics have been excluded from this analysis. Here, we report the preliminary results of our study, referring to a 12-month period (October 2016-September 2017). During this period, the study population included 254 adult patients and a total of 291 SSTI diagnoses were posed, with 36 patients presenting more than one SSTIs. The type of infection diagnosed, the aetiological micro-organisms involved and some notes on their antimicrobial susceptibilities were collected and are reported herein. The enrichment of our registry is ongoing, but these preliminary results suggest that further analysis could soon provide useful information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy.

Entheseal involvement in asymptomatic human immunodeficiency virus infected patients: preliminary results of a clinical and ultrasonographic study.

OBJECTIVES: As a strong association between human immunodeficiency virus (HIV) infection and spondyloarthritis (SpA) has been hypothesised, our main objective was to explore by power Doppler ultrasonography (PDUS) the presence of subclinical enthesitis in asymptomatic HIV patients. The presence of subclinical synovitis was also evaluated. METHODS: Consecutive asymptomatic HIV patients were studied and compared with asymptomatic HCV patients and healthy controls (HC). All subjects underwent a clinical and PDUS bilateral examination of the following entheses and joints: epicondyle, quadriceps, patellar, Achilles and plantar fascia; wrists, II and III metacarpo-phalangeal, knee and ankle. RESULTS: Twenty-nine HIV, 32 HCV and 25 HC were recruited; 1.032 entheses and 860 joints were examined. Clinical diagnosis of enthesitis was made in 10.3% HIV patients, 6.2% HCV patients (p=0.66) and none HC (p=0.24). PDUS enthesitis was found in 72.4% HIV, 28.1% HCV (p=0.0008) and 12% HC (p<0.0001). Clinical diagnosis of synovitis was made in 3.4% HIV patients, 9.3% HCV patients (p=0.61) and none HC (p=1). PDUS abnormalities were documented in 24.1% HIV patients, 71.8% HCV patients (p=0.0003) and none HC (p=0.0001). In detecting enthesitis and synovitis, PDUS was more sensitive than clinical examination both in HIV and HCV patients. CONCLUSIONS: Our preliminary study shows the high frequency of PDUS enthesitis in asymptomatic HIV patients, which highlights the close link between HIV and SpA. Further studies are desirable on a larger number of HIV patients to confirm these results. PDUS proved to be more sensitive than clinical examination in detecting subclinical involvement of entheses and joints.

Diagnostic and therapeutic appropriateness in bone and joint infections: results of a national survey.

The impact of infectious diseases (ID) specialist consultation in the management of many types of bacterial infections has been fully demonstrated but not for bone and joint infections (BJIs). Nineteen ID Italian centres collected of data from June 2009 to May 2012. Italian guidelines (2009) were used to determine the appropriateness of the diagnostic and therapeutic process of BJIs before and after consulting an ID specialist. Data on 311 patients were collected: 111 cases of prosthetic joint infection, 99 osteomyelitis, 64 spondylodiscitis and 37 fixation device infection. A significant increase of microbiological investigations, imaging techniques and blood inflammation markers were noted after consulting the ID specialist. Moreover, inappropriateness of treatment duration, dosage, and number of administrations significantly decreased after consultation. Infectious disease specialist intervention in the management of BJIs significantly increases the appropriateness both in performing instrumental and laboratory analysis, but especially in determining the correct therapy.

[Vector-borne diseases. Recent advances in the diagnosis, treatment and prevention]. / Patologie a trasmissione vettoriale.

Vector borne diseases are infections transmitted by arthropods. The vector can mechanically spread the infectious disease or give hospitality to microrganisms for their biological cycle. The etiologic agents of these infections are viruses as yellow fever and Dengue, protozoans as plasmodium of malaria, Leishmania spp., bacteria as Borrelia burgdorferi, Rickettsia spp. or worms as lymphatic filariasis. They are emerging infectious diseases for the epidemiological changes of our national territory (ex. Lyme disease) but especially for the significant increase of the imported forms. Malaria is the more important infection for its clinical management but also for its remote possibility of a further transmission in Italy. In this review are illustrated the recent progresses in the diagnosis, treatment and prevention of the main vector borne infections that the clinical physicians may frequently observe. It is very important to know these diseases because an adequate preparation and continuous updating are necessarily required.