Editorial for the Special Issue “Epidemiology of Enterovirus Disease”

Enteroviruses (Enterovirus genus, Picornaviridae family) are distributed worldwide and are among the most common causes of human disease globally [...]

Recommendations for enterovirus diagnostics and characterisation within and beyond Europe.

Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European level. In order to improve EV diagnostics, collate data on severe EV infections and monitor the circulation of EV types, we have established European non-polio enterovirus network (ENPEN). First task of this cross-border network has been to ensure prompt and adequate diagnosis of these infections in Europe, and hence we present recommendations for non-polio EV detection and typing based on the consensus view of this multidisciplinary team including experts from over 20 European countries. We recommend that respiratory and stool samples in addition to cerebrospinal fluid (CSF) and blood samples are submitted for EV testing from patients with suspected neurological infections. This is vital since viruses like EV-D68 are rarely detectable in CSF or stool samples. Furthermore, reverse transcriptase PCR (RT-PCR) targeting the 5'noncoding regions (5'NCR) should be used for diagnosis of EVs due to their sensitivity, specificity and short turnaround time. Sequencing of the VP1 capsid protein gene is recommended for EV typing; EV typing cannot be based on the 5'NCR sequences due to frequent recombination events and should not rely on virus isolation. Effective and standardized laboratory diagnostics and characterisation of circulating virus strains are the first step towards effective and continuous surveillance activities, which in turn will be used to provide better estimation on EV disease burden

Detection of SARS-CoV-2 in Cancellous Bone of Patients with COVID-19 Disease Undergoing Orthopedic Surgery: Laboratory Findings and Clinical Applications

An emerging issue for orthopedic surgeons is how to manage patients with active or previous COVID-19 disease, avoiding any major risks for the surgeons and the O.R. personnel. This monocentric prospective observational study aims to assess the prevalence of SARS-CoV-2 viral RT-PCR RNA in cancellous bone samples in patients with active or previous COVID-19 disease. We collected data about 30 consecutive patients from our institution from January 2021 to March 2021 with active or previous COVID-19 disease. The presence of SARS-CoV-2 in the samples was determined using two different PCR-based assays. Eighteen of the thirty patients included in the study had a positive nasopharyngeal swab at the time of surgery. Twelve patients had a negative nasopharyngeal swab with a mean days since negativization of 138 ± 104 days, ranging from 23 to 331 days. Mean days of positivity to the nasal swab were 17 ± 17. Twenty-nine out of thirty (96.7%) samples were negative for the presence of SARS-CoV-2 RNA. In one sample, low SARS-CoV-2 load (Cycle threshold (Ct) 36.6.) was detected but not confirmed using an additional confirmatory assay. The conducted study demonstrates the absence of the viral genome within the analyzed cancellous bone. We think that the use of personal protection equipment (PPE) to only protect from aerosol produced during surgery, both in active and recovered patients, is not strictly necessary. We think that the use of PPE should not be employed by surgeons and the O.R. personnel to protect themselves from aerosols produced from the respiratory tract. Moreover, we think that our results could represent a valid basis for further studies related to the possibility of bone donation in patients that suffered and recovered from COVID-19

Life-Threatening Protein-Losing Enteropathy Due To Human Cytomegalovirus Infection Upon Immunochemotherapy

Immunochemotherapy adverse events affecting the gastrointestinal tract usually consist of self-limiting nausea/ vomiting or diarrhoea, while bleeding and perforation are rare. A 42-year-old woman treated with bendamustine/ rituximab for splenic marginal zone lymphoma developed alife-threatening protein-losing enteropathy that was a diagnosis conundrum, ranging from drug-induced, immunemediated, neoplastic and infectious forms. Suspecting opportunistic viral infection but with unremarkable immunohistochemistry and peripheral blood tests, the diagnosis of Human Cytomegalovirus enteritis was made only by means of quantitative real-time polymerase chain reaction carried out on mucosal specimens. Steroid discontinuation and a prolonged course of antiviral therapy allowed the patient to overcome the critical phase and to achieve gradual normalisation of stool frequency, body mass index, laboratory tests lasting one year, while disappearance of mucosal viral load resulted soon evident. Human Cytom-egalovirus end-organ disease localised at the gastrointestinal tract is a serious condition whose prompt diagnosis and treatment prevents poor patients prognosis

Predictability of viral load kinetics in the early phases of SARS-CoV-2 through a model-based approach

A pipeline to evaluate the evolution of viral dynamics based on a new model-driven approach has been developed in the present study. The proposed methods exploit real data and the multiscale structure of the infection dynamics to provide robust predictions of the epidemic dynamics. We focus on viral load kinetics whose dynamical features are typically available in the symptomatic stage of the infection. Hence, the epidemiological evolution is obtained by relying on a compartmental approach characterized by a varying infection rate to estimate early-stage viral load dynamics, of which few data are available. We test the proposed approach with real data of SARS-CoV-2 viral load kinetics collected from patients living in an Italian province. The considered database refers to early-phase infections, whose viral load kinetics are not affected by mass vaccination policies in Italy. Our contribution is devoted to provide an effective computational pipeline to evaluate in real time the evolution of infectivity. Comprehending the factors influencing the in-host viral dynamics represents a fundamental tool to provide robust public health strategies. This pilot study could be implemented in further investigations involving other respiratory viruses, to better clarify the process of viral dynamics as a preparatory action for future pandemics

Sequence analysis of respiratory syncytial virus cases reveals a novel subgroup -B strain circulating in north-central Italy after pandemic restrictions

Background: Following the pandemic restrictions, the epidemiology of respiratory syncytial virus (RSV) has changed, leading to intense hospitalization peaks. Objectives: This study, conducted at multiple sites in Italy, aimed to describe the temporal dynamics of two post-COVID-19 RSV epidemics. Additionally, the circulating RSV-A and -B lineages were characterized and compared to those found in 2018 and 2019. Study design: Respiratory specimens and data were collected from RSV-positive patients, both inpatients, and outpatients, of all ages at three sites in north-central Italy. To analyze these samples, roughly one-sixth were sequenced in the attachment glycoprotein G gene and subjected to phylogenetic and mutational analyses, including pre-pandemic sequences from north-central Italy. Results: The first post-pandemic surge of RSV cases was quite intense, occurring from October 2021 to early January 2022. The subsequent RSV epidemic (from November 2022 to early March 2023) also had a high impact, characterized by a rise in elderly patient cases. Post-pandemic cases of RSV-A were caused by various strains present in Italy prior to COVID-19. In contrast, a distinct RSV-B lineage, which was concurrently spreading in other countries, was identified as the main cause of the surge in 2022-2023 but remained undetected in Italy before the pandemic. Conclusions: This study describes the temporal dynamics of post-pandemic RSV subgroups and uncovers a lineage of RSV-B with high genetic divergence that may have increased the impact of decreased population immunity

Kinetics of cytomegalovirus and Epstein-Barr virus DNA in whole blood and plasma of kidney transplant recipients: Implications on management strategies

This retrospective multicenter cohort study investigated the kinetics (ascending and descending phases) of cytomegalovirus (CMV) and Epstein-Barr virus (EBV)-DNA in whole blood (WB) and plasma samples collected from adult kidney transplant (KT) recipients. CMV-DNA kinetics according to antiviral therapy were investigated. Three hundred twenty-eight paired samples from 42 episodes of CMV infection and 157 paired samples from 26 episodes of EBV infection were analyzed by a single commercial molecular method approved by regulatory agencies for both matrices. CMV-DNAemia followed different kinetics in WB and plasma. In the descending phase of infection, a slower decay of viral load and a higher percentage of CMV-DNA positive samples were observed in plasma versus WB. In the 72.4% of patients receiving antiviral therapy, monitoring with plasma CMV-DNAemia versus WB CMV-DNAemia could delay treatment interruption by 7-14 days. Discontinuation of therapy based on WB monitoring did not result in relapsed infection in any patients. Highly different EBV-DNA kinetics in WB and plasma were observed due to lower positivity in plasma; EBV positive samples with a quantitative result in both blood compartments were observed in only 11.5% of cases. Our results emphasize the potential role of WB as specimen type for post-KT surveillance of both infections for disease prevention and management