Antibody Response against SARS-CoV-2 after mRNA Vaccine in a Cohort of Hospital Healthy Workers Followed for 17 Months.

The assessment of antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of critical importance to verify the protective efficacy of available vaccines. Hospital healthcare workers play an essential role in the care and treatment of patients and were particularly at risk of contracting the SARS-CoV-2 infection during the pandemic. The vaccination protocol introduced in our hospital protected the workers and contributed to the containment of the infection' s spread and transmission, although a reduction in vaccine efficacy against symptomatic and breakthrough infections in vaccinated individuals was observed over time. Here, we present the results of a longitudinal and prospective analysis of the anti-SARS-CoV-2 antibodies at multiple time points over a 17-month period to determine how circulating antibody levels change over time following natural infection and vaccination for SARS-CoV-2 before (T0-T4) and after the spread of the omicron variant (T5-T6), analyzing the antibody response of 232 healthy workers at the Pio XI hospital in Desio. A General Estimating Equation model indicated a significant association of the antibody response with time intervals and hospital area, independent of age and sex. Specifically, a similar pattern of antibody response was observed between the surgery and administrative departments, and a different pattern with higher peaks of average antibody response was observed in the emergency and medical departments. Furthermore, using a logistic model, we found no differences in contracting SARS-CoV-2 after the third dose based on the hospital department. Finally, analysis of antibody distribution following the spread of the omicron variant, subdividing the cohort of positive individuals into centiles, highlighted a cut-off of 550 BAU/mL and showed that subjects with antibodies below this are more susceptible to infection than those with a concentration above the established cut-off value.

Characterization of a New Variant in ARHGAP31 Probably Involved in Adams-Oliver Syndrome in a Family with a Variable Phenotypic Spectrum.

Adams-Oliver syndrome is a rare inherited condition characterized by scalp defects and limb abnormalities. It is caused by variants in different genes such as ARHGAP31. Here, we used an interdisciplinary approach to study a family with lower limb anomalies. We identified a novel variant in the ARHGAP31 gene that is predicted to result in a truncated protein with a constitutively activated catalytic site due to the loss of 688 amino acids involved in the C-terminal domain, essential for protein auto-inhibition. Pathogenic variants in ARHGAP31 exon 12, leading to a premature protein termination, are associated with Adams-Oliver syndrome. Bioinformatic analysis was useful to elucidate the impact of the identified genetic variant on protein structure. To better understand the impact of the identified variant, 3D protein models were predicted for the ARHGAP31 wild type, the newly discovered variant, and other pathogenetic alterations already reported. Our study identified a novel variant probably involved in Adams-Oliver syndrome and increased the evidence on the phenotypic variability in patients affected by this syndrome, underlining the importance of translational research, including experimental and bioinformatics analyses. This strategy represents a successful model to investigate molecular mechanisms involved in syndrome occurrence.

Echovirus 11 lineage I and other enterovirus in hospitalized children with acute respiratory infection in Southern Italy (2022- 2023).

OBJECTIVES: A new variant of echovirus 11 (E11) infection is a major health concern in neonates. Here, we describe the clinical and virological characteristics of enterovirus (EV) infections in children hospitalized with acute respiratory infection in Southern Italy. METHODS: Between July 2022-August 2023, 173 EV infections were identified. Demographic and clinical characteristics, comorbidities, and coinfections were analyzed. Genotypes were identified by sequencing of VP1. Whole-genome sequencing of five E11 strains was performed. RESULTS: Case numbers peaked in July 2022, November-December 2022, and June-July 2023. Coxsackievirus A2 was identified in 36.7%, coxsackievirus B5 in 13.8%, echovirus E11 in 9.2%, and EV-D68 in 6.4% of cases. No child had critical symptoms or a severe infection. The only neonate infected by E11 recovered fully after 5 days in hospital. Phylogenetic analysis revealed that four E11 strains were closely related to divergent lineage I E11 strains identified in France and Italy. CONCLUSIONS: The new variant of E11 was identified in children in Southern Italy. Although the cases were mild, the data suggest that transmission routes and host factors are likely to be main drivers for the development of potentially severe diseases. Systematic epidemiological/molecular surveillance will help us better understand the clinical impact of EV infections and develop preventive strategies.

Antibody Response after 3-Dose Booster against SARS-CoV-2 mRNA Vaccine in Kidney Transplant Recipients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in kidney transplant recipients (KTRs). Current vaccine strategies for KTRs seem to be unable to provide effective protection against coronavirus disease 2019 (COVID-19), and the occurrence of severe disease in some vaccinated KTRs suggested a lack of immunity. We initially analyzed the antibody response in a group of 32 kidney transplant recipients (KTRs) followed at the nephrology and dialysis unit of the Hospital Pio XI of Desio, ASST-Brianza, Italy. Thus, we studied the differences in antibody levels between subjects who contracted SARS-CoV-2 after the booster (8 individuals) and those who did not contract it (24 individuals). Furthermore, we verified if the antibody response was in any way associated with creatinine and eGFR levels. We observed a significant increase in the antibody response pre-booster compared to post-booster using both a Roche assay and DIAPRO assay. In the latter, through immunotyping, we highlight that the major contribution to this increase is specifically due to IgG S1 IgM S2. We observed a significant increase in IgA S1 and IgA NCP (p = 0.045, 0.02) in the subjects who contracted SARS-CoV-2. We did not find significant associations for the p-value corrected for false discovery rate (FDR) between the antibody response to all assays and creatinine levels. This observation allows us to confirm that patients require additional vaccine boosters due to their immunocompromised status and therapy in order to protect them from infections related to viral variants. This is in line with the data reported in the literature, and it could be worthwhile to deeply explore these phenomena to better understand the role of IgA S1 and IgA NCP antibodies in SARS-CoV-2 infection.

Genomic surveillance of carbapenem-resistant Klebsiella pneumoniae reveals a prolonged outbreak of extensively drug-resistant ST147 NDM-1 during the COVID-19 pandemic in the Apulia region (Southern Italy).

OBJECTIVES: The recent worldwide spread of New Delhi metallo-beta-lactamase-producing Klebsiella pneumoniae (NDM-KP) in health-care settings remains a concern. The aim of the study was to describe an outbreak of extensively drug-resistant ST147 NDM-1-KP in the Apulia region of Southern Italy that occurred between 2020 and 2022 through genomic surveillance of carbapenem-resistant Enterobacterales. METHODS: A total of 459 carbapenem-resistant KP isolates collected from patients hospitalised with bloodstream infections were tested using a commercial multiplex real-time polymerase chain reaction to identify carbapenemase genes. A subset of 27 isolates was subjected to whole-genome sequencing. Core-genome multilocus sequence typing was performed by analysing a panel of 4884 genes. RESULTS: Molecular testing revealed that 104 (22.6%) isolates carried the carbapenemase NDM gene. Phylogenetic analysis of the 27 isolates subjected to whole-genome sequencing revealed high genetic relatedness among strains. All isolates were resistant to all first-line antibiotics. Virulome analysis identified the ybt locus, the two well-recognised virulence factors iucABCDiutA and rmpA, and the genes encoding the type 3 pilus virulence factor. Plasmids IncFIB(pkPHS1), IncFIB(pNDM-Mar), IncFIB(pQil), IncHI1B(pNDM-MAR), IncR, and Col(pHAD28) were identified in all isolates. Moreover, further analysis identified the IncFIB-type plasmid carrying the NDM-1 genes. CONCLUSION: The increasing circulation of extensively drug-resistant NDM-1 ST147 KP strains in Southern Italy in recent years is worrisome, because these clones pose a real risk, particularly in hospital settings. Genomic surveillance is a crucial tool for early identification of emerging threats such as the spread of high-risk pathogens. Rapid infection control measures and antimicrobial stewardship are key to preventing further spread of hypervirulent KP strains.

What's Next for Flu? Out-of-Season Circulation of Influenza Viruses in Southern Italy, August 2022.

The COVID-19 pandemic has modified the seasonal pattern of respiratory infections. The objective of the present study is to characterize the out-of-season circulation of influenza viruses and an influenza outbreak that occurred in southern Italy in August 2022. Nasopharyngeal swabs collected from patients with influenza-like illnesses (ILI) were tested for the presence of influenza and other respiratory viruses. Epidemiological investigations on 85 patients involved in an influenza outbreak were performed. Sequencing and phylogenetic analysis of hemagglutinin genes was undertaken on samples positive for influenza A. In August 2022, in the Apulia region (Italy), influenza A infection was diagnosed in 19 patients, 18 infected with A/H3N2 and one with A/H1N1pdm09 virus. Seven influenza-positive patients were hospitalized with ILI. A further 17 symptomatic subjects, associated with an influenza outbreak, were also tested; 11 were positive for influenza A/H3N2 virus. Phylogenetic analysis of 12 of the A/H3N2 sequences showed that they all belonged to subclade 3C.2a1b.2a.2. The A/H1N1pdm09 strain belonged to subclade 6B.1A.5a.2. The out-of-season circulation of the influenza virus during the summer months could be linked to changing dynamics in the post-COVID-19 era, as well as to the impact of climate change. Year-round surveillance of respiratory viruses is needed to monitor this phenomenon and to provide effective prevention strategies.

Characteristics of the First 284 Patients Infected with the SARS-CoV-2 Omicron BA.2 Subvariant at a Single Center in the Apulia Region of Italy, January-March 2022.

Since its initial detection, the SARS-CoV-2 Omicron sublineage BA.2 has been spreading rapidly worldwide. The aims of this study were to describe the first 284 patients infected with the Omicron BA.2 variant of concern (VOC) in the Apulia region of southern Italy and to assess the differences in the demographic and clinical characteristics of patients infected with the SARS-CoV-2 BA.1 and BA.2 variants. The demographic characteristics of patients, as well as information about symptoms, vaccinations and hospitalizations for COVID-19, were collected. A subset of samples from patients infected with the BA.2 variant was subjected to whole-genome sequencing. The characteristics of the first 284 patients infected with Omicron BA.2 and the first 175 patients infected with Omicron BA.1 were compared. The proportion of patients infected with the BA.2 variant rapidly increased, from 0.5% during the third week of 2022 to 29.6% during the tenth week of 2022. Ten isolates (out of 34 BA.2 isolates) contain the substitutional mutation, H78K in ORF3a, and four isolates include two mutations, A2909V in ORF1a and L140F in ORDF3a. Compared with patients infected with BA.1, those infected with BA.2 were more likely to be symptomatic and booster-vaccinated, and showed a shorter time from the last dose of vaccine to infection. The high transmissibility and immune-evasive properties of Omicron BA.2, which will become the leading SARS-CoV-2 VOC, suggest that short-term public health measures should not be discontinued in Italy.