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In early February 2023, the Omicron subvariant XBB.1.5, also known as “Kraken”, accounted for more than 44% of new COVID-19 cases worldwide, whereas a relatively new Omicron subvariant named CH.1.1, deemed “Orthrus”, accounted for less than 6% of new COVID-19 cases during the subsequent weeks. This emerging variant carries a mutation, L452R, previously observed in the highly pathogenic Delta and the highly transmissible BA.4 and BA.5 variants, necessitating a shift to active surveillance to assure adequate preparedness for likely future epidemic peaks. We provide a preliminary understanding of the global distribution of this emerging SARS-CoV-2 variant by combining genomic data with structural molecular modeling. In addition, we shield light on the number of specific point mutations in this lineage that may have functional significance, thereby increasing the risk of disease severity, vaccine resistance, and increased transmission. This variant shared about 73% of the mutations with Omicron-like strains. Our homology modeling analysis revealed that CH.1.1 may have a weakened interaction with ACE2 and that its electrostatic potential surface appears to be more positive than that of the reference ancestral virus. Finally, our phylogenetic analysis revealed that this likely-emerging variant was already cryptically circulating in European countries prior to its first detection, highlighting the importance of having access to whole genome sequences for detecting and controlling emerging viral strains.

Avian influenza virus (AIV) poses a significant challenge to poultry production, with negative repercussions for both the economy and public health worldwide. Since January 2003, a total of 868 human cases of AIV H5N1 have been reported from four countries in the Western Pacific Region, as of 9 March 2023. When AIVs are circulating in poultry, there is a risk of sporadic infections and small clusters of human cases due to exposure to infected poultry or contaminated environments. The increase in reported A(H5N1) infections may reflect continued virus circulation in birds, as well as enhanced surveillance and diagnostic capacity resulting from the response to the COVID-19 pandemic. Numerous countermeasures, including vaccines and antiviral treatments, are available for influenza infection. However, their effectiveness is often debated due to the ongoing resistance to antivirals and the relatively low and unpredictable efficiency of influenza vaccines compared to other vaccines. Vaccination remains the primary method for preventing influenza acquisition or avoiding serious complications related to the disease. In this review, we summarize the global landscape of the Influenza A virus and provide insights into human clinical symptomatology. We call for urgent investment in genomic surveillance strategies to timely detect and shape the emergence of any potential viral pathogen, which is essential for epidemic/pandemic preparedness.

Tweetable abstract The SARS-CoV-2 Spike receptor binding domain and N-terminal domain interact with each other in an intricate mechanism. Mutations modulate the interplay between the Spike and host molecules. This editorial comments on the intricacies of SARS-CoV-2 Spike interactions.

Merkel cell polyomavirus (MCPyV) is an oncogenic virus that has been etiologically linked to Merkel cell carcinoma. Low levels of MCPyV DNA have been detected in blood donors with unclear impact on transfusion. The prevalence of MCPyV DNA in Brazilian blood donors is unclear. Therefore, the objective of this study was to evaluate the MCPyV DNA prevalence among Brazilian blood donors. We examined the presence of MCPyV DNA by real-time PCR (qPCR) in a total of 450 serum samples obtained from blood donors from three Brazilian regions (North, Central-West and South). The overall estimated MCPyV DNA prevalence was 1.1% (CI = 95%, 0.16-2.06%). Divided by region, in North Brazil (city of Macapa, state of Amapá) and South Brazil (city of Santa Maria, state of Rio Grande do Sul), the MCPyV prevalence was the same: 1.33% (CI = 95%, range 0.0-3.14%). In Central-West Brazil (city of Brasilia), the MCPyV prevalence was 0.6% (CI = 95%, 0.0-1.96%). All MCPyV positive samples showed a high cycle threshold (median Ct = 35.5), most probably related to the low viral load. More studies are necessary to unveil the impact of this oncogenic virus on transfusion medicine and if such exists, especially in regards of its infectivity and transmission potential.

A relevant gradual reduction of both the incidence rate of acute hepatitis B (AHB) and prevalence of chronic hepatitis B has occurred in Italy in the last 50 years, due to substantial epidemiological changes: Improvement in socioeconomic and hygienic conditions, reduction of the family unit, accurate screening of blood donations, abolition of re-usable glass syringes, hepatitis B virus (HBV)-universal vaccination started in 1991, use of effective well tolerated nucleo(t)side analogues able to suppress HBV replication available from 1998, and educational mediatic campaigns against human immunodeficiency virus infection focusing on the prevention of sexual and parenteral transmission of infections. As an example, AHB incidence has gradually decreased from 10/100000 inhabitants in 1985 to 0.21 in 2020. Unfortunately, the coronavirus disease 2019 (COVID-19) pandemic has interrupted the trend towards HBV eradication. In fact, several HBV chronic carriers living in the countryside have become unable to access healthcare facilities for screening, diagnosis, clinical management, and nucleo(t)side analogue therapy in the COVID-19 pandemic, mainly for anxiety of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), movement restrictions, and reduced gains from job loss. In addition, one-third of healthcare facilities and personnel for HBV patients have been devolved to the COVID-19 assistance. (C) The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

Since COVID-19 began to spread, hypotheses about the possible causes of the disease and its treatment have increased worldwide, engenedering fears and concerns. This context of uncertainty, as well as the great changes that people were forced to accept in their daily lives, have challenged the general population, affecting public opinion and collective imagination inevitably, with also a negative impact on compliance with public health policies. This study explored the personal attitudes towards the COVID-19 pandemic and their association with denial stances in the Italian context. The aim was to address the relevance of these phenomena and in what guise they are present in relation to the grounds supporting them, as an avenue to be more effective in public health under different domains. An online questionnaires was set out to survey the general population over 18 throughout the Italian country, including students and health professionals, to offer geographic and professional diversity. General population was also stratified based on their direct or indirect experience of COVID-19, whilst health participants were recruited with regard to their involvement in a COVID centre. A total of 2110 questionnaire were filled out between December 2020 and April 2021. Of the participants, 85.45% completely disagree with the possibility that COVID-19 is not real and that the cultural, social and economic system wanted us to believe otherwise, whereas 69% had doubts about what has been claimed to date about the existence of COVID-19. Trust in institutions and types of COVID-19 experience affected these beliefs. The results also show that stress, anxiety, sadness, and vulnerability increased as compared to the pre-COVID- 19 pandemic timeframe. The fundings of this national survey revealed how much behaviors based on social responsibility and rational prudence are important for defensing human life.

Purpose Women with type 1 diabetes mellitus (T1D), especially those with suboptimal glucose control, have 3–4 greater chances of having babies with birth defects compared to healthy women. We aimed to evaluate glucose control and insulin regimen modifications during the pregnancy of women with T1D, comparing the offspring’s weight and the mother’s weight change and diet with those of non-diabetic, normal-weight pregnant women. Methods Women with T1D and age-matched healthy women controls (CTR) were consecutively enrolled among pregnant women with normal weight visiting our center. All patients underwent physical examination and diabetes and nutritional counseling, and completed lifestyle and food intake questionnaires. Results A total of 44 women with T1D and 34 healthy controls were enrolled. Women with T1D increased their insulin regimen during pregnancy, going from baseline 0.9 ± 0.3 IU/kg to 1.1 ± 0.4 IU/kg (p = 0.009), with a concomitant significant reduction in HbA1c (p = 0.009). Over 50% of T1D women were on a diet compared to p p = 0.044) and gave birth to babies with higher mean birth weight (p = 0.043), likely due to the daily increase in insulin regimen. Conclusion A balance between achieving metabolic control and avoiding weight gain is crucial in the management of pregnant women with T1D, who should be encouraged to further improve lifestyle and eating habits with the aim of limiting upward insulin titration adjustments to a minimum.

Prosthetic joint infection (PJI) and fracture-related infection (FRI) are difficult-to-treat conditions in patients with severe comorbidity or significant surgical risk. In cases not eligible for standard strategy, debridement procedures with the retention of prosthesis or internal fixation device, combined with long-term antibiotic treatment and subsequent indefinite chronic oral antimicrobial suppression (COAS), can be the only reasonable choice. The aim of this study was to investigate the role of COAS and its follow-up in the management of these cases. We retrospectively analyzed a cohort of 16 patients with a follow-up of at least 6 months (mean age 75 yo, 9F, 7M, 11 PJI, 5 FRI). All microbiological isolates were tetracycline-susceptible staphylococci and for this reason a minocycline-based COAS was adopted after debridement and 3 months of antibiogram-guided antibiotic treatment. Patient monitoring was carried out on a clinical basis, with bimonthly execution of the inflammation indices and serial radiolabeled leukocyte scintigraphy (LS). The overall median time of COAS follow-up was 15 months (min 6–max 30). Moreover, 62.5% of patients were still taking COAS with no relapse after cure at the last evaluation available. Clinical failure with a relapse of the infection was observed in 37.5% of patients; interestingly, 50% of them had previously stopped COAS due to side effects of the antibiotic used. In the COAS follow-up, a combination of clinical, laboratory and LS evaluation seems to monitor the infection properly. COAS can be considered as an interesting approach in patients not suitable for standard treatments of PJI or FRI but it requires careful monitoring.

Since the beginning of the pandemic, the generation of new variants periodically recurs. The XBB.1.5 SARS-CoV-2 variant is one of the most recent. This research was aimed at verifying the potential hazard of this new subvariant. To achieve this objective, we performed a genome-based integrative approach, integrating results from genetic variability/phylodynamics with structural and immunoinformatic analyses to obtain as comprehensive a viewpoint as possible. The Bayesian Skyline Plot (BSP) shows that the viral population size reached the plateau phase on 24 November 2022, and the number of lineages peaked at the same time. The evolutionary rate is relatively low, amounting to 6.9 × 10−4 subs/sites/years. The NTD domain is identical for XBB.1 and XBB.1.5 whereas their RBDs only differ for the mutations at position 486, where the Phe (in the original Wuhan) is replaced by a Ser in XBB and XBB.1, and by a Pro in XBB.1.5. The variant XBB.1.5 seems to spread more slowly than sub-variants that have caused concerns in 2022. The multidisciplinary molecular in-depth analyses on XBB.1.5 performed here does not provide evidence for a particularly high risk of viral expansion. Results indicate that XBB.1.5 does not possess features to become a new, global, public health threat. As of now, in its current molecular make-up, XBB.1.5 does not represent the most dangerous variant.

Recombination is the main contributor to RNA virus evolution, and SARS-CoV-2 during the pandemic produced several recombinants. The most recent SARS-CoV-2 recombinant is the lineage labeled XBB, also known as Gryphon, which arose from BJ.1 and BM. 1.1.1. Here we performed a genome-based survey aimed to compare the new recombinant with its parental lineages that never became dominant. Genetic analyses indicated that the recombinant XBB and its first descendant XBB.1 show an evolutionary condition typical of an evolutionary blind background with no further epidemiologically relevant descendant. Genetic variability and expansion capabilities are slightly higher than parental lineages. Bayesian Skyline Plot indicates that XBB reached its plateau around October 6, 2022 and after an initial rapid growth the viral population size did not further expand, and around November 10, 2022 its levels of genetic variability decreased. Simultaneously with the reduction of the XBB population size, an increase of the genetic variability of its first sub-lineage XBB.1 occurred, that in turn reached the plateau around November 9, 2022 showing a kind of vicariance with its direct progenitors. Structure analysis indicates that the affinity for ACE2 surface in XBB/XBB.1 RBDs is weaker than for BA.2 RBD. In conclusion, nowadays XBB and XBB.1 do not show evidence about a particular danger or high expansion capability. Genome-based monitoring must continue uninterrupted in order to individuate if further mutations can make XBB more dangerous or generate new subvariants with different expansion capability.

The existing literature estimates a significantly reduced odds of hospitalisation and death among individuals. However, though less severe than other variants, the Omicron variant may still lead to excess mortality compared to pre-pandemic years.A generalized linear mixed model is introduced to model weekly mortality from 2011 to 2019, taking into account seasonal patterns and year-specific trends. Based on the 2019 year-specific conditional best linear unbiased predictions, excess of mortality is estimated.In Italy, 14 and 11 regions suffered from relevant excess mortality in January and February, respectively. However, the situation is far from being as critical as during previous waves.We can conclude that no matter which variant (or multiple inter-variant recombination) we are facing, excess mortality will appear in correspondence of any incidence peak.

Vaccines against SARS-CoV-2 are very effective, but some mutations could reduce protection. Here we report a case of SARS-CoV-2 infection with a P.1.1 variant lacking the Y501 mutation in a vaccinated individual in Italy. Carefully monitoring breakthrough infections is important for assessing viral spreading of potential vaccine-resistant variants.

Background: Monitoring antibody response following SARS-CoV-2 vaccination is strategic, and neutralizing antibodies represent the gold standard. The neutralizing response to Beta and Omicron VOCs was evaluated versus the gold standard by a new commercial automated assay. Methods: Serum samples from 100 healthcare workers from the Fondazione Policlinico Universitario Campus Biomedico and the Pescara Hospital were collected. IgG levels were determined by chemiluminescent immunoassay (Abbott Laboratories, Wiesbaden, Germany) and serum neutralization assay as the gold standard. Moreover, a new commercial immunoassay, the PETIA test Nab (SGM, Rome, Italy), was used for neutralization evaluation. Statistical analysis was performed with R software, version 3.6.0. Results: Anti-SARS-CoV-2 IgG titers decayed during the first ninety days after the vaccine second dose. The following booster dose significantly (p < 0.001) increased IgG levels. A correlation between IgG expression and neutralizing activity modulation was found with a significant increase after the second and the third booster dose (p < 0.05. Compared to the Beta variant of the virus, the Omicron VOC was associated with a significantly larger quantity of IgG antibodies needed to achieve the same degree of neutralization. The best Nab test cutoff for high neutralization titer (≥1:80) was set for both Beta and Omicron variants. Conclusion: This study correlates vaccine-induced IgG expression and neutralizing activity using a new PETIA assay, suggesting its usefulness for SARS-CoV2 infection management.

HPV Selfy clinical sensitivity and specificity resulted non-inferior to those of HC2. By analysis of a total of 889 cervical liquid-based cytology samples from a screening population, of which 98 were from women with CIN2+, HPV Selfy showed relative sensitivity and specificity for CIN2+ of 0.98 and 1.00 respectively (non-inferiority score test: P = 0.01747 and P = 0.00414, respectively); the test reached adequate intra- and inter-laboratory reproducibility. Moreover, we demonstrated that the performance of HPV Selfy on self-collected vaginal samples was non-inferior to the performance obtained on clinician-collected cervical specimen (0.97 relative sensitivity and 0.97 relative specificity). Finally, through HPV Selfy genotyping, we were able to describe HPV types prevalence in the study population. Clinical validation of HPV Selfy on self‑collected vaginal samples (VALHUDES) Next, we aimed at evaluating HPV Selfy performance on self-collected samples, as indicated by VALHUDES protocol. Hence, we needed to assess whether HPV testing on vaginal self-samples was as accurate as HPV testing on a cervical sample taken by a clinician. To do so, we identified 119 CIN2+ cases (age 25–65 years) and 791 ≤ CIN1 cases, for which we had available paired cervical specimen and self-collected vaginal samples. HPV Selfy testing in self-collected samples was found similarly sensitive (93/96; relative sensitivity 0.97; 95% CI 0.90–1.04) and specific (722/745; relative specificity 0.97; 95% CI 0.95–0.99) to detect CIN2+ in the total study population (Table 4), in comparison with HPV Selfy performed on paired ThinPrep. Thus, HPV Selfy assay fulfills VALHUDES requirements for use of HR-HPV DNA tests on self-collected samples according to non-inferiority analysis (relative sensitivity > 0.90 with T = 1.70, p = 0.044; relative specificity > 0.95 with T = 1.87, p =0.031). Secondary objectives of VALHUDES protocol include the assessment of the absolute accuracy of HR-HPV DNA test applied according to the sampling device and the proportion of adequate samples as determined by amplification of an internal control (a ubiquitous human gene). HPV Selfy assay provides a human beta-globin internal control, used to evaluate sample quality. In the whole study cohort, mean Ct value for the human beta-globin internal control for the HPV Selfy test on self-collected samples, obtained with the direct analysis on self-collected samples, was 26.1 Ct (median value 25.9 Ct, maximum 30.7 Ct, minimum 16.5 Ct). In the subgroup of women with biopsy-diagnosis of cervical lesions CIN2+, the same analysis resulted in 26.7 Ct (median value 26.5 Ct, maximum 30.7 Ct, minimum 24.2 Ct). This means that all women were able to self-collect a similar amount of specimen, confirming self-collected samples’ quality adequacy and so the easiness of the self-sampling procedure using the FLOQSwabs® (Copan, Brescia, Italy).

Severe COVID-19 is characterized by angiogenic features, such as intussusceptive angiogenesis, endothelialitis, and activation of procoagulant pathways. This pathological state can be ascribed to a direct SARS-CoV-2 infection of human lung ECs. Recently, we showed the capability of SARS-CoV-2 to infect ACE2-negative primary human lung microvascular endothelial cells (HL-mECs). This occurred through the interaction of an Arg-Gly-Asp (RGD) motif, endowed on the Spike protein at position 403–405, with αvβ3 integrin expressed on HL-mECs. HL-mEC infection promoted the remodeling of cells toward a pro-inflammatory and pro-angiogenic phenotype. The RGD motif is distinctive of SARS-CoV-2 Spike proteins up to the Omicron BA.1 subvariant. Suddenly, a dominant D405N mutation was expressed on the Spike of the most recently emerged Omicron BA.2, BA.4, and BA.5 subvariants. Here we demonstrate that the D405N mutation inhibits Omicron BA.5 infection of HL-mECs and their dysfunction because of the lack of Spike/integrins interaction. The key role of ECs in SARS-CoV-2 pathogenesis has been definitively proven. Evidence of mutations retrieving the capability of SARS-CoV-2 to infect HL-mECs highlights a new scenario for patients infected with the newly emerged SARS-CoV-2 Omicron subvariants, suggesting that they may display less severe disease manifestations than those observed with previous variants.

The new virus called severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) causing Coronavirus disease 2019 (COVID-19) has spread to several countries and caused the current pandemic. Different types of clinical manifestations are associated with that infection. Some drugs have been approved such as anti-viral agents but the use of corticosteroids is controversial. Pulmonary fibrosis is a frequent consequence of Covid-19 that may requires a special attention and a specific follow up. Herein we report a case of a 68-years-old patient affected by SARS-Cov-2 infection complicated by pulmonary fibrosis who healed from Covid-19 infection after a total inpatient stay of 12 days by with remdesivir treatment. The patient presented a chest fibrosis picture at the discharge that went on at 10 days check with a decline of respiratory functional parameters. For this reason a combined treatment with high dose prednisone and N-acetyl-cysteine was started. The patients benefited from high dose corticosteroids plus N-acetyl-cysteine leading to a clinical and functional improvement. Indeed, the patient underwent a chest CT-scan and spirometry at one month check after the beginning of the treatment. Notably both the radiological pattern of fibrosis and respiratory function improved after treatment with prednisone 50 mg a day for 15 days followed by 25 mg for additional 15 days and N-acetylcisteine 600 mg twice a day.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a multifactorial etiology. The primary aim of this study was to estimate HCV and HBV infection prevalence in a cohort of SLE and Cutaneous Lupus Erythematosus (CLE). We assessed the frequency of these infections in our cohort and the possible associations with disease clinical/laboratory features and disease activity status. The prevalence of chronic HBV infection was 2.2% in the CLE group, while no HBsAg positive patients were identified in the SLE group. Conversely, the prevalence of anti-HCV positive was 2.2% in the SLE group while no anti-HCV positive patients were identified in the CLE group. We found no significant association between anti-HBc positive status and clinical manifestations or disease activity status in either group of patients. Hemodialysis resulted significantly associated with anti-HBc positivity in SLE. In the present study, we found HBsAg positivity in CLE patients but not in the Systemic form (SLE); conversely, a similar prevalence of anti-HBc antibodies in both groups was observed. A possible protective role exerted by SLE in HBV infection may be hypothesized. A higher frequency of HCV infection in SLE compared to CLE suggests a possible involvement of HCV in some SLE-related clinical and immunological features.

The syndemic framework proposed by the 2021–2030 World Health Organization (WHO) action plan for patient safety and the introduction of enabling technologies in health services involve a more effective interpretation of the data to understand causation. Based on the Systemic Theory, this communication proposes the “Systemic Clinical Risk Management” (SCRM) to improve the Quality of Care and Patient Safety. This is a new Clinical Risk Management model capable of developing the ability to observe and synthesize different elements in ways that lead to in-depth interventions to achieve solutions aligned with the sustainable development of health services. In order to avoid uncontrolled decision-making related to the use of enabling technologies, we devised an internal Learning Algorithm Risk Management (LARM) level based on a Bayesian approach. Moreover, according to the ethics of Job Well Done, the SCRM, instead of giving an opinion on events that have already occurred, proposes a bioethical co-working because it suggests the best way to act from a scientific point of view.

The dramatic emergence of SARS-CoV-2 infection worldwide opened the Pandora’s box of fears and frights for new emerging infections [...]

BACKGROUND The role of preoperative inflammatory biomarkers (PIBs) in predicting postoperative morbidity has been assessed in colorectal and otorhinolaryngeal surgery. However, data regarding the role that preoperative inflammatory biomarkers have on morbidity after pancreaticoduodenectomiy (PD) are less consistent. AIM To assess the utility of PIBs in predicting postoperative complications after pancreaticoduodenectomy. METHODS A database of 317 consecutive pancreaticoduodenectomies performed from April 2003 to November 2018 has been retrospectively analyzed. Data regarding preoperative neutrophil-to-lymphocyte ratio (NLR), derived NLR and C-reactive protein (CRP), and postoperative complications of 238 cases have been evaluated. Exclusion criteria were: age < 18-years-old, previous neoadjuvant treatment, absence of data about PIBs, concomitant hematological disorders, and presence of active infections at the moment of the surgery. PIBs were compared using Mann-Whitney’s test and receiver operating characteristic (ROC) analysis was performed to define the cutoffs. The positive predictive value (PPV) was computed to evaluate the probability to develop complication. P-values < 0.05 were considered statistically significant. RESULTS According to the literature findings, only four papers have been published reporting the relation between the inflammatory biomarkers and PD postoperative morbidity. A combination of preoperative and postoperative inflammatory biomarkers in predicting complications after PD and the utility of preoperative NLR in the development of postoperative pancreatic fistula (POPF) have been reported. The combination of PIBs and postoperative day-1 drains amylase has been reported to predict the incidence of POPF. According to our results, CRP values were significantly different between patients who had/did not have postoperative complications and abdominal collections (P < 0.05). Notably, patients with preoperative CRP > 8.81 mg/dL were at higher risk of both overall complications and abdominal collections (respectively P = 0.0037, PPV = 0.95, negative predictive value [NPV] = 0.27 and P = 0.016, PPV = 0.59, NPV = 0.68). Preoperative derived neutrophil-to-lymphocyte ratio (dNLR) (cut off > 1.47) was also a predictor of abdominal collection (P = 0.021, PPV = 0.48, NPV = 0.71). Combining CRP and dNLR, PPV increased to 0.67. NLR (cut off > 1.65) was significantly associated with postoperative hemorrhage (P = 0.016, PPV = 0.17, NPV = 0.98). CONCLUSION PIBs may predict complications after PD. During postoperative care, PIB levels could influence decisions regarding the timing of drains removal and the selection of patients who might benefit from second level diagnostic exams.

Despite the SARS‐CoV‐2 pandemic not yet being under control, post‐Covid‐19 syndrome is already a challenging topic: long‐term multiorgan sequelae, although increasingly described, have not yet been systematized. As post‐Covid‐19 syndrome can significantly impact both the working capacity and the relationship life of surviving patients, we performed a systematic review of the evidence published over the last year and currently available in medical literature search databases (MEDLINE/Pubmed) and searching clinical trial registries, to evaluate the available evidence among workers. From 31 publications that initially matched inclusion criteria, 13 studies have been considered suitable for relevance and age of subjects. A wide range of patients (16%–87%) have post‐Covid syndrome; pneumological and neuropsychological symptoms were the most common disorders reported. The most frequent organic sequel found in post‐Covid patients was pulmonary fibrosis. The number of symptoms during acute SARS‐CoV‐2 infection, severity of the disease, and high serum levels of d‐dimer were related to high risk of post‐Covid syndrome. In conclusion, post‐Covid‐19 syndrome can significantly impact the health conditions of surviving patients. Rehabilitation and follow‐up in multidisciplinary rehabilitation programs should be considered for working‐age patients.

In December 2020, Italy experienced the first case of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) B.1.1.7 lineage. In January 2021, we identified 21 cases of this variant in Corzano, defining the first outbreak of SARS‐CoV‐2 B.1.1.7 lineage in Italy. The high transmissibility of the B.1.1.7 variant represented an important benefit for the virus, which became rapidly dominant on the territory. Containment measures induced the epidemic curve onto a decreasing trajectory underlining the importance of appropriate control and surveillance for restraint of virus spread. Highlights The first Italian outbreak of SARS‐CoV‐2 B.1.1.7 lineage occurred in Lombardy in January 2021. The outbreak originated by a single introduction of the B.1.1.7 lineage. The genomic sequencing revealed, for the first time, the presence of the V551F mutation in the B.1.1.7 lineage in Italy. Surveillance, prompt sequencing and tracing efforts were fundamental to identify and to quickly contain the outbreak.

Early detection and prompt response are crucial measures to prevent and control outbreaks. Public health agencies, therefore, designed the Communicable Disease Surveillance System (CDSS) to obtain essential data instantaneously to be used for appropriate action. However, a periodic evaluation of CDSS is indispensable to ensure the functionality of the system. For this reason, this study aims to assess the performance of the core and support functions of the CDSS in the Kurdistan Region of Iraq. A descriptive cross-sectional study was used. From a total of 291 health facilities HFs (Primary health care centers and Hospitals) in the Kurdistan region of Iraq that have surveillance activities, 74 HFs were selected using a random stratified sampling approach. The World Health Organization (WHO) generic questionnaire has been used to interview the surveillance staff, together with direct collection of the data. Our analysis shows a lack of surveillance guiding manual in the HFs. Even at the district level, where a surveillance manual existed, case definitions, thresholds, and control measures were still missing. To note, more than 93% of HFs had organized and comprehensive patients registers for the collection of their clinical and secondary data. Also, all HFs had functioning laboratories. The majority of them (almost 93%) were equipped to collect, process, and store blood, stool, and urine specimens. About 72% of these laboratories were also able to transport timely the specimens to more specialized laboratories. At all levels, data reporting to the higher level exceeded the recommended minimum rate of 80%. The reporting system at the district level was based on emails, while in the periphery on hand-delivered in paper-based formats (50%), telephone (22%), and social media (22%). Furthermore, our analysis highlights the lack of data analysis: only 3.8% of Primary Health Care Centers conduct simple data analysis regularly, while hospitals do not do any sort of analysis. Also, only a few HFs investigated an outbreak, though using system routine sources to capture these public health events. Our findings show a lack in epidemic preparedness (3%), in feedback (53%), in standard guidelines, training, supervision, and resource allocations in HFs (0%). Taken together, our data show the importance of strengthening the CDSS in the Kurdistan region of Iraq, by reinforcing the surveillance system with continuous feedback, supervision, well-trained and motivated staff, technical support, and coordination between researchers and physicians.

Multidrug-resistant (MDR) Gram-negative bacteria (GNB) have raised concerns as common, frequent etiologic agents of nosocomial infections, and patients admitted to intensive care units (ICUs) present the highest risk for colonization and infection. The incidence of colonization and infection in trauma patients remains poorly investigated. The aim of this study was to assess the risk factors for Carbapenem-resistant (CR)-GNB colonization and the clinical impact of colonization acquisition in patients with severe trauma admitted to the ICU in a CR-GNB hyperendemic country. This is a retrospective observational study; clinical and laboratory data were extracted from the nosocomial infection surveillance system database. Among 54 severe trauma patients enrolled in the study, 28 patients were colonized by CR-GNB; 7 (12.96%) patients were already colonized at ICU admission; and 21 (38.89%) patients developed a new colonization during their ICU stay. Risk factors for colonization were the length of stay in the ICU (not colonized, 14.81 days ± 9.1 vs. colonized, 38.19 days ± 27.9; p-value = 0.001) and days of mechanical ventilation (not colonized, 8.46 days ± 7.67 vs. colonized, 22.19 days ± 15.09; p-value < 0.001). There was a strong statistical association between previous colonization and subsequent development of infection (OR = 80.6, 95% CI 4.5–1458.6, p-value < 0.001). Factors associated with the risk of infection in colonized patients also included a higher Charlson comorbidity index, a longer length of stay in the ICU, a longer duration of mechanical ventilation, and a longer duration of treatment with carbapenem and vasopressors (not infected vs. infected: 0(0–4) vs. 1(0–3), p = 0.012; 24.82 ± 16.77 vs. 47 ± 28.51, p = 0.016; 13.54 ± 15.84 vs. 31.7 ± 16.22, p = 0.008; 1.09 ± 1.14 vs. 7.82 ± 9.15, p = 0.008). The adoption of MDR-GNB colonization prevention strategies in critically ill patients with severe trauma is required to improve the quality of care and reduce nosocomial infections, length of hospital stay and mortality.

Functional and structural damage of the intestinal mucosal barrier significantly contribute to translocation of gut microbial products into the bloodstream and are largely involved in HIV-1 associated chronic immune activation. This microbial translocation is largely due to a progressive exhaustion of intestinal macrophage phagocytic function, which leads to extracellular accumulation of microbial derived components and results in HIV-1 disease progression. This study aims to better understand whether the modulation of gut microbiota promotes an intestinal immune restoration in people living with HIV (PLWH). Long-term virologically suppressed PLWH underwent blood, colonic, and fecal sampling before (T0) and after 6 months (T6) of oral bacteriotherapy. Age- and gender-matched uninfected controls (UC) were also included. 16S rRNA gene sequencing was applied to all participants' fecal microbiota. Apoptosis machinery, mitochondria, and apical junctional complex (AJC) morphology and physiological functions were analyzed in gut biopsies. At T0, PLWH showed a different pattern of gut microbial flora composition, lower levels of occludin (p = 0.002) and zonulin (p = 0.01), higher claudin-2 levels (p = 0.002), a reduction of mitochondria number (p = 0.002), and diameter (p = 0.002), as well as increased levels of lipopolysaccharide (LPS) (p = 0.018) and cCK18 (p = 0.011), compared to UC. At T6, an increase in size (p = 0.005) and number (p = 0.008) of mitochondria, as well as amelioration in AJC structures (p 0.0001) were observed. Restoration of bacterial richness (Simpson index) and biodiversity (Shannon index) was observed in all PLWH receiving oral bacteriotherapy (p 0.05). Increased mitochondria size (p = 0.005) and number (p = 0.008) and amelioration of AJC structure (p 0.0001) were found at T6 compared to T0. Moreover, increased occludin and zonulin concentration were observed in PLWH intestinal tracts and decreased levels of claudin-2, LPS, and cCK18 were found after oral bacteriotherapy (T0 vs. T6, p 0.05 for all these measures). Oral bacteriotherapy supplementation might restore the balance of intestinal flora and support the structural and functional recovery of the gut mucosa in antiretroviral therapy treated PLWH.

ObjectiveCoronavirus disease 2019 (COVID-19) is a systemic disease induced by SARS-CoV-2 causing myocardial injury. To date, there are few data on the correlation between mid-regional proAdrenomedullin (MR-proADM) and myocardial injury. The aim of this study was to evaluate whether the association of myocardial injury and elevated mid-regional proAdrenomedullin values could predict mortality of SARS-CoV-2 patients, to offer the best management to COVID-19 patients.Materials and methodsAll patients hospitalized for SARS-CoV-2 infection at the COVID-19 Center of the Campus Bio-Medico of Rome University were included between October 2020 and March 2021 and were retrospectively analyzed. Myocardial injury was defined as rising and/or fall of cardiac hs Troponin I values with at least one value above the 99th percentile of the upper reference limit (≥15.6 ng/L in women and ≥34.2 ng/L in men). The primary outcome was 30-day mortality. Secondary outcomes were the comparison of MR-proADM, CRP, ferritin, and PCT as diagnostic and prognostic biomarkers of myocardial injury. Additionally, we analyzed the development of ARDS, the need for ICU transfer, and length of stay (LOS).ResultsA total of 161 patients were included in this study. Of these, 58 (36.0%) presented myocardial injury at admission. An MR-proADM value ≥ 1.19 nmol/L was defined as the optimal cut-off to identify patients with myocardial injury (sensitivity 81.0% and specificity 73.5%). A total of 121 patients (75.2%) developed ARDS, which was significantly more frequent among patients with myocardial injury (86.2 vs. 68.9%, p = 0.015). The overall 30-day mortality was 21%. Patients with myocardial injury presented significantly higher mortality compared to those without the same (46.6 vs. 6.8%, p < 0.001). When dividing the entire study population into four groups, based on the presence of myocardial injury and MR-proADM values, those patients with both myocardial injury and MR-proADM ≥ 1.19 nmol/L presented the highest mortality (53.2%, p < 0.001). The combination of myocardial injury and MR-proADM values ≥ 1.19 nmol/L was an independent predictor of death (OR = 7.82, 95% CI = 2.87–21.30; p < 0.001).ConclusionThe study is focused on the correlation between myocardial injury and MR-proADM. Myocardial injury induced by SARS-CoV-2 is strongly associated with high MR-proADM values and mortality.

Monkeypox is caused by a sylvatic, double-stranded DNA zoonotic virus. Since 1 January 2022, monkeypox cases have been reported to WHO from 106 Member States across six WHO regions, and as of 2 October 2022, a total of 68,900 confirmed cases, including 25 deaths, occurred. Here, by using a whole genome approach, we perform a genetic and phylodynamic survey of the monkeypox virus Clade IIb B.1, which is the lineage causing the current multi-country outbreak. Results suggest that outbreaks seem to be isolated and localized in several epidemic clusters with geographic consistency. Currently, monkeypox appears to be a virus with a flattened genetic variability in terms of evolutionary path, with a very slow rate of growth in the population size. This scenario confirms that the monkeypox virus lacks the evolutionary advantage, given by the high level of mutation rate, which is very strong in RNA viruses. Of course, constant genome-based monitoring must be performed over time in order to detect the change in its genetic composition, if any.

Introduction. Knowledge of local and regional antimicrobial resistance (AMR) is crucial in clinical decision-making, especially with critically ill patients. The aim of this study was to investigate the rate and pattern of infections in valvular heart disease patients admitted to the intensive care unit (ICU) at the Salam Centre for Cardiac Surgery in Khartoum, Sudan (run by EMERGENCY NGO). Methods. This is a retrospective, observational study from a single, large international referral centre (part of a Regional Programme), which enrolled patients admitted to the ICU between 1 January and 31 December 2019. Data collected for each patient included demographic data, operating theatre/ICU data and microbiological cultures. Results. Over the study period, 611 patients were enrolled (elective surgery n = 491, urgent surgery n = 34 and urgent medical care n = 86). The infection rate was 14.2% and turned out to be higher in medical than in surgical patients (25.6% vs. 12.4%; p = 0.002; OR = 2.43) and higher in those undergoing urgent surgery than those undergoing elective (29.4% vs. 11.2%; p = 0.004; OR = 3.3). Infection was related to (a) SOFA score (p < 0.001), (b) ICU length of stay (p < 0.001) and (c) days from ICU admission to OT (p = 0.003). A significant relationship between the type of admission (elective, urgent surgery or medical) and the presence of infections was found (p < 0.001). The mortality rate was higher among infected patients (infected vs. infection-free: 10.3% vs. 2.1%; p < 0.001; OR = 5.38; 95% CI: 2.16–13.4; p < 0.001). Conclusions. Hospital-acquired infections remain a relevant preventable cause of mortality in our particular population.

We propose a parametric regression model for incidence indicators based on the use of the Richards' curve (a generalized logistic function) to analyse the current Monkeypox epidemic data for the most 10 affected countries worldwide. At present, results show that the outbreak is under control in most countries.

While the number of detected Monkeypox infections are widely available, an understanding of the extent of undetected cases is urgently needed for an effective tackling of its spread. The aim of this study is to estimate the true number of Monkeypox (detected and undetected) infections in most affected countries. The question being asked is: How many cases have actually occurred? We propose a lower bound estimator for the true number of Monkeypox cases. The estimator is data-driven and can be easily computed from the cumulative distributions of weekly cases. We focused on the ratio of the total estimated cases to the observed cases on July 31, 2022: The proportion of undetected cases was relevant in all countries, with countries whose estimated true number of infections could be more than three times the observed one. We provided a practical contribution to the understanding of the current Monkeypox wave and reliable estimates on how many undetected cases are going around in several countries, where the epidemic spreads differently.

Since 2020, the COVID-19 pandemic represented an important worldwide burden. Well-structured surveillance by reliable and timely genomic data collection is crucial. In this study, a genomic monitoring analysis of all SARS-CoV-2 positive samples retrieved at the Fondazione Policlinico Universitario Campus Bio-Medico, in Rome, Italy, between December 2021 and June 2022, was performed. Two hundred and seventy-four SARS-CoV-2-positive samples were submitted to viral genomic sequencing by Illumina MiSeqII. Consensus sequences were generated by de novo assembling using the iVar tool and deposited on the GISAID database. Lineage assignment was performed using the Pangolin lineage classification. Sequences were aligned using ViralMSA and maximum-likelihood phylogenetic analysis was performed by IQ-TREE2. TreeTime tool was used to obtain dated trees. Our genomic monitoring revealed that starting from December 2021, all Omicron sub-lineages (BA.1, BA.2, BA.3, BA.4, and BA.5) were circulating, although BA.1 was still the one with the highest prevalence thought time in this early period. Phylogeny revealed that Omicron isolates were scattered throughout the trees, suggesting multiple independent viral introductions following national and international human mobility. This data represents a sort of thermometer of what happened from July 2021 to June 2022 in Italy. Genomic monitoring of the circulating variants should be encouraged considering that SARS-CoV-2 variants or sub-variants emerged stochastically and unexpectedly.

The best nutritional strategy to fight the rise in obesity remains a debated issue. The Mediterranean diet (MD) and the Very Low-Calorie Ketogenic diet (VLCKD) are effective at helping people lose body weight (BW) and fat mass (FM) while preserving fat-free mass (FFM). This study aimed to evaluate the time these two diets took to reach a loss of 5% of the initial BW and how body composition was affected. We randomized 268 subjects with obesity or overweight in two arms, MD and VLCKD, for a maximum of 3 months or until they reached 5% BW loss. This result was achieved after one month of VLCKD and 3 months of MD. Both diets were effective in terms of BW (p < 0.0001) and FM loss (p < 0.0001), but the MD reached a higher reduction in both waist circumference (p = 0.0010) and FM (p = 0.0006) and a greater increase in total body water (p = 0.0017) and FFM (p = 0.0373) than VLCKD. The population was also stratified according to gender, age, and BMI. These two nutritional protocols are both effective in improving anthropometrical parameters and body composition, but they take different time spans to reach the goal. Therefore, professionals should evaluate which is the most suitable according to each patient’s health status.

The SARS-CoV-2 pandemic resulted in an unprecedented global crisis. SARS-CoV-2 primarily causes lung infection trough the binding of the virus with the ACE-2 cell receptor located on the surface of the alveolar epithelial cells. Notably, ACE-2 cell receptors are also expressed in the epithelial cells of the intestinal tract (GI). Recent data showed that the microbial communities of the GI might act as local and systematic inflammatory modulators. Gastrointestinal symptoms, including diarrhea, are frequently observed in infected individuals, and recent released data indicate that SARS-CoV-2 may also spread by fecal–oral transmission. Moreover, the gut microbiota’s ecosystem can regulate and be regulated by invading pathogens, including viruses, facilitating an effective immune response, which in turn results in less severe diseases. In this regard, increased SARS-CoV-2 mortality and morbidities appear to be frequently observed in elderly immunocompromised patients and in people with essential health problems, such as diabetes, who, indeed, tend to have a less diverse gut microbiota (dysbiosis). Therefore, it is important to understand how the interaction between the gut microbiota and SARS-CoV-2 might shape the intensity of the infection and different clinical outcomes. Here, we provide insights into the current knowledge of dysbiosis during SARS-CoV-2 infection and methods that may be used to re-establish a more correct microbiota composition.

The evolution of the emerging SARS-CoV-2 variants carrying mutations in the spike protein raises concerns about the possibility of accelerated transmission in the ever-evolving COVID-19 pandemic worldwide. AY.4.2, a sublineage of the Delta variant, was considered a variant under investigation (VUI) and also gained the nickname "Delta Plus," due to its extra mutations, Y145H and A222V. In this study, using genomic epidemiology, we provide the first insights into the introduction of AY.4.2 in Bulgaria and the AY.4.2.1 sublineage that found larger dissemination only in Bulgaria and the United Kingdom.

BackgroundOver the past few months, we have witnessed a new outbreak of a MPXV that has been detected without a clear link to Africa and has quickly spread globally.MethodsIn this article we investigate the mutational pattern of the MPXV and provide evidence for the presence of 6 new mutations that appear to characterize the current MPX-2022 outbreak. With the use of a number of chemical and physical parameters, we predict the stability of the mutated proteins, and propose an interpretation of the impact of these mutations on viral fitness).FindingsMost mutations, particularly the Immunomodulator A46, TNFr and Large transcript constituent, affect proteins playing an important role in host response to MPVX infection and could also be relevant to the clinical features of the 2022 MPXV outbreak.InterpretationAlthough further, experimental work is necessary for a full understanding of the impact of the mutations here reported on virus replication pathways and host immunomodulation, our in-silico data suggest the importance of monitoring the emergence of new MPXV mutations for the prevention of future outbreaks potentially dangerous for public health.FundingNo funding to declare

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has pushed the scientific community to undertake intense research efforts. Understanding SARS-CoV-2 biology is necessary to discover therapeutic or preventive strategies capable of containing the pandemic. Knowledge of the structural characteristics of the virus genome and proteins is essential to find targets for therapies and immunological interventions. Areas covered: This review covers different areas of expertise, genomic analysis of circulating strains, structural biology, viral mutations, molecular diagnostics, disease, and vaccines. In particular, the review is focused on the molecular approaches and modern clinical strategies used in these fields. Expert opinion: Molecular approaches to SARS-CoV-2 pandemic have been critical to shorten time for new diagnostic, therapeutic and prevention strategies. In this perspective, the entire scientific community is moving in the same direction. Vaccines, together with the development of new drugs to treat the disease, represent the most important strategy to protect human from viral disease and prevent further spread. In this regard, new molecular technologies have been successfully implemented. The use of a novel strategy of communication is suggested for a better diffusion to the broader public of new data and results.

The role of viruses in community acquired pneumonia (CAP) has been largely underestimated in the pre‐coronavirus disease 2019 age. However, during flu seasonal early identification of viral infection in CAP is crucial to guide treatment and in‐hospital management. Though recommended, the routine use of nasopharyngeal swab (NPS) to detect viral infection has been poorly scaled‐up, especially in the emergency department (ED). This study sought to assess the prevalence and associated clinical outcomes of viral infections in patients with CAP during peak flu season. In this retrospective, observational study adults presenting at the ED of our hospital (Rome, Italy) with CAP from January 15th to February 22th, 2019 were enrolled. Each patient was tested on admission with Influenza rapid test and real time multiplex assay. Seventy five consecutive patients were enrolled. 30.7% (n = 23) tested positive for viral infection. Of these, 52.1% (n = 12) were H1N1/FluA. 10 patients had multiple virus co‐infections. CAP with viral infection did not differ for any demographic, clinic and laboratory features by the exception of CCI and CURB‐65. All intra‐ED deaths and mechanical ventilations were recorded among CAP with viral infection. Testing only patients with CURB‐65 score ≥2, 10 out of 12 cases of H1N1/FluA would have been detected saving up to 40% tests. Viral infection occurred in one‐third of CAP during flu seasonal peak 2019. Since not otherwise distinguishable, NPS is so far the only reliable mean to identify CAP with viral infection. Testing only patients with moderate/severe CAP significantly minimize the number of tests., Highlights This study stresses the incidence of viral pneumonia during the flu season and underlies the role of viral infection screening at the ED regardless of the current COVID‐19 pandemic.

PubMed, Scopus, and ISI Web of Knowledge databases were searched to identify studies published up to December 2020 on the involvement of urinary and male genital systems in COVID-19. Sixteen studies involving a total of 575 patients (538 males and 37 females) were included in this systematic review. The COVID-19 phase was available for 479 patients: 426 in the acute and 53 in the recovery phase. De novo lower urinary tract symptoms (LUTS) were observed in 43 patients and deterioration of preexisting LUTS in 7. Bladder hemorrhage was observed in 3 patients and acute urinary retention in one. Regarding male genital system, scrotal discomfort was observed in 8 patients, swelling in 14, pain in 16, and erythema in one; low flow priapism was observed in 2 patients. Ultrasound examination identified acute orchitis in 10 patients, acute epididymitis in 7, and acute epididymo-orchitis in 16. A case-control study reported that patients with moderate COVID-19 show a significant reduction in sperm concertation, total number of sperms per ejaculate, progressive motility, and complete motility. Contrary to what known from the first studies on the subject, this review also including subsequent studies give evidence of an involvement of lower urinary tract and male genital system in COVID-19. This article is protected by copyright. All rights reserved.

Italy was the first European country to be significantly impacted by the COVID-19 pandemic. The lack of similar previous experiences and the initial uncertainty regarding the new virus resulted in an unpredictable health crisis with 243,506 total confirmed cases and 34,997 deaths between February and July 2020. Despite the panorama of precariousness and the impelling calamity, the country successfully managed many aspects of the early stages of the health and socio-economic crisis. Nevertheless, many disparities can be identified at the regional level. The study aims to determine which aspects of regional management were considered more important by the citizens regarding economic and health criteria. A survey was designed to gather responses from the population on the Italian regions’ response and provide a ranking of the regions. The 29-item online survey was provided to 352 individuals, and the collected data were analyzed using the Analytic Hierarchy Process methodology. The results show a general agreement in considering of greater relevance the healthcare policies rather than the economic countermeasures adopted by regional governments. Our analysis associated a weight of 64% to the healthcare criteria compared to the economic criteria with a weight of 36%. In addition to the results obtained from the Analytic Hierarchy Process, the sample’s composition was analyzed to provide an overall assessment of the Italian regions. To do so, we collected objective data for each region and multiplied them by the overall weight obtained for each sub-criteria. Looking at the propensity to vaccination or the belief in a relation between COVID-19 and 5G according to age and educational qualification helps understand how public opinion is structured according to cultural and anthropological differences.