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To investigate relevant biomarkers that might aid in the diagnosis and monitoring of long COVID (LC), an analysis of IFN-α, IFN-β, ISG15, and ISG56 transcripts was performed by Real-Time PCR among people of working age who had been infected with SARS-CoV-2 one year prior to the study [LC and non-long COVID (NLC)]. Despite no differences in the transcript levels of IFN-α, IFN-β, ISG15, and ISG56 between LC and NLC, higher IFN-β mRNA levels were observed among LC compared to NLC individuals who were hospitalized for more than 10 days during acute SARS-CoV-2 infection. Moreover, previously SARS-CoV-2 infected participants that did not require respiratory support and developed LC exhibited higher levels of IFN-α and IFN-β compared to NLC with the same clinical characteristics. These results highlight that SARS-CoV-2 infection leads to changes in peripheral innate immune pathways, which could have implications for the development of LC.

Children generally develop a mild disease after SARS-CoV-2 infection whereas older adults are at risk of developing severe COVID-19. Recent transcriptomic analysis showed pre-activated innate immunity in children, resulting in a more effective anti-SARS-CoV-2 response upon infection. To further characterize age-related differences, we studied type I and III interferon (IFN) response in SARS-CoV-2 infected and non-infected individuals of different ages. Specifically, levels of expression of type I (IFN-α, -β, -ε and -ω), type III (IFN-λ1, -λ2 and -λ3) IFNs and of the IFN-stimulated genes, ISG15 and ISG56 were quantified in nasopharyngeal cells from diagnostic swabs. Basal transcription of type I/III IFN genes was highest among children and decreased with age. Among SARS-CoV-2-infected individuals, only IFN-ε and -ω levels were significantly higher in children and young adults whereas ISGs were overexpressed in infected adults. The occurrence of symptoms in children and the need for hospitalization in adults were associated to higher transcription of several IFN genes. Starting from a pre-activated transcription level, the expression of type I and III IFNs was not highly up-regulated in children upon SARS-CoV-2 infection; young adults activated IFNs’ transcription at intermediate levels whereas older adults were characterized by higher ISGs and lower IFN-ε and -ω relative expression levels. Overall, our findings contribute to recognize components of a protective IFN response as a function of age, in the context of SARS-CoV-2 infection.

Background Pandemic restrictions caused variation in respiratory virus circulation until the winter of 2022/23. The aim of this study was to monitor respiratory virus cases in the 2023/24 epidemic season. Methods Children and adults attending Sapienza University Hospital for acute respiratory infections (October 2023-June 2024) were tested for respiratory viruses via molecular methods. Results Of the 1121 patients included, 880 (78%) were positive for rhinovirus (HRV, 32%), Influenza A (IAV, 29%), and respiratory syncytial virus (RSV, 28%). RSV is more common in infants, and IAV is more common in adults, whereas HRV is more common in children aged 1–5 years. IAV, RSV and HRV cocirculate in winter; HRV cases also occur in spring, along with Influenza B (IBV) and other viruses. Despite circulating in the same weeks, the number of observed coinfections was much lower than that predicted for IAV and RSV ( p  <.0001) and lower also for the IAV/IBV, IBV/RSV and RSV/HRV pairs ( p  <.0001, p  =.0059, p  =.015, respectively). IAV and RSV cocirculated with different patterns in different age groups. In fact, in children aged 1–5 years, the RSV peak preceded that of IAV, whereas in older age groups, the RSV peak occurred toward the end of IAV circulation. Sequencing of HRV/EV cases in spring revealed 25 HRV genotypes and two EV-C105 cases. Conclusions Respiratory viruses can cause age-specific seasonal peaks that are modulated by viral interference phenomena. Molecular diagnostic data should be integrated with surveillance programs to characterize seasonal circulation patterns of common respiratory viruses and to rapidly detect the next pandemic threat.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recognized by pattern recognition receptors (PRRs), which play a vital role in triggering innate immune responses such as the production of type I and III interferons (IFNs). While modest PRR activation helps to defend against SARS-CoV-2, excessive or sustained activation can cause harmful inflammation and contribute to severe Coronavirus Disease 2019 (COVID-19). Altered expression of Toll-like receptors (TLRs), which are among the most important members of the PRR family members, particularly TLRs 2, 3, 4, 7, 8 and 9, has been strongly linked to COVID-19 severity. Furthermore, retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), collectively known as RLRs (RIG-I-like receptors), act as sensors that detect SARS-CoV-2 RNA. The expression of these receptors, as well as that of different DNA sensors, varies in patients infected with SARS-CoV-2. Changes in PRR expression, particularly that of TLRs, cyclic GMP-AMP synthase (cGAS), and the stimulator of interferon genes (STING), have also been shown to play a role in the development and persistence of long COVID (LC). However, SARS-CoV-2 has evolved strategies to evade PRR recognition and subsequent signaling pathway activation, contributing to the IFN response dysregulation observed in SARS-CoV-2-infected patients. Nevertheless, PRR agonists and antagonists remain promising therapeutic targets for SARS-CoV-2 infection. This review aims to describe the PRRs involved in recognizing SARS-CoV-2, explore their expression during SARS-CoV-2 infection, and examine their role in determining the severity of both COVID-19 and long-term manifestations of the disease. It also describes the strategies developed by SARS-CoV-2 to evade PRR recognition and activation. Moreover, given the considerable interest in modulating PRR activity as a novel immunotherapy approach, this review will provide a description of PRR agonists and antagonists that have been investigated as antiviral strategies against SARS-CoV-2. This review aims to explore the complex interplay between PRRs and SARS-CoV-2 in depth, considering its implications for prognostic biomarkers, targeted therapeutic strategies and the mechanistic understanding of long LC. Additionally, it outlines future perspectives that could help to address knowledge gaps in PRR-mediated responses during SARS-CoV-2 infection.

In recent decades, increases in temperature and tropical rainfall have facilitated the spread of mosquito species into temperate zones. Mosquitoes are vectors for many viruses, including West Nile virus (WNV) and dengue virus (DENV), and pose a serious threat to public health. This review covers most of the current knowledge on the mosquito species associated with the transmission of WNV and DENV and their geographical distribution and discusses the main vertebrate hosts involved in the cycles of WNV or DENV. It also describes virological and pathogenic aspects of WNV or DENV infection, including emerging concepts linking WNV and DENV to the reproductive system. Furthermore, it provides an epidemiological analysis of the human cases of WNV and DENV reported in Europe, from 1 January 2018 to 31 December 2023, with a particular focus on Italy. The first autochthonous cases of DENV infection, with the most likely vector being Aedes albopictus, have been observed in several European countries in recent years, with a high incidence in Italy in 2023. The lack of treatments and effective vaccines is a serious challenge. Currently, the primary strategy to prevent the spread of WNV and DENV infections in humans remains to limit the spread of mosquitoes.

ABSTRACT Background Several respiratory viruses, including Severe Acute Respiratory Syndrome‐Coronavirus‐2 (SARS‐CoV‐2), suppress nuclear factor‐E2‐related factor‐2 (NRF2) antioxidant response, generating oxidative stress conditions to its advantage. NRF2 has also been reported to regulate the innate immune response through the inhibition of the interferon (IFN) pathway. However, its modulation in younger individuals and its correlation with the IFN response remain to be elucidated. Methods The NRF2 and redox‐related genes expression was examined in nasopharyngeal swabs from children attending the pediatric hospital for SARS‐CoV‐2 molecular testing. Expression levels were analyzed by stratifying the population according to the SARS‐CoV‐2 positivity, age, or the presence of symptoms. The results were correlated with Types I and III IFN genes and IFN‐stimulated genes (ISGs). Results We found that NRF2 expression was markedly diminished in positive patients compared to negative. Moreover, it correlated with higher expression of IFNα2 and IFNλ3, as well as ISG15 and ISG56. Interestingly, symptomatic patients with anosmia/ageusia showed pronounced expression of apurinic/apyrimidinic endonuclease1/redox factor 1 (APE1), together with Type I IFNs, ISG56, and the inflammasome component NLRP3. Conclusion The results indicate an interdependence between NRF2 antioxidant pathway and IFN‐mediated response during SARS‐CoV‐2 infection in young subjects. This study highlights the role of NRF2 and related genes in the regulation of the IFN response in SARS‐CoV‐2‐positive children. We confirmed that SARS‐CoV‐2 infection inhibits the NRF2‐mediated antioxidant response in the upper respiratory tract also in pediatric subjects, although NRF2 was less expressed in asymptomatic subjects compared to groups with mild symptoms, in which inflammatory genes were upregulated. The observed suppression of NRF2 and its correlation with high increases of IFNα2 and IFNλ3 response, along with increased expression of ISGs, provide valuable insights into the host response to the virus in the young population. Further investigations are warranted to explore the potential of NRF2 modulators as therapeutic strategies for COVID‐19, particularly, in children.

Merkel Cell Polyomavirus (MCPyV) is recognized as the major aetiological agent of Merkel Cell Carcinoma (MCC), an aggressive skin tumor. MCPyV-mediated oncogenesis is strictly dependent on viral integration and the expression of a truncated form of the Large T Antigen (LT). Moreover, like other oncogenic DNA viruses, MCPyV may interfere with the DNA damage response (DDR) machinery, thus promoting genomic instability and tumorigenesis. Therefore, the objective of this study was to characterize MCPyV infection in 7 MCC patients and to elucidate the plausible role of the virus in the DDR pathway. MCPyV DNA was detected in 3/7 MCC patients and, as expected, viral integration and LT truncation were observed in virus-positive MCCs, along with the expression of early genes only. Over-expression of DDR genes such as ATM , ATR and their downstream kinases Chk1 and Chk2 was reported in MCPyV-positive MCCs supporting the potential role of the virus in interfering with DDR. Our findings support the established viral aetiology of MCC, and describe, for the first time, an over-expression of DDR components in MCPyV-positive MCC, laying the basis for future studies aimed at investigating the contribution of this pathway to MCPyV-mediated carcinogenesis and exploring the plausible clinical implications of host DDR factors for the treatment of MCC.

The anti-COVID-19 intramuscular vaccination induces a strong systemic but a weak mucosal immune response in adults. Little is known about the mucosal immune response in children infected or vaccinated against SARS-CoV-2. We found that 28% of children had detectable salivary IgA against SARS-CoV-2 even before vaccination, suggesting that, in children, SARS-CoV-2 infection may be undiagnosed. After vaccination, only receptor-binding domain (RBD)–specific IgA1 significantly increased in the saliva. Conversely, infected children had significantly higher salivary RBD-IgA2 compared to IgA1, indicating that infection more than vaccination induces a specific mucosal immune response in children. Future efforts should focus on development of vaccine technologies that also activate mucosal immunity.

Human papillomaviruses (HPVs) commonly infect the anogenital mucosa; most infections are transient, but a fraction of those caused by high-risk (HR) types persist and may lead to anogenital cancer. The epidemiology of HPV genotypes in anal infections in groups at different risk for anal cancer has not been well described in Italy. This retrospective study reports the results of HPV DNA testing and complete genotyping performed on anal swabs from 691 female and male patients attending proctology clinics in Rome during 2012–2021; one-third had repeated testing. Cumulative HPV positivity in 1212 anal swabs was approximately 60%, was not age related, and showed an increasing trend over the study period. HPV rates differed significantly by sex and HIV status: HIV-negative women had the lowest (43.6%) and HIV-positive men the highest (83.5%) HPV prevalence. HIV-positive men had more oncogenic HPV genotypes detected, more multiple infections, and the highest frequency of persistent infections. Two-thirds of all infections were vaccine-preventable. This study found that anal HPV infection rates are still elevated and even increasing in groups at low and high risk of developing anal cancer. Prevention programs need to be improved to reduce rates of anal infection in young women and men.

The SARS-CoV-2 protease (3CLpro) is one of the key targets for the development of efficacious drugs for COVID-19 treatment due to its essential role in the life cycle of the virus and exhibits high conservation among coronaviruses. Recent studies have shown that flavonoids, which are small natural molecules, have antiviral activity against coronaviruses (CoVs), including SARS-CoV-2. In this study, we identified the docking sites and binding affinity of several natural compounds, similar to flavonoids, and investigated their inhibitory activity towards 3CLpro enzymatic activity. The selected compounds were then tested in vitro for their cytotoxicity, for antiviral activity against SARS-CoV-2, and the replication of other coronaviruses in different cell lines. Our results showed that Baicalein (100 μg/mL) exerted strong 3CLpro activity inhibition (>90%), whereas Hispidulin and Morin displayed partial inhibition. Moreover, Baicalein, up to 25 μg/mL, hindered >50% of SARS-CoV-2 replication in Vero E6 cultures. Lastly, Baicalein displayed antiviral activity against alphacoronavirus (Feline-CoV) and betacoronavirus (Bovine-CoV and HCoV-OC43) in the cell lines. Our study confirmed the antiviral activity of Baicalein against SARS-CoV-2 and demonstrated clear evidence of its pan-coronaviral activity.