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The COVID-19 pandemic has highlighted the relevance of proper disinfection procedures and renewed interest in developing novel disinfectant materials as a preventive strategy to limit SARS-CoV-2 contamination. Given its widely known antibacterial, antifungal, and antiviral properties, Melaleuca alternifolia essential oil, also named Tea tree oil (TTO), is recognized as a potential effective and safe natural disinfectant agent. In particular, the proposed antiviral activity of TTO involves the inhibition of viral entry and fusion, interfering with the structural dynamics of the membrane and with the protein envelope components. In this study, for the first time, we demonstrated the virucidal effects of TTO against the feline coronavirus (FCoVII) and the human coronavirus OC43 (HCoV-OC43), both used as surrogate models for SARS-CoV-2. Then, to atomistically uncover the possible effects exerted by TTO compounds on the outer surface of the SARS-CoV-2 virion, we performed Gaussian accelerated Molecular Dynamics simulations of a SARS-CoV-2 envelope portion, including a complete model of the Spike glycoprotein in the absence or presence of the three main TTO compounds (terpinen-4-ol, γ-terpinene, and 1,8-cineole). The obtained results allowed us to hypothesize the mechanism of action of TTO and its possible use as an anti-coronavirus disinfectant agent.

Background Dengue virus (DENV), with its four antigenically distinct serotypes, is the etiological agent of dengue fever, which is endemic in tropical and subtropical regions but has recently spread to previously non-endemic areas such as Europe. Given the growing body of evidence suggesting that sequence diversification in the 3′ UTR of DENV contributes to its epidemiological fitness and host adaptation, we conducted phylogenetic and genetic diversity analyses on four DENV 3′ UTR datasets (DENV-1, DENV-2, DENV-3 and DENV-4). Methods A maximum likelihood phylogenetic analysis was performed using IQ-TREE, and the average evolutionary divergence was estimated using MEGA X. Maximum likelihood analysis combined with genetic distance calculations provided insight into the evolutionary dynamics of the DENV 3′ UTR. Results A higher number of supported internal clusters/clades were found in the DENV-2 and DENV-1 3′ UTR trees, probably indicating strains with similar evolutionary histories. In terms of cluster composition, apart from a general mixing of DENV 3′ UTR sequences from different sites and years, the majority of supported internal clusters were composed of sequences aggregated according to their location. Genetic distances showed that the DENV-1 3′ UTR has a higher variability (5%) compared to DENV-2 (3%), DENV-3 and DENV-4 (2%). The average length of the 3′ UTR, as estimated from our datasets, showed that it was longest in DENV-2, followed by DENV-3, DENV-1 and DENV-4. Conclusions In conclusion, this study provided a comprehensive analysis of 3′ UTR evolution and phylogenies in all four DENV serotypes, suggesting that this viral genomic sequence is subject to genetic variability and length changes.

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.

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.

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.

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.

The clinical presentation of dengue virus (DENV) infection is variable. Severe complications mainly result from exacerbated immune responses. Type I interferons (IFN-I) are important in antiviral responses and form a crucial link between innate and adaptive immunity. Their contribution to host defense during DENV infection remains under-studied, as direct quantification of IFN-I is challenging. We combined ultra-sensitive single-molecule array (Simoa) digital ELISA with IFN-I gene expression to elucidate the role of IFN-I in a well-characterized cohort of hospitalized Cambodian children undergoing acute DENV infection. Higher concentrations of type I IFN proteins were observed in blood of DENV patients, compared to healthy donors, and correlated with viral load. Stratifying patients for disease severity, we found a decreased expression of IFN-I in patients with a more severe clinical outcome, such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). This was seen in parallel to a correlation between low IFNα protein concentrations and decreased platelet counts. Type I IFNs concentrations were correlated to frequencies of plasmacytoid DCs, not DENV-infected myloid DCs and correlated inversely with neutralizing anti-DENV antibody titers. Hence, type I IFN produced in the acute phase of infection is associated with less severe outcome of dengue disease.

Estimating the burden of Zika virus (ZIKV) and dengue virus (DENV) infections in migrants is important to promote their health status and recommend appropriate interventions. We aimed to estimate the seroprevalence of ZIKV and DENV in migrants from high endemic countries attended at a referral center in Rome (Italy), arriving via the Mediterranean from North and sub-Saharan Africa and South-East Asia. Sixty-four serum samples from migrants were tested for anti-ZIKV and anti-DENV immunoglobulin (Ig) G and IgM by ELISA. Serum samples with detectable Ig were analyzed by indirect immunofluorescence assay (IFA). For confirmatory testing and given the cross-reactivity of antibodies between orthoflaviviruses, all positive IFA sera were tested by virus neutralization test. ZIKV and DENV RNA were assessed by RT Real-Time PCR. All serum samples were negative for anti-ZIKV IgG, while 12.50% (n=8/64) were positive for anti-ZIKV IgM by ELISA. IFA showed that only 1 of 8 serum samples (12.50%) was positive for anti-ZIKV IgM, but ZIKV RNA was undetectable. The seroprevalence of anti-DENV IgG by ELISA was 59.37% (n=38/64), mostly confirmed by IFA (97.36%, n=37/38). Furthermore, anti-DENV IgM were detected in 9 serum samples (n=9/64, 14.06%) by ELISA, previously tested negative for anti-DENV IgG. Of these, 2 sera were confirmed by IFA, but DENV RNA was not detectable. Anti-DENV neutralizing antibodies (nAbs) were detected in 27% of anti-DENV IgG sera (n=10/37) tested by IFA. Multiple linear regression analysis showed that sub-Saharan African origin was an independent factor for the development of anti-DENV nAbs (p=0.009), while age and gender had no effect. Sera negatives for anti-DENV nAbs but with detectable anti-DENV IgG tested by IFA had nAbs to another orthoflavivirus (n=25/27, 92.59%) such as West Nile virus (WNV) (n=17/25, 68%), Yellow fever virus (YFV) (n=7/25, 28%) and Usutu virus (USUV) (n=1/25, 4%). A high prevalence of anti-orthoflavivirus IgG, especially against DENV, was found in the migrant population studied, but no infections were detected. With the recent outbreaks of autochthonous DENV infections in Italy, the risk of secondary DENV infection - and severe disease - could be high. Robust serological surveillance, vaccination and prevention strategies for this vulnerable group are needed.

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.