Avian influenza viruses (AIVs) are widely distributed and have a wide range of hosts. Recently, the number of cases of infection associated with the circulation of highly pathogenic avian influenza H5N1 2.3.4.4b has raised concerns about its high transmission capacity in birds and mammals. This study analyzed swabs from bird and mammal species from the coast of Paraná and the northwest region of São Paulo, Brazil, for the presence of AIV in animals that did not present clinical or histopathological lesions of infection that indicated the need for molecular characterization during monitoring. Of the 661 animals analyzed, three tested positive, two of which were birds (Sula leucogaster and Thalasseus acuflavidus) while one was a mammal (Otaria flavescens) (0.45%, CI 95%: 0.16-1.33). A complete genome sequence of H5N1 AIV was obtained from a brown booby (Sula leucogaster) from the Paraná coast (GISAID accession number: EPI_ISL_1897537). Our study reinforces the importance of continuous genomic surveillance, especially in AIV hosts that do not show signs of infection, to enhance the One-Health assessment approach.

Influenza A virus (IAV) remains a significant public health threat due to its high mutation rate and increasing resistance to existing antiviral drugs. The viral RNA-dependent RNA polymerase (RdRp) is essential for viral replication and represents a promising target for new therapeutics. We screened our in-house chemical library of 103 compounds against two domains of the IAV RdRp complex using molecular docking. Based on computational findings, we selected eleven coumarin-phenolic acid hybrids and one thiazolidinone compounds for in vitro evaluation against H1N1 and H5N1. LMed 93 and LMed 99 exhibited potent antiviral activity, with EC50 values of 5.66 and 1.21 μM against H1N1 respectively, and high selectivity indices. Mechanistic studies showed that LMed 99 acts throughout early to late stages of infection, while LMed 93 impacts early and intermediate stages. Both compounds significantly inhibited viral RNA synthesis, with LMed 99 achieving 82% inhibition at 1- and 3-h post-infection (hpi) and 80% at 6 hpi, and LMed 93 achieving 82% (1 hpi), 78% (3 hpi), and 60% (6 hpi). LMed 99 reduced viral proteins and mRNA in a time-dependent manner, indicating interference with viral transcription. A mini-replicon assay showed that LMed 93, at 70 and 35 μM, reduces polymerase activity by 53.7% and 38.7%, while LMed 99 at 9 and 4.5 μM increased expression by 108.97% and 61.37%, respectively. Structure-activity relationship analysis highlighted that catechol groups and halogenation enhance antiviral potency. These findings suggest that LMed 93 and LMed 99 are promising coumarin-based scaffolds for developing new anti-Influenza A agents, also offering potential strategies for combating other RNA viruses.

ABSTRACT Background & Aims The origin of hepatitis D virus (HDV) and related deltaviruses remains elusive. Contrarily, hepatitis B virus, HDV’s helper virus, and related hepadnaviruses display long-term association with primates. Current data suggest cross-order host shifts as a common mechanism in deltavirus ecology, but corroborative evidence is lacking. Here, we aimed to elucidate the genealogy of primate deltaviruses. Methods We screened 961 non-human primate (NHP) liver specimens obtained in Brazil between 2017-2023 for deltaviruses and hepadnaviruses. Complete deltaviral genomes were obtained via overlapping nested RT-PCR, cloned, expressed in vitro and analyzed via immunoblot and immunofluorescence analysis. Anti-deltaviral antibodies in NHP and vampire bats were detected via immunofluorescence analysis. Results We detected deltaviruses in two NHP. Complete deltaviral genomes exhibited common features including high self-complementarity, genomic and antigenomic ribozymes, and a delta antigen open reading frame. NHP deltaviruses were phylogenetically related to viruses found in common vampire bats. The NHP deltaviruses replicated in vitro without the expression of a large delta antigen. We did not detect anti-deltaviral antibodies in NHP sera (0/249), in contrast to sera from common vampire bats (7/112; 6.2%, 95% CI: 1.8-10.7), indicating viral circulation in bats. Ancestral state reconstruction suggested a bat origin of NHP deltaviruses. Targeted screening excluded a coinfecting hepadnavirus in the deltavirus-positive animals but led to the discovery of a hepadnavirus, corroborating a non-recent introduction of hepadnaviruses into the primate stem-lineage. Conclusions Our data are consistent with deltaviral cross-order host shifts and suggestive of the susceptibility of primates to reservoir-bound deltaviruses, lending credibility to a zoonotic origin of HDV.

Seaweed polysaccharides, particularly the sulfated varieties, have demonstrated potent activity against various enveloped viruses, including respiratory syncytial (RSV) and herpes simplex (HSV) viruses. Herein, we report the synthesis, structural characterization, and antiviral evaluation of two chemically engineered galactan sulfates-G-102 and G-103-from Gracilaria corticata via a novel one-step extraction-sulfation process using ClSO₃H·Pyr/DMF and SO₃·Pyr/DMF reagent systems, respectively. These compounds, which contained (1,3)-and (1,4)-linked galactan backbone, exhibited higher sulfate content (G-102: 11 %, G-103: 8 %) and distinct structural features compared to the water-extracted galactan (G-101). Structural analysis using FT-IR and NMR revealed regioselective sulfation, predominantly at the C6 position of galactose residues in G-102, alongside altered 3,6-anhydrogalactose content. Among these compounds, G-102 demonstrated promising antiviral activity with low cytotoxicity (CC₅₀ >500 μg/mL) and potent inhibition against HSV-1 (IC₅₀ = 2.7 μg/mL, SI >185.18) and RSV (IC₅₀ = 18.03 μg/mL, SI >27.73). Notably, this is the first report of anti-RSV activity from galactans of G. corticata. Mechanistic studies revealed that G-102 exerted multi-stage inhibition of HSV-1, including virucidal effects, viral adsorption and penetration blockade, and prophylactic action, while anti-RSV effects were mainly due to virucidal and adsorption inhibition. These findings establish G-102 as a promising candidate for further development as a broad-spectrum antiviral agent targeting enveloped viruses.

Influenza A and B viruses (IAV and IBV, respectively) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are major causes of acute respiratory infections; however, they can also be shed in feces, enabling their detection in domestic sewage. In the present study, we investigated the circulation of IAV, IBV, and SARS-CoV-2 in raw sewage from São José do Rio Preto, Brazil. A total of 110 sewage samples collected over two years were detected by reverse transcription quantitative PCR (RT-qPCR) and quantified by digital PCR (dPCR), with pepper mild mottle virus used as a fecal strength indicator to normalize viral concentrations. The detection rates of IAV and SARS-CoV-2 RNA were 24.5% and 17.2%, respectively. Longitudinal monitoring of viral load concentrations in sewage revealed two distinct peaks of IAV in May and December 2023, with maximum concentrations of 2.8×10⁶ genomic copies (GC)/L. In contrast, SARS-CoV-2 exhibited a single peak in January 2023, reaching 1.1×10⁶ GC/L. The analytical limits of detection were estimated at 62 GC/reaction for IAV and 0.35 GC/reaction for SARS-CoV-2. Statistical analyses identified significant associations between viral detection and the physicochemical characteristics of sewage. Notably, sewage temperature showed a moderate positive correlation with both the number of SARS-CoV-2-positive samples (Spearman's ρ = 0.556, p = 0.005) and IAV viral concentrations (Spearman's ρ = 0.431, p = 0.020). Additionally, seasonal differences were observed, with higher detection of SARS-CoV-2 in the summer ( p = 0.042) and IAV in the fall ( p = 0.032). Overall, the results demonstrate that sewage monitoring is an effective tool that complements clinical surveillance, contributing to the understanding of the dynamics of respiratory virus circulation.

In this study, we conducted a molecular investigation of hemotropic Mycoplasma spp. in bat species captured in the northern region of the Pantanal biome, Mato Grosso State, Brazil. Tissue samples were screened by qPCR targeting the 16S rRNA gene. Positive samples were subsequently subjected to conventional PCR assays targeting partial fragments of the 16S rRNA (~900 bp) and 23S rRNA (~800 bp) genes. Hemoplasma DNA was detected in four bat species: Glossophaga soricina, Molossops temminckii, Molossus rufus, and Desmodus rotundus. Phylogenetic analyses based on partial 16S and 23S rRNA gene sequences demonstrated that the detected hemoplasmas clustered predominantly with previously described bat-associated hemoplasmas from Brazil and other countries in the Americas. Notably, the detection in M. temminckii represents, to our knowledge, the first molecular evidence of hemotropic Mycoplasma infection in this bat species. These findings expand current knowledge regarding the occurrence, host range, and genetic diversity of hemotropic Mycoplasma spp. in bats from the Pantanal biome and contribute to wildlife surveillance efforts in this ecologically important region.

The migratory bird orders Anseriformes and Charadriiformes are natural reservoirs of avian influenza virus (AIV) and key contributors to its global dissemination. Stopover and wintering areas used by these species are critical hotspots for virus transmission, underscoring the need for routine surveillance. The Pantanal biome in central South America—an extensive floodplain crossed by two major intercontinental migratory routes—hosts numerous species of migratory birds. Given the ecological relevance of this biome and the health risks associated with AIV, this study aimed to investigate AIV circulation in the region. A total of 1,108 orotracheal and cloacal swab samples from 157 bird species were analyzed using RT-qPCR targeting the matrix gene of AIV. Influenza A virus RNA was detected in Charadrius collaris. Subsequent sequencing of the HA and NA genes revealed 94% similarity with H5N2 strains previously identified in Colombian Anatidae in 2011. Additional gene segments (NP;NS;PA;M;PB1;PB2) showed similarity to strains from America and Asia continents. This is the first report of an AIV-infected bird in the Brazilian Pantanal and confirms the presence of a low-pathogenic H5N2 subtype. The findings highlight the role of migratory birds in viral dissemination inland and the potential role of resident species as local reservoirs.

The air-liquid interface (ALI) model using Calu-3 cells has been used to model lung diseases. In ALI, Calu-3 polarizes and changes to a mucus-producing cell. Polarized Calu-3 similarity with primary cells has been proven; however, no studies have been focusing on the pathways differentially expressed in ALI. Here, we profiled the proteome and transcriptome of Calu-3 from submerged (nonpolarized) to ALI (polarized) conditions, and in the omics data, we observed an increase in cell replication in the nonpolarized condition while polarized cells presented higher activation of cellular energy production, protein maturation and recycle, and expression of immune molecules. Moreover, the omics findings showed upregulation of different biological processes related to the protein quality control system and antigen processing presentation in polarized cells. Immunoblot and fluorescence microscopy confirmed increased expression of bronchial epithelium integrity components such as mucus and tight junctions in polarized cells and revealed a characteristic protein expression and cellular organization found in normal lung epithelium. Furthermore, SARS-CoV-2 infection in polarized cells revealed increased cell death associated with the higher expression of ACE2. The differences observed in this study give us a better understanding of how ALI can mimic human bronchial-epithelial cells and its applications in different contexts of lung diseases.

Staphylococcus epidermidis is an opportunistic commensal cutaneous biofilm-producing agent frequently causing musculoskeletal infections (MSI) with/without implants. This study was design to evaluate phenotypic and genomic relatedness between commensal skin and MSI S. epidermidis isolates and to assess patient-related and microbial markers in the outcome of patients after one-year follow-up. Demographics, clinical data and monomicrobial S. epidermidis isolates of MSI patients (n = 31) and healthy individuals (n = 15) were analyzed. Phenotypic profile was assessed by susceptibility tests by broth microdilution and biofilm formation. Phylogenetic relationships, resistome characterization, and virulome analysis were carried out by complete genome sequencing (n = 46). Overall, MSI-derived isolates were significantly more strong/moderate biofilm producers and depicted higher rates of resistance to methicillin (MRSE), ciprofloxacin, gentamicin and rifampicin. Demographics and clinical characteristics did not significantly affect MSI patients' outcomes. In the whole-genomic sequencing (WGS) phylogeny, most MSI-derived isolates were grouped into the pathogenic-associated clonal complex CC2, and significantly higher prevalence of mecA gene and pathogenic marker IS256. Following multivariate analysis, MSI-derived isolates carrying transposable element IS256 are more likely to develop a persistent infection (odds ratio [OR], 8.00, [95% confidence interval (CI), 1.06 to 60.31], P = 0.044), while weaker biofilm producer were protectors (OR, 0.070, 95%CI, 0.005-0.979, P = 0.048), reducing the chance of recurrence by 93% (1-0.070). The logistic regression model's performance was evaluated by Nagelkerke's R, which resulted in 47.21%. In conclusion, S. epidermidis isolates producing MSI were phenotypically and genetically distinct from commensals, proven the association between independent genetic traits and patient's outcome.

NeuroCOVID-19 has emerged as a significant global health concern, presenting a wide spectrum of neurological manifestations, including headaches, brain fog and anosmia. While mounting evidence indicates that SARS-CoV-2 infection compromises central nervous system (CNS) function, the precise processes underlying these effects remain incompletely understood. Although neurons have been extensively studied, astrocytes - critical regulators of brain homeostasis - have been largely overlooked in this context. In this study, we position astrocytes as central players in the neuropathological landscape of neuroCOVID-19, challenging their traditionally supportive role. We evaluated the frequent neurological symptoms in a Brazilian cohort of COVID-19 patients and investigated whether SARS-CoV-2 infection of cortical astrocytes induces neuroinflammation, glutamatergic imbalance, vasoregulatory disruption, and apoptosis as likely pathogenic processes. Among 162 COVID-19-positive patients, headache (53.09 %), brain fog (42.15 %), and anosmia (38.72 %) were the most commonly reported symptoms. Using human-induced pluripotent stem cell (hiPSC)-derived astrocytes, we found that SARS-CoV-2 infection promotes a pronounced pro-inflammatory response, evidenced by elevated levels of IL-6, IL-15, and IL-4 in the culture supernatant. Infected astrocytes also showed reduced mRNA expression of KLK1 and EAAT1, key genes involved in vasodilation and glutamate clearance, respectively. Additionally, a significant increase in cleaved caspase-3-positive cells indicated enhanced apoptosis. Overall, these findings demonstrate that SARS-CoV-2 disrupts astrocyte homeostatic functions, leading to neuroinflammation, excitatory neurotransmission dysregulation, and cell death that may, hypothetically, underlie the neurological sequelae of COVID-19. By reframing astrocytes as active protagonists, this study highlights their essential role in CNS vulnerability. It also suggests potential targets for the future investigation in the development of therapies against the neurological complications of COVID-19.

Background/Objectives:H5N1 influenza viruses are spreading worldwide and threaten global public health. Preparedness is necessary to mitigate the worst-case scenario should an H5N1 influenza pandemic occur and justify the development of vaccines against circulating H5N1 viruses of concern. Methods: The production and characterization of egg-based split and inactivated H5Nx of three distinct monovalent antigens from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were performed at an industrial scale. These antigens were formulated and their immune responses, when combined or not with IB160 squalene-based oil-in-water emulsion adjuvant in a rat model, were evaluated in a one- or two-dose immunization schedule. IgG antibodies, hemagglutination inhibitions, and microneutralization titers were measured for vaccine-induced immunity and cross-reactivity. Results: Three monovalent vaccines from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were produced at an industrial scale and characterized. The immune responses against the monovalent vaccines showed a clade-specific antibody response and the need to combine with IB160 adjuvant for a required immune response. Conclusions: Considering the candidate vaccine viruses (CVVs) with the testing potency reagents available and that the antibody response obtained against the CVVs produced was clade-specific, IDCDC RG-71A is the indicated CVV for the predominant currently circulating H5N1 influenza virus of clade 2.3.4.4b and must be combined with adjuvant to induce a higher and efficacious immune response in a two-dose immunization protocol.

The SARS-CoV-2 Omicron variant caused a global surge in COVID-19 cases following its emergence in November 2021, rapidly diversifying in the subsequent months. Although many studies have documented Omicron’s diversification, few have explored its impact on pediatric populations or the seasonality of other respiratory viruses in children. This study aims to investigate the diversity and circulation patterns of SARS-CoV-2 Omicron sublineages in pediatric patients in São Paulo, Brazil, and assess their co-circulation with other respiratory pathogens. Respiratory samples collected from patients under 18 years old across five hospitals between January 2022 and April 2023 were tested for different respiratory viruses using real-time RT-PCR. Whole-genome sequencing was performed on SARS-CoV-2-positive samples. Among the 7868 pediatric respiratory samples tested, 3902 were positive for viral pathogens. Respiratory Syncytial Virus accounted for the highest number of positive cases (n = 1248), exhibiting an atypical off-season peak in November 2022. SARS-CoV-2 was detected in 297 samples, of which 103 were sequenced. BA.1 and BA.5 sublineages had predominant genomic diversity and circulation time. These findings highlight the Omicron variant’s significant impact on the epidemiology and seasonal distribution of respiratory viruses in children, emphasizing the ongoing need for vaccination and robust surveillance efforts in pediatric populations.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), identified in late 2019, spurred a global pandemic, prompting an unprecedented international mobilization in vaccination and public health strategies. Although the pandemic is now under greater control, the worldwide dissemination of variants of concern (VOCs) has led to resistance and decreased vaccine efficacy, highlighting the urgent need for broad-spectrum therapeutic and preventive solutions. In this study, we employed hybridoma technology to generate monoclonal antibodies (mAbs) from mice immunized with the SARS-CoV-2 Wuhan Spike protein trimer. We selected clones producing anti-Spike receptor-binding domain (RBD) mAbs and characterized a panel of four mAbs to assess their potential as antiviral agents and their utility as tools in research and diagnostics. Our results showed that all mAbs recognized the SARS-CoV-2 Wuhan strain in infected cells through immunofluorescence assay. Moreover, the binding profiles of these mAbs against the RBD protein from various SARS-CoV-2 variants revealed distinct reactivity and loss of binding as VOCs emerged. However, one mAb, named 4B1D3, showed the most promising features, exhibiting broad binding and neutralizing capacity across all tested SARS-CoV-2 variants, including Omicron BA.2, BA.4/5 and XBB.1.5 sublineages. Furthermore, a single prophylactic dose of the 4B1D3 mAb provided protection to K18-hACE2 mice against a lethal challenge with SARS-CoV-2 Wuhan strain. In conclusion, these mAbs represent valuable tools for research and diagnostics and have significant potential for the development of new therapeutic strategies against SARS-CoV-2 variants.

COVID-19 is a human respiratory syndrome caused by the infection of the SARS-CoV-2 virus that has a high rate of infection and mortality. Viruses modulate the host machinery by altering cellular mechanisms that favor their replication. One of the mechanisms that viruses exploit is the protein folding and processing of post-translational modifications that occur in the endoplasmic reticulum (ER). When ER function is impaired, there is an accumulation of misfolded proteins leading to endoplasmic reticulum stress (ER stress). To maintain homeostasis, cells trigger an adaptive signaling mechanism called the Unfolded Protein Response (UPR) which helps cells deal with stress, but under severe conditions, can activate the apoptotic cell death mechanism. This study elucidated an activation of a diversity of molecular mechanisms by Brazilian variants of SARS-CoV-2 by a time-resolved and large-scale characterization of SARS-CoV-2-infected cells proteomics and immunoblotting. Furthermore, it was shown that pharmacological UPR modulation could reduce viral release by counteracting the different viral activations of its cellular response. Analysis of human clinical specimens and disease outcomes focusing on ER stress reinforces the importance of UPR modulation as a host regulatory mechanism during viral infection and could point to novel therapeutic targets. Significance Since the emergence of SARS-CoV-2 and the consequent COVID-19 pandemic, the rapid emergence of variants of this new coronavirus has been a cause for concern since many of them have significantly higher rates of transmissibility and virulence, being called Variants of Concern (VOC). In this work, we studied the VOCs Gamma (P.1) and Zeta (P.2), also known as Brazilian variants. Constant evidence has reported that there are particularities related to each variant of SARS-CoV-2, with different rates of transmissibility, replication and modulation of host biological processes being observed, in addition to the mutations present in the variants. For this reason, this work focused on infections caused by the Brazilian variants of SARS-CoV-2 in different cell lines, in which we were able to observe that the infections caused by the variants induced endoplasmic reticulum stress in the infected cells and activated the UPR pathways, presenting specific modulations of each variant in this pathway. Furthermore, transcriptome analysis of patients revealed a correlation between ER-related genes and COVID-19 progression. Finally, we observed that the use of UPR modulators in host cells decreased viral release of all variants without affecting cell viability. The data presented in this work complement the observations of other studies that aim to understand the pathogenicity of SARS-CoV-2 VOCs and possible new therapeutic strategies, mainly targeting biological processes related to the endoplasmic reticulum.

Coronaviruses (CoV) infect a wide variety of hosts, causing epidemics in humans, birds, and mammals over the years. Bats (order Chiroptera) are one of the natural hosts of the Coronaviridae family. They represent 40% of the total number of mammal species in the Pantanal, a biodiversity hotspot in South America. Given the recent SARS-CoV-2 pandemic, we investigated the presence of CoV in bats captured in the Brazilian Pantanal. Oral and rectal swabs collected in 2021 from 419 bats were analyzed using Pancoronavirus-nested PCR targeting the RNA-dependent RNA-polymerase (RdRp) gene. Orthocoronavirinae was detected in 16.7% (70/419) of the bats; nine samples were sequenced, confirming that Carollia perspicillata (4), Phyllostomus hastatus (2), Desmodus rotundus (1), Molossus rufus (1), and Myotis cf. nigricans (1) collected in buildings formally used by humans were infected by Alphacoronavirus genera. This is the first description of Alphacoronavirus in bats from the Pantanal. As they are natural reservoirs of CoVs, constant monitoring of bats is important to comprehend the epidemiology of emerging viruses, especially in the Pantanal biome.

Coinfection and secondary infection by fungi in patients with viral pulmonary infection, especially SARS-CoV-2, are important factors that worsen the prognosis and are associated to increased death rates. This work aims to report the prevalence of Candida isolates in bronchoalveolar and nasopharyngeal samples from suspected COVID-19 patients in the first-second pandemic waves and their antifungal resistance profile. From 2321 patients, 29.04% were diagnosed with SARS-CoV-2 infection. The yeast isolation rate of 6.97% (47/674) from positive SARS-CoV-2 was statistically higher than 4.43% (73/1647) from negative SARS-CoV-2 patients (p = 0.0177). Among yeasts, the most prevalent species was Candida albicans (63/120), with four being azole-resistant isolates (6.35%); however, other emerging and less susceptible species were also isolated, such as Candida guilliermondii (11), Candida glabrata (5), Candida lusitaniae (4), Candida krusei (1), and Candida norvegensis (1). Here, we highlighted Candida prevalence in respiratory tract, emphasizing the relevance for surveillance in SARS-CoV-2/COVID patients for improvement of management as well as patient outcomes.

Introduction:The rapid development and deployment of multiple safe and effective COVID-19 vaccines were critical cornerstones of pandemic control. However, vaccine inequity and the emergence of new variants of concern (VOCs) highlighted major gaps in the global strategy to control SARS-CoV-2 infection. Despite the use of distinct platforms, most approved vaccines utilize the Spike protein as the main antigen due to its pivotal role in virus entry, mediated by the receptor binding domain (RBD). In this context, RBD stands out as a promising antigen for a subunit vaccine candidate, as it is the main target of neutralizing antibodies, has a well-established scalable production pipeline, and has proven safety. Approaches to enhance RBD immunogenicity encompass the addition of adjuvants and antigen multimerization. Methods:In this study, we compared the immunogenic properties of the Wuhan RBD monomer and homodimer with an RBD heterotrimer formulation composed of the Delta, Beta and Gamma variants. We also screened different adjuvants to optimize both humoral and cellular immunity. Results:Our results showed that immunization with the RBD dimer and trimer, in the presence of the adjuvant AddaS03, elicited a higher humoral response and a broader neutralization profile. Additionally, RBD-trimer immunization more efficiently inhibited viral replication in the lungs of mice challenged with the ancestral Wuhan strain compared to the monomer. We further optimized our vaccine formulation by combining the adjuvants AddaS03 and Poly I:C, which demonstrated a synergistic effect, integrating the potent humoral response induced by AddaS03 with the cellular Th1 skewing capacity of Poly I:C. The AddaS03+ Poly I:C mixture induced antibodies with higher affinity and an increased frequency of RBD-specific IgG2c-producing bone marrow plasma cells, highlighting the potential of this adjuvant combination to generate long-lived memory plasma cells. Additionally, we identified sequences within the RBD that induced specific IFNγ T cell responses. Peptide 12 (393-TNVYADSFVIRGDEVRQ-409) emerged as the immunodominant CD4 T cell epitope, whereas peptides 28 (505-YQPYRVVVLSFELLHAP-521) and 29 (512-VLSFELLHAPATVCGPK-528) successfully activated CD8 T cells. Conclusions:These findings underscore that antigen multimerization and the strategic combination of adjuvants can significantly improve vaccine immunogenicity.

COVID-19 pandemic continues to challenge the world with a major public health problem, long COVID (LC), which is estimated to affect over 400 million people worldwide. Many unknowns remain regarding the mechanisms involved in LC. We investigated the impact of anti-SARS-CoV-2 antibody and IFN-γ responses on the development of LC and its various phenotypes. We studied a cohort of 137 convalescents following predominantly mild COVID-19 during the first pandemic wave (2020) and up to one-year post-infection. We found 45% of LC cases that were associated with a greater number and duration of acute-phase symptoms. Cardiovascular and/or gastrointestinal symptoms in the acute phase were associated to protection against LC development, while pulmonary, otorhinolaryngological, musculoskeletal and other symptoms were associated with increased risk of LC development. Regarding LC phenotypes, we observed risk associations and potentially deleterious effects of anti-SARS-CoV-2 antibodies for LC symptoms classified as general or other. In contrast, for vital organ-related LC symptoms, we found only protective associations, particularly for cardiovascular symptoms, which indeed had a low prevalence in LC (16%). Collectively, our data suggest that anti-SARS-CoV-2 antibodies play a protective role against vital organ-related LC symptoms, especially cardiovascular symptoms, but are insufficient in preventing or limiting other highly prevalent LC symptoms, such as neurological, psychiatric and pulmonary.

Avian species pose risks for transmitting viruses, including avian circoviruses, that could be a threat for conservation and introduction into commercial flocks. This study investigated the presence of circovirus in 81 avian species from different regions of Brazil, including the northwest region of São Paulo and the coast of Paraná. Blood samples and oropharyngeal, cloacal, and other organ swabs were collected. The samples were extracted and screened using nested PCR for the replicase gene. In positive cases, the samples were sequenced. Regarding the results, a total of 1528 swab samples were collected from 601 birds, of which 24 (4%, 95% CI: 2.4-5.6) tested positive for various circovirus subtypes. Most positive birds (92%, 22/24) were from the northwest region of São Paulo, mainly from the city of São José do Rio Preto (54%, 12/22). The study also identified the presence of circovirus subtypes in avian families that were not previously described. Furthermore, the presence of raven circovirus in the blood sample of a Nyctibius griseus (potoo), suggests the possibility of a new carrier of the virus. Ultimately, the findings underscore the complexity of the viral ecology of avian circoviruses, highlight the necessity of enhancing future studies, and emphasize the need to support health assessment of wildlife, including marine birds.