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The first approved vaccines for human use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are nanotechnology-based. Although they are modular, rapidly produced, and can reduce disease severity, the currently available vaccines are restricted in preventing infection, stressing the global demand for novel preventive vaccine technologies. Bearing this in mind, we set out to develop a flexible nanovaccine platform for nasal administration to induce mucosal immunity, which is fundamental for optimal protection against respiratory virus infection. The next-generation multiepitope nanovaccines co-deliver immunogenic peptides, selected by an immunoinformatic workflow, along with adjuvants and regulators of the PD-L1 expression. As a case study, we focused on SARS-CoV-2 peptides as relevant antigens to validate the approach. This platform can evoke both local and systemic cellular- and humoral-specific responses against SARS-CoV-2. This led to the secretion of immunoglobulin A (IgA), capable of neutralizing SARS-CoV-2, including variants of concern, following a heterologous immunization strategy. Considering the limitations of the required cold chain distribution for current nanotechnology-based vaccines, it is shown that the lyophilized nanovaccine is stable for long-term at room temperature and retains its in vivo efficacy upon reconstitution. This makes it particularly relevant for developing countries and offers a modular system adaptable to future viral threats.
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We report the use of a new multiplex Real-Time PCR platform to simultaneously identify 24 pathogens and 3 antimicrobial-resistance genes directly from respiratory samples of COVID-19 patients. Results were compared to culture-based diagnosis. Secondary infections were detected in 60% of COVID-19 patients by molecular analysis and 73% by microbiological assays, with no significant differences in accuracy, indicating Gram-negative bacteria as the predominant species. Among fungal superinfections, Aspergillus spp. were detected by both methods in more than 7% of COVID-19 patients. Oxacillin-resistant S. aureus and carbapenem-resistant K. pneumoniae were highlighted by both methods. Secondary microbial infections in SARS-CoV-2 patients are associated with poor outcomes and an increased risk of death. Since PCR-based tests significantly reduce the turnaround time to 4 hours and 30 minutes (compared to 48 hours for microbial culture), we strongly support the routine use of molecular techniques, in conjunction with microbiological analysis, to identify co/secondary infections.
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Humans are exposed every day to innumerable external stimuli, both environmental and microbial. Immunological memory recalls each specific stimulus and mounts a secondary response that is faster and of a larger magnitude than the primary response; this process constitutes the basis for vaccine development. The COVID-19 pandemic offers a unique opportunity to study the development of immune memory against an emergent microorganism. Memory T cells have an important role in the resolution of COVID-19, and they are key pillars of immunological memory. In this review, we summarize the main findings regarding anti-SARS-CoV-2 memory T cells after infection, after vaccination, and after the combination of these two events ("hybrid immunity"), and analyze how these cells can contribute to long-term protection against the infection with SARS-CoV-2 variants.
Los humanos se exponen cada día a innumerables estímulos externos, tanto ambientales como microbianos. La memoria inmunológica registra de manera específica un estímulo y articula una respuesta secundaria más rápida y de mayor magnitud que la respuesta primaria; este proceso constituye la base del desarrollo de vacunas. La pandemia de COVID-19 ofreció la oportunidad de estudiar el desarrollo de la memoria inmunológica contra un microorganismo emergente. Las células T de memoria tienen un papel importante en la resolución de COVID-19 y son pilares importantes de la memoria inmunológica. En esta revisión se resumen los principales hallazgos de la respuesta de las células T de memoria contra la infección por SARS-CoV-2, a la vacunación o a la combinación de ambos procesos ("inmunidad híbrida"), y se discute cómo estas células pueden contribuir a la protección a largo plazo contra distintas variantes del virus.
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Vacinas contra COVID-19 , COVID-19 , Memória Imunológica , Células T de Memória , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , Memória Imunológica/imunologia , Células T de Memória/imunologia , Vacinas contra COVID-19/imunologia , SARS-CoV-2/imunologiaRESUMO
OBJECTIVE: To investigate the effects of repeated vaccination with ancestral SARS-CoV-2 (Wuhan-hu-1)-based inactivated, recombinant protein subunit or vector-based vaccines on the neutralizing antibody response to Omicron subvariants. METHODS: Individuals who received four-dose vaccinations with the Wuhan-hu-1 strain, individuals who were infected with the BA.5 variant alone without prior vaccination, and individuals who experienced a BA.5 breakthrough infection following receiving 2-4 doses of the Wuhan-hu-1 vaccine were enrolled. Neutralizing antibodies against D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 were detected using a pseudovirus-based neutralization assay. Antigenic cartography was used to analyze cross-reactivity patterns among D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 and sera from individuals. RESULTS: The highest neutralizing antibody titers against D614G were observed in individuals who only received four-dose vaccination and those who experienced BA.5 breakthrough infection, which was also significantly higher than the antibody titers against XBB.1.5, EG.5.1, and BA.2.86. In contrast, only BA.5 infection elicited comparable neutralizing antibody titers against the tested variants. While neutralizing antibody titers against D614G or BA.5 were similar across the cohorts, the neutralizing capacity of antibodies against XBB.1.5, EG.5.1, and BA.2.86 was significantly reduced. BA.5 breakthrough infection following heterologous booster induced significantly higher neutralizing antibody titers against the variants, particularly against XBB.1.5 and EG.5.1, than uninfected vaccinated individuals, only BA.5 infected individuals, or those with BA.5 breakthrough infection after primary vaccination. CONCLUSIONS: Our findings suggest that repeated vaccination with the Wuhan-hu-1 strain imprinted a neutralizing antibody response toward the Wuhan-hu-1 strain with limited effects on the antibody response to the Omicron subvariants.
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The present study aimed to evaluate the effectiveness of two doses of CoronaVac in preventing SARS-CoV-2 symptomatic disease with virological confirmation, as well as in the prevention of COVID-19 moderate and severe cases. A test-negative unmatched case-control design was used, in which cases were patients with suspected COVID-19 (presenting at least two of the following symptoms: fever, chills, sore throat, headache, cough, runny nose, olfactory or taste disorders) with virological confirmation, and controls were those whose SARS-CoV-2 test was negative. As for exposure, participants were classified as unvaccinated, or vaccinated with a complete schedule. Suspected COVID-19 cases were identified from March to November 2021, in two cities located in the State of São Paulo, Brazil. All participants signed the Informed Consent Form before enrollment. RT-PCR results and vaccination data were obtained from the local surveillance systems. Up to two phone calls were made to obtain information on the outcome of the cases. A total of 2981 potential participants were screened for eligibility, of which 2163 were included, being 493 cases and 1670 controls. Vaccination, age, the reported contact with a COVID-19 suspected or confirmed case in the 14 days before symptoms onset, and the educational level were the variables independently associated with the outcome. The adjusted vaccine effectiveness for symptomatic COVID-19 (AVE) was 39.0â¯% (95â¯% CI 6.0-60.0â¯%). The AVE in the prevention of moderate and severe disease was 91.0â¯% (95â¯% CI 76.0-97.0â¯%). Our results were influenced by the waning of the Gamma variant, in the second trimester of 2021, followed by the increase in vaccination coverage, and a drop in the number of cases in the second half of the year. The study demonstrated the high effectiveness of CoronaVac in preventing moderate/severe COVID-19 cases.
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Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infections in children. This syndrome manifests about a month after the initial viral infection and is characterized by fever, multiorgan dysfunction, and systemic inflammation. This chapter will review the emergence, epidemiology, clinical characteristics, diagnosis, pathophysiology, immunomodulatory treatment, prognosis, outcomes, and prevention of MIS-C. While the pathophysiology of MIS-C remains to be defined, it is a post-infection, hyperinflammatory syndrome of childhood with elevated inflammatory cytokines.
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COVID-19 , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica , Humanos , COVID-19/complicações , COVID-19/imunologia , COVID-19/virologia , COVID-19/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/terapia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Criança , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Prognóstico , Citocinas/metabolismoRESUMO
Interleukin-6 (IL-6) is a pro-inflammatory cytokine elevated in cytokine storm syndromes, including hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). It is also elevated in cytokine release syndrome (CRS) after immune activating cancer therapies such as chimeric antigen receptor (CAR) T-cells or bispecific T-cell engagers (BITEs) and in some patients after infection with SARS-CoV-2. The interaction of IL-6 with its receptor complex can happen in several forms, making effectively blocking this cytokine's effects clinically challenging. Fortunately, effective clinical agents targeting the IL-6 receptor (tocilizumab) and IL-6 directly (siltuximab) have been developed and are approved for use in humans. IL-6 blockade has now been used to safely and effectively treat several cytokine storm syndromes (CSS). Other methods of investigation in effective IL-6 blockade are underway.
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Anticorpos Monoclonais Humanizados , COVID-19 , Síndrome da Liberação de Citocina , Interleucina-6 , Receptores de Interleucina-6 , Humanos , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Interleucina-6/antagonistas & inibidores , Interleucina-6/imunologia , Interleucina-6/metabolismo , Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/imunologia , Receptores de Interleucina-6/antagonistas & inibidores , Receptores de Interleucina-6/imunologia , SARS-CoV-2/imunologia , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Síndrome de Ativação Macrofágica/imunologia , Síndrome de Ativação Macrofágica/tratamento farmacológicoRESUMO
COVID-19 convalescent plasma (CCP) is an important therapeutic option for immunocompromised patients with COVID-19. Such patients are at increased risk for serious complications of infection and may also develop a unique syndrome of persistent infection. This article reviews the rationale for CCP utilization in immunocompromised patients and the evidence for its value in immunosuppressed patients with both acute and persistent COVID-19. Both historical precedence and understanding of the mechanisms of action of antibody treatment support this use, as do several lines of evidence derived from case series, comparative studies, randomized trials, and systematic reviews of the literature. A summary of recommendations from multiple practice guidelines is also provided.
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Antiviral passive antibody therapy includes convalescent plasma, hyperimmune globulin, and monoclonal antibodies. Passive antibodies have proven effective in reducing morbidity and mortality for SARS-CoV-2 and other infectious diseases when given early in the disease course with sufficiently high specific total and neutralizing antibody levels. Convalescent plasma can be delivered to patients before vaccination implementation or novel drug production. Carefully designed and executed randomized controlled trials near the pandemic outset are important for regulatory bodies, healthcare workers, guideline committees, the public, and the government. Unfortunately, many otherwise well-designed antibody-based clinical trials in COVID-19 were futile, either because they intervened too late in the disease or provided plasma with insufficient antibodies. The need for early treatment mandates outpatient clinical trials in parallel with inpatient trials. Early outpatient COVID-19 convalescent plasma transfusion with high antibody content within 9 days of symptom onset has proven effective in blunting disease progression and reducing hospitalization, thus reducing hospital overcrowding in a pandemic. Convalescent plasma offers the opportunity for hope by enabling community participation in outpatient curative therapy while monoclonal therapies, vaccines, and drugs are being developed. Maintaining the appropriate infrastructure for antibody infusion in both outpatient and inpatient facilities is critical for future pandemic readiness.
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[This corrects the article DOI: 10.3389/fimmu.2024.1397040.].
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Despite the progress in medical data collection the actual burden of SARS-CoV-2 remains unknown due to under-ascertainment of cases. This was apparent in the acute phase of the pandemic and the use of reported deaths has been pointed out as a more reliable source of information, likely less prone to under-reporting. Since daily deaths occur from past infections weighted by their probability of death, one may infer the total number of infections accounting for their age distribution, using the data on reported deaths. We adopt this framework and assume that the dynamics generating the total number of infections can be described by a continuous time transmission model expressed through a system of nonlinear ordinary differential equations where the transmission rate is modeled as a diffusion process allowing to reveal both the effect of control strategies and the changes in individuals behavior. We develop this flexible Bayesian tool in Stan and study 3 pairs of European countries, estimating the time-varying reproduction number ( R t $$ {R}_t $$ ) as well as the true cumulative number of infected individuals. As we estimate the true number of infections we offer a more accurate estimate of R t $$ {R}_t $$ . We also provide an estimate of the daily reporting ratio and discuss the effects of changes in mobility and testing on the inferred quantities.
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A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes mild-to-severe respiratory symptoms, including acute respiratory distress. Despite remarkable efforts to investigate the virological and pathological impacts of SARS-CoV-2, many of the characteristics of SARS-CoV-2 infection still remain unknown. The interferon-inducible ubiquitin-like protein ISG15 is covalently conjugated to several viral proteins to suppress their functions. It was reported that SARS-CoV-2 utilizes its papain-like protease (PLpro) to impede ISG15 conjugation, ISGylation. However, the role of ISGylation in SARS-CoV-2 infection remains unclear. We aimed to elucidate the role of ISGylation in SARS-CoV-2 replication. We observed that the SARS-CoV-2 nucleocapsid protein is a target protein for the HERC5 E3 ligase-mediated ISGylation in cultured cells. Site-directed mutagenesis reveals that the residue K374 within the C-terminal spacer B-N3 (SB/N3) domain is required for nucleocapsid-ISGylation, alongside conserved lysine residue in MERS-CoV (K372) and SARS-CoV (K375). We also observed that the nucleocapsid-ISGylation results in the disruption of nucleocapsid oligomerization, thereby inhibiting viral replication. Knockdown of ISG15 mRNA enhanced SARS-CoV-2 replication in the SARS-CoV-2 reporter replicon cells, while exogenous expression of ISGylation components partially hampered SARS-CoV-2 replication. Taken together, these results suggest that SARS-CoV-2 PLpro inhibits ISGylation of the nucleocapsid protein to promote viral replication by evading ISGylation-mediated disruption of the nucleocapsid oligomerization.IMPORTANCEISG15 is an interferon-inducible ubiquitin-like protein that is covalently conjugated to the viral protein via specific Lys residues and suppresses viral functions and viral propagation in many viruses. However, the role of ISGylation in SARS-CoV-2 infection remains largely unclear. Here, we demonstrated that the SARS-CoV-2 nucleocapsid protein is a target protein for the HERC5 E3 ligase-mediated ISGylation. We also found that the residue K374 within the C-terminal spacer B-N3 (SB/N3) domain is required for nucleocapsid-ISGylation. We obtained evidence suggesting that nucleocapsid-ISGylation results in the disruption of nucleocapsid-oligomerization, thereby suppressing SARS-CoV-2 replication. We discovered that SARS-CoV-2 papain-like protease inhibits ISG15 conjugation of nucleocapsid protein via its de-conjugating enzyme activity. The present study may contribute to gaining new insight into the roles of ISGylation-mediated anti-viral function in SARS-CoV-2 infection and may lead to the development of more potent and selective inhibitors targeted to SARS-CoV-2 nucleocapsid protein.
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The effects of co-infections with SARS-CoV-2 and parasitic diseases have been little investigated in terms of immune response, disease dynamics, and clinical outcomes. This study aimed to explore the impact of co-infection with Opisthorchis viverrini and SARS-CoV-2 on the immune response concerning clinical symptoms and the severity of pulmonary abnormalities. A cross-sectional study was conducted, including healthy participants as controls, participants with opisthorchiasis, SARS-CoV-2 infection, and a co-infection group with both diseases. Characteristics of SARS-CoV-2 infection were assessed based on clinical parameters and severity of pulmonary abnormalities, whereas opisthorchiasis burden was evaluated by eggs-per-gram (EPG) counts. Immune responses were assessed by measuring levels of interferon-γ (IFN-γ), SARS-CoV-2 anti-spike receptor binding domain (RBD) IgG, and neutralizing antibody against SARS-CoV-2. In the co-infected group, clinical parameters and hospitalization rates were lower than in the SARS-CoV-2 group. Pulmonary abnormalities, such as bronchial fibrosis, were commonly observed in the SARS-CoV-2 group, leading to hospitalization in some cases. Participants with opisthorchiasis had higher IFN-γ levels than healthy individuals. IFN-γ levels were significantly lower in the co-infection group compared with the SARS-CoV-2 group (P = 0.002). There was a significant (P = 0.044) positive correlation between RBD-specific IgG and percent neutralization levels in the SARS-CoV-2 group. Levels of both were somewhat lower (not statistically significant) in the co-infection group. A negative correlation was observed between opisthorchiasis burden (EPG counts) and IFN-γ and RBD-specific IgG levels in the co-infected group. Following vaccination, the increase in IgG levels against the RBD protein was significantly lower in the co-infected group than in the SARS-CoV-2 group. These results suggest that O. viverrini infection suppresses immune responses and may lead to a reduction in severity in cases of SARS-CoV-2 co-infection.
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COVID-19 , Coinfecção , Opistorquíase , Opisthorchis , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/complicações , Opistorquíase/imunologia , Opistorquíase/complicações , Coinfecção/imunologia , Coinfecção/parasitologia , Animais , Masculino , Opisthorchis/imunologia , Feminino , Estudos Transversais , SARS-CoV-2/imunologia , Adulto , Pessoa de Meia-Idade , Interferon gama/sangue , Anticorpos Neutralizantes/sangue , Imunoglobulina G/sangue , Idoso , Anticorpos Antivirais/sangue , Anticorpos Anti-Helmínticos/sangueRESUMO
Introduction: SARS-CoV-2 infection is hypothesized to be more severe in immunocompromised patients; however, clinical outcomes in children with inborn errors of immunity (IEI) during the Omicron pandemic in China have not been reported. Methods: This cohort study retrospectively reviewed 71 SARS-CoV-2-infected children with IEI using nationwide data from the National Center for Children's Health of China. COVID-19 was diagnosed by a positive rapid antigen or nucleic acid test result. Results: Among 71 SARS-CoV-2-infected children with IEI, male preponderance (male: female ratio of ~1.8:1), a median age of 8 years (IQR 3-11), and a predominance of antibody deficiency (19/71, 26.8%) were detected. Most of the patients got infected through household transmission, while a small proportion of them did so during hospital visits. The mean time periods were 3.3 days (n=44) for incubation, 8.4 days for symptoms (n=69), and 8.8 days for viral shedding (n=37). The time to viral shedding was proportional to the symptomatic period (R2 = 0.1243, p=0.0323) and prolonged in children with X- linked agammaglobulinemia. The most common symptoms of COVID-19 were fever, and some children showed only aggravation of the underlying disease. 15% of IEI children progress to pneumonia, 85% require medication, 17% are admitted to hospital, and 4.1% are classified as critical. Previously application of anti- infective medications was associated with an increased risk of hospitalization after COVID-19 infection. Of the 71 children with IEI, all recovered from COVID- 19. Conclusion: Overall, Omicron variant did not cause significant life-threatening infections among children with IEI in China, and most of them had a good clinical outcome. Nevertheless, these children exhibit an increased vulnerability to higher hospitalization rates, pneumonia, and severe illness compared to the general pediatric population.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/epidemiologia , Masculino , Feminino , China/epidemiologia , Criança , Pré-Escolar , SARS-CoV-2/imunologia , Estudos Retrospectivos , Eliminação de Partículas Virais , AdolescenteRESUMO
Introduction: During the COVID-19 pandemic, pediatric cases typically exhibit milder symptoms and lower mortality rates. However, the delay in pediatric vaccination poses major risks for children. This multicenter study aimed to comprehensively analyze demographic characteristics, clinical features, disease severity, and risk factors for ICU admission in Iran. Materials and methods: This observational study enrolled children aged 0-21 years with confirmed or probable COVID-19 diagnoses, referred from selected hospitals across 17 counties in Mazandaran province, Iran, between February 19 and August 14, 2021. Patients were categorized into mild, moderate, severe, or critical cases based on clinical and radiographic criteria. Data were extracted from medical records and analyzed using statistical methods. Logistic regression analysis was performed to identify factors associated with ICU admission and disease severity. Results: Among the 1,031 children included in the study, 61 were diagnosed with MIS-C. The distribution of patients by severity was 156 mild, 671 moderate, and 204 severe/critical cases. Age distribution significantly differed across severity groups (P < 0.001), with 55.19% aged over 5 years and 54% being male. 11.44% had underlying diseases. Fever (71.97%) was the most common symptom, followed by cough (34.43%) and dyspnea (24.83%). Within the inpatient group, 19.77% required ICU admission, with 0.91% mortality, including 3 MIS-C cases. Children with underlying diseases, gastrointestinal symptoms, and obesity had 4.16, 3.10-, and 2.17-times higher likelihood of ICU admission, respectively. Conclusion: Our study emphasized the importance of recognizing pediatric COVID-19 severity and symptoms. While fever, cough, and dyspnea prevailed, mortality rates were relatively low. However, comorbidities, obesity, and gastrointestinal symptoms linked to ICU admission, stressing early intervention. BMI also impacted disease severity and admission rate. Vaccination and targeted interventions are essential for protecting vulnerable children and easing healthcare strain.
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Background: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial for ending the pandemic of coronavirus disease 2019 (COVID-19). Currently, the cumulative effect of booster shots of mRNA vaccines on adverse events is not sufficiently characterized. Methods: A survey-based study on vaccine adverse events was conducted in a Japanese medical institute after the third dose of Pfizer BNT162b2. Adverse events were grouped using network analysis, and a heteroscedastic probit model was built to analyse adverse events. Results: There were two main clusters of adverse events, systemic and local injection site-associated events. Subject background and the experience of previous vaccine-related adverse events were variably associated with the occurrence and intensity of adverse events following the third dose. Among adverse events, only lymphadenopathy increased prominently following the third dose, while the largest increase in other systemic adverse events occurred generally following the second dose. Conclusions: The effect of repeated booster vaccines on the frequency and intensity of adverse events differs depending on the kind of adverse event.
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Background: Little is known about the impact of the COVID-19 pandemic on hepatitis C (HCV) screening efforts in carceral settings. We explored the impact of the pandemic on HCV screening in two of Quebec's largest provincial prisons. Methods: Retrospective data of HCV-related laboratory tests between July 2018 and February 2022 at l'Établissement de détention de Montréal (EDM) and l'Établissement de détention de Rivière-des-Prairies (EDRDP) were obtained. To examine the association between the pandemic and the number of HCV-antibody (HCV-Ab) tests, a three-level time period variable was created: pre-outbreak, outbreak, and post-outbreak. Negative binomial regression (with monthly admissions as an offset) was used to assess the change in HCV-Ab tests across time periods and by prisons. Adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) were calculated. Results: A total of 1,790 HCV-Ab tests were performed; 56 (3%) were positive. Among these, 44 (79%) HCV RNA tests were performed; 23 (52%) were positive. There was a significant decrease in HCV-Ab screening at EDM during the outbreak (aOR 0.29; 95% CI 0.17-0.48) and post-outbreak (aOR 0.49; 95% CI 0.35-0.69) periods, compared to the pre-outbreak period. There was no significant change in HCV-Ab screening at EDRDP during the outbreak (aOR 0.98; 95% CI 0.49-2.11) but a significant increase in HCV-Ab screening post-outbreak (aOR 1.66; 95% CI 1.04-2.72). Conclusion: The COVID-19 pandemic negatively affected HCV screening at EDM but had minimal impact at EDRDP. To eliminate HCV from carceral settings, minimizing screening interruptions during future outbreaks and combined HCV/SARS-CoV-2 screening should be prioritized.
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COVID-19 , Hepacivirus , Hepatite C , Programas de Rastreamento , Prisões , Humanos , Quebeque/epidemiologia , COVID-19/epidemiologia , COVID-19/diagnóstico , Hepatite C/epidemiologia , Hepatite C/diagnóstico , Estudos Retrospectivos , Prisões/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Masculino , Feminino , Hepacivirus/isolamento & purificação , Adulto , Pessoa de Meia-Idade , SARS-CoV-2 , PandemiasRESUMO
SARS-CoV-2 infection during pregestational and early pregnancy periods has an unclear impact on fetal development. Although vertical transmission is rare, potential effects on the developing fetal brain are plausible. However, robust evidence linking maternal SARS-CoV-2 infection to congenital anomalies is limited due to inadequate tracking of infection history and methodological flaws in published studies. This is further complicated by limitations, such as restricted testing access and undiagnosed infections, particularly in low- and middle-income countries. Most data focus on hospitalized women near term, lacking information on first- and second-trimester infections. Thus, an accurate assessment of the impact of COVID-19 on congenital anomalies is essential. It should however be emphasised that we have robust evidence that vaccination against COVID-19 before or during early pregnancy is not associated with malformations, ruling out any role of COVID-19 vaccines in these increased rates of congenital abnormalities. This viewpoint discusses findings from surveillance registries, highlights study limitations, and offers research recommendations to inform clinical guidelines and public health strategies, aiming to mitigate the effects of viral infections on early neurodevelopment.
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BACKGROUND AND OBJECTIVE: Viral respiratory infections stand as a considerable global health concern, presenting significant risks to the health of both humans and animals. This study aims to conduct a preliminary analysis of the time series of viral load in the nasal cavity-nasopharynx (NC-NP) of the human and rhesus macaque (RM). METHODS: Taking into account the random uniform distribution of virus-laden droplets with a diameter of 10 µm in the mucus layer, this study applies the computational fluid dynamics-host cell dynamics (CFD-HCD) method to 3D-shell NC-NP models of human and RM, analyzing the impact of initial distribution of droplets on the viral dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), estimating parameters in the HCD model based on experimental data, integrating them into simulations to predict the time series of viral load and cell counts, and being visualized. The reproductive number (R0) are calculated to determine the occurrence of infection. The study also considers cross-parameter combinations and cross-experimental datasets to explore potential correlations between the human and RM. RESULTS: The research findings indicate that the uniform distribution of virus-laden droplets throughout the whole NC-NP models of human and RM is reasonable for simulating and predicting viral dynamics. The visualization results offer dynamic insights into virus infection over a period of 20 days. Studies involving parameter and dataset exchanges between the two species underscore certain similarities in predicting virus infections between the human and RM. CONCLUSIONS: This study lays the groundwork for further exploration into the parallels and distinctions in respiratory virus dynamics between humans and RMs, thus aiding in making more informed decisions in research and experimentation.