Search Results (11,671)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces direct cytopathic effects, complicating the establishment of low-cytotoxicity cell culture models for studying its replication. We initially developed a DNA vector-based replicon system utilizing the CMV promoter to generate a recombinant viral genome bearing reporter genes. However, this system frequently resulted in drug resistance and cytotoxicity, impeding model establishment. Herein, we present a novel cell culture model with SARS-CoV-2 replication induced by Cre/LoxP-mediated DNA recombination. An engineered SARS-CoV-2 transcription unit was subcloned into a bacterial artificial chromosome (BAC) vector. To enhance biosafety, the viral spike protein gene was deleted, and the nucleocapsid gene was replaced with a reporter gene. An exogenous sequence was inserted within NSP1 as a modulatory cassette that is removable after Cre/LoxP-mediated DNA recombination and subsequent RNA splicing. Using the PiggyBac transposon strategy, the transcription unit was integrated into host cell chromatin, yielding a stable cell line capable of inducing recombinant SARS-CoV-2 RNA replication. The model exhibited sensitivity to the potential antivirals forsythoside A and verteporfin. An innovative inducible SARS-CoV-2 replicon cell model was introduced to further explore the replication and pathogenesis of the virus and facilitate screening and assessment of anti-SARS-CoV-2 therapeutics. Full article

Background: Respiratory syncytial virus (RSV) is an important cause of childhood hospitalizations. The aim of the study was to estimate the rates of RSV-related hospitalizations in children aged less than 5 years in Poland. Methods: This retrospective observational cohort study was based on data obtained from the National Health Fund in Poland regarding all acute respiratory tract infections and RSV-coded admissions of children (age <5 years) to public hospitals between July 2015 and June 2023. Patients were stratified based on the following age groups: 0–1 month, 2–3 months, 4–6 months, 7–12 months, 13–24 months, and 25–60 months. Results: The number of RSV-related hospitalizations increased every season, both before and through the ending phase of the coronavirus disease 2019 (COVID-19) pandemic. The COVID-19 pandemic was associated with a shift in the seasonality pattern of RSV infection. Hospitalization rates per 1000 inhabitants were the highest for children aged 0–12 months, reaching 47.3 in the 2022/23 season. Within this group, the highest hospitalization rate was observed for children aged 2–3 months—94.9 in the 2022/23 season. During the ending phase of the COVID-19 pandemic, the observed increase in admission rates was 2-, 4-, and 5-fold the pre-COVID rate for children aged <12 months, 12–24 months, and 25–60 months, respectively. Conclusions: In Poland, RSV infections cause a significant burden in hospitalized children aged less than 5 years. RSV-related hospitalizations were most frequent in children aged less than 1 year. The COVID-19 pandemic was associated with a shift in the seasonality pattern of RSV infections. After the pandemic, more RSV-related hospitalizations were observed in older children (aged 13 months and older) vs. the pre-pandemic phase. Full article

During the COVID-19 pandemic, several vaccines were developed to limit the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, due to SARS-CoV-2 mutations and uneven vaccination coverage among populations, a series of COVID-19 waves have been caused by different variants of concern (VOCs). Despite the updated vaccine formulations for the new VOC, the benefits of additional COVID-19 vaccine doses have raised many doubts, even among high-risk groups such as healthcare workers (HCWs). We examined the factors underlying hesitancy to receive COVID-19 booster vaccine doses and analysed the anti-SARS-CoV-2 IgG antibody response after booster vaccination among HCWs. Our study found that 42% of the HCWs were hesitant about the second booster dose, while 7% reported no intent to get vaccinated with any additional doses. As reasons for not vaccinating, participants most frequently highlighted lack of time, negative experiences with previous vaccinations, and immunity conferred by past infections. In addition, we found the lowest post-vaccination antibody titres among HCWs who did not receive any vaccine booster dose and the highest among HCWs vaccinated with two booster doses. Full article

Porcine epidemic diarrhea virus (PEDV) is an acute enteric coronavirus, inducing watery diarrhea and high mortality in piglets, leading to huge economic losses in global pig industry. Ivermectin (IVM), an FDA-approved antiparasitic agent, is characterized by high efficacy and wide applicability. However, the poor bioavailability limits its application. Since the virus is parasitized inside the host cells, increasing the intracellular drug uptake can improve antiviral efficacy. Hence, we aimed to develop nanostructured lipid carriers (NLCs) to enhance the antiviral efficacy of IVM. The findings first revealed the capacity of IVM to inhibit the infectivity of PEDV by reducing viral replication with a certain direct inactivation effect. The as-prepared IVM-NLCs possessed hydrodynamic diameter of 153.5 nm with a zeta potential of −31.5 mV and high encapsulation efficiency (95.72%) and drug loading (11.17%). IVM interacted with lipids and was enveloped in lipid carriers with an amorphous state. Furthermore, its encapsulation in NLCs could enhance drug internalization. Meanwhile, IVM-NLCs inhibited PEDV proliferation by up to three orders of magnitude in terms of viral RNA copies, impeding the accumulation of reactive oxygen species and mitigating the mitochondrial dysfunction caused by PEDV infection. Moreover, IVM-NLCs markedly decreased the apoptosis rate of PEDV-induced Vero cells. Hence, IVM-NLCs showed superior inhibitory effect against PEDV compared to free IVM. Together, these results implied that NLCs is an efficient delivery system for IVM to improve its antiviral efficacy against PEDV via enhanced intracellular uptake. Full article

Wastewater surveillance (WS) has been used globally as a complementary tool to monitor the spread of coronavirus disease 2019 (COVID-19) throughout the pandemic. However, a concern about the appropriateness of WS in low- and middle-income countries (LMICs) exists due to low sewer coverage and expensive viral concentration methods. In this study, influent wastewater samples (n = 63) collected from two wastewater treatment plants (WWTPs) of the Kathmandu Valley between March 2021 and February 2022 were concentrated using the economical skimmed-milk flocculation method (SMFM). The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was tested by qPCR using assays that target the nucleocapsid (N) and envelope (E) genes. Overall, 84% (53/63) of the total samples were positive for SARS-CoV-2 according to at least one of the tested assays, with concentrations ranging from 3.5 to 8.3 log₁₀ gene copies/L, indicating the effectiveness of the SMFM. No correlation was observed between the total number of COVID-19 cases and SARS-CoV-2 RNA concentrations in wastewater collected from the two WWTPs (p > 0.05). This finding cautions the prediction of future COVID-19 waves and the estimation of the number of COVID-19 cases based on wastewater concentration in settings with low sewer coverage by WWTPs. Future studies on WS in LMICs are recommended to be conducted by downscaling to sewer drainage, targeting a limited number of houses. Overall, this study supports the notion that SMFM can be an excellent economical virus-concentrating method for WS of COVID-19 in LMICs. Full article

Background: feline infectious peritonitis (FIP) is a fatal disease in cats classified as either effusive (‘wet’), non-effusive (‘dry’), or a mixture of both forms (‘mixed’). The anti-FIP therapeutic effects of Mutian and molnupiravir, two drugs with a nucleic acid analog as an active ingredient, have been confirmed recently. Methods: Of the cats with FIP, we observed a total of 122 and 56 cases that achieved remission after the administration of Mutian and molnupiravir as routine treatments, respectively. Changes in clinical indicators suggested to be correlated with FIP remission (weight, hematocrit, and albumin-to-globulin ratio) before and after the administration of each drug and during follow-up observation were statistically compared for each FIP type. Results: In all three FIP types, the administration of either Mutian or molnupiravir resulted in statistically significant increases in these indicators. Furthermore, the effect of Mutian on improving the albumin-to-globulin ratio was not observed at all in wet FIP, as compared with that of molnupiravir, but statistically significant in mixed and dry (p < 0.02 and p < 0.003, respectively). The differences in albumin-to-globulin ratio were all due to those of circulating globulin levels. Conclusions: These results indicate that slight inflammatory responses might be elicited continuously by a residual virus that persisted through molnupiravir treatments. Full article

Since the SARS-CoV-2 Omicron virus has gained dominance worldwide, its continual evolution with unpredictable mutations and patterns has revoked all authorized immunotherapeutics. Rapid viral evolution has also necessitated several rounds of vaccine updates in order to provide adequate immune protection. It remains imperative to understand how Omicron evolves into different subvariants and causes immune escape as this could help reevaluate the current intervention strategies mostly implemented in the clinics as emergency measures to counter the pandemic and, importantly, develop new solutions. Here, we provide a review focusing on the major events of Omicron viral evolution, including the features of spike mutation that lead to immune evasion against monoclonal antibody (mAb) therapy and vaccination, and suggest alternative durable options such as the ACE2-based experimental therapies superior to mAbs to address this unprecedented evolution of Omicron virus. In addition, this type of unique ACE2-based virus-trapping molecules can counter all zoonotic SARS coronaviruses, either from unknown animal hosts or from established wild-life reservoirs of SARS-CoV-2, and even seasonal alpha coronavirus NL63 that depends on human ACE2 for infection. Full article

Acute respiratory infections are a major global burden in resource-limited countries, including countries in Africa. Although COVID-19 has been well studied since the pandemic emerged in Gabon, Central Africa, less attention has been paid to other respiratory viral diseases, and very little data are available. Herein, we provide the first data on the genetic diversity and detection of 18 major respiratory viruses in Gabon during the COVID-19 pandemic. Of 582 nasopharyngeal swab specimens collected from March 2020 to July 2021, which were SARS-CoV-2 negative, 156 were positive (26%) for the following viruses: enterovirus (20.3%), human rhinovirus (HRV) (4.6%), human coronavirus OC43 (1.2%), human adenovirus (0.9%), human metapneumovirus (hMPV) (0.5%), influenza A virus (IAV) (0.3%), and human parainfluenza viruses (0.5%). To determine the genetic diversity and transmission route of the viruses, phylogenetic analyses were performed using genome sequences of the detected viruses. The IAV strain detected in this study was genetically similar to strains isolated in the USA, whereas the hMPV strain belonging to the A2b subtype formed a cluster with Kenyan strains. This study provides the first complete genomic sequences of HRV, IAV, and hMPV detected in Gabon, and provides insight into the circulation of respiratory viruses in the country. Full article

The primary targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the lungs are type I pneumocytes, macrophages, and endothelial cells. We aimed to identify lung cells targeted by SARS-CoV-2 using viral nucleocapsid protein staining and morphometric features on patients with fatal COVID-19. We conducted a retrospective analysis of fifty-one autopsy cases of individuals who tested positive for SARS-CoV-2. Demographic and clinical information were collected from forensic reports, and lung tissue was examined for microscopic lesions and the presence of specific cell types. Half of the evaluated cohort were older than 71 years, and the majority were male (74.5%). In total, 24 patients presented diffuse alveolar damage (DAD), and 50.9% had comorbidities (56.9% obesity, 33.3% hypertension, 15.7% diabetes mellitus). Immunohistochemical analysis showed a similar pattern of infected macrophages, infected type I pneumocytes, and endothelial cells, regardless of the presence of DAD (p > 0.5). The immunohistochemical reactivity score (IRS) was predominantly moderate but without significant differences between patients with and without DAD (p = 0.633 IRS for type I pneumocytes, p = 0.773 IRS for macrophage, and p = 0.737 for IRS endothelium). The nucleus/cytoplasm ratio shows lower values in patients with DAD (median: 0.29 vs. 0.35), but the difference only reaches a tendency for statistical significance (p = 0.083). Our study confirms the presence of infected macrophages, type I pneumocytes, and endothelial cells with a similar pattern in patients with and without diffuse alveolar damage. Full article

Healthcare-associated infections (HAIs) remain a significant patient safety problem that can lead to illness and death, despite the implementation of clinical bundles to prevent HAIs. Management practices can support HAI prevention, but their role in HAI performance monitoring and feedback is not well understood. To address this knowledge gap, we previously conducted semi-structured interviews with staff at 18 hospitals to examine the role of management practices around the prevention of central line-associated bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs). Interview transcripts were analyzed to identify themes related to HAI performance monitoring and feedback. The current analysis focuses on 10 higher-performing hospitals that were successful in preventing CLABSIs and CAUTIs. These institutions had robust practices including timely event analysis, leadership engagement, and multidisciplinary participation in HAI reviews. Across these sites, we found common goals including investigating HAIs without blame and identifying opportunities for improvement. Management practices such as timely analysis of HAIs, collaboration between facility leadership and multidisciplinary team members, and a focus on identifying the failure of a procedure or protocol, rather than the failure of staff members, are all approaches that can support infection prevention efforts. These management practices may be especially important as hospitals attempt to address increases in CLABSI and CAUTI rates that may have occurred during the coronavirus pandemic. Full article

This study aimed to explore the correlation between Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) concentrations and the Angiopoietin-2/Angiopoietin-1 ratio (Ang-2/Ang-1) with clinical outcomes, potentially serving as disease severity and survival biomarkers. A study at AHEPA University Hospital involved 90 Coronavirus Disease 2019 (COVID-19) adult patients, 30 hospitalized intensive care units (ICU), 30 inward units (non-ICU), and 30 asymptomatic non-hospitalized individuals as controls. Estimated endothelial dysfunction markers related to angiogenesis were measured. There was a statistically significant difference only between outpatient and hospitalized patients (non-ICU–ICU groups) for the Ang-1 and Ang-2 indices. The Ang-2/Ang-1 ratio has differed significantly among the individual patient groups. An ROC analysis was conducted to find an optimal threshold for distinguishing between (outpatients–non-ICU) and (non-ICU–ICU) groups. It was based on Youden’s index of 0.1122 and 0.3825, respectively. The Ang-1, Ang-2 levels, and Ang-2/Ang-1 ratio were analyzed as severity indicators in COVID-19 patients. The Ang-2/Ang-1 ratio demonstrated better prognostic and diagnostic utility than individual biomarker levels. Monitoring the Ang-2/Ang-1 ratio can identify COVID-19 patients at risk and assist clinicians in tailoring treatment strategies to improve outcomes. Full article

Background: Coronavirus disease 2019 (COVID-19) can lead to persistent and debilitating symptoms referred to as Post-Acute sequelae of SARS-CoV-2 infection (PASC) This broad symptomatology lasts for months after the acute infection and impacts physical and mental health and everyday functioning. In the present study, we aimed to evaluate the prevalence and predictors of long-term impairment of working ability in non-elderly people hospitalised for COVID-19. Methods: This cross-sectional study involved 322 subjects hospitalised for COVID-19 from 1 March 2020 to 31 December 2022 in the University Hospital of Bari, Apulia, Italy, enrolled at the time of their hospital discharge and followed-up at a median of 731 days since hospitalization (IQR 466–884). Subjects reporting comparable working ability and those reporting impaired working ability were compared using the Mann-Whitney test (continuous data) and Fisher’s test or Chi-Square test (categorical data). Multivariable analysis of impaired working ability was performed using a logistic regression model. Results: Among the 322 subjects who were interviewed, 184 reported comparable working ability (57.1%) and 134 reported impaired working ability (41.6%) compared to the pre-COVID-19 period. Multivariable analysis identified age at hospital admission (OR 1.02, 95% CI 0.99 to 1.04), female sex (OR 1.90, 95% CI 1.18 to 3.08), diabetes (OR 3.73, 95% CI 1.57 to 9.65), receiving oxygen during hospital stay (OR 1.76, 95% CI 1.01 to 3.06), and severe disease (OR 0.51, 95% CI 0.26 to 1.01) as independent predictors of long-term impaired working ability after being hospitalised for COVID-19. Conclusions: Our findings suggest that PASC promotes conditions that could result in decreased working ability and unemployment. These results highlight the significant impact of this syndrome on public health and the global economy, and the need to develop clinical pathways and guidelines for long-term care with specific focus on working impairment. Full article

Background: Tuberculosis has been considered a global emergency since 1993, and controlling it has become even more challenging since 2020 due to the health and social crisis resulting from the COVID-19 pandemic. This study aimed to identify the impact of the COVID-19 pandemic on tuberculosis case detection activities within primary health Care in the largest city in Brazil. Methods: This is a cross-sectional and analytical study on the provision of tuberculosis detection actions in primary healthcare units during the pandemic period. A descriptive analysis was performed for characterization, and Generalized Mixed Models were used for evaluating associations, with a Bonferroni post hoc test applied. Results: The study sample comprised 80 health units in the municipality. There was a moderate alteration level in the provision of consultations for individuals with signs and symptoms of tuberculosis in 2020 (13.8%) and in 2021 (15.1%). Statistical significance (p < 0.05) was found between the pandemic period and detection actions, with a lower alteration level in 2022. Conclusions: Tuberculosis detection activities underwent changes due to the COVID-19 pandemic, mainly in 2020, which was associated with alterations in consultation and case notification provision. Full article

Monitoring the long-term changes in antibody and cellular immunity following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is crucial for understanding immune mechanisms that prevent reinfection. In March 2023, we recruited 167 participants from the Changning District, Shanghai, China. A subset of 66 participants that were infected between November 2022 and January 2023 was selected for longitudinal follow-up. The study aimed to investigate the dynamics of the immune response, including neutralizing antibodies (NAbs), anti-spike (S)-immunoglobulin G (IgG), anti-S-IgM, and lymphocyte profiles, by analyzing peripheral blood samples collected three to seven months post infection. A gradual decrease in NAbs and IgG levels were observed from three to seven months post infection. No significant differences in NAbs and IgG titers were found across various demographics, including age, sex, occupation, and symptomatic presentation, across five follow-up assessments. Additionally, a strong correlation between NAbs and IgG levels was identified. Lymphocyte profiles showed a slight change at five months but had returned to baseline levels by seven months post infection. Notably, healthcare workers exhibited lower B-cell levels compared to police officers. Our study demonstrated that the immune response to SARS-CoV-2 infection persisted for at least seven months. Similar patterns in the dynamics of antibody responses and cellular immunity were observed throughout this period. Full article

Background: Routine vaccination coverage in Latin America and the Caribbean declined prior to and during the coronavirus pandemic. We assessed the pandemic’s impact on national coverage levels and analyzed whether financial and inequality indicators, immunization policies, and pandemic policies were associated with changes in national and regional coverage levels. Methodology: We compared first- and third-dose coverage of diphtheria–pertussis–tetanus-containing vaccine (DTPcv) with predicted coverages using time series forecast modeling for 39 LAC countries and territories. Data were from the PAHO/WHO/UNICEF Joint Reporting Form. A secondary analysis of factors hypothesized to affect coverages during the pandemic was also performed. Results: In total, 31 of 39 countries and territories (79%) had greater-than-predicted declines in DTPcv1 and DTPcv3 coverage during the pandemic, with 9 and 12 of these, respectively, falling outside the 95% confidence interval. Within-country income inequality (i.e., Gini coefficient) was associated with significant declines in DTPcv1 coverage, and cross-country income inequality was associated with declines in DTPcv1 and DTPcv3 coverages. Observed absolute and relative inequality gaps in DTPcv1 and DTPcv3 coverage between extreme country quintiles of income inequality (i.e., Q1 vs. Q5) were accentuated in 2021, as compared with the 2019 observed and 2021 predicted values. We also observed a trend between school closures and greater-than-predicted declines in DTPcv3 coverage that approached statistical significance (p = 0.06). Conclusion: The pandemic exposed vaccination inequities in LAC and significantly impacted coverage levels in many countries. New strategies are needed to reattain high coverage levels. Full article