INO-4800 represents a DNA-based vaccine encoding the spike protein of SARS-CoV-2. This phase 2 trial evaluated the immunogenicity and safety of INO-4800 as a primary vaccination series in adults. We conducted a randomized, observer-blind, placebo-controlled phase 2 trial of intradermal injection of INO-4800 in both healthy adults and elderly individuals. Eligible participants from each age group were enrolled and randomly assigned in a 3:3:2 ratio to receive two doses of INO-4800 (1.0 mg or 2.0 mg) or placebo, followed by electroporation on day 0 and day 28. The primary immunogenicity endpoints focused on determining the geometric mean titers (GMTs) of spike-binding antibodies and live SARS-CoV-2 neutralizing antibody at day 30 after the second dose. The primary endpoint for safety was the occurrence of adverse events within 30 days after vaccination. A total of 781 volunteers were recruited and screened for eligibility, with 320 eligible young adults (≥18 to <60 years old) and 320 elderly (≥60 to ≤85 years old) were randomly assigned to receive the low-dose (1.0 mg, n = 120) or high-dose (2.0 mg, n = 120) INO-4800, or placebo (n = 80). Notably, both dose groups exhibited significant increases in spike-binding antibodies at day 30 after the second dose, with GMTs of 1609.3 (95% CI: 1385.5-1869.3) for the low-dose group and 3016.7 (95% CI: 2577.4-3530.8) for the high-dose group. Additionally, both dose groups induced neutralizing antibodies against live SARS-CoV-2, with GMTs of 4.7 (95% CI: 4.2-5.3) and 6.6 (95% CI: 5.9-7.4) at day 30 after the second dose. The incidence of adverse events within 30 days after vaccination was slightly higher in the high-dose group (115 [47.9%]) than that in the low-dose group (105 [43.8%]) (p = .0060). All adverse reactions were grade 1 or 2, primarily occurring within 14 days after vaccination. No vaccine-related serious adverse events were reported. The COVID-19 DNA vaccine INO-4800 at two doses (1.0 mg or 2.0 mg) showed an acceptable safety profile and modest immunogenicity, with the high-dose slightly more immunogenic than the low-dose.Clinical Trials Registration: www.chictr.org.cn, identifier is ChiCTR2000040146.

The COVID-19 pandemic highlighted the potential of peptide-based therapies as an alternative to traditional pharmaceutical treatments for SARS-CoV-2 and its variants. Our review explores the role of therapeutic peptides in modulating immune responses, inhibiting viral entry, and disrupting replication. Despite challenges such as stability, bioavailability, and the rapid mutation of the virus, ongoing research and clinical trials show that peptide-based treatments are increasingly becoming integral to future viral outbreak responses. Advancements in computational modelling methods in combination with artificial intelligence will enable mass screening of therapeutic peptides and thereby, comprehending a peptide repurposing strategy similar to the small molecule repurposing. These findings suggest that peptide-based therapies play a critical and promising role in future pandemic preparedness and outbreak management.

The SARS-CoV-2 (COVID-19) outbreak has presented a global challenge for both rapid diagnostic tests and therapeutic drugs. In this context, the electrochemical DNA-based biosensor was designed for the investigation of DNA and Favipiravir (FAV) which was one of the drugs used in patients infected SARS-CoV-2 during the pandemic interaction by using bare and multi-walled carbon nanotube (MWCNTs) modified disposable pencil graphite electrode (PGE) for the first time. This drug and its derivatives were used extensively during the pandemic period, and the possible effects of Favipiravir on DNA have not yet been investigated in detail with electrochemical (nano) biosensor technologies. In this study, both the standard form of FAV and the tablet form were used and tested with differential pulse voltammetry (DPV) and cyclic voltammetry (CV) to compare their effects on DNA. Besides, scanning electron microscopy (SEM) was used for the characterization of the developed MWCNTs modified electrochemical DNA biosensor. It was observed that FAV interacts with DNA and causes a significant decrease in the guanine oxidation signal at about +1.00 V. The designed MWCNT-based nanobiosensor was able to detect DNA-Favipiravir drug interaction in FAV concentration as low as 0.66 μg/mL (LOD) with a linear range from 150 to 500 μg/mL. Rapid analysis due to short interaction time (nearly 32 min) was performed.

COVID-19 has become a global pandemic. However, studies examining the outcomes for pediatric patients after hospital discharge, post-COVID-19, and the predictive factors influencing their high mortality rates, are still limited, especially in Indonesia. Therefore, this study aimed to determine the predictor that predict mortality six months after hospitalization for COVID-19.

A retrospective cohort study was performed. The participants were children who were admitted to Dr. Sardjito General Hospital from February-April 2022. The inclusion criteria were pediatric patients who were hospitalized in the pediatric ward and discharged after recovering or completing isolation. COVID-19 hospitalization deaths and incomplete medical records were omitted from the study. Bivariate analysis was performed with chi-square log rank test. Kaplan-Meier method was used for calculating the cumulative survival between comparison groups of the predictor variables. Multivariate analysis was performed with a Cox regression. The relationships between the variables are presented as the Hazard ratios (HRs), confidence intervals of 95% (95%CI), and statistical significance levels, with p < 0.05.

Among the 114 patients studied, the mortality rate during the six months after COVID-19 was 29.8%. The multivariate analysis revealed that mortality was correlated with comorbidities (p < 0.021; HR 11.415; CI 95% 1.449-89.912) and obesity (p = 0.032; HR 4.617; CI 95% 1.139-18.721).

The presence of comorbidities and obesity are significant predictors of mortality in pediatric patients with COVID-19 within six months following hospital discharge.

Not applicable.

Our study aimed to investigate the prevalence and timing of ocular surface manifestations in hospitalized COVID-19 patients, providing insights into the occurrence of eye involvement before, during, or after the illness. This study contributes to understanding the extent of ocular involvement in COVID-19, which has been suggested to occur due to potential viral entry through the eyes.

451 confirmed COVID-19 patients had a history of hospitalization in Styria, Austria. The study included 176 patients aged 18-95 years who tested positive for SARS-CoV-2 in nasopharyngeal swabs by RT-PCR and received treatment at two hospitals. Telephone interviews were conducted after recovery, focusing on ocular symptoms and medical history (openMEDOCS).

Seventeen percent (n=30) reported new-onset ocular symptoms in the context of COVID-19. Patients with ocular symptoms were younger (p<0.001). Sore throat (p=0.013) and high fever (p=0.038) were significantly more prevalent in patients with new-onset ocular symptoms. Persistent ocular symptoms beyond the duration of hospitalization affected more than half (56.7%) of the participants with new-onset ocular symptoms. However, there were no differences in blood parameters, lung imaging, or comorbidities between groups with and without ocular symptoms.

In hospitalized COVID-19 patients, ocular symptoms occur with a significant prevalence of 17%. Younger age (p<0.001) and the presence of sore throat (p=0.013) are associated with an increased risk of developing new-onset ocular symptoms in the context of COVID-19.

The SARS-CoV-2 virus is continuously evolving, such that JN.1 and its subvariants, including KP.2, KP.3, and LB.1, are now predominant variants globally. JN.1 is derived from BA.2.86, which harbors more than 30 mutations in the spike protein compared with those of XBB and BA.2, and it carries an additional L455S mutation. Given the rapid evolution of these variants, assessing the neutralization capacity of current JN.1 lineage vaccines against prevalent variants, such as KP.3, is critical. Phylogenetic trees using spike protein sequences and antigenic cartography based on neutralization results reveal that JN.1 lineage variants are antigenically distant from previously circulating variants. Moreover, JN.1 subvariants showed inadequate neutralization titers compared with other variants against XBB.1.5-containing vaccine in mice. Immunization with vaccines targeting the JN.1, KP.2, KP.3, and LB.1 variants demonstrated significant neutralizing activity against predominant variants in mice. These results highlight the importance of vaccine development to keep pace with the evolution of SARS-CoV-2 variants and the need for updated vaccines targeting the JN.1 variant.

Isolation as a public health practice encompasses physical and social separation of individuals from others, and it was key in preventing human-to-human spread of the coronavirus disease 2019 (COVID-19) virus. Yet, experiences of patients in isolation have been mostly studied in the general population and qualified health professionals, excluding nursing students who were also part of the frontliners and therefore, part of the population at risk of infections.

The study explored how nursing students who tested positive for the COVID-19 virus have experienced the process of being in isolation and understanding their source of resilience.

Northeastern Namibia.

A qualitative phenomenological study was conducted. Data were collected from 14 nursing students via face-to-face and telephone interviews, while recruitment was conducted through purposive and snowballing sampling techniques. Data were analysed by interpretative phenomenological analysis.

Five themes that emerged from data analysis are the physiological spectrum, psychosocial spectrum, the value of isolation, source of resilience and coping mechanisms and the impact of isolation.

Students experienced isolation as a period of reflecting on how their symptoms commenced and progressed from minor to major. Students' sources of resilience and coping mechanisms were to remain opportunistic, learn new skills and lean on family support. Moreover, isolation negatively affected students' academic life and human connectedness.

The findings have implications in preparation for future pandemics, promoting the resilience and mental health of nursing students. Moreover, they may assist in developing a coordinated counselling and psychological support system for nursing students.

A considerable amount of research has revealed that there exists an evolutionary mismatch between ancestral environments and conditions following the rise of agriculture regarding the contact between humans and animal reservoirs of infectious diseases. Based on this evolutionary mismatch framework, we examined whether visual attention exhibits adaptive attunement toward animal targets' pathogenicity. Consistent with our predictions, faces bearing heuristic infection cues held attention to a greater extent than did animal vectors of zoonotic infectious diseases. Moreover, the results indicated that attention showed a specialized vigilance toward processing facial cues connoting the presence of infectious diseases, whereas it was allocated comparably between animal disease vectors and disease-irrelevant animals. On the other hand, the pathogen salience manipulation employed to amplify the participants' contextual-level anti-pathogen motives did not moderate the selective allocation of attentional resources. The fact that visual attention seems poorly equipped to detect and encode animals' zoonotic transmission risk supports the idea that our evolved disease avoidance mechanisms might have limited effectiveness in combating global outbreaks originating from zoonotic emerging infectious diseases.

The resurgence of influenza viruses as a significant global threat emphasizes the urgent need for innovative antiviral strategies beyond existing treatments. Here, we present the development and evaluation of a novel super-multivalent sialyllactosylated filamentous phage, termed t-6SLPhage, as a potent entry blocker for influenza A viruses. Structural variations in sialyllactosyl ligands, including linkage type, valency, net charge, and spacer length, were systematically explored to identify optimal binding characteristics against target hemagglutinins and influenza viruses. The selected SLPhage equipped with optimal ligands, exhibited exceptional inhibitory potency in in vitro infection inhibition assays. Furthermore, in vivo studies demonstrated its efficacy as both a preventive and therapeutic intervention, even when administered post-exposure at 2 days post-infection, under 4 lethal dose 50% conditions. Remarkably, co-administration with oseltamivir revealed a synergistic effect, suggesting potential combination therapies to enhance efficacy and mitigate resistance. Our findings highlight the efficacy and safety of sialylated filamentous bacteriophages as promising influenza inhibitors. Moreover, the versatility of M13 phages for surface modifications offers avenues for further engineering to enhance therapeutic and preventive performance.

Compromising between accuracy and rapidity is an important issue in analytics and diagnostics, often preventing timely and appropriate reactions to disease. This issue is particularly critical for infectious diseases, where reliable and rapid diagnosis is crucial for effective treatment and easier containment, thereby reducing economic and societal impacts. Diagnostic technologies are vital in disease modeling, tracking, treatment decision making, and epidemic containment. At the point-of-care level in modern healthcare, accurate diagnostics, especially those involving genetic-level analysis and nucleic acid amplification techniques, are still needed. However, implementing these techniques in remote or non-laboratory settings poses challenges because of the need for trained personnel and specialized equipment, as all nucleic acid-based diagnostic techniques, such as polymerase chain reaction and isothermal nucleic acid amplification, require temperature cycling or elevated and stabilized temperatures. However, in smart food packaging, there are approved and commercially available methods that use temperature regulation to enable autonomous heat generation without external sources, such as chemical heaters with phase change materials. These approaches could be applied in diagnostics, facilitating point-of-care, electricity-free molecular diagnostics, especially with nucleic acid-based detection methods such as isothermal nucleic acid amplification. In this review, we explore the potential interplay between self-heating elements, isothermal nucleic acid amplification techniques, and phase change materials. This paves the way for the development of truly portable, electricity-free, point-of-care diagnostic tools, particularly advantageous for on-site detection in resource-limited remote settings and for home use.

The ongoing COVID-19 pandemic has underscored the need for alternative prophylactic measures, particularly for populations for whom vaccines may not be effective or accessible. This study aims to evaluate the efficacy of intranasally administered IgY antibodies derived from hen egg yolks as a protective agent against SARS-CoV-2 infection in Syrian golden hamsters, a well-established animal model for COVID-19.

Hens were immunized with the spike protein of SARS-CoV-2 to generate IgY antibodies. These antibodies were extracted from the egg yolks, purified, and their neutralizing activity was tested in vitro. Syrian golden hamsters were then treated with the IgY antibodies before being challenged with SARS-CoV-2. Viral loads were quantified using droplet digital PCR (ddPCR), and lung pathology was assessed through histopathological analysis.

The in vitro assays showed that IgY effectively neutralized SARS-CoV-2. In the in vivo hamster model, IgY treatment led to a significant reduction in viral loads and a marked decrease in lung consolidation and inflammation compared to the positive control group. Histopathological findings further supported the protective role of IgY in reducing lung damage caused by SARS-CoV-2.

The results demonstrate that IgY antibodies exhibit strong antiviral activity and can significantly reduce SARS-CoV-2 viral loads and associated lung pathology in hamsters. These findings suggest that IgY could be a viable prophylactic option for preventing SARS-CoV-2 infection, particularly for individuals who cannot receive or respond to vaccines. Further studies are warranted to optimize dosage and explore the long-term efficacy of IgY antibodies.

Understanding the evolutionary patterns and geographic spread of SARS-CoV-2 variants, particularly Omicron, is essential for effective public health responses. This study focused on the genomic analysis of the Omicron variant in Cordoba, Argentina from 2021 to 2022. Phylogenetic analysis revealed the dominant presence of BA.1 and BA.2 lineages, with BA.5 emerging earlier than BA.4, aligning with observations from other regions. Haplotype network analysis showed significant genetic divergence within Omicron samples, forming distinct clusters. In comparison to global datasets, we identified mutations in the Omicron genomes (A27S, Y145D, and L212I) situated within the NTD region of the Spike protein. These mutations, while not widespread globally, showed higher prevalence in our region. Of particular interest were the Y145D and L212I substitutions, previously unreported in Argentina. In silico analysis revealed that both mutations impact the binding affinity of T-cell epitopes to HLA type I and II alleles. Notably, these alleles are among the most common in the Argentinian population, with some associated with protection against and others with susceptibility to SARS-CoV-2 infection. These findings strongly suggest that these prevalent mutations likely influence the immunogenicity of the Spike protein and contribute to immune evasion mechanisms. This study provides valuable insights into the genomic dynamics of the Omicron variant in Cordoba, Argentina and highlights unique mutations with potential implications for COVID-19 vaccines.

Identification of risk factors for severe COVID-19 can help to inform case management in resource-constrained settings. We aimed to rigorously but retroactively address data issues to identify risk factors for COVID-19 morbidity and mortality among cases seeking care in Liberia.

Chart data on confirmed cases were extracted at the national COVID-19 treatment unit. Due to the use of paper charts, assignment of non-unique identifiers and incomplete documentation, data required cleaning to remove duplicates per three sets of predefined criteria. Associations between epidemiological, clinical and demographic variables and indicators of disease severity were assessed using multivariable logistic regression.

The raw data set for patients classified between 15 March and 1 September 2020 included 2703 cases or 107% more than the 1303 cases reported by the national surveillance system during the same period. The median age of cases was found to be 38 years (IQR: 27-50); most cases were men (65%). The rates of continuous positive airway pressure (CPAP) use for breathing support and of case fatality were 5% (71/1330) and 5% (52/981), respectively. Increased odds of breathing assistance with CPAP use were associated with self-reported diabetes (aOR: 4.37; 95% CI: 1.72 to 10.4) and/or hypertension (aOR: 4.86; 95% CI: 1.81 to 12.2) and increasing age (aOR: 1.06; 95% CI: 1.04 to 1.08). Recent travel history (aOR: 5.13; 95% CI: 1.13 to 19.3) and residence outside of urban Montserrado County (aOR: 22.7; 95% CI: 8.08 to 76.4) were associated with increased odds of death.

Results from this retrospective analysis highlight self-reported non-communicable diseases as well as residence outside of largely urbanised Montserrado County as factors associated with COVID-19 severity among presenting cases in Liberia. The findings, both in terms of analytical results and data quality concerns, offer insight into how access to the highly centralised health systems and processes in Liberia may have affected populations distant from the central response in terms not only of COVID-19 disease outcomes but also care-seeking behaviour and surveillance effectiveness. This has implications for surveillance and response across priority diseases.

The COVID-19 pandemic posed a major public health challenge during its early stages, and vaccine distribution played a critical role in the initial response. This cohort study examines the socioeconomic and demographic factors influencing attitudes towards COVID-19 vaccination in Western Attica, Greece. The data was collected in two phases: In the first phase (December 2021-January 2022), 269 people who had initially refused the vaccination were surveyed. By June 2022, 207 people had agreed to be vaccinated, while 62 people remained unvaccinated, with 48 people giving reasons for their refusal. Statistical analysis showed that higher income and higher education levels significantly increased acceptance of vaccination (p=0.003 for income; p=0.001 for education), while participants with chronic conditions were also more likely to be vaccinated (p=0.024). External factors such as government-imposed fines motivated 29.47% of participants, and 26.57% were influenced by personal experiences with COVID-19. These findings emphasise the need for targeted public health interventions to reduce vaccination hesitancy among lower socioeconomic groups and focus on vulnerable populations, particularly those with chronic health conditions. The study adds to the growing body of research on vaccine hesitancy and provides evidence for policy strategies to improve immunisation coverage in underserved populations.

Bacterial coinfection in patients with SARS-CoV-2 infection is an important risk factor for death. This study investigated whether there were differences in levels of serum inflammatory markers in COVID-19 patients with bacterial coinfections compared with those without bacterial infection.

A total of 235 inpatients with SARS-CoV-2 infection admitted to Qingdao Central Hospital from December 7, 2022, to August 7, 2024, were included. Patients were divided into a bacteria-positive group (115 cases) and a bacteria-negative group (120 cases) according to whether they had bacterial coinfections. PCT, CRP, and 12 kinds of cytokines were compared between groups, and the distribution of bacterial species in the positive group was statistically analyzed.

The serum levels of CRP (Z = 8.94, p < 0.001), PCT (Z = 5.59, p < 0.001), IL-1β (t = 4.863, p < 0.001), IL-2 (t = 5.810, p < 0.001), IL-5 (t = 3.837, p < 0.001), IL-6 (t = 4.910, p < 0.001), IL-8 (t = 3.325, p < 0.001), ILIL-12p70 (t = 4.722, p < 0.001), IL-17 (t = 3.315, p = 0.001) and TNF-α (t = 4.251, p < 0.001) between the two groups were significantly different. IL-4, IL-10, IFN-α, and IFN-γ were not statistically significant (p > 0.05). Among the 115 bacteria-positive patients, 56 patients were positive for one species and 59 patients were multiple infections. Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae were common species.

Serum PCT and CRP levels in COVID-19 patients with bacterial coinfection are higher than those without bacterial infection. Cytokines such as IL-1β, IL-2, IL-5, IL-6, IL-8, IL-12p70, IL-17, and TNF-α may be involved in the progression of COVID-19 combined with bacterial infection. They can be used as potential markers to evaluate the disease condition and prognosis.

Introduction Efficient and practical healthcare based on prognostic indicators can reduce morbidity and mortality in hospitalized COVID-19 patients. Soluble urokinase plasminogen activator receptor (suPAR) predicts clinical outcomes and respiratory failure in SARS-CoV-2 patients, but additional research is needed. Among other characteristics, we aimed to evaluate the predictive value of suPAR in COVID-19 patients. Methods This observational study was conducted at the All India Institute of Medical Sciences in New Delhi between January and April 2022. Patients within the age range from 18 to 85 years with mild, moderate, or severe COVID-19 infections were included in the study. Twenty-one patients (group 1) had positive RT-PCR throat and nasal swabs. Nine patients (group 2) with fever but without COVID-19 were recruited as controls. Ninety patient samples were tested for suPAR on days 1, 5, and 10 utilizing suPARnostic AUTO Flex ELISA kits (ViroGates, Denmark). Results The median age was 59 years in both groups. COVID-19 was mild in six patients (29%), moderate in seven patients (33%), and severe in eight patients (38%). At a median follow-up of 10 days, 8 out of 21 patients (38%) in group 1 died, while none in group 2 died. Patients' median suPAR levels were 4.35 ng/ml on day 1, 4.68 ng/ml on day 5, and 4.37 ng/ml on day 10. In the control group, suPAR levels were 1.6 ng/ml on day 1, 1.7 ng/ml on day 5, and 2.02 ng/ml on day 10. The suPAR levels were statistically significant on day 1 (p = 0.004), day 5 (p = 0.04), and day 10 (p = 0.007) between the patient and the control groups. Conclusion Patients who died had higher suPAR levels on days 1 (p = 0.007), 5 (p = 0.01), and 10 (p = 0.03) than survivors. The suPAR cut-off ≥ 3.64 (AUC = 0.82) predicts mortality with 88% sensitivity and 73% specificity.

The restrictions during the COVID-19 pandemic, along with people's avoidance of hospital exposure, led to a reduction in medical consultations and delays in care seeking. Numerous reports have shown a decrease in the number of appendectomies performed and an increased incidence of complicated appendicitis during the pandemic. We aimed to investigate these findings during and after the cessation of COVID-19-related restrictions.

This retrospective cohort study was conducted in a single centre, including consecutive adult patients who underwent appendectomy for acute appendicitis during three different periods: the pandemic cohort (7 March-30 June 2020), the post-pandemic cohort (7 March-30 June 2022) and the pre-pandemic control cohort (7 March-30 June 2019). A total of 103 patients were included and divided into the three cohorts. The patients' demographics, clinical presentation, investigations, and operative data were compared.

The three groups did not differ significantly regarding demographics, clinical characteristics, or the number of appendectomies. However, a duration of symptoms at presentation of less than 2 days was significantly more frequent in the pre-pandemic and post-pandemic groups than the pandemic group (p = 0.001). The interval between admission and operation was significantly shorter in the post-pandemic group than in the pandemic group. The pandemic group also showed a higher incidence of complicated appendicitis compared to the others (p = 0.025).

The termination of the COVID-19 pandemic and its related restrictions promoted the earlier presentation of acute appendicitis cases and lowered the incidence of complicated appendicitis. This emphasises the impact of the COVID-19 pandemic on acute appendicitis.

Codon bias analysis of SARS-CoV-2 reveals suboptimal adaptation for translation in human cells it infects. The detailed examination of the codons preferentially used by SARS-CoV-2 shows a strong preference for LysAAA, GlnCAA, GluGAA, and ArgAGA, which are infrequently used in human genes. In the absence of an adapted tRNA pool, efficient decoding of these codons requires a 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2) modification at the U34 wobble position of the corresponding tRNAs (tLysUUU; tGlnUUG; tGluUUC; tArgUCU). The optimal translation of SARS-CoV-2 open reading frames (ORFs) may therefore require several adjustments to the host's translation machinery, enabling the highly biased viral genome to achieve a more favorable "Ready-to-Translate" state in human cells. Experimental approaches based on LC-MS/MS quantification of tRNA modifications and on alteration of enzymatic tRNA modification pathways provide strong evidence to support the hypothesis that SARS-CoV-2 induces U34 tRNA modifications and relies on these modifications for its lifecycle. The conclusions emphasize the need for future studies on the evolution of SARS-CoV-2 codon bias and its ability to alter the host tRNA pool through the manipulation of RNA modifications.

To assess the changes in maternal-fetal outcomes in a nonepidemic designated hospital during the COVID-19 pandemic.

This retrospective cohort study was conducted between January 1, 2019, and December 31, 2021 on pregnant patients. The fixed-effects regression model was used to determine changes in birth outcomes and pregnancy-related complications between three periods with the pre-epidemic cohort as the control group. Logistic regression was applied to determine the odds ratio (OR) for binary outcomes.

There were 15,261 births during the pre-epidemic period, and this number decreased by 15% and 23% to 12,980 and 11,736 in the first and second epidemic cohorts, respectively. The mean birth weight during the pre-epidemic period was 3319 which decreased to 3309 and 3272 g in the following periods. Excluding stillbirth and preterm, all other outcomes differed significantly between the three periods. Gestational diabetes mellitus (GDM) (17-19%) and maternal hypertension (9.2-11%) appeared to increase. Compared to the pre-epidemic period, the odds of macrosomia and LGA significantly decreased in the second epidemic cohort (adjusted ORs: 0.76 and 0.8), while the odds of low birth weight (LBW) and small gestation age (SGA) increased (ORs: 1.25 and 1.16). The odds of neonatal asphyxia (OR: 1.4), and hypertension (OR: 1.29) appeared to increase in the second epidemic cohort, while GDM decreased in the first cohort (OR: 0.88) and increased in the second cohort (OR: 1.15). Vaginal delivery underwent a marginal decrease in both the first and second epidemic cohorts (ORs: 0.89 and 0.92).

The COVID-19 pandemic may have had a substantial and long-term impact on non-infected pregnant women and newborns. Our research results provided precious research information and clinical experience summary for population health research in the future.

Our cohort study aimed to investigate the dynamic changes of lymphocyte subsets and their abilities to predict disease severity and prognosis in primary infection and unvaccinated COVID-19 patients.

A total of 773 cases, including 718 primary infection and unvaccinated COVID-19 patients and 55 controls. COVID-19 patients were assigned to severe and nonsevere groups according to disease severity, as well as survival and death groups according to prognosis. Serum samples were collected to measure the numbers of total lymphocytes and lymphocyte subsets. The differences among different severity groups were analyzed. Spearman correlation was performed to assess associations between lymphocyte subsets and disease severity and prognosis. Meanwhile, receiver operating characteristic (ROC) curves were also analyzed to find optimal cutoff points.

At admission, the severe group demonstrated significantly lower total lymphocyte counts and percentages, CD3+ and CD3+CD4+ T cell counts and percentages, CD3+CD8+ T cell counts, CD19+ B cell counts and CD56+ NK cell counts and percentages than the nonsevere group. Meanwhile, compared with the survival group, the death group also had lower total lymphocyte counts and percentages, CD3+, CD3+CD4+ and CD3+CD8+ T cell counts. Additionally, differences in these parameters were also noticed within four weeks after admission. Furthermore, Spearman analysis reported that disease severity was negatively correlated with lymphocyte counts and percentages, CD3+, CD3+CD4+ and CD3+CD8+ T cell counts, CD3+ and CD3+CD4+ T cell percentages (r=-0.166, -0.179, -0.173, -0.186, -0.127, -0.117, -0.149, respectively)(all P<0.05). The prognosis of death was also negatively correlated with total lymphocyte counts and percentages, CD3+, CD3+CD4+ and CD3+CD8+ T cell counts (r=-0.125, -0.121, -0.123, -0.123, -0.091, respectively)(all P<0.05).

In primary infection and unvaccinated COVID-19 patients total lymphocytes and T cell, B cell and NK cell subsets at COVID-19 onset play valuable roles in predicting disease severity and prognosis.

Chinese Clinical Trial Register ChiCTR2000034563.

The purpose of this study was to identify independent risk factors affecting patient survival and explore predictors of severe cases of coronavirus disease 2019 (COVID-19).

We conducted a retrospective, observational, case-control study on adult patients with severe COVID-19 who were admitted to affiliated hospitals in Tianjin between December 18, 2022, and January 31, 2023. We used univariate and multifactorial logistic regression analyses to analyze demographic indicators, comorbidity profiles, and laboratory parameters in two groups of patients (deceased and surviving) to identify independent risk factors for death in patients with severe COVID-19.

Patients in the deceased group were older than those in the survival group (p = 0.018), and there were more cases of coexisting respiratory insufficiency in the deceased group (p = 0.002). Additionally, laboratory test results for white blood cell count (WBC) and creatine kinase (CK) showed significantly higher values in the deceased group (p = 0.047 and p = 0.029, respectively), while arterial oxygen partial pressure (PAO2) showed significantly lower values compared to the survival group (p = 0.021). Age, respiratory insufficiency, WBCH (highest WBC value), CKH (highest CK value), and PAO2F (first PAO2 value) had area under curve (AUC) values of 0.698, 0.838, 0.721, 0.744, and 0.633, respectively.

The main risk factors for mortality in patients with severe COVID-19 that we identified in this study were the advanced age of patients, coexisting respiratory insufficiency, elevated levels of WBC and CK, and decreased levels of PAO2. Elevated WBC and CK laboratory parameters, in particular, demonstrated good predictive value for in-hospital mortality risk.

Stringent public health and social measures against COVID-19 infection were implemented to avoid an overwhelming hospital caseload and excessive number of deaths, especially among elderly people. We analyzed population-level immunity and predicted mortality, calculated as the potential number of deaths on a given calendar date in Japan, to develop a science-based exit strategy from stringent control measures.

Immune proportions were inferred by age group using vaccination coverage data and the estimated number of naturally infected individuals. Immunity against symptomatic illness and death were estimated separately, allowing for inference of the immune fraction that was protected against either COVID-19-related symptomatic infection or death. By multiplying the infection fatality risk by age group for the immune fraction, the potential number of deaths was obtained.

Accounting for a second and third dose of messenger RNA vaccine in the present-day population, approximately 155,000 potential deaths would be expected among people aged ≥ 60 years if all individuals were infected at the very end of 2022. A fourth dose (i.e., second booster) with a coverage identical to that of the third dose could reduce mortality by 60%. In all examined settings, the largest number of deaths occurred among people aged 80 years and older.

Our estimates can help policymakers understand the mortality impact of the COVID-19 epidemic in a quantitative manner and the critical importance of timely immunization so as to assist in decision making.

Generating drug candidates with desired protein-ligand interactions is a significant challenge in structure-based drug design. In this study, a new generative model, IEV2Mol, is proposed that incorporates interaction energy vectors (IEVs) between proteins and ligands obtained from docking simulations, which quantitatively capture the strength of each interaction type, such as hydrogen bonds, electrostatic interactions, and van der Waals forces. By integrating this IEV into an end-to-end variational autoencoder (VAE) framework that learns the chemical space from SMILES and minimizes the reconstruction error of the SMILES, the model can more accurately generate compounds with the desired interactions. To evaluate the effectiveness of IEV2Mol, we performed benchmark comparisons with randomly selected compounds, unconstrained VAE models (JT-VAE), and compounds generated by RNN models based on interaction fingerprints (IFP-RNN). The results show that the compounds generated by IEV2Mol retain a significantly greater percentage of the binding mode of the query structure than those of the other methods. Furthermore, IEV2Mol was able to generate compounds with interactions similar to those of the input compounds, regardless of structural similarity. The source code and trained models for IEV2Mol, JT-VAE, and IFP-RNN designed for generating compounds active against the DRD2, AA2AR, and AKT1, as well as the data sets (DM-QP-1M, active compounds to each protein, and ChEMBL33) utilized in this study, are released under the MIT License and available at https://github.com/sekijima-lab/IEV2Mol.

Co-infection with diverse bacteria is commonly seen in patients infected with the novel coronavirus, SARS-CoV-2. This type of co-infection significantly impacts the occurrence and development of novel coronavirus infection. Bacterial co-pathogens are typically identified in the respiratory system and blood culture, which complicates the diagnosis, treatment, and prognosis of COVID-19, and even exacerbates the severity of disease symptoms and increases mortality rates. However, the status and impact of bacterial co-infections during the COVID-19 pandemic have not been properly studied. Recently, the amount of literature on the co-infection of SARS-CoV-2 and bacteria has gradually increased, enabling a comprehensive discussion on this type of co-infection. In this study, we focus on bacterial infections in the respiratory system and blood of patients with COVID-19 because these infection types significantly affect the severity and mortality of COVID-19. Furthermore, the progression of COVID-19 has markedly elevated the antimicrobial resistance among specific bacteria, such as Klebsiella pneumoniae, in clinical settings including intensive care units (ICUs). Grasping these resistance patterns is pivotal for the optimal utilization and stewardship of antibiotics, including fluoroquinolones. Our study offers insights into these aspects and serves as a fundamental basis for devising effective therapeutic strategies. We primarily sourced our articles from PubMed, ScienceDirect, Scopus, and Google Scholar. We queried these databases using specific search terms related to COVID-19 and its co-infections with bacteria or fungi, and selectively chose relevant articles for inclusion in our review.

Coronaviruses (CoV) are highly pathogenic single-strand RNA viruses. CoV infections cause fatal respiratory symptoms and lung injuries in humans and significant economic losses in livestock. Since the SARS-2 outbreak in 2019, the highly conserved main protease (Mpro), also termed 3-chymotrypsin-like protease (3CLpro), has been considered an attractive drug target for treating CoV infections. Mpro mediates the proteolytic cleavage of eleven sites in viral polypeptides necessary for virus replication. Here, we report that disulfiram, an FDA-approved drug for alcoholic treatment, exhibits a broad-spectrum inhibitory effect on CoV Mpros. Analytical ultracentrifugation and circular dichroism analyses indicated that disulfiram treatment blocks the dimeric formation of SARS and PEDV Mpros and decreases the thermostability of SARS, SARS-2, and PEDV Mpros, whereas it facilitates the dimerization and stability of MERS Mpro. Furthermore, mass spectrometry and structural alignment revealed that disulfiram targets the Cys44 residue of Mpros, which is located at the substrate entrance and close to the catalytic His41. In addition, molecular docking analysis suggests that disulfiram conjugation interferes with substrate entry to the catalytic center. In agreement, mutation of Cys44 modulates the disulfiram sensitivity of CoV Mpros. Our study suggests a broad-spectrum inhibitory function of disulfiram against CoV Mpros.

Increased circulating tissue inhibitor of metalloproteinases-1 (TIMP-1) levels have been observed in patients with acute lung injury (ALI). However, the sex-specific regulation of TIMP-1 and the underlying molecular mechanisms have not been well elucidated. In this study, we found that plasma TIMP-1 levels were significantly higher in COVID-19 and H1N1 patients compared with those in healthy subjects (n = 25). TIMP-1 concentrations were significantly different between males and females in each disease group. Among female but not male patients, TIMP-1 levels significantly correlated with the PaO2/FiO2 ratio and hospital length of stay. Using the mouse model of ALI induced by the H1N1 virus, we found that TIMP-1 is strikingly induced in PDGFRα-positive cells in the murine lungs. Moreover, female mice showed a higher Timp-1 expression in the lungs on day 3 postinfection. Mechanistically, we observed that estrogen can upregulate TIMP-1 expression in lung fibroblasts, not epithelial cells. In addition, overexpression of estrogen receptor α (ERα) increased the TIMP-1 promoter activity. In summary, TIMP-1 is an estrogen-responsive gene, and its promoter activity is regulated by ERα. Circulating TIMP-1 may serve as a sex-specific marker, reflecting the severity and worst outcomes in female patients with SARS-CoV2- and IAV-related ALI.

Coronaviruses constitute a significant threat to the human population. Severe acute respiratory syndrome coronavirus-2, SARS-CoV-2, is a highly pathogenic human coronavirus that has caused the coronavirus disease 2019 (COVID-19) pandemic. It has led to a global viral outbreak with an exceptional spread and a high death toll, highlighting the need for effective antiviral strategies. 3-Chymotrypsin-like protease (3CLpro), the main protease in SARS-CoV-2, plays an indispensable role in the SARS-CoV-2 viral life cycle by cleaving the viral polyprotein to produce 11 individual non-structural proteins necessary for viral replication. 3CLpro is one of two proteases that function to produce new viral particles. It is a highly conserved cysteine protease with identical structural folds in all known human coronaviruses. Inhibitors binding with high affinity to 3CLpro will prevent the cleavage of viral polyproteins, thus impeding viral replication. Multiple strategies have been implemented to screen for inhibitors against 3CLpro, including peptide-like and small molecule inhibitors that covalently and non-covalently bind the active site, respectively. In addition, allosteric sites of 3CLpro have been identified to screen for small molecules that could make non-competitive inhibitors of 3CLpro. In essence, this review serves as a comprehensive guide to understanding the structural intricacies and functional dynamics of 3CLpro, emphasizing key findings that elucidate its role as the main protease of SARS-CoV-2. Notably, the review is a critical resource in recognizing the advancements in identifying and developing 3CLpro inhibitors as effective antiviral strategies against COVID-19, some of which are already approved for clinical use in COVID-19 patients.

The Coronavirus disease-2019 (COVID-19) vaccines were rolled out in many countries; however, sub-optimal COVID-19 vaccine uptake remains a major public health concern globally. This study aimed at assessing the factors that affected the uptake, hesitancy, and resistance of the COVID-19 vaccine among university undergraduate students in Malawi, a least developed country in Africa.

A descriptive cross-sectional study design was conducted using an online semi-structured questionnaire. A total of 343 University undergraduate students in Blantyre participated in this study after obtaining ethical clearance. Data was exported from Survey Monkey to Microsoft Excel version-21 for cleaning and was analysed using SPSS version-29. Descriptive statistics, including percentages, were performed to define the sample characteristics. Pearson Chi-square and Fisher's exact test were performed to identify significant relationships between vaccine uptake and demographics. A 95% confidence interval was set, and a p-value of < 0.05 was considered statistically significant.

Of the 343 participants, 43% were vaccinated. Among the vaccinated, the majority (47.3%, n = 69/146) received Johnson & Johnson vaccine followed by AstraZeneca (46.6%, n = 68/146). The commonly reported reason for vaccine acceptance was 'to protect me against getting COVID-19' (49%); whereas vaccine hesitancy was attributed to 'lack of knowledge (34%), and concerns about vaccine safety (25%).

This study found that adequate knowledge about benefits and safety of COVID-19 vaccine could potentially increase uptake. Lack of credible information or misinformation contributed to vaccine hesitancy. The findings provide insights for design of strategies to increase future vaccine uptake and reduce determinants of vaccine hesitancy. To reduce vaccination hesitancy in any population with or without higher education, we recommend that institutions entrusted with vaccine management must optimise health messaging, and reduce mis-information and dis-information.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new emerging coronavirus that caused coronavirus disease 2019 (COVID-19). Whole-genome tracking of SARS-CoV-2 enhanced our understanding of the mechanism of the disease, control, and prevention of COVID-19.

we analyzed 3368 SARS-CoV-2 protein sequences from Iran and compared them with 15.6 million global sequences in the GISAID database, using the Wuhan-Hu-1 strain as a reference.

Our investigation revealed that NSP12-P323L, ORF9c-G50N, NSP14-I42V, membrane-A63T, Q19E, and NSP3-G489S were found to be the most frequent mutations among Iranian SARS-CoV-2 sequences. Furthermore, it was observed that more than 94% of the SARS-CoV-2 genome, including NSP7, NSP8, NSP9, NSP10, NSP11, and ORF8, had no mutations when compared to the Wuhan-Hu-1 strain. Finally, our data indicated that the ORF3a-T24I, NSP3-G489S, NSP5-P132H, NSP14-I42V, envelope-T9I, nucleocapsid-D3L, membrane-Q19E, and membrane-A63T mutations might be responsible factors for the surge in the SARS-CoV-2 Omicron variant wave in Iran.

real-time genomic surveillance is crucial for detecting new SARS-CoV-2 variants, updating diagnostic tools, designing vaccines, and understanding adaptation to new environments.

This alteration in the policy of COVID-19 resulted in widespread infections throughout China. Most people only need some antiviral drugs such as lopinavir/ritonavir or Chinese herbal preparations for treatment. In this context, the lack of drug knowledge and inadequate drug availability are evident. This study aims to explore the factors influencing drug use and demand during the COVID-19 epidemic.

This study used quota sampling based on gender, age, and place of residence to perform a cross-sectional survey on a sample of 771 adults. The researchers used chi-square tests to understand differences in drug use and demand across characteristics, and binary logistic regression to analyse the influencing factors.

The study revealed that 85.9% of the participants used drugs following the COVID-19 infection. Participants with college and above, (OR=2.49, 95% CI=1.27-4.88) annual personal income between 30,000 and 80,000CNY (OR=2.19, 95% CI=1.35-3.55) and over 80,000CNY (OR=1.96, 95% CI=1.05-3.66) were more knowledgeable about using drugs. Gender, (OR=0.69, 95% CI=0.50-0.95) age, (OR=2.11, 95% CI=1.15-3.88) residence, (OR=1.58, 95% CI=1.06-2.37) chronic disease conditions (OR=0.46, 95% CI=0.27-0.78) and infection symptoms (OR=0.60, 95% CI=0.38-0.93) as factors influencing the need for drug delivery services. (P<0.05).

Research has revealed that a significant proportion of infected people in China chose drug treatment during COVID-19. Individuals with severe symptoms use more medication and require more drug delivery and storage. Low-education and low-income populations are lacking in drug knowledge, and older adults with underlying medical conditions are more likely to need drug delivery services. Therefore, governments should prioritize vulnerable groups when formulating drug policies and target drug literacy and guidance. In addition, it is recommended that a drug distribution system be set up within the community so that those in need can have quick and easy access to drugs.

SARS-CoV-2 continues to evolve and circulate globally. In recent weeks, variants such as KP.2 and KP.3 have been rapidly increasing in many countries. Prevention strategies such as receiving updated COVID-19 vaccines, wearing masks when recommended, washing hands frequently, getting tested if symptoms appear, and staying home when sick can help protect individuals and others from COVID-19.

To find drugs against COVID-19, caused by the SARS-CoV-2, promising targets include the fusion of the viral spike with the human angiotensin-converting enzyme 2 (ACE2) as well as the main protease (Mpro). These proteins are responsible for viral entry and replication, respectively. We combined several state-of-the-art computational methods, including, protein-ligand interaction fingerprint, 3D-pharmacophores, molecular-docking, MM-GBSA, DFT, and MD simulations to explore two databases: ChEMBL and NANPDB to identify molecules that could both block spike/ACE2 fusion and inhibit Mpro. A total of 1,690,649 compounds from the two databases were screened using the pharmacophore model obtained from PLIF analysis. Five recent complexes of Mpro co-crystallized with different ligands were used to generate the pharmacophore model, allowing 4,829 compounds that passed this prefilter. These were then submitted to molecular docking against Mpro. The 5% top-ranked docking hits from docking result having scores < -8.32 kcal mol-1 were selected and then docked against spike/ACE2. Only four compounds: ChEMBL244958, ChEMBL266531, ChEMBL3680003, and 1-methoxy-3-indolymethyl glucosinolate (4) displayed binding energies < - 8.21 kcal mol-1 (for the native ligand) were considered as putative dual-target inhibitors. Furthermore, predictive ADMET, MM-GBSA and DFT/6-311G(d,p) were performed on these compounds and compared with those of well-known antivirals. DFT calculations showed that ChEMBL244958 and compound 4 had significant predicted reactivity values. Molecular dynamics simulations of the docked complexes were run for 100 ns and used to validate the stability docked poses and to confirm that these hits are putative dual binders of the spike/ACE2 and the Mpro.

Severe Acute Respiratory Syndrome caused by a coronavirus is a recent viral infection. There is no scientific evidence or clinical trials to indicate that possible therapies have demonstrated results in suspected or confirmed patients. This work aims to perform a virtual screening of 1430 ligands through molecular docking and to evaluate the possible inhibitory capacity of these drugs about the Mpro protease of Covid-19. The selected drugs were registered with the FDA and available in the virtual drug library, widely used by the population. The simulation was performed using the MolAiCalD algorithm, with a Lamarckian genetic model (GA) combined with energy estimation based on rigid and flexible conformation grids. In addition, molecular dynamics studies were also performed to verify the stability of the receptor-ligand complexes formed through analyses of RMSD, RMSF, H-Bond, SASA, and MMGBSA. Compared to the binding energy of the synthetic redocking coupling (-6.8 kcal/mol/RMSD of 1.34 Å), which was considerably higher, it was then decided to analyze the parameters of only three ligands: ergotamine (-9.9 kcal/mol/RMSD of 2.0 Å), dihydroergotamine (-9.8 kcal/mol/RMSD of 1.46 Å) and olysio (-9.5 kcal/mol/RMSD of 1.5 Å). It can be stated that ergotamine showed the best interactions with the Mpro protease of Covid-19 in the in silico study, showing itself as a promising candidate for treating Covid-19.

The COVID-19 pandemic initiated public interest in wastewater-based epidemiology (WBE). Public and private entities responded to the need to produce timely and accurate data. LuminUltra and Hach partnered to provide a rapid, field-based quantitative polymerase chain reaction (qPCR) test for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in wastewater. This study evaluates the Hach GeneCount SARS-CoV-2 Wastewater RT-qPCR Assay Kit and LuminUltra GeneCount® Q-16 RT-PCR instrument. The Hach LuminUltra methods were compared to the Promega Wizard® Enviro Total Nucleic Acid kit and Bio-Rad CFX Opus 96 Real-time PCR Detection System. Over a 12-week period, wastewater samples were collected weekly from seven locations in the Roanoke/Salem, VA sewersheds. Concentration and extraction of the viral RNA were followed by qPCR analysis. The target gene for detection was the nucleocapsid gene (N1) of the SARS-CoV-2 virus. Costs, ease of use, time to produce results, sample preparation, and data comparisons were considered. The comparison determined that the Hach LuminUltra method and instrument were more affordable, consumed less time, and required less technical expertise. While the new method was specific, it had low sensitivity. This evaluation suggests the Hach LuminUltra method should be reserved for limited situations requiring onsite field analysis where data accuracy is not essential.

Psychological distress, as a key indicator, describes a person's emotional problems and psychological reactions to adapt to the environment. This study aimed to investigate the relationship between psychological distress and coping strategies used by individuals during the crisis caused by COVID-19.

The current research is an analytical cross-sectional study that was designed in 2021. The sampling area included the three cities of Lar, Gerash, and Evaz in the south of Fars province in the south of Iran. The study population was the residents of these three cities during the COVID-19 pandemic. The final sample size in the present study was 384 people. Individuals were selected through available sampling. By answering questions from the self-assessment system of COVID-19 disease, the Ministry of Health and Medical Education filled out the necessary information for individual screening and registration of the symptoms of COVID-19 disease. Then, they completed the Coping Methods Questionnaire and the Psychological Distress Questionnaire.

The mean age of the participants was 40.90 years. One hundred sixty-seven (43.5%) participants were male, and 217 (56.5%) were female. The mean score of problem-oriented coping style was significantly different between the levels of education (P = 0.001). The mean score of problem-solving coping style for the participants suspected of being infected with COVID-19 was 6.18 scores lower than others, and the difference was statistically significant (P = 0.001). Multiple regression with a forward selection also showed that among the studied variables, age, problem-oriented, and emotion-oriented coping strategies were important variables affecting mental distress.

People who were not suspected of having COVID-19 symptoms had a higher mean problem-oriented coping score than those who were suspected of having COVID-19. Therefore, early identification of suspects and the implementation of counseling and training programs can be very effective.

At present, COVID-19 remains a public health concern due to the ongoing evolution of SARS-CoV-2 and its prevalence in particular countries. This paper provides an updated overview of the epidemiology and pathogenesis of COVID-19, with a focus on the emergence of SARS-CoV-2 variants and the phenomenon known as 'long COVID'. Meanwhile, diagnostic and detection advances will be mentioned. Though many inventions have been made to combat the COVID-19 pandemic, some outstanding ones include multiplex RT-PCR, which can be used for accurate diagnosis of SARS-CoV-2 infection. ELISA-based antigen tests also appear to be potential diagnostic tools to be available in the future. This paper also discusses current treatments, vaccination strategies, as well as emerging cell-based therapies for SARS-CoV-2 infection. The ongoing evolution of SARS-CoV-2 underscores the necessity for us to continuously update scientific understanding and treatments for it.