It has been five years since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and we are also approaching the five-year mark of the COVID-19 pandemic. The vaccine is a significant weapon in combating infectious diseases like SARS-CoV-2. Several vaccines were developed against SARS-CoV-2, and they demonstrated efficacy and safety during these five years. The rapid development of multiple next-generation vaccine candidates in different platforms with very little time is the success story of the vaccine development endeavor. This remarkable success of rapid vaccine development is a new paradigm for fast vaccine development that might help develop infectious diseases and fight against the pandemic. With the completion of five years since the beginning of SARS-CoV-2 origin, we are looking back on the five years and reviewing the milestones, vaccine platforms, animal models, clinical trials, successful collaborations, vaccine safety, real-world effectiveness, and challenges. Lessons learned during these five years will help us respond to public health emergencies and to fight the battle against future pandemics.

IntroductionThe COVID-19 pandemic led to nationwide stay at home orders, leading to delays in medical care. We sought to identify if the severity of appendicitis changed during the pandemic due to these delays and if there were differences in appendicitis severity in patients with simultaneous COVID-19 infection. We hypothesized that pandemic-related restrictions led to more severe cases of appendicitis.MethodsWe performed a retrospective study (4/2018-4/2022) of all patients ≥ 5y with appendicitis. Patients with a malignant appendiceal specimen were excluded. Clinical outcomes and characteristics were compared in those with appendicitis prior to the COVID-19 (PC) era to those in the COVID-19 (C) era, as well as between COVID-19 positive (C+) and negative (C-) individuals. Univariate analyses were conducted. A P-value <0.05 was considered to be statistically significant.ResultsA total of 1665 patients met inclusion criteria, 806 (48.4%) in PC era, and 859 (51.6%) in C era. Age and gender did not differ from PC era to C era, nor did they differ from the C- group to the C+ group. The C era had significantly higher 30-day readmissions than the PC era (C 6.29% (n = 54) v. PC 2.73% (n = 22), P = 0.001). The C era also had more greater than 30-day readmissions than the PC era (C 3.26% (n = 28) v. PC 1.74% (n = 14), P = 0.048). There was no significant difference in the reason for 30-day or greater than 30-day readmissions for the PC vs C eras. Of the C era, 833 (97.0%) were C- and 26 (3.0%) were C+. Rates of nonoperative management at index admission were not different between groups. The white blood cell (WBC) count was significantly lower in C+, 11.9 (8.55-13.35 IQR), vs C- group, 12.85 (9.9-15.3 IQR), P = 0.0336. There was no significant difference in the severity of appendicitis nor readmission status in C+ vs C- groups during the C era.ConclusionOur data indicates that the PC era had more severe cases of appendicitis as shown by higher rates of perforated and gangrenous appendicitis on pathology reports compared to the C era. Interestingly, readmissions were more prevalent in the C era as opposed to the PC era, which coincided with an increase in complications requiring readmission following laparoscopic appendectomies. In evaluating appendicitis patients according to COVID-19 status, we saw no significant differences in the severity of appendicitis in C- and C+ individuals.

In the biomedical field, translational science is the process of applying basic scientific knowledge to advance clinical research through the creation of new drugs, devices, medical procedures, preventive measures, and diagnostic kits. The Covid-19 pandemic exposed a shortage of professionals trained in translational research, essential for responding to global demands. To drive advancements, researchers must overcome the 'valley of death', a critical phase in clinical investigation. In response, CEVAP at São Paulo State University (UNESP), Botucatu, Brazil, has developed a strong 'knowledge industry' centered on Translational Science. As part of its research and innovation efforts, CEVAP has developed two biopharmaceuticals, the fibrin sealant and the apilic antivenom, which are currently in the final stage of development. In 2024, CEVAP began the first Brazilian Contract Development and Manufacturing Organization (CDMO) for developing and producing validated and qualified pilot-scale batches to generate clinical trial material.

The implementation of the optional undergraduate course in Translational Science marks a crucial step in strengthening the 'knowledge industry'. The program, developed in collaboration with São Paulo's three public universities (USP, UNESP, and UNICAMP), also involves an international partnership with the University of Oxford's Department of Pediatrics and the Oxford Research Group LATAM. The successful launch of this course underscores its importance in interdisciplinary education and institutional collaboration. By bridging gaps between research and application, the program equips professionals to meet the growing demand for expertise in translational science. Given the project's success, it will transition into a one-year 'Qualification in Translational Science', available to students enrolled in São Paulo state universities.

The preparation of these professionals will be strategic for transforming basic research into products for health, saving lives, and combating future pandemics that will emerge around the world.

The JAK family, particularly JAK3, plays a crucial role in immune signaling and inflammatory responses. Dysregulated JAK3 activation in SARS-CoV-2 infections has been associated with severe inflammation and respiratory complications, making JAK inhibitors a viable therapeutic option. However, their use raises concerns regarding immunosuppression, which could increase susceptibility to secondary infections. While long-term adverse effects are less of a concern in acute COVID-19 treatment, patient selection and monitoring remain critical. Furthermore, adverse effects associated with oral JAK3 inhibitors necessitate the exploration of alternative strategies to optimize therapeutic efficacy while minimizing risks. This review highlights the role of JAK3 in immune and epithelial cells, examines the adverse effects of oral JAK3 inhibitors in COVID-19 and other treatments, and discusses alternative therapeutic strategies for improving patient outcomes.

Emergency medical technicians (EMTs), positioned at the forefront of medical services, are at greater risk of contracting COVID-19 and passing it on to their families and communities than others. Recognizing the risks associated with this disease can play a crucial role in the care and prevention process. Consequently, this study evaluated the level of risk perception (RP) regarding COVID-19 among EMTs and compared it between those who have contracted the disease and those who have not.

This was a cross-sectional descriptive-analytical study conducted in 2021. This study employed simple random sampling to select 200 EMTs affiliated with Birjand University of Medical Sciences. The sample included 100 EMTs who had contracted COVID-19 and 100 who had not. Data were collected through a researcher-designed questionnaire, distributed online via WhatsApp and Telegram groups among the participants. The data were analyzed using SPSS version 16, utilizing descriptive statistical methods (frequency, mean, and standard deviation) along with inferential statistical tests such as independent t-tests, chi-square, and two-way analysis of variance (ANOVA).

The infected EMTs exhibited a moderate perception of the risk of COVID-19, while the non-infected EMTs reported a high level of RP. The independent t-test confirmed that the mean total score for COVID-19 RP was significantly lower in the infected EMTs compared to the non-infected group (mean RP score: infected 150.82 ± 32.24 vs. non-infected 161.54 ± 22.50, P = 0.007). Additionally, ANOVA revealed that none of the demographic variables individually had a significant impact on the level of COVID-19 RP (P > 0.05). Furthermore, the interaction effect between the demographic variables and the groups was also insignificant (P > 0.05).

EMTs who contracted COVID-19 had a significantly lower RP compared to their non-infected counterparts. This reduced awareness of COVID-19 risks likely contributed to their infection, highlighting the critical role of RP in disease prevention. Targeted educational programs to enhance RP among EMTs could foster stronger adherence to preventive measures, ultimately reducing infection rates during future biological disasters. Therefore, this study not only contributes to expanding existing knowledge in this field but also assists policymakers and health administrators in improving decision-making to strengthen epidemic preparedness.

To identify subgroups of older adults whose mental health was affected by the COVID-19 pandemic.

Interrupted time series (ITS) analyses were used to measure the long-term impact of the COVID-19 pandemic on symptoms of depression (mCES-D) and anxiety (GAD-7) among participants aged 65 years and older (n = 708) from a prospective, longitudinal cohort study.

Symptoms of depression, but not anxiety, significantly increased at the start of the pandemic, while long-term trends in depression and anxiety during the pandemic were similar to pre-pandemic trends. Participants aged 75 years and older exhibited a more rapid decline in depression symptoms over time than expected after an initial increase. Women experienced a greater immediate increase in anxiety that decreased over time, while men's anxiety increased over time. Cognitively normal participants experienced a greater than expected immediate increase in symptoms of depression that decreased over time, while symptoms were unchanged by the pandemic for those with cognitive impairment.

Despite an initial increase in depression symptoms, the pandemic did not result in elevated symptoms of depression and anxiety long-term. The impact of the pandemic on mental health varied by age, gender, and cognitive status, suggesting some groups may have been more vulnerable than others.

Current research has examined emergency general surgery (EGS) rates and COVID-19 complications for some procedures, but none have explored complications for all seven EGS procedures before and during the pandemic. Our study addresses this gap, aiming to understand how pandemic-related challenges impact patient outcomes. Utilizing data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) spanning 2018 to 2021, we conducted a retrospective cohort study with analysis of open and laparoscopic partial colectomy, enterectomy, cholecystectomy, operative management of peptic ulcer disease, adhesiolysis, appendectomy, and laparotomy. Patient outcomes, including 30-day mortality and morbidity, were assessed. The likelihood of complications in EGS has risen compared to pre-COVID levels. Specifically, there is a greater risk of morbidity in open EGS cases intra-COVID compared to laparoscopic, particularly in colectomy and appendectomy procedures. Conversely, laparoscopic procedures have seen a decrease in readmissions, notably in cases involving cholecystectomy and colectomy. The study highlights a rise in complications for EGS intra-COVID, with open procedures demonstrating higher risks than laparoscopic counterparts.

Disorders like obsessive-compulsive disorder are associated with heightened disgust. Research suggests that dominant methods for treating such disorders (e.g., exposure therapies) are less effective at targeting disgust. Alternative strategies are needed to enhance treatment effectiveness.

In two studies, we investigated positive emotion (elicited via humorous content) for attenuating disgust responses to film clips. In Study 1, n = 174 undergraduates were randomized to view either a humorous, sad, or neutral clip prior to a disgusting clip. In study 2, n = 294 undergraduate participants were randomized to either view two clips with discrete emotional content (purely disgusting and purely amusing) or two mixed emotional clips (disgust mixed with amusement, amusement mixed with disgust).

Results of Study 1 showed that the humorous clip buffered against ratings of disgust. In Study 2, humorous content reduced reports of disgust. For both studies, the effect of the manipulation was not moderated by clinical characteristics, like disgust proneness, contamination concerns, or depression.

Findings suggest that positive emotions can alter the appraisal of disgusting content, attenuating feelings of disgust, with potential clinical implications for treatment.

Women undergoing in vitro fertilization-embryo transfer (IVF-ET) can suffer from anxiety and depression at various levels during the process. This study aimed to assess the anxiety and depression statuses (primary outcome) and influencing factors (secondary outcome) among patients undergoing IVF-ET. A 2019-2020 survey at Northwest Women's and Children's Hospital studied IVF-ET patients, evaluating anxiety and depression with GAD-7 and PHQ-9 alongside demographic data, using logistic regression for influencing factors. Among the 2465 women who undergoing IVF-ET, 27.18% had depression, and 18.46% had anxiety. Bachelors' degree (OR = 0.659, 95%CI: 0.503-0.864), male factor infertility (OR = 0.745, 95%CI: 0.558-0.995), and assessment on the day of starting gonadotropin stimulation (OR = 0.781, 95%CI: 0.626-0.974) were negatively independently associated with depression, while comorbidities (OR = 1.541, 95%CI: 1.281-1.854) and an extended ART strategy (OR = 1.394, 95%CI: 1.162-1.672) were independently associated with depression. High school/technical school education (OR = 0.669, 95%CI: 0.490-0.915) and bachelor's degree (OR = 0.640, 95%CI: 0.472-0.868) were negatively independently associated with anxiety, while an extended ART strategy (OR = 1.476, 95%CI: 1.197-1.820) was independently associated with anxiety. In conclusion, the prevalence of depression and anxiety was high in women undergoing IVF-ET. The study identified factors independently associated with depression and anxiety that could be used to guide the psychological management of women undergoing IVF-ET.

On January 30, 2020, the World Health Organization declared COVID-19 a Public Health Emergency of International Concern (PHIEC). On March 11, 2020, it was characterized as a pandemic, prompting the Government of Sierra Leone to implement response plans. The first case in the country was reported on March 31, 2020. To build resilient public health systems after the Ebola crisis, the Sierra Leone Field Epidemiology Training Program (SLFETP) was launched in 2016 with funding from the U.S. CDC in collaboration with the Ministry of Health and the African Field Epidemiology Network (AFENET). The program started at the FETP Frontline level, a 3-month in-service training program, followed by the FETP Intermediate, a 9-month in-service training program launched in 2017. Both levels adopted the CDC curriculum to the local context. The curriculum consists of classroom modules focusing on surveillance, outbreak investigation, and field projects. The SLFETP graduates and trainees were deployed to assist in COVID-19 response efforts. While reports indicate the SLFETP's contributions to COVID-19 preparedness and response, the specific roles of its graduates and trainees remain undocumented. This paper outlines their crucial involvement during the pandemic in Sierra Leone.

We reviewed 12 documents from the SLFETP, including work plans, outbreak investigation reports, and success stories, to assess the FETP's contributions during the COVID-19 pandemic. We interviewed graduates and trainees about their roles and conducted discussions with stakeholders and FETP staff to explore the FETP's role during the pandemic's preparedness and response phases. A thematic analysis was performed.

The SLFETP played a critical role during the preparedness and response phase of the COVID-19 pandemic. The trainees and graduates enhanced the surveillance system and led key response pillars, such as coordination, surveillance, and quarantine. SLFETP supported districts by building their capacity, especially in the district surveillance pillar, to conduct case investigations, contact tracing, quarantine monitoring, and data management.

The graduates and trainees reportedly played critical roles in key response pillars across the country in the preparedness and response phase of the COVID-19 pandemic. These gains should be maintained and scaled up to build a strong and resilient public health workforce in Sierra Leone, which is crucial for preparedness and response to future outbreaks.

This genome-wide association study (GWAS) explores the genetic components of severe adverse events following COVID-19 vaccination, with focus on myocarditis and pericarditis. Three SNPs (rs536572545, rs146289966 and rs142297026) near the SCAF11 gene were linked to pericarditis, while rs570375365 in the LRRC4C gene was associated with myocarditis. These findings suggest that genetic variants may influence inflammation pathways, providing a basis for further investigation into the immunological responses triggered by vaccines.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a serious condition associated with SARS-CoV-2 infection. The relationship between SARS-CoV-2 variants of concern (VOCs) and the occurrence and severity of MIS-C is unknown. We analyzed the dynamics of MIS-C in the Milan metropolitan area (Italy) during the COVID-19 pandemic, focusing on the epidemiologic trends and disease severity in relation to different VOCs in a single-center study. Fifty-seven MIS-C patients (mean 8.3 ± 3.8 years) admitted to the Pediatric Department of Buzzi Children's Hospital in Milan, Italy, between November 2020 and July 2022, were retrospectively included in the study. The SARS-CoV-2 variant was retrospectively identified from serological fingerprinting (profiles of serum antibodies targeting different variants of SARS-CoV-2 obtained by a label-free microarray biosensor) or by the variant of prevalence. Two main periods of MIS-C case accumulation were observed. The peak of MIS-C cases rate in December 2020 reached 0.6 cases per day, which is nearly double the rate observed in February 2022, despite the larger number of infected subjects. Although the WT variant exhibited a broader range of severity score values, the score distributions for the different variants do not show statistically relevant differences.

The results clearly show a decrease in the incidence of MIS-C in relation to infections, but also support the concept that severity of MIS-C remained essentially unchanged across different virus variants, including Omicron. The course of MIS-C, once initiated, is independent from the characteristics of the triggering variants, although later variants may be considered less likely to induce MIS-C.

• MIS-C is a rare systemic inflammatory disorder that arises as a post-infectious complication temporally related to SARS-CoV-2 infection. • Fluctuations in MIS-C incidence were observed throughout the pandemic, with the latest variants associated with a lower incidence.

• The SARS-CoV-2 variant of infection can be retrospectively confirmed by serum antibody fingerprinting using a label-free microarray biosensor. • Despite the decreasing incidence, MIS-C severity has remained essentially unchanged across SARS-CoV-2 variants.

To assess how efficient the local team attained skills are after several visits made by international missions in respect to number of coronary artery bypass grafting surgery performed and the overall patient outcome.

This was a retrospective study that included all patients who were operated on at the center after being diagnosed with chronic coronary artery disease from May 2016 to December 2023. Patients' demographic data were retrieved from patients' files coupled with theatre record file, entered into a structured questionnaire, and then, in a statistical program.

A total of 290 patients underwent coronary artery bypass grafting at the center. The international missions performed a total of 159 (54.8%) operations, while the local team operated a total of 131 (45.2%) patients. The study showed significant statistical difference in terms of total operation time (95% confidence interval [CI] = 5.67, 6.01 vs. 95% CI = 6.32, 6.66), aortic cross-clamping time (95% CI = 75.92, 90.00 vs. 95% CI = 111.19, 126.65), and total cardiopulmonary bypass time (95% CI = 115.9, 134.75 vs. 95% CI = 174.52, 201.27) between the international missions and local surgical team, respectively. The mortality rate was higher in patients operated on by the local team (13.7%) than by international missions (8.8%), however there was no statistical difference.

This study has shown the beneficial advantage of international surgical missions to newly established open-heart centers with advanced facilities and skill-deprived team. International surgical missions have greatly contributed to the progression of the center as they oversee and support the programs.

Diabetes mellitus (DM) and hyperglycemia are associated with poor outcome(s) in COVID-19 hospitalized patients, but their independent impact on prognosis remains unclear. We aimed to assess the impact of DM and hyperglycemia on COVID-19 outcomes.

Clinical data/records from COVID-19 patients admitted to the Parma University-Hospital (February 23rd to March 31st, 2020) were retrieved and analysed (NCT04550403). Fasting plasma glucose (FPG), inflammatory markers and the main biochemical variables were collected at admission. Patients underwent chest high-resolution CT and arterial blood gas analysis to determine the PaO2/FiO2 ratio (P/F ratio). The primary outcome was a composite of intensive care unit admission and/or death.

Among 756 subjects, 143 (19%) had DM. These patients were older with higher comorbidity rates. The primary outcome occurred in 61.5% DM patients versus 43.4% without DM (p < 0.001). In multivariable analysis (accuracy UC = 0.93), older age, cardiovascular and kidney diseases, FPG ≥ 126 mg/dl, C-reactive protein, and P/F ratio, but not previous DM, were independent risk indicators.

DM indicated poor COVID-19 outcomes, but not when adjusted for other clinical variables/comorbities, suggesting that its impact was mostly driven by concomitant factors. The independent role of fasting hyperglycemia points to the need for further research on its contribution to COVID-19.

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 current study evaluated the effects of different COVID-19 vaccines on Saudi Arabian residents, focusing on their safety, acceptance, and effectiveness. Gaining a better knowledge of these vaccination results will help develop more successful public health initiatives and increase confidence in vaccination campaigns throughout the Kingdom.

A cross-sectional study was conducted with 401 participants from diverse backgrounds, covering different ages, genders, nationalities, weights, and education levels. The survey gathered information about participants' health conditions, their vaccines, side effects, and infection rates before and after vaccination. The data were analyzed to compare vaccine preferences, side effects, and infection trends overtime.

Sociodemographic-wise, most participants were men (62.84%) and Saudi nationals (96.01%), showing significant differences by gender and nationality (P < 0.001). The largest age group was 21-30 years (45.89%, P < 0.001), with 66.58% being university graduates (P < 0.001). Pfizer/BioNTech was the top choice across all doses, with 83.46% receiving it for the first dose, 78.1% for the second, and 39.28% for the third, reflecting a clear preference over other vaccines (P < 0.001). Pfizer/BioNTech recipients reported side effects after the first dose in 36.53% of cases, but only 1.86% needed medical help. Vaccination significantly reduced infection rates: Pfizer/BioNTech dropped infection rates from 43.18% to 8.33% after the third dose (P < 0.001), while Oxford/AstraZeneca saw rates fall from 12.88% to 0.76% after the third dose, but did not reach significance (P = 0.34). Overall, vaccinated individuals had much lower infection rates (28.17%) than among unvaccinated ones (100%), with a P-value of 0.020.

Our results concluded that Saudi Arabia's vaccination campaign has proven effective, especially after the second and third doses. Pfizer/BioNTech was the most preferred vaccine, demonstrating strong efficacy and safety, which helped build public confidence. Ongoing monitoring is crucial to maintaining pandemic control, post-marketing and public health strategies.

When WHO declared the SARS-CoV- 2 respiratory virus pandemic in 2020, Uganda was unprepared to prevent and control its spread or manage the COVID- 19 and non-COVID patients. A community trial to assess the efficacy of an intensive community engagement and risk communication (CERC) was contemplated. However, a baseline assessment of the existing CERC status and the challenges of conducting community research in the early months of the pandemic was necessary.

A community baseline qualitative research (in-depth interviews, key informant interviews, focus group discussions, and household conversations) was implemented in 15 parishes (6 and 9 in Kawempe and Nakawa divisions respectively) of Kampala Capital City Authority, Uganda. Qualitative in-depth interviews with 20 household heads (n = 10 in each division), 50 household conversations (n = 25 in each division), and focus group discussions (n = 10, five in each division) were conducted during the pandemic from October 2020 to February 2021.

Many potential challenges to research involving CERC were identified and were categorized into three main interrelated domains: (a) implementation challenges (b) social, cultural, and political context of the research, and (c) budgetary and funding constraints.

The three interrelated challenges identified in this study should be considered in future plans for epidemic and pandemic preparedness. The practical application of conventional concepts like CE, risk communication, qualitative research methods must be re-examined prior to epidemics and pandemics to improve their applicability and responsiveness during complex, dynamic epidemics and pandemics.

We evaluated the hospitalization rate, length of stay, and management of patients with ureteric lithiasis admitted under emergency conditions at a single institution during the COVID-19 pandemic.

A retrospective study was conducted on 219 patients with ureteral lithiasis, divided into pre-COVID-19 (1.10.2019-29.02.2020) and COVID-19 groups (1.10.2020-29.02.2021). The study examined patient and stone characteristics, hospitalization duration, surgical interventions, creatinine levels, and associated urinary tract infections. It also evaluated the complications related to delayed treatment during the pandemic.

The study found a 73.41% reduction in admissions for obstructive ureteral lithiasis during the COVID-19 pandemic compared to the pre-pandemic period. Notable differences were observed in age (61.5 vs 46 years, p=0.000), gender (p=0.046), stone laterality (p=0.024), location (p=0.002), serum creatinine levels (1.59 vs 1.09 mg/dL, p=0.000), and urine cultures (45.65% vs 23.12%, p=0.002). During the pandemic period, the rate of primary stone extraction procedures decreased (32.6% vs 59%, p<0.001), while operative time (52.89 vs 39.84 minutes, p<0.001) and hospital stay significantly increased (13.09 vs 3.76 days, p<0.001).

The pandemic resulted in fewer hospitalizations for ureteral lithiasis and an increase in complications, likely due to reduced access to medical care and a greater tendency for upper urinary tract drainage.

Understanding viral evolution and predicting future mutations are crucial for overcoming drug resistance and developing long-lasting treatments. Previously, we established machine learning (ML) models using dynamic residue network (DRN) metric data and leveraging a vast amount of existing mutation data from the SARS-CoV-2 main protease (Mpro). Here, we sought to assess the generalizability and robustness of the current models across other SARS-CoV-2 proteins. To achieve this, for the first time, we employed a transfer learning (TL) approach, allowing us to determine the extent to which Mpro trained models could be applied to other SARS-CoV-2 proteins. The TL results were highly promising, with artificial neural network (ANN) and random forest (RF) correlation coefficients for Mpro closely matching those of NSP10, NSP16, and PLpro. The ANN |R| value for Mpro was 0.564, while NSP10, NSP16, and PLpro had values of 0.533, 0.527, and 0.464, respectively. Similarly, the RF |R| value for Mpro was 0.673, compared to 0.457, 0.460, and 0.437 for NSP10, NSP16, and PLpro, respectively. Interestingly, we did not observe a strong correlation for the spike (S) protein monomer and its domains. The low p-values that are associated with the correlation |R| values show that the linear correlations between predicted and actual mutation frequencies are statistically significant. This indicates that TL may generalize well across structurally related viral proteins using DRN-derived ML model from Mpro. Overall, we aim to develop a universal ML model for predicting missense mutation frequencies in viral proteins, and this study lays the foundation for that goal.

The COVID-19 pandemic has underscored the need for fast and accurate epidemiology, particularly due to the high observed mutation frequency in SARS-CoV-2. This study aims to explore the evolution of SARS-CoV-2 through a global analysis. To facilitate a comparative analysis of temporal mutation data, we developed CovidTGI, a Shiny web application. CovidTGI provides insights into observed mutation frequencies and the temporal relationships among mutations across various clades in different geographical regions. Our tool relies on a database that includes 2 million samples obtained from the National Center for Biotechnology Information (NCBI), along with 500 in-house Sicilian samples collected between May 2021 and June 2022. From this smaller group of samples, we identified key variants that are prevalent within a specific clade. Our tool is designed to study the evolution of SARS-CoV-2, which clearly follows a complex trajectory. This complexity highlights the necessity for sophisticated tools like CovidTGI to understand and track the evolution of this virus.

Frequent outbreaks of respiratory infectious diseases, driven by diverse pathogens, have long posed significant threats to public health, economic productivity, and societal stability. Respiratory infectious diseases are highly contagious, characterized by short incubation periods, diverse symptoms, multiple transmission routes, susceptibility to mutations, and distinct seasonality, contributing to their propensity for outbreaks. The absence of effective antiviral treatments and the heightened vulnerability of individuals with weakened immune systems make them more susceptible to infection, with severe cases potentially leading to complications or death. This situation becomes particularly concerning during peak seasons, such as influenza outbreaks. Therefore, early detection, diagnosis, and treatment are critical, alongside the prevention of cross-infection, ensuring patient safety, and controlling healthcare costs. To address these challenges, this review aims to identify a comprehensive, rapid, safe, and cost-effective diagnostic approach for respiratory infectious diseases. This approach is framed within the existing hierarchical healthcare system, focusing on establishing diagnostic capabilities at hospitals, community, and home levels to effectively tackle the above issues. In addition to PCR and isothermal amplification, the review also explores emerging molecular diagnostic strategies that may better address the evolving needs of respiratory disease diagnostics. A key focus is the transition from amplification technologies to amplification-free biosensing approaches, with particular attention given to their potential for home-based testing. This shift seeks to overcome the limitations of conventional amplification methods, particularly in decentralized and home diagnostics, offering a promising solution to enhance diagnostic speed and safety during outbreaks. In the future, with the integration of AI technologies into molecular amplification technologies, biosensors, and various application levels, the inclusively economic, rapid, and safe respiratory disease diagnosis solutions will be further optimized, and their accessibility will become more widespread.

The COVID-19 pandemic has been spreading rapidly since 2019, leading to devastating consequences worldwide, as well as putting healthcare providers at high risk. This study intends to assess the awareness and preparedness activities among maternal healthcare (MHC) workers and to determine factors that lead to obstetric services' preparedness in ten Government Hospitals in Selangor, Malaysia.

A cross-sectional survey was conducted among 409 MHC workers which include doctors, nurses, and midwives in the government hospitals in Selangor, Malaysia between May 2022 till June 2022. Respondents were given validated questionnaires which include socio-demographic background, knowledge, awareness, and attitude as well as the obstetric services' preparedness activities in managing the COVID-19 pandemic.

Majority of the respondents were nurses/midwives (87.5%), female (98.5%), age 35-45 years old (48.5%), had working experience of more than 5 years (92.7%), had good knowledge and awareness (92.2%) and good obstetric services preparedness (88.3%). However, only about half (54.0%) of them had positive attitude towards COVID-19. When controlling for confounding factors, multivariate analysis showed that working period factor (p < 0.001), knowledge and awareness factor (p < 0.001) and attitude factor (p < 0.001) were significant predictive factors of obstetric services preparedness during the COVID-19 pandemic.

Majority of the respondents had good knowledge and awareness, as well as good level of obstetric services preparedness. However, only about half of them had a positive attitude towards COVID-19. The findings in this study revealed that efforts should be made to further increase the knowledge and attitude of MHC workers on COVID-19 and more so to further improve the positivity of their attitude towards this pandemic so that they can provide better obstetric services especially in the current and future pandemics to come.

To assess whether there were any differences in patient presentation, morphological and functional features as well as surgical treatment for full-thickness macular holes (FTMH) during the lockdown periods amidst the COVID-19 pandemic compared to the previous year. A retrospective analysis was conducted on all patients with FTMH who received treatment at a large tertiary center during the lockdown periods from March 16 to June 16, 2020, and December 9, 2020, to June 6, 2021 (35 eyes, mean age 66 years). Corresponding periods from the previous year were chosen as a control group (41 eyes, mean age 71 years). The patients' demographics, preoperative and postoperative best-corrected visual acuity (BCVA), symptom duration, time from presentation to surgical treatment, and surgical technique were determined. The minimal and base diameters of the FTMH were assessed using spectral-domain optical coherence tomography. During the lockdown periods in the COVID-19 pandemic, there were no significant differences in the number of patients, duration of symptoms, time from presentation to surgical treatment, surgical technique, macular hole size, base diameter, closure rate or pre- and postoperative BCVA between the two groups. However, there was a significant increase in the number of patients who presented directly at the clinic on an emergency basis without prior contact with a community-based ophthalmologist. This study suggests that the diagnosis and the provision of timely surgical treatment of FTMH were not affected by the COVID-19 pandemic. However, patients more frequently sought immediate emergency care at the hospital. This could be attributed to challenges in scheduling and obtaining appointments at outpatient clinics during the COVID-19 pandemic.

The novel coronavirus (COVID-19) pandemic has had a devastating global impact, profoundly affecting daily life, healthcare systems, and public health infrastructure. Despite the availability of treatments and vaccines, hospitalizations and deaths continue. Real-time surveillance of infection trends supports resource allocation and mitigation strategies, but reliable forecasting remains a challenge. While deep learning has advanced time-series forecasting, its effectiveness relies on large datasets, a significant obstacle given the pandemic's evolving nature. Most models use national or state-level data, limiting both dataset size and the granularity of insights. To address this, we propose the Fine-Grained Infection Forecast Network (FIGI-Net), a stacked bidirectional LSTM structure designed to leverage county-level data to produce daily forecasts up to two weeks in advance. FIGI-Net outperforms existing models, accurately predicting sudden changes such as new outbreaks or peaks, a capability many state-of-the-art models lack. This approach could enhance public health responses and outbreak preparedness.

In early 2020, severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infections leading to COVID-19 disease reached a global level leading to the World Health Organization (WHO) declaration of a pandemic. Scientists around the globe rapidly responded to try and discover novel therapeutics and repurpose extant drugs to treat the disease. This work describes the preclinical discovery efforts that led to the invention of PF-07321332 (nirmatrelvir, 14), a potent and orally active inhibitor of the SARS CoV-2 main protease (Mpro) enzyme. At the outset we focused on modifying PF-00835231 (1) discovered in 2004 as a potent inhibitor of the SARS CoV-1 Mpro with poor systemic exposure. Our effort was focused on modifying 1 with the goal of engineering in oral bioavailability by design, while maintaining cellular potency and low metabolic clearance. Modifications of 1 ultimately led to the invention of nirmatrelvir 14, the Mpro inhibitor component in PAXLOVID.

The COVID-19 pandemic has claimed many lives and continues to impact individuals through post-COVID-19 conditions. Osteonecrosis of the femoral head (ONFH) is increasingly recognized as a major post-COVID-19 complication, yet most studies are limited to case reports and small series. This study aimed to evaluate COVID-19-related factors potentially contributing to ONFH development in post-COVID-19 patients.

A retrospective analysis was conducted on 84 patients with ONFH and a confirmed history of COVID-19. Baseline characteristics were collected, and patients were categorized into the following groups for comparative analysis: (1) vaccinated vs. unvaccinated, (2) unilateral vs. bilateral ONFH, (3) dexamethasone (DEX) and methylprednisolone (MPS) vs. DEX therapy, and (4) Association Research Circulation Osseus (ARCO) stage 2 vs. stage 3. Group differences and associations were analyzed.

The DEX and MPS-treated group had a greater extent of COVID-19 lung involvement compared to the DEX-treated group (59.2% vs. 36.3%, p = 0.002), as well as longer hospital stays in both general ward (14.2 days vs. 10.6 days, p = 0.018) and ICU (5.4 days vs. 3 days, p = 0.017). The DEX and MPS-treated group also had a longer duration of steroid therapy (19.3 days vs. 12.3 days, p < 0.001) and received higher DEX-equivalent cumulative steroid doses (380 mg vs. 125 mg, p < 0.001). Notably, ONFH symptoms developed earlier in the DEX and MPS-treated group compared to the DEX-treated group (7.5 months vs. 12 months, p = 0.004). Multivariable logistic regression analysis identified cumulative steroid dose as the sole predictor of ONFH severity (OR: 1.015, 95% CI: 1.001-1.028, p = 0.032), with ARCO stage 3 patients receiving higher cumulative steroid doses than stage 2 patients (240 mg vs. 126 mg, p = 0.018).

Our study demonstrated that cumulative steroid dose is the primary determinant of ONFH severity in post-COVID-19 patients. Additionally, combined use of corticosteroids may accelerate the onset of ONFH, highlighting the need for cautious steroid management in COVID-19 patients.

The Sars-Cov-2 infection disease (COVID-19) causes symptoms during both acute and post-COVID phases. This study assessed exercise capacity and occupational competence of 20 hospitalized COVID-19 patients, at discharge and three months later using the 6-Minute Step Test and Occupational Self-Assessment. Significant differences were found in both exercise capacity and occupational competence scores between discharge and three months later (p < 0.05). However, these measurements were not correlated (p > 0.05). Although patients show improvement after discharge, some symptoms persisted, affecting their exercise, and occupational performance. Further research is needed to explore long-term occupational outcomes of COVID-19 beyond one year.

Coronavirus disease-2019 (COVID-19) remains a critical global health concern. We developed a fully automated, high-throughput competition immunoassay to elucidate how epitope recognition on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) correlates with neutralizing activity. Analysis of clinical samples from both SARS-CoV-2-infected and vaccinated individuals revealed that vaccination elicits significantly higher antibody titers across multiple S1 subunit epitopes compared to natural infection. Notably, median antibody levels against the receptor-binding motif (RBM) exceeded 50% in both cohorts, highlighting the RBM as a key target for antibody induction irrespective of immune origin. Furthermore, the strongest correlation with neutralizing activity was observed for antibodies directed against the broader S1 subunit, indicating that epitopes outside the RBM also contribute to neutralization. These findings underscore the importance of both RBM- and non-RBM-directed antibodies in effective immune defense against SARS-CoV-2. Our assay enables large-scale, reliable quantification of neutralizing antibodies and provides critical insights for developing improved diagnostic antigens and vaccine strategies aimed at eliciting robust, multi-epitope immune responses.

To evaluate the quality of life (QOL) of postmenopausal women during the COVID-19 pandemic in Thailand and the associated factors.

A cross-sectional study using a validated Thai version of the WHOQOL-BREF questionnaire to assess QOL was conducted.

A total of 453 postmenopausal women participated in the study, with a median age of 58 years (ranging from 41 to 65). These women, residing in urban areas of Thailand such as Bangkok, Nonthaburi, Nakhon Pathom, Pathum Thani, Samut Prakan, and Samut Sakhon, completed a survey questionnaire with the assistance of health volunteers during the COVID-19 pandemic, between October 2021 and April 2022. The study revealed that 55.85% of participants reported experiencing poor quality of life (QOL) during the pandemic. Stepwise logistic regression analysis identified several significant associations with QOL. Factors linked to a poorer QOL included lower levels of well-being index (odds ratio [OR] 7.89, 95% confidence interval [CI] 3.16-19.75, P < 0.01), reduced physical activity (OR 2.72, 95% CI 1.62-4.54, P < 0.01), and the severity of menopausal symptoms (OR 1.94, 95% CI 1.42-2.66, P < 0.01). Conversely, higher education (OR 0.28, 95% CI 0.10-0.75, P < 0.01), an earlier onset of menopause (OR 0.55, 95% CI 0.39-0.78, P < 0.01), and occasional social alcohol consumption (OR 0.56, 95% CI 0.33-0.94, P = 0.03) were identified as protective factors for QOL.

These findings highlight the importance of comprehensive menopausal care, addressing both physical and mental well-being, and providing specific care for menopausal symptoms during challenging times of the COVID-19 pandemic.

To assess the prevalence of SARS-CoV-2 antibodies in the residents of Kibera informal settlement in Nairobi, Kenya, before vaccination became widespread, and explore demographic and health-related risk factors for infection.

A cross-sectional study.

Kibera informal settlement, Nairobi, Kenya.

Residents of Kibera informal settlement between October 2019 and August 2021, age 1 year and above who reported no current symptoms of COVID-19.

Associations were determined between SARS-CoV-2 positive tests measured with one rapid test and two ELISAs and demographic and health-related factors, using Pearson's χ2 test. Crude OR and adjusted OR were calculated to quantify the strength of associations between variables and seropositive status.

A total of 438 participants were recruited. Most (79.2%) were age 18-50 years; females (64.2%) exceeded males. More than one-third (39.1%) were unemployed; only 7.4% were in formal, full-time employment. Less than one-quarter (22.1%) self-reported any underlying health conditions. Nearly two-thirds (64.2%) reported symptoms compatible with COVID-19 in the previous 16 months; only one (0.23%) had been hospitalised with a reported negative COVID-19 test. 370 (84.5%) participants tested positive in any of the three tests. There was no significant difference in SARS-CoV-2 seropositivity across age, sex, presence of underlying health conditions, on medication or those ever tested for SARS-CoV-2. Multiple logistic regression analysis showed that COVID-19 symptoms in the previous 16 months were the only significant independent predictor of seropositivity (p=0.0085).

High SARS-CoV-2 exposure with limited morbidity was found in the residents of Kibera informal settlement. The study confirms other reports of high SARS-CoV-2 exposure with limited morbidity in slum communities. Reasons cited include the high infectious disease burden on the African continent, demographic age structure and underreporting due to limited testing and lack of access to healthcare services; genetic factors may also play a role. These factors require further investigation.

Although COVID-19 was experienced as a traumatic event with long-lasting effects, there is limited data on its traumatic impact in relation to factors that can promote or threaten young people's mental wellbeing. This study investigated the association between sensory-processing sensitivity (SPS), resilience, and life satisfaction with COVID-19 trauma-related stress and whether resilience mediates the relationship between SPS and COVID-19 traumatic stress in a young sample. A total of 441 individuals aged between 16 and 25 years (Mage = 19.26, SD = 1.65) participated in an online survey in the UK between November 2021 and April 2022. We found that SPS was positively correlated, and resilience was negatively correlated with COVID-19 trauma-related stress. Life satisfaction was not significantly related to COVID-19 trauma-related stress. A mediation analysis showed that the relationship between SPS and COVID-19 trauma-related stress was mediated by resilience. Our findings suggest that resilience can be a protective factor against the traumatic effect of COVID-19 in young people, but other factors should also be considered. Our study makes implications about the potential benefits of including resilience in interventions which target young people's mental wellbeing.

COVID-19 pandemic resulted in a huge setback in health care sector causing morbidity, mortality, lack of manpower, resources, in hospitals. Apart from the direct effects of the disease, the indirect effects include, lockdowns, restriction of movement of people for food, work, medicines, etc. There are certain non-communicable diseases for which lifelong treatment and continuation of care is required and the patients suffering from these diseases were also highly affected during pandemic. The major pillars of health care services are accessibility, affordability, availability appropriateness, adequacy and adherence and it is true that the pandemic had its impact on all these pillars.

A prospective cross sectional study in which 284 patients with NCD answered a questionaire and the responses were analysed.

There was a lack of accessibility (48%), affordability (42%) availability (54%) appropriateness and 71% of population took self-medication during the period. There was discontinuity in 16% of the population and the reasons for discontinuation include depression, lack of motivation, forgetfulness, financial crisis etc.

The pandemic exerted a greater influence on saturation of health care services by increasing the mortality, morbidity and as a consequence decreased the health care services to communicable/non-communicable diseases. Our study shows the need and demand for robust health care services during critical times.

To compare mental health indicators among undergraduates in Fall 2019, before the COVID-19 pandemic, and Fall 2020, when many students returned to campus amidst restrictions on in-person contact.

Analyses included 26,881 undergraduate students, aged 18-24, from 70 U.S. institutions.

Students completed the National College Health Assessment-III survey in Fall 2019 or Fall 2020.

The prevalences of high stress, loneliness, a low flourishing score, and serious psychological distress increased in 2020 compared to 2019. Serious psychological distress increased substantially in 2020 among students not living with family (adjusted prevalence ratio (aPR)=1.36, 95% CI 1.29-1.45) but not among students living with family (aPR = 1.09, 95% CI 0.95-1.26).

These results suggest prevalences of several indicators of poor mental health were elevated among U.S. undergraduates several months into the pandemic. The pandemic may have had greater impact on mental health among students not living with family.

Objective: To examine international student-athletes' (ISAs) rates of depression, perceived stress, problematic drinking, and sleep disturbance. Participants: 509 ISAs (Mage = 20.39 years, women = 63.1%) from over 80 NCAA institutions. Methods: Survey data were collected in April/May 2020. Results: Overall, 27.9% and 9.2% endorsed clinical and high levels of depression and stress, respectively; 2.4% (n = 12) reported severe sleep disturbances and 12.4% (n = 63) problematic drinking. Except problematic drinking, being a woman ISA was associated with significantly higher levels of disturbance. Year in school interacted with gender for perceived stress; men ISAs in their 2nd year or higher reported the lowest levels. Conclusions: Large numbers of ISAs endorsed clinical/severe levels of psychological concerns at onset of COVID-19, likely due to the unique stressors experienced by this international college population. Athletic departments, like universities in general, must provide culturally-sensitive mental health services for their ISAs.

Access, demand, and acceptance of coronavirus disease 2019 (COVID-19) testing have varied globally. This study explored the sociodemographic and psychosocial risk factors that contribute to the uptake of COVID-19 testing in community settings in South Africa. This paper presents a cross-sectional secondary analysis using data from a cluster randomized controlled trial and a nested perception survey of COVID-19 antigen testing in communities located in urban (eThekwini, KwaZulu-Natal) and rural settings (Worcester, Eastern Cape) in South Africa. Individuals who were reluctant to get tested participated in the perception survey. Data were analyzed using descriptive statistics and multivariable logistic regression to assess linear associations and estimate adjusted odds ratios (ORs). The analysis was conducted on 3,074 individuals, of whom 2,509 (81.6%) provided consent for COVID-19 testing. Among those, 2,505 (81.5%) tested negative, and 4 (0.1%) tested positive for COVID-19. The mean age of participants was 38 (SD = 14.61), and 57% were male. Females (OR: 1.27; 95% CI = 1-1.6), individuals older than 56 years (OR: 1.95; 95% CI = 1.24-3.07), and those who were vaccinated (OR: 1.99; 95% CI = 1.53-2.60) were more likely to consent. Individuals who had previously tested positive for severe acute respiratory syndrome coronavirus 2 were less likely to consent to testing (OR: 0.64; 95% CI = 0.11-0.46). No link was found between depression, anxiety, substance use, and willingness to undergo COVID-19 testing. A perceptions survey involving 704 participants, which explored factors influencing testing willingness, found that older adults, and urban populations were less likely to undergo COVID-19 testing. Targeted health campaigns may improve testing rates. Larger-scale implementation research is required to explore best practices for improving testing rates and confidence in population-level detection within South Africa.

The aim of this study was to analyze whether patients with SARS-CoV-2 who received surgical tracheotomy had a lower incidence of postoperative bleeding if their LMWH was postponed or canceled on the day of surgery.

Patients with SARS-CoV-2 admitted to the intensive care units who underwent surgical tracheotomy were assessed retrospectively through their medical records. Data on comorbidity, LMWH dose, and timing were collected. Bleedings < 72 h post surgery were noted as stomal or airway bleedings.

All 101 patients included were on LMWH. Twenty-two patients had no change of dose of LMWH, 24 patients had their dose of LMWH postponed to post surgery, and 50 patients had their dose reduced to only the evening dose on the day of surgery. Twenty-six patients had a stomal bleeding, one patient had an airway bleeding, and four patients had both stomal and airway bleedings. No significant difference in the incidence of bleeding was identified between various groups of different LMWH doses or timing, reduced dose versus no change of dose, OR 1.29 (95% CI 0.42-3.92). Postponed dose versus no change of dose of LMWH, OR 1.03 (95% CI 0.28-3.75). Increasing age was correlated to a higher risk of bleeding post-surgery by an OR of 1.64 (95% CI 1.06-2.54, p = 0.026 for every 10 years added). No fatal bleeding related to surgical tracheotomy was observed.

Decreased doses of LMWH on the day of surgery were not associated with a risk reduction for post-surgical bleeding in patients with SARS-CoV-2 who received tracheotomy. Increasing age was a risk factor for post-surgical bleeding.

Retrospective, level 3.

Objectives: Despite research showing the impact of the threat of COVID-19 on mental health, scholars have failed to examine the relationship between perceived disaster threat and COVID-19 anxiety. Factors that buffer that positive relationship (e.g., optimism and emergency preparedness self-efficacy or EPSE) are also understudied. Thus, we examined the relationship between the perceived threat of disasters and COVID-19-related anxiety, as well as potential moderating factors of this relationship, including optimism and EPSE. Participants and methods: Participants were a representative sample of U.S. college students (N = 392) recruited through Prolific.co who completed measures in an online Qualtrics survey. Results: Both optimism and EPSE were significant moderators of the relationship between perceived threat and symptoms of anxiety related to COVID-19. When both moderators were included in a double moderation model analysis, only EPSE remained a significant moderator. Conclusions: These findings reflect the importance of cultivating protective psychological resources to protect college students' well-being during disasters.