Coronavirus Disease Research Articles

Trends and implications of antimicrobial resistance in Pseudomonas aeruginosa: Insights from a 19-year study in Zhejiang Province.

This study aimed to elucidate the resistance trends of P. aeruginosa isolates from 2005 to 2023 in Zhejiang Province, emphasizing the impact of Coronavirus disease 2019 (COVID-19) on antimicrobial resistance patterns and clinical management. We retrospectively analyzed 7326 P. aeruginosa isolates collected from diverse clinical sources in a tertiary hospital in Zhejiang Province from 2005 to 2023. Identification and antibiotic susceptibility testing of each isolate were performed using the VITEK-32 automated system and the disk diffusion method, following Clinical and Laboratory Standards Institute guidelines. We assessed resistance patterns for key antibiotic classes relevant to P. aeruginosa treatment, including carbapenems, β-lactams, aminoglycosides, and quinolones. Statistical analyses, including trend evaluations and resistance determinant assessments, were conducted in R software (version 4.2.2), with visualizations generated through ggplot2 to illustrate resistance trends over time. This study focused on key anti-pseudomonal agents including carbapenems (imipenem and meropenem), β-lactams (piperacillin), and quinolones (ciprofloxacin and levofloxacin). We observed a progressive increase in resistance to imipenem from 6.8% in 2005 to 48.2% in 2023 and meropenem from 25.4% to 44.2% over the same period. Conversely, resistance rates to aminoglycosides declined, with gentamicin resistance dropping from 22.0% in 2005 to 5.0% in 2019. Cephalosporins exhibited variable trends, with cefepime resistance peaking at 40.4% in 2013 before declining to 12.1% in 2023. The findings indicated a progressive increase in resistance rates for these antibiotics, with notable peaks coinciding with changes in clinical practices and the COVID-19 pandemic. The analysis demonstrated that shifts in prescription habits, particularly during the COVID-19 pandemic, influenced resistance patterns, underscoring the need for context-specific antimicrobial stewardship strategies. This study identifies significant, evolving resistance patterns in P. aeruginosa over a 19-year period, with marked increases in resistance to critical antibiotics, including carbapenems (imipenem, meropenem), quinolones (levofloxacin, ciprofloxacin), and certain β-lactams (piperacillin). These findings underscore an urgent need for dynamic, tailored infection control measures, emphasizing the importance of robust antibiotic stewardship programs, localized treatment guidelines, and proactive monitoring of resistance trends. Implementing these strategies is essential to effectively counter the challenges posed by multi-drug resistant P. aeruginosa, improve patient outcomes, and sustain the efficacy of vital antibiotic therapies.

Analysis of the invasion mechanism of novel coronavirus and the novel coronavirus vaccine

Abstract. From the time the first case was identified to the time the novel coronavirus swept the world, developing a reliable, defensible vaccine has been a priority and the common aspiration of the people. Through literature analysis and review, this paper mainly explores the invasion mechanism of the novel coronavirus and the relevant principles of the novel coronavirus vaccine. Based on the above research, this paper finds that the research process and development of coronavirus disease 2019(COVID-19) vaccine is a course of continuous enrichment of varieties and continuous maturation of biochemical research components. Amid the innovation and progress, it is clear to all that vaccines can better cater to the needs of different populations. This paper collects a few typical vaccine examples to reflect a comprehensive. At the same time, the intrusion mechanism of virus is explained in detail. Basic questions about COVID-19 vaccines and how they work can be answered in this paper.

Application of ketogenic diet in the treatment of diseases

Abstract. The ketogenic diet (KD) has gained recognition for its unique dietary composition that focuses on high fat, low carbohydrate, and moderate protein intake. Originally developed as a treatment for refractory epilepsy, the KD has expanded its applications to address a variety of health conditions, including obesity, diabetes, cancer, and even novel coronavirus pneumonia (COVID-19). This review delves deeply into existing literature to uncover the historical origins of KD, shed light on the complexities of ketogenic metabolism, and summarize the therapeutic benefits of KD in various diseases along with its mechanisms. In addition to exploring the positive aspects of KD, this study meticulously scrutinizes the potential short- and long-term adverse reactions and contraindications associated with the diet. Furthermore, strategic recommendations are proposed to optimize the outcomes of KD therapy. By offering a comprehensive analysis, this review endeavors to furnish valuable theoretical foundations that can elevate the clinical implementation of the KD in medical practice.

Saliva as a diagnostic tool for COVID-19 (Novel Coronavirus)

The coronavirus disease (COVID-19) is an emerging illness that has rapidly spread across the globe. First identified in late December 2019, this new strain had not previously been detected in humans. The novel coronavirus isolated by researchers was subsequently named the 2019 novel coronavirus (2019-nCoV). COVID-19 can be diagnosed through various methods, with RT-PCR being the gold standard for these tests. The most common sampling techniques involve swabs from the nose, throat, or mouth. Saliva, a critical biological fluid containing several diagnostic biomarkers, plays an important role in detecting SARS-CoV-2 and other coronaviruses. Its use offers numerous benefits and helps researchers better distinguish between symptomatic and asymptomatic patients.

Home remedies: flexibilities to onshore pharmaceutical manufacturing under WTO rules

Abstract In the wake of the Coronavirus Disease 2019 pandemic, governments globally have intensified efforts to localize the production of pharmaceuticals, leveraging local content requirements and incentives to mitigate supply chain vulnerabilities. This shift has revealed tensions with World Trade Organization (WTO) regulations, notably highlighted in Turkey—Pharmaceutical Products (EU). This article explores policy-based flexibilities within the General Agreement on Tariffs and Trade (GATT) 1994, the Agreement on Trade-Related Investment Measures, and the Subsidies and Countervailing Measures (SCM) Agreement that may justify measures inconsistent with WTO norms under specific conditions. Analysing public health exceptions, national security imperatives, and government procurement policies, the paper elucidates how these flexibilities can be mobilized to support onshoring initiatives while adhering to international trade obligations. The findings suggest a nuanced approach to reconciling public health goals and economic strategies with global trade rules, providing a critical framework for policymakers navigating the complex interplay between national interests and international legal commitments.

Brain-wide alterations revealed by spatial transcriptomics and proteomics in COVID-19 infection.

Understanding the pathophysiology of neurological symptoms observed after severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is essential to optimizing outcomes and therapeutics. To date, small sample sizes and narrow molecular profiling have limited the generalizability of findings. In this study, we profiled multiple cortical and subcortical regions in postmortem brains of patients with coronavirus disease 2019 (COVID-19) and controls with matched pulmonary pathology (total n = 42) using spatial transcriptomics, bulk gene expression and proteomics. We observed a multi-regional antiviral response without direct active SARS-CoV2 infection. We identified dysregulation of mitochondrial and synaptic pathways in deep-layer excitatory neurons and upregulation of neuroinflammation in glia, consistent across both mRNA and protein. Remarkably, these alterations overlapped substantially with changes in age-related neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Our work, combining multiple experimental and analytical methods, demonstrates the brain-wide impact of severe acute/subacute COVID-19, involving both cortical and subcortical regions, shedding light on potential therapeutic targets within pathways typically associated with pathological aging and neurodegeneration.

Comparative analysis of the epidemiological characteristics of adenovirus, rotavirus A, and coinfection in children during 2014–2023 in Guangzhou, China

BackgroundInfection is the cause of diarrhoea, and rotaviruses and adenoviruses are important pathogens in children.MethodsA retrospective study was conducted on 144,067 children with diarrhoea between 2014 and 2023 in China. We used the colloidal gold method to detect intestinal adenovirus and rotavirus A antigens in faeces. The epidemiological characteristics of these viruses and the impact of meteorological factors on them were analysed before and after coronavirus disease 2019 (COVID-19) pandemic.ResultsDuring this decade, the positive rate of adenovirus infection was 6.41%, while the positive rate of rotavirus A infection was 11.81%, higher than that of adenovirus infection. The positive rate of adenovirus and rotavirus A coinfection was 1.92%. The positive rates of adenovirus, rotavirus A and coinfection showed a fluctuating trend, and suddenly decreased in 2020. There was an apparent decrease of positive rate of rotavirus A, with a decrease of 57.27%, during 2020–2023. Surprisingly, the positive rate of adenovirus infection exceeded that of rotavirus A infection in 2021 and 2023. During the COVID-19 pandemic, the proportion of female patients and children over two years of age infected with adenovirus or rotavirus A increased, while the proportion of cases in winter decreased. In addition, we found that the positive rate of rotavirus A infection was related to average temperature and sunshine, and the positive rate of adenovirus and rotavirus A coinfection was only related to sunshine. However, these correlations disappeared during the COVID-19 pandemic.ConclusionsThis study revealed the recent prevalence of adenovirus and rotavirus A infections in children with diarrhoea in south-central China and provided a theoretical basis for the prevention and control of viral diarrhoea.

Pandemic preparedness of Egyptian community pharmacists and potential facilitators to the successful implementation of a community pharmacy coronavirus disease 2019 referral service: a cross-sectional survey.

The coronavirus disease 2019 (COVID-19) pandemic resulted in an increased need for essential community services including new roles for pharmacists. Globally, community pharmacists are a highly accessible point of contact for referral. To assess the preparedness of and facilitators to community pharmacists referring patients with suspected COVID-19 symptoms for testing. A cross-sectional survey was administered using a structured questionnaire to 1023 pharmacists (one respondent in each pharmacy) in Egypt between 17 and 30 May 2020. Pharmacists who had received pandemic referral training were significantly more familiar with the referral system in comparison to those who had not (n = 180; 17.6% vs. n = 841; 82.4%, P = .014). Case referral was significantly associated with the referrer (n = 161, 15.8%), demographics of region (P = .001), graduation year (P = .035), and gender (P = .015). The vast majority of respondents identified facilitators to referring, namely university-level teaching (n = 984, 96.7%), continuing professional development (n = 958, 94.3%), smartphone app (n = 809, 80.5%) or telephone hotline (n = 933, 91.5%), IT access (n = 861, 84.7%), and managing patients' attitudes through the media in terms of the importance of declaring symptoms to (n = 998, 97.7%) and cooperating with (n = 977, 96.2%) referrers. Pharmacists' lack of preparedness to engage with the referral process and related roles contributing to tracking the national COVID-19 infection rate could be mitigated by the provision of facilitators suggested by respondents. These included improved cooperation from local healthcare authorities, educational interventions, technological solutions, and the use of the media. Demographics associated with pharmacists' attitudes to referral, and hence the reliability and validity of the national infection rate, demand further investigation.

Dynamics of SARS-CoV-2 Spike RBD Protein Mutation and Pathogenicity Consequences in Indonesian Circulating Variants in 2020-2022.

Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak, dynamic mutations in the receptor-binding domain (RBD) in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have altered the pathogenicity of the variants of the virus circulating in Indonesia. This research analyzes the mutation trend in various RBD samples from Indonesia published in the Global Initiative on Sharing All Influenza Data (GISAID) database using genomic profiling. Patients in Indonesia infected with SARS-CoV-2, whose samples have been published in genomic databases, were selected for this research. The collected data were processed for analysis following several bioinformatics protocols: visualization into phylogenetic trees, 3D rendering, and the assessment of mutational impact. In Indonesia, there are 25 unique SARS-CoV-2 clades and 318 unique SARS-CoV-2 RBD mutations from the earliest COVID-19 sample to samples collected in 2022, with T478K being the most prevalent RBD mutation and 22B being the most abundant clade. The Omicron variant has a lower docking score, higher protein destabilization, and higher KD than the Delta variant and the original virus. The study findings reveal a decreasing trend in virus pathogenicity as a potential trade-off to increase transmissibility via mutations in RBD over the years.

Early physiologic changes after awake prone positioning predict clinical outcomes in patients with acute hypoxemic respiratory failure.

The optimal physiologic parameters to monitor after a session of awake prone positioning in patients with acute respiratory failure are not well understood. This study aimed to identify which early physiologic changes after the first session of awake prone positioning are linked to the need for invasive mechanical ventilation or death in patients with acute respiratory failure. We performed a secondary analysis of a prospective cohort study of adult patients with acute respiratory failure related to coronavirus disease 2019 (COVID-19) treated with awake prone positioning. We assessed the association between relative changes in physiological variables (oxygenation, respiratory rate, pCO2 and respiratory rate-oxygenation [ROX] index) within the first 6h of the first awake prone positioning session with treatment failure, defined as endotracheal intubation and/or death within 7days. 244 patients [70 female (29%), mean age 60 (standard deviation [SD] 13) years] were included. Seventy-one (29%) patients experienced awake prone positioning failure. ROX index was the main physiologic predictor. Patients with treatment failure had lower mean [SD] ROX index at baseline [5 (1.4) versus 6.6 (2.2), p < 0.0001] and within 6h of prone positioning [5.6 (1.7) versus 8.7 (2.8), p < 0.0001]. After adjusting for baseline characteristics and severity, a relative increase of the ROX index compared to baseline was associated with lower odds of failure [odds ratio (OR) 0.37; 95% confidence interval (CI) 0.25-0.54 every 25% increase]. Relative changes in the ROX index within 6h of the first awake prone positioning session along with other known predictive factors are associated with intubation and mortality at day 7.

Cocrystallization Enables Ensitrelvir to Overcome Anomalous Low Solubility Caused by Strong Intermolecular Interactions between Triazine-Triazole Groups in Stable Crystal Form.

Ensitrelvir is a nonpeptide 3CL protease inhibitor used for coronavirus disease 2019 treatment. Four crystalline forms of ensitrelvir, metastable (Form I), acetonate (Form II), stable (Form III), and hydrate (Form IV), have been analyzed as pharmaceutical crystals. Their rank order of solubility is Form I > IV > III. Form III is the stable crystal with a significantly lower solubility than that predicted from its log P value of 2.7. Here, single-crystal structural analysis revealed strong intermolecular interactions between the triazine (acidic) and triazole (basic) groups of Form III not Forms I and IV. Multicomponent crystals were also designed to improve the solubility by altering the intermolecular interactions in Form III. Slurry conversion with equal molar ratios of ensitrelvir and fumaric acid successfully induced the formation of a novel cocrystal (Form V). Fumaric acid inhibited the triazine-triazole interactions, and dissolution of Form V was approximately 8- and 13-fold higher than that of Form III in pH 1.2 and 6.8 media, respectively. Furthermore, Form V exhibited an approximately 16-fold higher flux value than that of Form III. Therefore, alterations in intermolecular interactions via cocrystallization significantly enhance the dissolution and permeation of ensitrelvir.

Evolving COVID-19 Landscape: Assessing the Effectiveness and Safety Profile of Nirmatrelvir/Ritonavir in Adolescents

This study evaluates nirmatrelvir/ritonavir (Paxlovid) in preventing severe coronavirus disease 2019 in adolescents (12–18). Conducted from January 2022 to July 2023, it compared hospital admissions and healthcare visits within 30 days post-treatment. Results showed similar follow-up rates between treated and untreated groups, with slightly more adverse effects in the nirmatrelvir/ritonavir group. Further research is needed to confirm its efficacy in this population.

An online survey of perspectives towards the impact of the covid-19 pandemic amongst caregivers of adolescents with ASD

BackgroundThe coronavirus disease (COVID-19) pandemic has had a negative impact on the health and mental health of adolescents and adolescents with autism spectrum disorders (ASD) and their caregivers, have been disproportionally affected. The purpose of this study was to investigate the impact of COVID-19 on Thai caregivers and adolescents with ASD.MethodsThis study used an online survey with closed and free text questions to investigate how the pandemic had impacted on social skills development and psychological variables, and perceived needs for support. The survey link was shared to parents via the Yuwaprasart Withayopathum Child and Adolescent Hospital and the social media platforms of known ASD stakeholder networks in Thailand. Binary logistic regression was used to investigate the relationships between sociodemographic characteristics, service use, and social skills problems experienced by adolescents during the pandemic. Content analysis was applied to analyse free-text data.ResultsA total of 376 caregivers of adolescents with ASD aged 10–19 years completed the survey, of which 364 were included in the analysis. In total, 38.7% of caregivers reported that during the pandemic the social skills of their adolescent family member had worsened. Most families reported that they were able to continue to access support from healthcare and educational services, albeit in different ways than pre-pandemic, during the acute stages of the pandemic which benefited the maintenance of ASD symptoms and social skills. Factors identified as reducing the odds of a worsening in social skills during the pandemic included; regular access to treatment for adolescents (odds ratio [OR] = 0.55, confidence interval 95% (CI) 0.32–0.98, p = 0.044), caregivers feeling that they had sufficient support from hospitals (OR = 0.46, 95% CI 0.26–0.81, p = 0.007) and older age of adolescents (OR = 0.53, CI 0.29–0.99, p = 0.047). The qualitative free text comments showed that the caregivers felt that greater information on managing adolescent behaviours, opportunities for adolescents to practice social skills, and the provision of greater emotional support and material assistance from healthcare professionals during the pandemic would have helped them to care for the adolescents with ASD.ConclusionRegular access to services, support from hospitals during the pandemic and older age in adolescence may have helped prevent the worsening of the social skills problems of adolescents with ASD.

Emerging and re-emerging viral exanthems among children: what a physician should know.

Viral exanthems can present with diverse morphologies of rash, including macular, maculopapular, papular, urticarial and vesicular, or sometimes a combination of these. There has been an increasing trend towards emerging and re-emerging viral exanthems in recent years, the cause of which is multifactorial, including changing environmental conditions and altered host-vector-agent interaction. The significant temperature variations brought on by climate change and ever-increasing international travel has modified the host-agent interactions, and many re-emerging viral illnesses are now presenting with atypical presentations, including an increased frequency of affliction across broader age groups and heightened manifestations often posing as 'great imitators' mimicking a myriad of other dermatoses. Although final diagnosis often relies on serological and molecular tests, certain cutaneous clues can help arrive at a probable clinical diagnosis and help the clinicians order specific and relevant investigations, especially in resource-poor settings where access to laboratory diagnostic tests is likely to be limited. In this review we explore the changing disease dynamics of common viral infections, especially in resource-poor settings, including coronavirus disease 2019, chikungunya, hand-foot-and-mouth disease and some newly emerging ones like mpox (previously referred to as monkeypox), and highlight recent developments in our understanding of the clinical variations seen in their presentations.

COVID-19 in Children and Vitamin D.

In December 2019, the so-called "coronavirus disease 2019" (COVID-19) began. This disease is characterized by heterogeneous clinical manifestations, ranging from an asymptomatic process to life-threatening conditions associated with a "cytokine storm". This article (narrative review) summarizes the epidemiologic characteristics and clinical manifestations of COVID-19 and multi-system inflammatory syndrome in children (MIS-C). The effect of the pandemic confinement on vitamin D status and the hypotheses proposed to explain the age-related difference in the severity of COVID-19 are discussed. The role of vitamin D as a critical regulator of both innate and adaptive immune responses and the COVID-19 cytokine storm is analyzed. Vitamin D and its links to both COVID-19 (low levels of vitamin D appear to worsen COVID-19 outcomes) and the cytokine storm (anti-inflammatory activity) are detailed. Finally, the efficacy of vitamin D supplementation in COVID-19 is evaluated, but the evidence supporting vitamin D supplementation as an adjuvant treatment for COVID-19 remains uncertain.

Clinical Characteristics and Mortality Risk Factors of Hospitalized COVID-19 in Children: An Experience of Two Years Pandemic in Regional Referral Hospital

Coronavirus disease 2019 (COVID-19) has spread worldwide rapidly. COVID-19 in children is relatively mild compared to adults. However, several studies showed high mortality rates in children with underlying diseases. This study aimed to describe the clinical characteristics and outcomes of pediatric COVID-19 cases in regional referral hospital. This study was retrospective observational study using data from Medical Record Dr. Moewardi General Hospital between October 1st, 2020 and October 30th, 2022. The epidemiological and clinical data were extracted from the database and were compared with outcomes of patients. All statistical analyses were performed by SPSS software version 27. This study enrolled 371 (19,9%) children with confirmed RT-PCR SARS CoV-2 from 1856 hospitalized suspected children whereas 55% were males, and 63% aged under 5 years old. Moderate-severe patients accounted for 18% of the cases. Cough (74,4%), fever (66,6%) and shortness of breath (22,6) are the most common symptoms while 99 (26,7%) patients who had chronic diseases with the most common diseases being congenital heart disease, hematological malignancy and neurological disorders. Patient outcomes were significantly related to age, degree of severity and chronic disease with p=0.004, p&lt; 0.001, and p&lt; 0.001 respectively. After performing multivariate regression analysis, degree of severity [p&lt;0.001; adjusted OR = 28.03, 95% CI (10.73–73.21)] was found to be significant predictors for mortality. The clinical and epidemiological data revealed that the majority symptom were cough, fever and shortness of breath. Mortality rate during hospitalization was higher in children with moderate-to-severe COVID-19.

Reduced Salivary Gustin and Statherin in Long-COVID Cohort with Impaired Bitter Taste.

Background/Objectives: Taste dysfunction is a frequent symptom of acute coronavirus disease (COVID)-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). While the majority of those affected reported recovery over time, emerging data suggest that 20-25% of individuals experience persistent taste dysfunction, constituting a common symptom of long COVID. Gustation is mediated by continuously renewing taste bud cells. A balance between the counteracting processes of cell generation and cell death maintains the homeostatic turnover. Sonic hedgehog (SHH) is a morphogenic protein that promotes taste cell proliferation and differentiation. Enzymatic proteins such as gustin modulate the environment around the taste receptors and influence taste perception. Hence, we hypothesized that increased taste cell turnover and reduced taste-related salivary proteins contribute to the taste dysfunction in long COVID. Methods: Unstimulated whole saliva (UWS) was collected from individuals with long COVID experiencing taste dysfunction after obtaining informed consent. The normal control included archived saliva samples catalogued prior to 2019. Taste perception was objectively determined by the waterless empirical taste test. The SHH, gustin, and inflammatory cytokines in UWS were determined with ELISA. The expressions of epithelial and taste-cell-specific markers in cellular saliva were assessed by immunoflurorescence. Results: Impaired bitter taste was the most common dysfunction in the long-COVID cohort. Salivary gustin was significantly lower in those with long COVID and correlated with lower bitter taste score. Cellular saliva showed keratin-10- and small-proline-rich protein-positive epithelial cells as well as SHH-, occluding- and KCNQ1-positive taste cells. Conclusions: Salivary gustin could be a marker for impaired bitter taste in long COVID.

What We Convey When We Talk About Public Health Crisis: A Case Study of Global Media Coverage of COVID-19 Using Big Data Approach

This article addresses the urgent need for a comprehensive understanding of the global media coverage of Coronavirus Disease 2019 (COVID-19) by conducting a massive-scale analysis using the Global Database of Events, Language, and Tone. With a dataset encompassing 53,967,878 news items from 4,708 online news sources across 67 countries, the study spans the entire trajectory of the pandemic from the first reported case on December 31, 2019, to September 11, 2020. The analysis aims to surpass the limitations of previous research by offering a worldwide perspective on COVID-19 media coverage over a significant timeframe. Additionally, the paper explores the intricate relationships between media portrayals and the epidemiological situations in primary countries. By examining the media's impact on public perceptions, the study contributes valuable insights to the ongoing discourse on COVID-19, addressing the limitations of prior research and emphasizing the importance of a nuanced and expansive approach to understanding the role of media in the context of global health crises.

AI Promoted Virtual Screening, Structure-Based Hit Optimization, and Synthesis of Novel COVID-19 S-RBD Domain Inhibitors.

Coronavirus disease 2019 (COVID-19) is caused by a new, highly pathogenic severe-acute-respiratory syndrome coronavirus 2 (SARS-CoV-2) that infects human cells through its transmembrane spike (S) glycoprotein. The receptor-binding domain (RBD) of the S protein interacts with the angiotensin-converting enzyme II (ACE2) receptor of the host cells. Therefore, pharmacological targeting of this interaction might prevent infection or spread of the virus. Here, we performed a virtual screening to identify small molecules that block S-ACE2 interaction. Large compound libraries were filtered for drug-like properties, promiscuity and protein-protein interaction-targeting ability based on their ADME-Tox descriptors and also to exclude pan-assay interfering compounds. A properly designed AI-based virtual screening pipeline was applied to the remaining compounds, comprising approximately 10% of the starting data sets, searching for molecules that could bind to the RBD of the S protein. All molecules were sorted according to their screening score, grouped based on their structure and postfiltered for possible interaction patterns with the ACE2 receptor, yielding 31 hits. These hit molecules were further tested for their inhibitory effect on Spike RBD/ACE2 (19-615) interaction. Six compounds inhibited the S-ACE2 interaction in a dose-dependent manner while two of them also prevented infection of human cells from a pseudotyped virus whose entry is mediated by the S protein of SARS-CoV-2. Of the two compounds, the benzimidazole derivative CKP-22 protected Vero E6 cells from infection with SARS-CoV-2, as well. Subsequent, hit-to-lead optimization of CKP-22 was effected through the synthesis of 29 new derivatives of which compound CKP-25 suppressed the Spike RBD/ACE2 (19-615) interaction, reduced the cytopathic effect of SARS-CoV-2 in Vero E6 cells (IC50 = 3.5 μM) and reduced the viral load in cell culture supernatants. Early in vitro ADME-Tox studies showed that CKP-25 does not possess biodegradation or liver metabolism issues, while isozyme-specific CYP450 experiments revealed that CKP-25 was a weak inhibitor of the CYP450 system. Moreover, CKP-25 does not elicit mutagenic effect on Escherichia coli WP2 uvrA strain. Thus, CKP-25 is considered a lead compound against COVID-19 infection.

Translation and cultural adaptation of the Long Coronavirus Disease (COVID) Symptom and Impact Tools for the Chilean population.

The Long Coronavirus Disease (COVID) Symptom and Impact Tools (ST and IT) were published in English in 2022 to monitor the symptoms and impact of persistent COVID-19. ST includes 53 symptoms selected by the patient. IT includes six aspects of life that the patient must rate from 1 to 10 points. We aim to report the results of the cultural adaptation of both instruments for the Chilean population, together with the content validity of the adapted instrument. The cultural adaptation was carried out in five steps: 1) translation from English to Spanish, 2) synthesis, 3) back-translation, 4) review by the editorial board, and 5) testing the questionnaire with ten patients; they answered both questionnaires and seven questions assessing their understanding of the TI and their opinion on whether the instrument reflected the impact of prolonged COVID-19 on their lives. The content validity of the final version of the IT was assessed by 14 experts. The main outcome is the two final questionnaires adapted for use in Chile. Most patients responded with the best concept or approval for all items. Content validity showed acceptable results, with an average content validity index of 0.9 and Aiken's V for the relevance of the questionnaire in general of 0.83 (95% CI 0.69 to 0.92). For one item, Aiken's V was less than 0.7 (95% CI 0.5 to 0.8). This study provides Chilean health authorities and health providers with an instrument for assessing the impact of prolonged COVID-19 on core aspects of people's lives.