Angiotensin-converting enzyme 2 (ACE2) is identified as the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing global coronavirus disease-2019 (COVID-19) pandemic. This study aimed to elucidate potential therapeutic avenues by scrutinizing approved drugs through the identification of the genetic signature associated with SARS-CoV-2 infection in individuals with asthma. This exploration was conducted through an integrated analysis, encompassing interaction networks between the ACE2 receptor and common host (co-host) factors implicated in COVID-19/asthma comorbidity. The comprehensive analysis involved the identification of common differentially expressed genes (cDEGs) and hub-cDEGs, functional annotations, interaction networks, gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and module construction. Interaction networks were used to identify overlapping disease modules and potential drug targets. Computational biology and molecular docking analyzes were utilized to discern functional drug modules. Subsequently, the impact of the identified drugs on the expression of hub-cDEGs was experimentally validated using a mouse model. A total of 153 cDEGs or co-host factors associated with ACE2 were identified in the COVID-19 and asthma comorbidity. Among these, seven significant cDEGs and proteins - namely, HRAS, IFNG, JUN, CDH1, TLR4, ICAM1, and SCD-were recognized as pivotal host factors linked to ACE2. Regulatory network analysis of hub-cDEGs revealed eight top-ranked transcription factors (TFs) proteins and nine microRNAs as key regulatory factors operating at the transcriptional and post-transcriptional levels, respectively. Molecular docking simulations led to the proposal of 10 top-ranked repurposable drug molecules (Rapamycin, Ivermectin, Everolimus, Quercetin, Estradiol, Entrectinib, Nilotinib, Conivaptan, Radotinib, and Venetoclax) as potential treatment options for COVID-19 in individuals with comorbid asthma. Validation analysis demonstrated that Rapamycin effectively inhibited ICAM1 expression in the HDM-stimulated mice group (p < 0.01). This study unveils the common pathogenesis and genetic signature underlying asthma and SARS-CoV-2 infection, delineated by the interaction networks of ACE2-related host factors. These findings provide valuable insights for the design and discovery of drugs aimed at more effective therapeutics within the context of lung disease comorbidities.

COVID-19 caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2, (SARS-CoV-2) is a highly contagious disease known for its significant lung damage. Although the impact of the COVID-19 pandemic on our daily lives has been limited, the virus has not vanished entirely and continues to undergo mutations. This calls for a concentrated focus on the matter of SARS-CoV-2 immune evasion. Drawing on observations of immune escape mechanisms in other viruses, some scholars have proposed that liquid-liquid phase separation might play a crucial role in SARS-CoV-2's ability to evade the immune system. Within the structure of SARS-CoV-2, the nucleocapsid protein plays a pivotal role in RNA replication and transcription. Concurrently, this protein can engage in phase separation with RNA. A thorough examination of the phase separation related to the nucleocapsid protein may unveil the mechanism by which SARS-CoV-2 accomplishes immune evasion. Moreover, this analysis may provide valuable insights for future development of innovative antiviral drugs or vaccines.

Russia's invasion of Ukraine contributed one of the largest migration movements in the 21st century. Refugees may become a source of severe acute respiratory syndrome coronavirus 2 infections for the residents of host countries. The study aim was to assess knowledge and preventive practices regarding coronavirus disease 2019 (COVID-19) among Ukrainian refugees in Poland. The cross-sectional study was conducted between March and April 2022 among Ukrainian refugees registering consecutively in Zielona Góra, Poland. Knowledge and preventive practices were assessed by giving 1 point for each correct answer by anonymous, self-administered questionnaire. The response rate was 96%, 190 participated (mean age 37.8 ± 15.5 years; 57.9% females); 61.6% self-reported their socio-economic status (SES) as high, 38.9% reported high level of education. The mean COVID-19 knowledge score was 3.06 ± 1.95; 19.5% scored >50%. The knowledge level was higher among migrants with high SES (P = .003). The mean preventive practices score was 2.56 ± 1.38; 54.0% scored ≥ 60%. 40.5% declared social distancing, 62.6% followed coughing etiquette, 69.0% home isolate themselves during COVID-19. 57.9% always used masks in public space, however 74.2% wore masks with uncovered nose. Refugees with higher education, high SES and knowledge level had significantly greater preventive practices scores (P = .002; P = .02; P = .03, respectively). The knowledge and preventive practices level was insufficient. Educational campaigns oriented to raising knowledge and prevention behavior skills should be implemented, especially targeting high-risk groups to avoid spread of COVID-19.

The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-prealbumin ratio (CPAR) are novel markers of inflammation. The CPAR is an indicator of inflammation and malnutrition. We evaluated NLR and CPAR in combination as indicators of disease severity and prognosis in hospitalized older patients with coronavirus disease 2019 (COVID-19). A total of 222 hospitalized patients with COVID-19 (aged > 60 years) were divided into non-severe and severe groups. The severe group was subdivided into the surviving and deceased subgroups. We retrospectively assessed the predictive power of NLR and CPAR in combination (NLR + CPAR) to determine the prognosis of hospitalized older patients with COVID-19. The NLR and CPAR were significantly higher in the severe group than in the non-severe group (P < .001). Furthermore, the NLR and CPAR were higher in the deceased subgroup than in the surviving subgroup (P < .001). Pearson correlation analysis showed a highly significant positive correlation between NLR and CPAR (P < .001, r = 0.530). NLR + CPAR showed an area under the curve of 0.827 and sensitivity of 83.9% in the severe group; the area under the curve was larger (0.925) and sensitivity was higher (87.1%) in the deceased subgroup. The receiver operating characteristic curve of NLR + CPAR was significantly different from the receiver operating characteristic curves of either biomarker alone (P < .001). Kaplan-Meier analysis showed that patients in the severe group with elevated NLR + CPAR had a significantly lower 90-day survival rate than patients who lacked this finding (odds ratio 7.87, P < .001). NLR + CPAR may enable early diagnosis and assessment of disease severity in hospitalized older patients with COVID-19. This may also enable the identification of high-risk older patients with COVID-19 at the time of admission.

Rationale: The novel coronavirus of 2019 (COVID-19) has inflicted significant harm on the cardiovascular system. Patients presenting with fatal chronic arrhythmias after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are rare, arrhythmia caused by SARS-CoV-2 infection need to be taken seriously.

Patient concerns: Three female patients were admitted to the hospital with syncopal symptoms. Previously, they had been identified to have COVID-19 infection and none of the patients had a preexisting history of arrhythmia, and upon hospital admission, no electrolyte imbalances associated with arrhythmias were observed. However, following SARS-CoV-2 infection, patients exhibit varying degrees of syncope symptoms.

Diagnoses: A high-degree atrioventricular block was diagnosed after a comprehensive evaluation of the patient's clinical manifestations and electrocardiogram (ECG) performance.

Interventions: We performed ECG monitoring of the patient and excluded other causes of arrhythmia. The patient was discharged from the hospital after permanent pacemaker implantation and symptomatic treatment.

Outcomes: The outpatient follow-ups did not reveal a recurrence of syncope or complications related to the pacemaker in any of the three patients.

Lessons: Some patients did not exhibit any obvious respiratory symptoms or signs following SARS-CoV-2 infection. This suggests that the cardiac conduction system may be the preferred target for some SARS-CoV-2 variants. Therefore, in addition to investigating the causes of malignant arrhythmias, special attention should be paid to SARS-CoV-2 infection in patients with developing arrhythmias. Additionally, permanent pacemaker implantation may be the most suitable option for patients who already have malignant arrhythmias.

Taiwan is one of the countries with the highest motorcycle per capita globally, and motorcycle crashes are predominant among traffic crashes. This study examines the impact of coronavirus disease 2019 restrictions on motorcycle crashes. We analyzed the trend of motorcycle crashes in Taipei City from 2019 to 2020 using the dataset provided by the Department of Transportation, Taipei City Government, Taiwan. We found 47,108 and 51,441 motorcycle crashes in 2019 and 2020, involving 61,141 and 67,093 motorcycles, respectively. Mopeds had the highest risk in 2020, followed by heavy motorcycles [≥550 cubic capacity (cc)] and scooters compared to 2019. Food delivery motorcycle crashes increased for scooters (0.93% in 2019 to 3.45% in 2020, P < .0001) and heavy motorcycles (250 < cc < 550) (0.90% in 2019 to 3.38% in 2020, P < .0001). While fatalities remained under 1%, 30% to 51% of motorcyclists sustained injuries. Food delivery with scooters or heavy motorcycles (250 < cc < 550) was significantly associated with motorcyclist injuries and deaths. Compared with 2019, the adjusted odds ratios of motorcyclist injuries and deaths in 2020 were 1.43 (95% confidence interval = 1.05-1.94) for heavy motorcycles (≥550 cc) and 1.07 (95% confidence interval = 1.04-1.09) for scooters. This study shows that coronavirus disease 2019 restrictions was associated with elevated risks of crashes, injuries, and deaths among motorcyclists, reflecting the general preference for private transport over public transport. The popularity of food delivery services also contributed to increased motorcycle crashes.

In condition of challenges from menaces to health due to COVID-19 the role of primary health care physicians increases that requires development of management decisions at the regional level. The purpose of the study. On the basis of analysis of medical demographic indicators and data concerning provision of primary health care personnel in the Russian Federation, proposals were made related to reforming of primary health care system in conditions of implementation of general medical practice with purpose to counteract menaces to population health. The analytical and statistical methods were applied. The official statistics data from the Minzdrav of the Russian Federation and Rosstat, results of original researches with content analysis and interpretation were used. The COVID-19 pandemic negatively impacted population health. The indicator of newly detected morbidity in the Russian Federation in 2020 decreased as compared to 2019 from 78024.3 to 75989.7‰oo (by 2.6%). This is the result of decreasing of dispensary and preventive activities among population. In next COVID-19 year (2021), as compared to 2020, indicator of primary morbidity increased to 85531.6‰oo that 12.6% higher than in 2020. The increase occurred in all classes of diseases that caused necessity of rehabilitation of these patients. The COVID-19 morbidity increased up to 2.4 times i.e. from 3391.1 in 2020 to 8085.7‰oo in 2021. The provision of physicians in the Russian Federation was 37.7‰o in 2021. Across the Federal Okrugs differences in indicators made up to 1.3 times and in subjects of the Russian Federation - up to 2.7 times. In conditions of COVID-19 significance of menaces to population health worsened. The situation requires both enhancement of primary health care and implementation of physicians of new formation - general practitioners responsible for patient health. The general practice (GP) widely developed in Russia in the 1990s during last ten years loses its significance in most subjects of the Russian Federation. In 2021, provision of general practitioners in the Russian Federation made up to 0.67‰o. In the Federal Okrugs, difference between indicators made up to 5.6 times. In the subjects of the Russian Federation the difference is enormous - 141.5 times. The article presents and scientifically substantiates prospective functional organizational models of general practice. The established situation with COVID-19 infection requires development of management decisions and measures at the regional level concerning improvement of organization of primary health care and implementation of general practice in conditions of counteracting risks of menaces to population health and health preservation.

The interest of population to biologically active additives drastically increased both due to consequences of the COVID-19 corona-virus infection and dynamic development of online trade and active propaganda of healthy lifestyle through mass media. Such production contains in its compound substances that are necessary for maintaining normal vital activity of organism and increasing human immunity. In other cases it can be used as additional and auxiliary agent of treatment of various diseases. In Russia, biologically active additives can be sold through three channels: pharmacies, on-line market and network marketing. In Russia, the results of monitoring of on-line market in 2021-2022 testifies that purchasing of such biologically active additives at on-line platforms turned out to be the riskiest action for human life and health. The biologically active additives were sold at on-line market with serious violations that confirms their danger to health and in some cases for human life. The study demonstrated that nowadays there is no clear-cut legal regulation of turn-over of imported biologically active additives at on-line market. The article presents detailed analysis of normative legal field that regulates in Russia on-line trade of imported biologically active additives and relevant conclusions and recommendations.

Background: The emotional impact of the coronavirus disease 2019 (COVID-19) pandemic on people with dementia has been quantified. However, little is known about the impact of change in home-care use owing to the pandemic.

Objective: To determine the longitudinal association between dementia, change in home-care use, and depressive symptoms during the pandemic.

Methods: We included data of 43,782 home-dwelling older adults from the English Longitudinal Study of Ageing (ELSA), Study of health, Ageing and Retirement in Europe (SHARE), and National Health and Aging Trends Study (NHATS). This study considered the latest main wave survey prior to the pandemic as the baseline, and the COVID-19 survey as follow-up. In a series of coordinated analyses, multilevel binomial logistic regression model was used to examine the association between baseline dementia, change in home-care use at follow-up, and presence of depressive symptoms.

Results: Dementia, using the ELSA, SHARE, and NHATS datasets, was identified in 2.9%, 2.3%, and 6.5% of older adults, and home-care use reduced in 1.7%, 2.8%, and 1.1% of individuals with dementia, respectively. Dementia was significantly associated with the increased risk of depressive symptoms in all three cohorts. However, the interaction between dementia and period (follow-up) was non-significant in SHARE and NHATS. Across all three cohorts, home-care use during the pandemic, regardless of change in amount, was significantly associated with increased depressive symptoms, compared to the non-use of home care.

Conclusions: These results highlight the need for tailoring dementia care at home to promote independence and provide sustainable emotional support.

Background: The number of coronavirus disease-19 (COVID-19) positive patients and fatalities keeps rising. It is important to recognize risk factors for severe outcomes. Evidence linking vitamin D deficiency and the severity of COVID-19 is tangential but substantial - relating to race, obesity, and institutionalization.

Objective: This study aims to examine the function of vitamin D and nutritional defense against infections such as COVID-19, which is the goal of this research.

Methods: This study includes observational cohort, cross-sectional, and case-control studies that estimated variances in serum levels of vitamin D among patients with mild or severe forms of COVID-19, and in patients who died or were discharged from hospitals. Studies that assessed the risk of developing severe disorder or death in patients with vitamin D deficiency, defined as levels of vitamin D< 20 ng/mL, were also encompassed.

Results: In a retrospective study on 464,383 individuals, results showed that individuals who had the highest risks for severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection, and for COVID-19 severity when infected, had vitamin D levels < 30 nmol/L; Odds Ratio (OR) were 1.246 [95% Confidence Interval (CI): 1.210-1.304] and 1.513 [95%CI: 1.230-1.861], respectively. Additionally, in a retrospective observational study of 191,779 individuals in the USA. The SARS-CoV-2 positivity rate was greater in the 39,190 subjects with vitamin D < 20 ng/mL [12.5%, 95% C.I. 12.2-12.8%] than in the 27,870 subjects with sufficient serum vitamin D levels [8.1%, 95% C.I. 7.8-8.4%] and in the 12,321 subjects with serum vitamin D ⩾ 55 ng/mL [5.9%, 95% C.I. 5.5-6.4%].

Conclusion: People hospitalized for COVID-19 should be checked for vitamin D status and supplemented, and high-dose-in testing should be considered in the recovery trial. More importantly, screening for malnutrition and the administration of the best nutritional supplements are essential for the immune system of the human body to function as it should be. Thus, nutritional supplementation is crucial for people with risk factors as well as older adults with compromised immune systems.

Background: The coronavirus-19 (COVID-19) pandemic caused delays in the diagnosis and management of breast cancer which may have affected disease presentation. The aim of this study was to compare rates of metastatic disease, tumour characteristics and management in breast cancer patients diagnosed before and after the onset of COVID-19.

Methods: A retrospective chart review was conducted on patients in a university teaching hospital who were diagnosed with invasive symptomatic breast cancer in 2019 (prepandemic control group) and in 2020, 2021, and 2022 (pandemic study groups). Rates of new metastatic presentations, tumour histopathological characteristics, operation type, and therapies administered were statistically compared.

Results: A total of 1416 patients were identified. There was a significant increase in new metastatic breast cancer presentations in 2022 compared to 2019 (14.0% vs 3.8%, p ≤ 0.001), with non-significant increases in 2020 and 2021. Rates of adjuvant radiotherapy increased in 2020 and decreased in 2022 compared to 2019, with no significant change in neoadjuvant or adjuvant chemotherapy rates. Rates of axillary surgery increased during 2020 and 2021. There was an increase in high-grade tumours and lymphovascular invasion (LVI), and less frequent oestrogen receptor (ER) positivity in pandemic groups. No significant change was noted in BCS to mastectomy ratios, overall nodal positivity rates, or median tumour size.

Conclusion: Symptomatic breast cancers diagnosed since the onset of COVID-19 demonstrated an increase in new metastatic presentations and more aggressive histopathological characteristics when compared to a pre-pandemic control group. Rates of adjuvant radiotherapy and axillary surgery increased during the pandemic.

At the end of 2022, the adjustment of the coronavirus disease 2019 (COVID-19) pandemic control policy in China resulted in a large-scale increase in public infection. To compare the fertility parameters of male patients before and after the adjustments of the COVID-19 pandemic control policy in China, we collected data on patients' medical histories and laboratory examinations on their first visits between June 2022 and March 2023 in five different hospitals. Data were divided into five groups according to the timeline of the policy adjustment. The data we collected from male patients included semen quality and serum reproductive hormone levels, and intergroup comparisons were made using the Mann-Whitney U and Chi-square tests. In total, 16 784 cases underwent regular semen analysis, 11 180 had sperm morphology assessments, and 7200 had reproductive hormone analyses. The data showed declining trends in semen volume, sperm motility, and the progressive sperm motility rate after the policy adjustment. Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate. Sperm morphology analysis showed increased neck and tail abnormalities after the policy adjustment. No significant change in hormone levels was observed. Following the adjustment of the COVID-19 prevention policy in China, a decline in sperm motility and morphology was observed. This trend may gradually recover over 2 months. After the policy adjustment, reproductive hormone levels were relatively stable throughout, except for an increase in luteinizing hormone (LH). These changes in semen parameters suggest that the policy adjustment had a short- to medium-term impact on male reproductive function.

Background aims: Long coronavirus disease (COVID) is estimated to occur in up to 20% of patients with coronavirus disease 2019 (COVID-19) infections, with many having persistent pulmonary symptoms. Mesenchymal stromal cells (MSCs) have been shown to have powerful immunomodulatory and anti-fibrotic properties. Autologous adipose-derived (AD) stromal vascular fraction (SVF) contains MSC and other healing cell components and can be obtained by small-volume lipoaspiration and administered on the same day. This study was designed to study the safety of AD SVF infused intravenously to treat the pulmonary symptoms of long COVID.

Methods: Five subjects with persistent cough and dyspnea after hospitalization and subsequent discharge for COVID-19 pneumonia were treated with 40 million intravenous autologous AD SVF cells and followed for 12 months, to include with pulmonary function tests and computed tomography scans of the lung.

Results: SVF infusion was safe, with no significant adverse events related to the infusion out to 12 months. Four subjects had improvements in pulmonary symptoms, pulmonary function tests, and computed tomography scans, with some improvement noted as soon as 1 month after SVF treatment.

Conclusions: It is not possible to distinguish between naturally occurring improvement or improvement caused by SVF treatment in this small, uncontrolled study. However, the results support further study of autologous AD SVF as a treatment for long COVID.

Objective: Bebtelovimab (BEB), Tixagevimab/Cilgavimab (TIX/CIL), and Sotrovimab (SOT) are important agents against the severe acute respiratory syndrome coronavirus 2-Omicron strain. However, due to their short duration of application, little is known about their safety profiles. This research aimed to explore the safety profile of these monoclonal antibodies (mAbs) via real-world evidence databases and data mining tools.

Materials and methods: Safety reports were retrieved from the database of the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System from April 2022 to March 2023. To detect the safety signal, the disproportionality analysis was performed using the reporting odds ratio method.

Results: SOT had the greatest proportion of "skin and subcutaneous tissue disorders" and "disorders of investigations"; BEB showed significant associations with "gastrointestinal disorders" and "nervous system disorders"; TIX/CIL had the weakest correlation with "skin and subcutaneous tissue disorders" and "general disorders and administration site conditions". Furthermore, there were still other signals related to nervous system disorders, gastrointestinal disorders only caused by BEB. TIX/CIL has been reported solely to be associated with multiple types of cardiovascular disorders. As for SOT alone, signals were strongly related to infusion reactions and hypersensitivity.

Conclusions: In summary, SOT may be unsuitable for allergic patients and may lead to abnormal test results. BEB showed the highest correlations with gastrointestinal and neuropsychiatric events. In addition, its infusion reactions should also be noted. TIX/CIL can lead to a variety of cardiovascular events.

Objective: The variant BA.2.86 of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing concern globally. The virus contains a large number of mutations, and transmission trends are rapidly changing globally. This study investigates the global epidemiological and transmission trends of SARS-CoV-2 new variant BA.2.86 in various continents and countries.

Materials and methods: The data were recorded using key terms, including SARS-CoV-2, Omicron, BA.2.86, epidemiology, occurrence, incidence, prevalence, and transmission trends. The data on SARS-CoV-2 variant BA.2.86 were searched by the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), the Global Initiative on Sharing All Influenza Data (GSIAD), PubMed, and Web of Science. Initially, 40 documents were identified, and finally, 8 documents were included for the data analysis and discussion. The analysis of findings on transmission trends was based on the data from August 14, 2023, to February 28, 2024.

Results: The SARS-CoV-2, novel variant BA.2.86, crossed the international borders of 6 continents and 89 countries and infected 19,532 people. In Europe, 32 countries are affected and involved 12,667 people (64.85%), North and South America 18 countries with 3,515 cases (17.99%), Asia 27 countries with 2,063 people (10.56%), Oceania 2 countries with 689 cases (3.52%), and Africa 10 countries with 598 (3.06%) cases. The BA.2.86 rapidly spread and mainly affected the people in the United Kingdom 3,228 (16.52%), Sweden 2,380 (12.18%), USA 1,929 (9.87%), Denmark 1,621 (8.29%), Canada 1,516 (7.67%), France 833 (4.26%), Japan 810 (4.14%), Netherlands 725 (3.71%), Germany 681 (3.48%), Spain 665 (3.40%), South Korea 556 (2.84%), and Australia 512 (2.62%).

Conclusions: The SARS-CoV-2, novel variant BA.2.86, spread over six continents and 89 countries and affected 19,532 people worldwide. The disease is more prevalent in the United Kingdom, United States of America, and European countries. The detection of the disease in multiple continents and countries suggests some degree of transmissibility. Global health authorities need to rethink their policies and implement strict strategies to eradicate emerging variants and minimize the global disease burden.

Objective: The global coronavirus pandemic has placed an unprecedented and enormous burden on health systems worldwide. In addition to a shortage of resources, nurses were also confronted with high levels of sick leave and an increasing exodus from the profession. Automating documentation obligations is an effective way of reducing the burden on the workplace.

Patients and methods: The study was conducted at a tertiary university hospital. The time required for the manual documentation of administered medication and dose changes of syringe and infusion pumps was recorded using the patient data management system (PDMS) representing all intensive and intermediate care wards (n = 6). Subsequently, all medication administration - grouped into five classes - was evaluated from January 1st, 2019, until December 31st, 2022.

Results: A total of 1,373,340 drug applications were studied, treating 32,499 patients. Data were obtained from ICUs (68%) and IMC wards (32%). This corresponds to an overall time of 2,901 ± 233 hours per year. Based on publicly known national rates for intensive care nurses, an annual financial expenditure of approximately 83,300 € (~ USD 89,300) per year was estimated.

Conclusions: A non-negligible part of the daily working time in the medical sector is spent on documentation duties. This aggravates the high workload, which has increased in recent years. Automated documentation systems can lead to considerable relief and the possibility of focusing primarily on the patient and on other core competencies and activities. This is even more important, as available staff will be a key resource in patient care for the foreseeable future.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the novel coronavirus severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has rapidly spread worldwide since its emergence in late 2019. Its ongoing evolution poses challenges for antiviral drug development. Coronavirus nsp6, a multiple-spanning transmembrane protein, participates in the biogenesis of the viral replication complex, which accommodates the viral replication-transcription complex. The roles of its structural domains in viral replication are not well studied. Herein, we predicted the structure of the SARS-CoV-2 nsp6 protein using AlphaFold2 and identified a highly folded C-terminal region (nsp6C) downstream of the transmembrane helices. The enhanced green fluorescent protein (EGFP)-fused nsp6C was found to cluster in the cytoplasm and associate with membranes. Functional mapping identified a minimal membrane-associated element (MAE) as the region from amino acids 237 to 276 (LGV-KLL), which is mainly composed of the α-helix H1 and the α-helix H2; the latter exhibits characteristics of an amphipathic helix (AH). Mutagenesis studies and membrane flotation experiments demonstrate that AH-like H2 is required for MAE-mediated membrane association. This MAE was functionally conserved across MERS-CoV, HCoV-OC43, HCoV-229E, HCoV-HKU1, and HCoV-NL63, all capable of mediating membrane association. In a SARS-CoV-2 replicon system, mutagenesis studies of H2 and replacements of H1 and H2 with their homologous counterparts demonstrated requirements of residues on both sides of the H2 and properly paired H1-H2 for MAE-mediated membrane association and viral replication. Notably, mutations I266A and K274A significantly attenuated viral replication without dramatically affecting membrane association, suggesting a dual role of the MAE in viral replication: mediating membrane association as well as participating in protein-protein interactions.IMPORTANCESevere acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) assembles a double-membrane vesicle (DMV) by the viral non-structural proteins for viral replication. Understanding the mechanisms of the DMV assembly is of paramount importance for antiviral development. Nsp6, a multiple-spanning transmembrane protein, plays an important role in the DMV biogenesis. Herein, we predicted the nsp6 structure of SARS-CoV-2 and other human coronaviruses using AlphaFold2 and identified a putative membrane-associated element (MAE) in the highly conserved C-terminal regions of nsp6. Experimentally, we verified a functionally conserved minimal MAE composed of two α-helices, the H1, and the amphipathic helix-like H2. Mutagenesis studies confirmed the requirement of H2 for MAE-mediated membrane association and viral replication and demonstrated a dual role of the MAE in viral replication, by mediating membrane association and participating in residue-specific interactions. This functionally conserved MAE may serve as a novel anti-viral target.

This research evaluated the relationship between daily new Coronavirus Disease 2019 (COVID-19) cases and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) concentrations in wastewater, followed by effects of differential SARS-CoV-2 shedding loads across various COVID-19 outbreaks. Linear regression analyses were utilized to examine the lead time of the SARS-CoV-2 signal in wastewater relative to new COVID-19 clinical cases. During the Delta wave, no lead time was evident, highlighting limited predictive capability of wastewater monitoring during this phase. However, significant lead times were observed during the Omicron wave, potentially attributed to testing capacity overload and subsequent case reporting delays or changes in shedding patterns. During the Post-Omicron wave (Febuary 23 to May 19, 2022), no lead time was discernible, whereas following the lifting of the COVID-19 state of emergency (May 30, 2022 to May 30, 2023), the correlation coefficient increased and demonstrated the potential of wastewater surveillance as an early warning system. Subsequently, we explored the virus shedding in wastewater through feces, operationalized as the ratio of SARS-CoV-2 concentrations to daily new COVID-19 cases. This ratio varied significantly across the Delta, Omicron, other variants and post-state-emergency phases, with the Kruskal-Wallis H test confirming a significant difference in medians across these stages (P < 0.0001). Despite its promise, wastewater surveillance of COVID-19 disease prevalence presents several challenges, including virus shedding variability, data interpretation complexity, the impact of environmental factors on viral degradation, and the lack of standardized testing procedures. Overall, our findings offer insights into the correlation between COVID-19 cases and wastewater viral concentrations, potential variation in SARS-CoV-2 shedding in wastewater across different pandemic phases, and underscore the promise and limitations of wastewater surveillance as an early warning system for disease prevalence trends.

Introduction Coronavirus-19 (COVID-19) plays a vital role in viral-induced hypercoagulability through the initiation of a cytokine storm. This mechanism has been found to predispose unvaccinated patients to systemic complications including arterial thrombosis (AT) with poor 30-day amputation-free survival rates. There remains, however, little understanding regarding the incidence in patients who have received a COVID-19 vaccination. This study aims to assess the incidence, management and outcomes of vaccinated patients with COVID-19 who develop thrombotic complications to reduce amputation and direct mortality. Methods The case notes of all emergency patients with COVID-19 referred to the vascular services in a tertiary referral centre between November 2021 and April 2022 were reviewed. Patients who were unvaccinated or admitted with stroke or coronary thrombosis were excluded. The study was undertaken to measure 30-day outcomes. Results Between November 2021 and April 2022, 167,290 people tested positive for COVID-19 in Norfolk. Thirty-one patients under the vascular service had COVID-19, of which, one patient was unvaccinated. Only one vaccinated patient was referred with AT and had a positive COVID-19 result two days after admission. Above-knee amputation was performed within 30 days and he survived. Seventeen percent of patients contracted COVID-19 during their hospital admission. Conclusion The incidence of acute limb ischaemia in vaccinated patients is low; however, the 30-day outcomes remain poor. Compared to unvaccinated patients, there was a significant reduction in the presentation of AT in vaccinated patients during that timeframe, despite a higher background number of COVID-19 cases. Therefore, vaccination may minimise the risk of AT.

Autonomic nervous system (ANS) regulation in hereditary angioedema (HAE) and coronavirus disease 2019 (COVID-19) is unknown. ANS alterations could be manifested during both the acute and post-acute phases of COVID-19. Implications of acute and chronic inflammation on ANS in HAE need to be addressed. In this case report, we monitored the systolic arterial blood pressure variability and baroreflex sensitivity in a female HAE patient both before experiencing COVID-19 symptoms and one month afterward. We also tracked the heart rate variability on the day preceding symptom onset, the day of symptom onset (SYM), the day following SYM, five days after SYM, the day of the first negative nasopharyngeal swab (i.e., 12 days after SYM), and one month after symptom onset. The results of this case report provide the characterization of vascular and cardiac autonomic profiles in an HAE patient until the resolution of an acute infection, a potential trigger for the acute HAE attack.

Background: Artificial intelligence (AI) based models are explored increasingly in the medical field. The highly contagious pandemic of coronavirus disease 2019 (COVID-19) affected the world and availability of diagnostic tools high resolution computed tomography (HRCT) and/or real-time reverse transcriptase-polymerase chain reaction (RTPCR) was very limited, costly and time consuming. Therefore, the use of AI in COVID-19 for diagnosis using cough sounds can be efficacious and cost effective for screening in clinic or hospital and help in early diagnosis and further management of patients.

Objectives: To develop an accurate and fast voice-processing AI software to determine voice-based signatures in discriminating COVID-19 and non-COVID-19 cough sounds for screening of COVID-19.

Methodology: A prospective study involving 117 patients was performed based on online and/or offline voice data collection of cough sounds of COVID-19 patients in isolation ward of a tertiary care teaching hospital and non-COVID-19 participants using a smart phone. A website-based AI software was developed to identify the cough sounds as COVID-19 or non-COVID-19. The data were divided into three segments including training set, validation set and test set. A pre-processing algorithm was utilized and combined with Short Time Fourier Transform feature representation and Logistic regression model. A precise software was used to identify vocal signatures and K-fold cross validation was carried out.

Result: A total of 117 audio recordings of cough sounds were collected through the developed website after inclusion-exclusion criteria out of which 52 have been marked belonging to COVID-19 positive, while 65 were marked as COVID-19 negative/unsure /never had COVID-19, which were assumed to be COVID-19 negative based on RT-PCR test results. The mean and standard error values for the accuracies attained at the end of each experiment in training, validation and testing set were found to be 67.34%±0.22, 58.57%±1.11 and 64.60%±1.79 respectively. The weight values were found to be positive which were contributing towards predicting the samples as COVID-19 positive with large spikes around 7.5 kHz, 7.8 kHz, 8.6 kHz and 11 kHz which can be used for classification.

Conclusion: The proposed AI based approach can be a helpful screening tool for COVID-19 using vocal sounds of cough. It can help the health system by reducing the cost burden and improving overall diagnosis and management of the disease.

Background Since February 2020, the number of coronavirus disease 2019 (COVID-19) cases in Saudi Arabia has been rising. The Saudi Arabian government implemented strict lockdown measures in March 2020 in an effort to stop the spread of the virus. Globally, changes in socioeconomic levels and health during quarantine have been reported. Additional detrimental effects of the stay-at-home mandate include less physical activity among adult populations, anxiety, stress, and emotional eating. This study aimed to assess the impact of quarantine during the COVID‑19 pandemic on physical activity practice and weight. Methodology This cross-sectional study was conducted using a newly developed validated online questionnaire survey. The data were collected during quarantine in June 2020, including each adult who lived in Saudi Arabia during the quarantine. The data were reviewed and analyzed using SPSS version 21 (IBM Corp., Armonk, NY, USA). Results A total of 4,970 eligible participants completed the study survey. About 78.1% of the study participants performed physical activity inside the house during the pandemic. Overall, 30.9% reported increased body weight during the lockdown, and the most reported cause of increased body weight was feeling bored and empty. Regarding factors associated with physical activity and weight changes, 82.2% of participants aged 25-30 years performed physical activity during the pandemic. Increased weight was significantly higher among participants aged more than 30 years. Conclusions This study shows an increased level of physical activity among the study participants during the COVID-19 pandemic, especially among younger, female, and unmarried participants. More than half of the participants reported weight change, either weight gain or weight loss. Weight gain was higher in older participants. Regarding eating habits, there was an increased tendency toward eating a healthy diet.

A primary reason for the ongoing spread of coronavirus disease 2019 (COVID-19) is the continuous acquisition of mutations by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanism of acquiring mutations is not fully understood. In this study, we isolated SARS-CoV-2 from an immunocompromized patient persistently infected with Omicron strain BF.5 for approximately 4 months to analyze its genome and evaluate drug resistance. Although the patient was administered the antiviral drug remdesivir (RDV), there were no acquired mutations in RDV binding site, and all isolates exhibited susceptibility to RDV. Notably, upon analyzing the S protein sequence of the day 119 isolate, we identified mutations acquired by mutant strains emerging from the BF.5 variant, suggesting that viral genome analysis in persistent COVID-19 patients may be useful in predicting viral evolution. These results suggest mutations in SARS-CoV-2 are acquired during long-term viral replication rather than in response to antiviral drugs.

Monitoring in vivo viral dynamics can improve our understanding of pathogenicity and tissue tropism. Because the gene size of RNA viruses is typically small, NanoLuc is the primary choice for accommodation within viral genome. However, NanoLuc/Furimazine and also the conventional firefly luciferase/D-luciferin are known to exhibit relatively low tissue permeability and thus less sensitivity for visualization of deep tissue including lungs. Here, we demonstrated in vivo sufficient visualization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using the pair of a codon-optimized Akaluc and AkaLumine. We engineered the codon-optimized Akaluc gene possessing the similar GC ratio of SARS-CoV-2. Using the SARS-CoV-2 recombinants carrying the codon-optimized Akaluc, we visualized in vivo infection of respiratory organs, including the tissue-specific differences associated with particular variants. Additionally, we could evaluate the efficacy of antivirals by monitoring changes in Akaluc signals. Overall, we offer an effective technology for monitoring viral dynamics in live animals.

Introduction: Trials have demonstrated the benefits of methylprednisolone in the treatment of coronavirus disease 2019 (COVID-19). However, data on optimal dose, duration and timing of administration are limited. This study investigates the outcome of various methylprednisolone treatment regimens among hospitalised COVID-19 patients.

Methods: A retrospective cohort study was conducted on hospitalised adult COVID-19 patients admitted between June and August 2021 in general COVID-19 wards, treated with methylprednisolone. Clinical outcomes evaluated include in-hospital mortality, thirty-day mortality, clinical efficacy (C-reactive protein (CRP), total white blood cells (TWBC) and oxygen requirement) as well as the safety of methylprednisolone.

Results: Of 278 patients, 1(0.4%) received weight-based dosing of 1 mg/kg/day, 101(36.3%) received weight-based dosing of 2 mg/kg/day, 130(46.8%) received fixed dosing methylprednisolone 250 mg/day and 46(16.5%) received fixed dosing methylprednisolone 500 mg/day. There was a significant difference in in-hospital mortality rates following different methylprednisolone doses whereby in-hospital mortality occurred in 22.5% (n = 23) of patients with 1 or 2 mg/kg/day methylprednisolone, 32.3% (n = 42) with 250 mg/day and 39.1% (n = 18) with 500 mg/day (p = 0.023). On the other hand, no significant difference in thirty-day mortality, clinical efficacy and safety was observed between different dosing regimens (p > 0.05).

Conclusion: The use of methylprednisolone weight-based dosing in hospitalised COVID-19 patients should be considered due to the positive outcome associated with lower in-hospital mortality.

Corona Virus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has presented unprecedented challenges to the world. Changes after acute COVID-19 have had a significant impact on patients with neurodegenerative diseases. This study aims to explore the mechanism of neurodegenerative diseases by examining the main pathways of central nervous system infection of SARS-CoV-2. Research has indicated that chronic inflammation and abnormal immune response are the primary factors leading to neuronal damage and long-term consequences of COVID-19. In some COVID-19 patients, the concurrent inflammatory response leads to increased release of pro-inflammatory cytokines, which may significantly impact the prognosis. Molecular imaging can accurately assess the severity of neurodegenerative diseases in patients with COVID-19 after the acute phase. Furthermore, the use of FDG-PET is advocated to quantify the relationship between neuroinflammation and psychiatric and cognitive symptoms in patients who have recovered from COVID-19. Future development should focus on aggressive post-infection control of inflammation and the development of targeted therapies that target ACE2 receptors, ERK1/2, and Ca²⁺.

Background: Following infection with severe acute respiratory syndrome coronavirus, a post-infectious multisystem inflammatory syndrome in adults (MIS-A) has been identified. It affects multiple organ systems and can lead to multi-organic failure.

Case summary: This case report describes a patient with MIS-A with significant cardiac involvement including peri-myocarditis, pulmonary hypertension, right-sided heart failure, tricuspid regurgitation, and cardiogenic shock. After being diagnosed and treated correctly for MIS-A, the patient recovered completely, without any cardiac sequelae.

Discussion: The hyperinflammation in MIS-A can have cardiac engagement. Although more research is required to further clarify the underlying mechanisms, prompt diagnosis and anti-inflammatory treatment are crucial for better outcomes and cardiac recovery.

Objectives: Understanding changes in food sufficiency within various demographic groups during emergency situations, such as the global coronavirus disease 2019 (COVID-19) pandemic, is crucial in formulating public health policies for future preparedness. This study investigated potential differences between urban and rural residents in food sufficiency trends during the COVID-19 pandemic and examined how these changes varied according to sociodemographic factors.

Methods: This cross-sectional study analyzed data from 19,724 adults aged 20 years and older, utilizing information from the 7th-8th Korea National Health and Nutrition Examination Survey (2018-2021).

Results: In urban areas, across all subpopulations, food sufficiency improved significantly during the COVID-19 period relative to pre-pandemic levels (p<0.001). However, in rural regions, a significant increase in food sufficiency during the COVID-19 era was observed only among women, with an odds ratio of 1.42 (confidence interval, 1.06 to 1.89). Nevertheless, no significant interaction terms were found between region and various sociodemographic factors regarding changes in food sufficiency during the COVID-19 period.

Conclusion: During the COVID-19 pandemic, food sufficiency among urban residents improved compared to the pre-pandemic era, whereas their rural counterparts saw no such improvement. Additionally, no significant interaction was detected between urban versus rural areas and changes in food sufficiency during the COVID-19 period. These findings indicate the need for targeted food policies to prepare for potential future pandemics, particularly in rural areas, where food sufficiency did not improve.

ObjectiveThe study aimed to explore the perspective of healthcare workers on the resources they need to provide quality rehabilitation for people recovering from coronavirus disease 2019 (COVID-19) infection.MethodsA descriptive qualitative approach using reflexive thematic analysis was employed. Focus groups and interviews were performed with nine healthcare workers (one intensive care unit physiotherapist, one respiratory therapist and seven occupational therapists) with experience treating patients recovering from COVID-19 infection within hospital and in the community. Verbatim transcripts were coded and analysed for themes.ResultsHealthcare workers perceive an urgent need for resources about recovery from COVID-19 infection to support quality care. They particularly want detailed guidance about potential trajectories of recovery, and what should be expected over time for people with long COVID. Many observed that this group of patients had higher oxygen requirement and experienced slower recovery than others with serious respiratory conditions. Supports for quality care do exist but were not perceived as sufficient by participants. They want any new resources developed to be accessible, quick to access and targeted to specific healthcare worker roles and services settings. Participants identified several barriers to accessing practice supports, including the time poor nature of health care and financial costs to both patients and healthcare workers.ConclusionHealthcare workers perceive an urgent need for the development of resources to support quality rehabilitation for people recovering from COVID-19 infection, to support best outcomes for this group of patients. Any resources developed must consider identified barriers to their access and use to maximise their impact.

Temporomandibular disorders are multi-factorial conditions affected by psychological, biomechanical, and neuromuscular factors. Stress and anxiety experienced during the pandemic are capable of influencing and aggravating temporomandibular disorders and orofacial pain. The study aimed to analyze whether the coronavirus infection can directly affect these diseases. All participants were asked to complete the Pain Screener and Patients Health Questionnaire and were assigned to Group I: healthy participants and Group 2: participants with existing complaints. In group II participants filled the questionnaires twice the Temporomandibular Disorders Symptom Questionnaire and Graded Chronic Pain Scale. The first time to self-report the severity of chronic pain before COVID-19 (T1 timeline) and the second time- to self-report the level of pain after COVID-19 infection (T2 timeline). Totally 150 participants were included in the study. In group II the difference between T1 and T2 timeline was significant for the level of average pain (p = 0.022) and highest facial pain (p = 0.043); Difference in level of interference of daily activities (p > 0.05), recreational activities (p > 0.05) and ability to work (p > 0.05) was statistically not significant. Graded chronic pain status was the same "Grade I" for T1 and T2 timeline. There was no statistically significant difference in stress level between group I and II.

Background: The STROMA-CoV-2 study was a French phase 2b, multicenter, double-blind, randomized, placebo-controlled clinical trial that did not identify a significant efficacy of umbilical cord-derived mesenchymal stromal cells in patients with SARS-CoV-2-induced acute respiratory distress syndrome. Safety on day 28 was found to be good. The aim of our extended study was to assess the 6- and 12-month safety of UC-MSCs administration in the STROMA-CoV-2 cohort.

Methods: A detailed multi-domain assessment was conducted at 6 and 12 months following hospital discharge focusing on adverse events, lung computed tomography-scan, pulmonary and muscular functional status, and quality of life in the STROMA-CoV-2 cohort including SARS-CoV-2-related early (< 96 h) mild-to-severe acute respiratory distress syndrome.

Results: Between April 2020 and October 2020, 47 patients were enrolled, of whom 19 completed a 1-year follow-up. There were no significant differences in any endpoints or adverse effects between the UC-MSCs and placebo groups at the 6- and 12-month assessments. Ground-glass opacities persisted at 1 year in 5 patients (26.3%). Furthermore, diffusing capacity for carbon monoxide remained altered over 1 year, although no patient required oxygen or non-invasive ventilatory support. Quality of life revealed declines in mental, emotional and physical health throughout the follow-up period, and the six-minute walking distance remained slightly impaired at the 1-year patient assessment.

Conclusions: This study suggests a favorable safety profile for the use of intravenous UC-MSCs in the context of the first French wave of SARS-CoV-2-related moderate-to-severe acute respiratory distress syndrome, with no adverse effects observed at 1 year.