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Information and communication technologies (ICTs) are known for supporting healthcare services in dealing with adverse situations. However, little is known on the contribution of ICTs in a prolonged crisis involving a new disease, such as the COVID-19 pandemic. In this study, we carry out an exploratory investigation of which ICTs contribute the most to the emergency care of patients diagnosed with COVID-19 according to healthcare technology experts and how physicians perceive these contributions. Initially, we applied an online survey to 109 healthcare technology experts. Then, we conducted 16 in-depth follow-up interviews with emergency medicine professionals from 10 countries to identify the ICTs contributing the most to treat COVID-19 patients. Results from the survey indicated four ICTs as the most useful to support the treatment of COVID-19 patients; they are remote consultations, digital platforms for data sharing, digital non-invasive care, and interconnected medical decision support. The interviews provided insight into the applicability of those ICTs for the studied context. The four main ICTs were also found to be logically compatible with the complexity of the pandemic, reducing undesirable complexity attributes (e.g. physical proximity between caregivers and infected patients) and amplifying desirable ones (e.g. interactions that support collaborative work and knowledge sharing). [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions Outcomes after bebtelovimab treatment for COVID‐19 were favorable for most but not all solid organ transplant recipients (SOTRs) during the era of Omicron BA.2 to BA.5, but effects of timing of bebtelovimab administration on these outcomes are unknown. We sought to compare outcomes of SOTR who received early bebtelovimab (“EBT”, given ≤ 2 days from diagnosis) versus late bebtelovimab (“LBT”, given between Days 3 and 7), versus no bebtelovimab (NBT).This was a retrospective cohort study of SOTRs with mild‐to‐moderate COVID‐19, with endpoint of 30‐day COVID‐19‐related hospitalization. Multivariable logistic regression was performed to determine variables associated with receiving EBT, and to assess impact of EBT on hospitalization. A propensity score (PS) was calculated for EBT versus NBT.Of 297 SOTRs, 162 (58.1%) received EBT, 46 (16.5%) LBT, and 71 (25.4%) NBT. Early bebtelovimab treatment was associated with a lower risk of 30‐day COVID‐19‐related hospitalization compared to NBT (OR, 0.112 [95% CI, 0.018–0.686]; p = 0.018). There was no significant difference in hospitalization risk between LBT and NBT, suggesting that delayed administration may not confer additional benefits over no treatment.Early bebtelovimab treatment in outpatient SOTRs was associated with a lower risk of hospitalization compared to no treatment, while late administration did not show a significant advantage over no treatment. Although bebtelovimab is no longer authorized, these findings suggest that the timing of COVID therapies for SOTRs may be important to optimize outcomes. [ABSTRACT FROM AUTHOR]

While molecular testing is recommended for symptomatic patients suspected of having coronavirus disease 2019 (COVID-19), limited data are available examining real-world use of tests for severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the impact of SARS-CoV-2 testing on patient outcomes. In this retrospective cohort study using de-identified administrative claims data in the Optum Labs Data Warehouse, we identified 2 groups of patients with ≥1 outpatient claims with a procedure code for SARS-CoV-2 testing between January 2021 and September 2022. Group 1 had ≥1 claims with CPT code 0240U or 0241U ("Xpert Xpress") (N = 51,602); Group 2 had ≥1 claims for laboratory-based molecular testing (N = 317,192). Outcomes assessed on the identification date and through the 90-day follow-up included claims evidence of use of SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) tests, diagnosis of active COVID-19, influenza, or RSV, and use of treatments (antivirals for COVID-19, influenza, and RSV and other treatments for COVID-19 and RSV). Patients in Group 1 had fewer tests for SARS-CoV-2, influenza, or RSV (mean ± standard deviation 1.6±1.4 versus 2.6±2.6, standardized difference -0.45), faster time to diagnosis of COVID-19 (median 0 versus 4 days, standardized difference -0.27) or influenza (median 0 versus 5 days, standardized difference -0.74), and faster time to treatment of COVID-19, influenza, or RSV (median 1 versus 5 days, standardized difference 0.16) than patients in Group 2. In this nationwide real-world study of outpatient testing, use of point-of-care molecular multiplex SARS-CoV-2 testing resulted in fewer claims for SARS-CoV-2, influenza, and RSV tests, faster time to diagnosis, and faster time to treatment than laboratory-based molecular testing. [ABSTRACT FROM AUTHOR]

Millions of people have died and a worldwide economic catastrophe has been brought on by the coronavirus disease 2019 (COVID-19) pandemic. Infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may presently be treated with less than 10 antiviral drugs such as Remdesivir. The need for medical intervention due to sickness has led to unprecedented research efforts to study the biology of coronaviruses. Additionally, there is a strong likelihood that coronaviruses will cause pandemics in the future. All viruses cannot replicate optimally due to host restriction factors. Given that they are genetically more stable than viral targets and may be shared by similar viruses, these antiviral host factors provide appealing targets for antiviral treatment. The identification of antiviral host factors that are a component of human innate immunity and that prevent the completion of the SARS-CoV-2 life cycle has been made possible by the deployment of several "omics" technologies. In this review, we provide an overview of the antiviral host factors that limit the replication of SARS-CoV-2 in this, which were mostly discovered using functional genetic and interactome screening. Important cellular mechanisms for the SARS-CoV-2 life cycle are covered. Finally, we highlight host restriction factors that could be targeted by clinically approved molecules and the induction of these factors as potential antiviral therapies for COVID-19. [ABSTRACT FROM AUTHOR]

Background: The most appropriate anti-inflammatory treatment for moderate COVID-19 pneumonia remains uncertain. We aimed to compare the effectiveness of a high-dose methylprednisolone versus a high-dose dexamethasone in hospitalized moderate COVID-19 pneumonia, regarding the WHO clinical progression scales, mortality, and the length of hospitalization. Methods: In this open-labeled randomized controlled trial, we enrolled patients with age > 18 years old who were diagnosed moderate COVID-19 pneumonia confirmed by real-time PCR, evidence of pneumonia by chest imaging and resting oxygen saturation between 90 and 94%. Patients were randomized at a 1:1 ratio to receive methylprednisolone 250 mg/day or dexamethasone 20 mg/day over the first three days. Then the patients in both groups received dexamethasone 20 mg/day on days 4–5, and 10 mg/day on days 6–10. Primary outcome was assessed by a 10-point WHO clinical progression scales ranging from uninfected (point 0) to death (point 10) on the fifth day of treatment. Secondary outcomes including 90-day mortality, length of hospitalization, rate of intensive care unit (ICU) transfer and complications were determined. Results: Of 98 eligible patients, the mean age was 76.0 ± 13.3 years. The median date of illness at the time of randomization was 3 days (interquartile range 2, 5). Baseline clinical characteristics and severity did not differ between groups. The WHO clinical progression scales were similar between methylprednisolone and dexamethasone group at 5 and 10 days of treatment [4.84, (95% confidence interval(CI), 4.35–5.33) vs. 4.76 (95% CI, 4.27–5.25), p = 0.821 and 4.32 (95% CI, 3.83–4.81) vs. 3.80 (95% CI, 3.31–4.29), p = 0.140, respectively)]. Both groups did not differ in-hospital mortality, length of hospitalization, and rate of ICU transfer. There were also no differences in steroid-related complications between groups until 90 days of follow-up. Conclusions: In patients with moderate COVID-19 pneumonia, initial anti-inflammatory treatment with 250 mg/day of methylprednisolone for three days does not yield better outcomes over high-dose dexamethasone. Trial registration: This study was registered at Thai Clinical Trials Registry on October 17, 2021, with the identifier TCTR20211017001. [ABSTRACT FROM AUTHOR]

Background: Many patients hospitalized for COVID-19 experience long-term health problems, but comprehensive longitudinal data up to 2 years remain limited. We aimed to (1) assess 2-year trajectories of health outcomes, including comparison between intensive care unit (ICU) treated and non-ICU-treated patients, and (2) identify risk factors for prominent health problems post-hospitalization for COVID-19. Methods: The CO-FLOW multicenter prospective cohort study followed adults hospitalized for COVID-19 at 3, 6, 12, and 24 months post-discharge. Measurements included patient-reported outcomes (a.o., recovery, symptoms, fatigue, mental health, sleep quality, return to work, health-related quality of life [HRQoL]), and objective cognitive and physical tests. Additionally, routine follow-up data were collected. Results: 650 patients (median age 60.0 [IQR 53.0–67.0] years; 449/650 [69%] male) surviving hospitalization for COVID-19 were included, of whom 273/650 (42%) received ICU treatment. Overall, outcomes improved over time. Nonetheless, 73% (322/443) of patients had not completely recovered from COVID-19, with memory problems (274/443; 55%), concentration problems (259/443; 52%), and dyspnea (251/493; 51%) among most frequently reported symptoms at 2 years. Moreover, 61% (259/427) had poor sleep quality, 51% (222/433) fatigue, 23% (102/438) cognitive failures, and 30% (65/216) did not fully return to work. Objective outcome measures showed generally good physical recovery. Most outcomes were comparable between ICU- and non-ICU-treated patients at 2 years. However, ICU-treated patients tended to show slower recovery in neurocognitive symptoms, mental health outcomes, and resuming work than non-ICU-treated patients, while showing more improvements in physical outcomes. Particularly, female sex and/or pre-existing pulmonary disease were major risk factors for poorer outcomes. Conclusions: 73% (322/443) of patients had not completely recovered from COVID-19 by 2 years. Despite good physical recovery, long-term neurocognitive complaints, dyspnea, fatigue, and impaired sleep quality persisted. ICU-treated patients showed slower recovery in neurocognitive and mental health outcomes and resumption of work. Tailoring long-term COVID-19 aftercare to individual residual needs is essential. Follow-up is required to monitor further recovery. Trial registration: NL8710, registration date 12-06-2020. [ABSTRACT FROM AUTHOR]

Background: Many patients experience persistent symptoms after COVID-19, a syndrome referred to as Long COVID (LC). The goal of this study was to identify novel new or worsening comorbidities self-reported in patients with LC. Methods: Patients diagnosed with LC (n = 732) at the Mayo Long COVID Care Clinic in Rochester, Minnesota and Jacksonville, Florida were sent questionnaires to assess the development of new or worsening comorbidities following COVID-19 compared to patients with SARS-CoV-2 that did not develop LC (controls). Both groups were also asked questions screening for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), generalized joint hypermobility (GJH) and orthostatic intolerance. 247 people with LC (33.7%) and 40 controls (50%) responded to the surveys. Results: In this study LC patients averaged 53 years of age and were predominantly White (95%) women (75%). The greatest prevalence of new or worsening comorbidities following SARS-CoV-2 infection in patients with LC vs. controls reported in this study were pain (94.4% vs. 0%, p < 0.001), neurological (92.4% vs. 15.4%, p < 0.001), sleep (82.8% vs. 5.3%, p < 0.001), skin (69.8% vs. 0%, p < 0.001), and genitourinary (60.6% vs. 25.0%, p = 0.029) issues. 58% of LC patients screened positive for ME/CFS vs. 0% of controls (p < 0.001), 27% positive for GJH compared to 10% of controls (p = 0.026), and a positive average score of 4.0 on orthostatic intolerance vs. 0 (p < 0.001). The majority of LC patients with ME/CFS were women (77%). Conclusion: We found that comorbidities across 12 surveyed categories were increased in patients following SARS-CoV-2 infection. Our data also support the overlap of LC with ME/CFS, GJH, and orthostatic intolerance. We discuss the pathophysiologic, research, and clinical implications of identifying these conditions with LC. [ABSTRACT FROM AUTHOR]

Long coronavirus disease 2019 (COVID-19) is linked to an increased risk of post-acute sequelae affecting the pulmonary and extrapulmonary organ systems. Up to 20% of COVID-19 patients may proceed to a more serious form, such as severe pneumonia, acute respiratory distress syndrome (ARDS), or pulmonary fibrosis. Still, the majority of patients may only have mild, self-limiting sickness. Of particular concern is the possibility of parenchymal fibrosis and lung dysfunction in long-term COVID-19 patients. Furthermore, it has been observed that up to 43% of individuals hospitalized with COVID-19 also had acute renal injury (AKI). Care for kidney, brain, lung, cardiovascular, liver, ocular, and tissue injuries should be included in post-acute COVID-19 treatment. As a powerful immunomodulatory tool in regenerative medicine, dental stem cells (DSCs) have drawn much interest. Numerous immune cells and cytokines are involved in the excessive inflammatory response, which also has a significant effect on tissue regeneration. A unique reservoir of stem cells (SCs) for treating acute lung injury (ALI), liver damage, neurological diseases, cardiovascular issues, and renal damage may be found in tooth tissue, according to much research. Moreover, a growing corpus of in vivo research is connecting DSC-derived extracellular vesicles (DSC-EVs), which are essential paracrine effectors, to the beneficial effects of DSCs. DSC-EVs, which contain bioactive components and therapeutic potential in certain disorders, have been shown as potentially effective therapies for tissue damage after COVID-19. Consequently, we explore the properties of DSCs in this work. Next, we'll look at how SARS-CoV-2 affects tissue damage. Lastly, we have looked at the use of DSCs and DSC-EVs in managing COVID-19 and chronic tissue damage, such as injury to the heart, brain, lung, and other tissues. Stem cells obtained from various dental tissues, including dental pulp stem cells, dental follicle stem cells, periodontal ligament stem cells, and exfoliated deciduous teeth stem cells, along with extracellular vesicles derived from dental stem cells, possess distinct capabilities such as immunomodulation, regeneration, and potent anti-inflammatory effects. These properties make them suitable for treating different types of tissue injuries resulting from COVID-19. [ABSTRACT FROM AUTHOR]

The most fruitful prevention and treatment tools for the COVID-19 pandemic have proven to be vaccines and therapeutic antibodies, which have reduced the spread of the disease to manageable proportions. The search for the most effective antibodies against the widest set of COV-2 variants has required a long time and substantial resources. It would be desirable to have a tool that will enable us to understand the structural basis on which mutants escape at least some of the epitope-bound antibodies, a tool that may substantially reduce the time and resources invested in this effort. In this work, we applied a computational-based tool (employed previously by us to understand COV-2 spike binding to its cognate cell receptor) to the study of the effect of Delta and Omicron mutations on the escape tendencies. Our binding energy predictions agree extremely well with the experimentally observed escape tendencies. They have also allowed us to set forth a structural explanation for the results that could be used for the screening of antibodies. Lastly, our results explain the differences in molecular interactions that govern interaction of the spike variants with the receptor as opposed to those with antibodies. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel betacoronavirus, is the causative agent of COVID-19, which has caused economic and social disruption worldwide. To date, many drugs and vaccines have been developed for the treatment and prevention of COVID-19 and have effectively controlled the global epidemic of SARS-CoV-2. However, SARS-CoV-2 is highly mutable, leading to the emergence of new variants that may counteract current therapeutic measures. Electron microscopy (EM) is a valuable technique for obtaining ultrastructural information about the intracellular process of virus replication. In particular, EM allows us to visualize the morphological and subcellular changes during virion formation, which would provide a promising avenue for the development of antiviral agents effective against new SARS-CoV-2 variants. In this review, we present our recent findings using transmission electron microscopy (TEM) combined with electron tomography (ET) to reveal the morphologically distinct types of SARS-CoV-2 particles, demonstrating that TEM and ET are valuable tools for visually understanding the maturation status of SARS-CoV-2 in infected cells. This review also discusses the application of EM analysis to the evaluation of genetically engineered RNA viruses. [ABSTRACT FROM AUTHOR]

Objective: Given the apparent life-threatening nature of COVID-19, finding an effective treatment is under investigation. Materials and Methods: We assessed effect of shallomin oral syrup (co IranAmin®) as a complementary treatment to improve the clinical outcomes in COVID-19 patients. Patients in the control group received the approved treatment protocol (lopinavir/ritonavir), while those in the intervention group were treated with the oral syrup shallomin in addition to the approved treatment. Clinical status of treated patients was recorded and compared. Results: There were meaningful differences between the two groups regarding shortened length of hospital stay and the recovery time for cough, myalgia, sore throat, and shortness of breath. No side effect occurred in the intervention group compared to the control group in terms of biochemical and hematological factors. Conclusion: It seems that the treatment with shallomin syrup showed remarkable contribution to the recovery of COVID-19 induced symptoms in the patients under lopinavir/ritonavir therapy. [ABSTRACT FROM AUTHOR]

Herbal medicines (HMs) have been utilized to prevent and treat human ailments for thousands of years. Especially, HMs have recently played a crucial role in the treatment of COVID-19 in China. However, HMs are susceptible to various factors during harvesting, processing, and marketing, affecting their clinical efficacy. Therefore, it is necessary to conclude a rapid and effective method to study HMs so that they can be used in the clinical setting with maximum medicinal value. Non-targeted analytical technology is a reliable analytical method for studying HMs because of its unique advantages in analyzing unknown components. Based on the extensive literature, the paper summarizes the benefits, limitations, and applicability of non-targeted analytical technology. Moreover, the article describes the application of non-targeted analytical technology in HMs from four aspects: structure analysis, authentication, real-time monitoring, and quality assessment. Finally, the review has prospected the development trend and challenges of non-targeted analytical technology. It can assist HMs industry researchers and engineers select non-targeted analytical technology to analyze HMs' quality and authenticity. [ABSTRACT FROM AUTHOR]

SARS CoV-2 virus (COVID-19) emerged as a highly infectious human pathogen in late 2019. Started in China but rapidly started spreading all over the world and soon became a pandemic. More than seven million deaths have been reported so far that devasted millions of families worldwide. Several drugs, such as hydroxychloroquine, chloroquine, remdesivir, favipiravir and arbidol have undergone some clinical studies since early 2020, but their safety concerns remained a serious issue. However, within an year from late 2019, several successful vaccines were invented to prevent people from the infection. Almost at the same time, two drugs were discovered. These are PAXLOVID™ (nirmatrelvir, ritonavir) from Pfizer and molnupiravir from Merck which were soon approved by the US-FDA, for emergency use in the treatment of COVID-19. But several challenges were soon reported in treatments with these drugs, particularly for those who are immunocompromised or have vaccine immunity and suffering for a long time from the infection (known as long-COVID). Complex issues for treatments of long-COVID patients continue to remain unresolved. Thus, discovery of new drugs to assist treatment for emerging COVID-19 problems is urgently needed. But it is important to note that discovery of new COVID-19 therapeutics, particularly small molecules is not a simple task. However, there are several excellent reviews on attempts for COVID-19 drug discovery including a handful of articles on theoretical approaches towards the goal. This review summarizes the theoretical attempts for discovery of COVID-19 drugs, their challenges and future opportunities along with efforts from the author's lab. [ABSTRACT FROM AUTHOR]

The letter to the editor responds to a critique of the evaluation period in a study on the effectiveness of Ensitrelvir in reducing severe outcomes in COVID-19 patients. The study found that Ensitrelvir reduced hospitalization rates in high-risk patients, including those with underlying diseases. Subgroup analyses were conducted to assess the impact of Ensitrelvir on different high-risk factors. The authors suggest further research to identify specific patient populations that may benefit from antiviral treatment. The study was supported by Shionogi & Co., Ltd., and the data used are available from JMDC Inc. with restrictions. [Extracted from the article]

The COVID-19 pandemic has exacerbated existing inequalities in care between mobile and immobile populations. It has highlighted the precarious situation of many migranticized individuals and their families worldwide, but it has also brought their situation into the public eye, providing opportunities for advances in social science understanding and policy reform. This Special Issue explores the interplay between transnational care arrangements, cross-border movement and mobility, and the production of social inequality in the post-COVID-19 world. The collected articles provide a comprehensive picture from different countries and fields, revealing three interrelated processes that reflect the complex dynamics during the pandemic: (1) the interruption of transnational care arrangements; (2) the reorganization of these arrangements; and (3) coping strategies to adapt to (post)pandemic immobilizations, restrictions, and modified patterns of care. In sum, this issue aims to contribute to the advancement of social science understanding and to benefit vulnerable populations. [ABSTRACT FROM AUTHOR]

Using network pharmacology and molecular docking, we predicted the potential mechanisms of Lonicerae japonicae flos (LJF) therapy for COVID-19. A total of 493 component-related targets and 6,233 COVID-19-related genes were identified, and 267 core genes with overlapping of the two types of genes were identified. The target AKT1, CASP3, IL1B, IL6, PTGS2, TNF and JUN were the hub genes in PPI network according to MCODE score. Component-Target analysis showed the close relationship between targets and components. The results of functional enrichment analyses revealed that LJF exerted pharmacological effects on COVID-19 by regulating IL-17 signalling pathway, TNF signalling pathway, AGE-RAGE signalling pathway in diabetic complications, and Toll-like receptor signalling pathway. Finally, molecular docking confirmed a strong binding affinity between the 7 main active components with the hub genes. The findings suggested that beta-sitosterol, kaempferol and luteolin might be the promising leading components due to their good molecular docking scores. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the potential relationship between multiple sclerosis (MS) and coronavirus disease 2019 (COVID-19) outcomes using Mendelian randomization analysis. Specifically, it evaluates whether genetic factors, including the single-nucleotide polymorphism (SNP) rs10191329, influence the susceptibility of MS patients to three COVID-19 outcomes [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospitalized COVID-19, and severe COVID-19]. This study utilized genomewide association study summary statistics from the International Multiple Sclerosis Genetics Consortium to conduct a Mendelian randomization analysis. SNPs strongly associated with MS were selected to examine their impact on COVID-19 outcomes. The analysis focused on identifying any causal associations between MS and COVID-19 severity, as well as assessing the role of interferon beta (IFNb) treatment in modifying these outcomes. The results suggest a potential association between MS and an increased risk of COVID-19, but individuals carrying the rs10191329 SNP appeared less likely to develop severe COVID-19. This SNP, located within the DYSF-ZNF638 locus, may influence immune responses and MS severity, highlighting its relevance for personalized treatment strategies. Importantly, no significant causal relationship was found between IFNb treatment and the three COVID-19 outcomes, indicating that the findings in treated patients differ from those observed in untreated patients. This suggests that IFNb may offer protective effects against SARS-CoV-2 in MS patients. These findings underscore the importance of genetic factors, such as rs10191329, in shaping the clinical outcomes of MS patients in the context of COVID-19. Further research should explore targeted therapies and personalized approaches for managing MS during the ongoing pandemic. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has left a profound mark on global health, leading to substantial morbidity and mortality worldwide. Beyond the immediate symptoms of infection, the emergence of "long COVID", the long-term effects of SARS-CoV-2, has become a significant public health concern. Long COVID is a multifaceted condition affecting various organs and systems, including the cardiovascular, digestive, nervous, and endocrine systems. Individuals diagnosed with polycystic ovary syndrome (PCOS)may face an increased risk of severe COVID-19 symptoms and infection. It is crucial to comprehend how long COVID affects PCOS patients to devise effective treatment and care strategies. Here, we review the detrimental effects of COVID-19 and its long-term effects on reproductive health, endocrine function, inflammation, metabolism, cardiovascular health, body composition, lifestyle, and mental health in patients with PCOS. We offer recommendations for the post-covid-19 management of PCOS, emphasizing the necessity of a comprehensive, multidisciplinary approach to patient care. Furthermore, we discuss prospective research directions, highlighting the significance of continued investigations and clinical trials to evaluate treatment approaches for long COVID and its ramifications in individuals with PCOS. [ABSTRACT FROM AUTHOR]

Backgrounds: During the Coronavirus Disease 2019 (COVID-19) epidemic, the massive spread of the disease has placed an enormous burden on the world’s healthcare and economy. The early risk assessment system based on a variety of machine learning (ML) algorithms may be able to provide more accurate advice on the classification of COVID-19 patients, offering predictive, preventive, and personalized medicine (PPPM) solutions in the future. Methods: In this retrospective study, we divided a portion of the data into training and validation cohorts in a 7:3 ratio and established a model based on a combination of two ML algorithms first. Then, we used another portion of the data as an independent testing cohort to determine the most accurate and stable model and compared it with other scoring systems. Finally, patients were categorized according to risk scores and then the correlation between their clinical data and risk scores was studied. Results: The elderly accounted for the majority of hospitalized patients with COVID-19. The C-index of the model constructed by combining the stepcox [both] and survivalSVM algorithms was 0.840 in the training cohort and 0.815 in the validation cohort, which was calculated to have the highest C-index in the testing cohort compared to the other 119 ML model combinations. Compared with current scoring systems, including the CURB-65 and several reported prognosis models previously, our model had the highest AUC value of 0.778, representing an even higher predictive performance. In addition, the model’s AUC values for specific time intervals, including days 7,14 and 28, demonstrate excellent predictive performance. Most importantly, we stratified patients according to the model’s risk score and demonstrated a difference in survival status between the high-risk, median-risk, and low-risk groups, which means a new and stable risk assessment system was built. Finally, we found that COVID19 patients with a history of cerebral infarction had a significantly higher risk of death. Conclusion: This novel risk assessment system is highly accurate in predicting the prognosis of patients with COVID-19, especially elderly patients with COVID19, and can be well applied within the PPPM framework. Our ML model facilitates stratified patient management, meanwhile promoting the optimal use of healthcare resources. [ABSTRACT FROM AUTHOR]

AbstractImmunocompromised people are facing ongoing inequality in health outcomes because of COVID-19. Let’s remain ambitious and improve availability and access to COVID-19 prevention therapies that protect patients and aid management. This article brings together opinions from four experts based in the United Kingdom who specialise in immunology, solid organ transplantation, respiratory medicine and critical care, oncology and haematology. In this article, they communicate the impact of SARS-CoV-2 infection on vulnerable patients with underlying conditions and the need for immediate policies to protect vulnerable people from COVID-19. [ABSTRACT FROM AUTHOR]

Background: Dexamethasone is currently administered for Coronavirus disease 2019(COVID-19); however, there are concerns about its effect on specific antibodies' production. The aim of this study was to evaluate whether specific antibodies were affected by COVID-19 severity and corticosteroid treatment. Methods: Of 251 confirmed COVID-19 patients admitted to our hospital between January 26 and August 10, 2020, the early period of the pandemic, 75 patients with sera within 1 month of onset and 1 month or longer were included in the research. A total of 253 serum samples from these patients were collected. The levels of specific antibodies for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), immunoglobulin G (IgG) and M (IgM), were measured retrospectively. The results were compared separately of each COVID-19 severity, and with or without corticosteroid treatment. Results: Among the 75 patients, 47, 18, and 10 had mild, moderate, and severe disease, respectively. The median age was 53.0 years and 22 (29%) were women. The most common comorbidities were hypertension and dyslipidemia. Corticosteroids were administered to 20 (27%) and 10 (53%), patients with moderate and severe disease, respectively. The positivity rates IgM increased first, and IgG was almost always positive after day 16, regardless of the severity of COVID-19. On days 6–10, both IgG and IgM positivity rates were higher in patients with moderate disease than in those with mild or severe disease. In patients with moderate disease, IgG positivity was similar over time, regardless of corticosteroid treatment. Conclusions: In COVID-19 patients, specific IgG is positive and maintained for a long period of time, even after corticosteroid treatment. The effect of corticosteroid treatment in a COVID-19 epidemiological study using specific IgG antibodies was considered minor. COVID-19 patients were more likely to receive oxygen if IgM was positive 1 week after onset, but not mechanical ventilation. IgM measurement 1 week after onset may predict COVID-19 severity. [ABSTRACT FROM AUTHOR]

Since December 2019, coronavirus disease 2019 (COVID-19) has been spreading worldwide with devastating immediate or long-term effects on people's health. Although the lungs are the primary organ affected by COVID-19, individuals infected with SARS-CoV-2 also develop systemic lesions involving multiple organs throughout the body, such as the cardiovascular system. Emerging evidence reveals that COVID-19 could generate myocardial fibrosis, termed "COVID-19-associated myocardial fibrosis." It can result from the activation of fibroblasts via the renin-angiotensin-aldosterone system (RAAS), transforming growth factor-ß1 (TGF-ß1), microRNAs, and other pathways, and can also occur in other cellular interactions with SARS-CoV-2, such as immunocytes, endothelial cells. Nonetheless, to gain a more profound insight into the natural progression of COVID-19-related myocardial fibrosis, additional investigations are necessary. This review delves into the underlying mechanisms contributing to COVID-19-associated myocardial fibrosis while also examining the antifibrotic potential of current COVID-19 treatments, thereby offering guidance for future clinical trials of these medications. Ultimately, we propose future research directions for COVID-19-associated myocardial fibrosis in the post-COVID-19 era, such as artificial intelligence (AI) telemedicine. We also recommend that relevant tests be added to the follow-up of COVID-19 patients to detect myocardial fibrosis promptly. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is linked to high mortality, primarily through an intense inflammatory response. Diacerein has emerged as a potential therapy for COVID-19 due to its potential impact in decreasing the inflammasome activation and coronavirus replication. This study aims to explore diacerein's influence in inhibiting both viral replication and the inflammatory response after SARS-CoV-2 infection. Methods: Human peripheral blood mononuclear cells (PBMCs) were obtained from healthy volunteers and infected in vitro with SARS-CoV-2. Additionally, we carried out a pilot randomized, double-blind, placebo-controlled study with 14 participants allocated to diacerein (n = 7) or placebo (n = 7) therapies every 12 h for 10 days. The primary endpoint was change in plasma markers of inflammasome activation (NLRP3, caspase-1, and gasdermin-D). Results: In vitro protocols have shown that rhein, diacerein's primary metabolite, decreased IL-1ß secretion caused by SARS-CoV-2 infection in human PBMCs (p < 0.05), and suppressed viral replication when administered either before or after the virus incubation (p < 0.05). This later effect was, at least partially, attributed to its inhibitory effect on 3-chymotrypsin-like protease (SARS-CoV-2 3CLpro) and papain-like protease in the SARS-CoV-2 (SARS-CoV-2 PLpro) virus and in the phosphorylation of proteins related cytoskeleton network (p < 0.05). Diacereintreated COVID-19 patients presented a smaller area under the curve for NLRP3, caspase-1 and GSDM-D measured on days 2, 5, and 10 after hospitalization compared to those receiving a placebo (p < 0.05). Conclusion: The indicated mechanisms of action of diacerein/rhein can reduce viral replication and mitigate the inflammatory response related to SARS-CoV-2. These findings are preliminary and require confirmation in clinical trials. [ABSTRACT FROM AUTHOR]

The document discusses the impact of COVID-19 on patients with relapsed/refractory multiple myeloma (RRMM) in the MajesTEC-1 study evaluating teclistamab. Patients with MM are vulnerable to COVID-19 infection, with high mortality rates reported. The study found that appropriate infection prevention and management are crucial for optimizing outcomes for RRMM patients treated with teclistamab. The findings highlight the importance of immunoglobulin replacement and COVID-19 vaccination in this population. The study provides insights into the impact of COVID-19 on heavily pretreated RRMM patients and emphasizes the need for further research in this area. [Extracted from the article]

Background: Coronavirus disease 2019 (COVID-19) has created a global pandemic with significant morbidity and mortality. SARS-CoV-2 primarily infects the lungs and is associated with various organ complications. Therapeutic approaches to combat COVID-19, including convalescent plasma and vaccination, have been developed. However, the high mutation rate of SARS-CoV-2 and its ability to inhibit host T-cell activity pose challenges for effective treatment. Mesenchymal stem cells (MSCs) and their extracellular vesicles (MSCs–EVs) have shown promise in COVID-19 therapy because of their immunomodulatory and regenerative properties. MicroRNAs (miRNAs) play crucial regulatory roles in various biological processes and can be manipulated for therapeutic purposes. Objective: We aimed to investigate the role of lyophilized MSC–EVs and their microRNAs in targeting the receptors involved in SARS-CoV-2 entry into host cells as a strategy to limit infection. In silico microRNA prediction, structural predictions of the microRNA–mRNA duplex, and molecular docking with the Argonaut protein were performed. Methods: Male Syrian hamsters infected with SARS-CoV-2 were treated with human Wharton's jelly-derived Mesenchymal Stem cell-derived lyophilized exosomes (Bioluga Company)via intraperitoneal injection, and viral shedding was assessed. The potential therapeutic effects of MSCs–EVs were measured via histopathology of lung tissues and PCR for microRNAs. Results: The results revealed strong binding potential between miRNA‒mRNA duplexes and the AGO protein via molecular docking. MSCs–EVs reduced inflammation markers and normalized blood indices via the suppression of viral entry by regulating ACE2 and TMPRSS2 expression. MSCs–EVs alleviated histopathological aberrations. They improved lung histology and reduced collagen fiber deposition in infected lungs. Conclusion: We demonstrated that MSCs–EVs are a potential therapeutic option for treating COVID-19 by preventing viral entry into host cells. [ABSTRACT FROM AUTHOR]

Corticosteroids have always been recommended for severe cases of COVID-19. However, the efficacy of treatment with corticosteroids for COVID-19 during the SARS-CoV-2 omicron outbreak in China has not been reported. Clinical data from 406 patients hospitalized for severe/critical COVID-19 from December 2022 to January 2023 at six hospitals in Chongqing were retrospectively analyzed. The primary outcome was all-cause mortality at 28 days in the groups with and without corticosteroids treatment after propensity score matching (PSM). Secondary outcomes were to compare in-hospital mortality and length of survival time with corticosteroids and those without corticosteroids. This study included 406 patients with severe or critical COVID-19, divided into the corticosteroids group (231, 56.9%) and non-corticosteroids group (175, 43.1%). After PSM, the use of corticosteroids did not reduce all-cause mortality at 28 days (42.5% vs. 39.1%). Univariate analysis showed that corticosteroids were not associated with improved all-cause mortality at 28 days [hazard ratio (HR), 1.019; 95% confidence interval (CI), 0.639–1.623; p = 0.938]. Multivariate analysis showed similar results (HR, 1.047; 95% CI, 0.633–1.732; p = 0.858). Among non-survivors, the survival time was significantly larger in those who received corticosteroids compared with the non-corticosteroid users [median 13 (IQR 6.5–15.5) vs. 6 (4-11.25), p = 0.007]. The use of systemic corticosteroids in severe/critical COVID-19 may provide certain potential survival benefits but does not improve prognosis. [ABSTRACT FROM AUTHOR]

Amid efforts to develop effective treatments for acute COVID-19, there is growing recognition of the need to address long COVID as a key outcome measure. We argue there are 7 compelling reasons to include long COVID measurements in clincal trials investigating acute COVID-19 treatments: (1) Long COVID is not rare. (2) Long COVID is debilitating to individuals and has a high societal cost. (3) Those at high risk of severe COVID-19 are also at higher risk of developing long COVID if they are infected with COVID-19. (4) Treatments for acute COVID-19 may reduce the risk of long COVID. (5) Measures exist to track long COVID. (6) Long COVID considerations are potentially important for acute COVID-19 treatment decision making. (7) Deaths and hospitalizations due to COVID-19 are increasingly rare. While not every trial needs to include assessments of long COVID, it is worth the research burden to include assessments where possible, as this could facilitate the uptake of acute COVID-19 treatments that lessen the societal burden of long COVID. [ABSTRACT FROM AUTHOR]

One of the main efforts of scientists to study drug development is the discovery of novel antiviral agents that could be beneficial in the struggle against viruses that cause diseases in humans. Natural products are complex metabolites that are designed and synthesised by different sources in an attempt to optimise nature. Recently, natural products are still a source of biologically active molecules, facilitating drug discovery. A p21-activating kinase PAK1 is a key regulator of cytoskeletal actin assembly, phenotypic signalling, and transcription process which affects a wide range of cellular processes such as cell motility, invasion, metastasis, cell growth, angiogenesis, and cell cycle progression. Most recently, PAK1 was shown to be involved in the progression of coronavirus-caused pulmonary inflammation (lung fibrosis), but clinical data is not currently available yet. This review highlights the naturally occurring compounds that inhibit the oncogenic, melanogenic, and ageing kinase PAK1. Additionally, the potent anti-inflammatory effects of natural products in an attempt to prevent pulmonary fibrosis in COVID-19 have also been discussed. [ABSTRACT FROM AUTHOR]

Despite effective countermeasures, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists worldwide because of its ability to diversify and evade human immunity. This evasion stems from amino acid substitutions, particularly in the receptor binding domain (RBD) of the spike protein that confers resistance to vaccine-induced antibodies and antibody therapeutics. To constrain viral escape through resistance mutations, we combined antibody variable regions that recognize different RBD sites into multispecific antibodies. Here, we describe multispecific antibodies, including a trivalent trispecific antibody that potently neutralized diverse SARS-CoV-2 variants and prevented virus escape more effectively than single antibodies or mixtures of the parental antibodies. Despite being generated before the appearance of Omicron, this trispecific antibody neutralized all major Omicron variants through BA.4/BA.5 at nanomolar concentrations. Negative stain electron microscopy suggested that synergistic neutralization was achieved by engaging different epitopes in specific orientations that facilitated binding across more than one spike protein. Moreover, a tetravalent trispecific antibody containing the same variable regions as the trivalent trispecific antibody also protected Syrian hamsters against Omicron variants BA.1, BA.2, and BA.5 challenge, each of which uses different amino acid substitutions to mediate escape from therapeutic antibodies. These results demonstrated that multispecific antibodies have the potential to provide broad SARS-CoV-2 coverage, decrease the likelihood of escape, simplify treatment, and provide a strategy for antibody therapies that could help eliminate pandemic spread for this and other pathogens. Editor's summary: Monoclonal antibodies were an essential component of the COVID-19 treatment toolbox, at least until Omicron and its subvariants arose. As new variants wipe out efficacy of existing monoclonal antibodies, new options are urgently needed, especially to protect immunocompromised individuals who cannot make antibodies of their own. Here, Misasi et al. developed a series of multispecific antibodies that were able to more broadly neutralize SARS-CoV-2 pseudoviruses than their monoclonal antibody counterparts. One trivalent trispecific antibody combination was also able to prevent pseudovirus escape in vitro. To avoid heavy/light chain mispairing, the authors made that trivalent trispecific antibody into a tetravalent trispecific antibody. When administered to mice prophylactically, this antibody was able to confer protection against challenge with BA.1, BA.2, and BA.5. These data highlight the potential of multispecific antibodies as a long-term component of the COVID-19 toolbox. —Courtney Malo [ABSTRACT FROM AUTHOR]

Objective: The epidemiology of COVID-19 has substantially changed since its emergence given the availability of effective vaccines, circulation of different viral variants, and re-infections. We aimed to develop models to predict 30-day COVID-19 hospitalization and death in the Omicron era for contemporary clinical and research applications. Methods: We used comprehensive electronic health records from a national cohort of patients in the Veterans Health Administration (VHA) who tested positive for SARS-CoV-2 between March 1, 2022, and March 31, 2023. Full models incorporated 84 predictors, including demographics, comorbidities, and receipt of COVID-19 vaccinations and anti-SARS-CoV-2 treatments. Parsimonious models included 19 predictors. We created models for 30-day hospitalization or death, 30-day hospitalization, and 30-day all-cause mortality. We used the Super Learner ensemble machine learning algorithm to fit prediction models. Model performance was assessed with the area under the receiver operating characteristic curve (AUC), Brier scores, and calibration intercepts and slopes in a 20% holdout dataset. Results: Models were trained and tested on 198,174 patients, of whom 8% were hospitalized or died within 30 days of testing positive. AUCs for the full models ranged from 0.80 (hospitalization) to 0.91 (death). Brier scores were close to 0, with the lowest error in the mortality model (Brier score: 0.01). All three models were well calibrated with calibration intercepts <0.23 and slopes <1.05. Parsimonious models performed comparably to full models. Conclusions: We developed prediction models that accurately estimate COVID-19 hospitalization and mortality risk following emergence of the Omicron variant and in the setting of COVID-19 vaccinations and antiviral treatments. These models may be used for risk stratification to inform COVID-19 treatment and to identify high-risk patients for inclusion in clinical trials. [ABSTRACT FROM AUTHOR]

Background: The potential efficacy of early combination therapy, based on an antiviral plus a monoclonal antibody, for COVID-19 in severely immunocompromised patients is matter of debate. Objectives: Our aim was to describe the impact on clinical outcomes of COVID-19 treatments in severely immunocompromised individuals, evaluating differences between a combination and a monotherapy. Methods: We included severely immunocompromised outpatients with mild-to-moderate COVID-19 who received an early treatment (either monotherapy with nirmatrelvir/ritonavir or remdesivir or the combination of an antiviral plus sotrovimab). We then assessed differences between the two treatment strategies on three main outcomes (30-day mortality, access to emergency department, hospitalization), separately and as a composite by using a propensity score weighted (PSW) approach. Results: Eighty one severely immunocompromised patients were included, 39 receiving early combination therapy and 42 receiving monotherapy. No significant difference was observed in the 30-day mortality rate and hospitalization rate between subjects in the two groups, while access to the emergency department following treatment administration was significantly higher in people who received a combination therapy. After applying the PSW, it was observed that combination therapy impacted favourably on the composite outcome, in a statistically significant fashion. In addition, PSW approach for mortality showed that age was the only significant factor influencing the death as stand-alone outcome. Conclusions: Early combination therapy showed a favourable impact on a composite outcome (including mortality, hospitalizations and access to emergency department) in severely immunocompromised hosts who were all vaccinated. However, further studies are needed to support our results. [ABSTRACT FROM AUTHOR]

Background. The emergence, global spread, and persistence of SARS-CoV-2 resulted in an unprecedented need for effective antiviral drugs. Throughout the pandemic, various drug development and treatment strategies were adopted, including repurposing of antivirals designed for other viruses along with a multitude of other drugs with varying mechanisms of action (MoAs). Furthermore, multidrug treatment against COVID-19 is an ongoing topic and merits further investigation. Method/Objectives. We assessed the efficacy of multidrug treatment against SARS-CoV-2 in reconstituted human nasal epithelia, using combinations of molnupiravir and nirmatrelvir as a baseline, adding suboptimal concentrations of either GS-441524 or ivermectin, attempting to increase overall antiviral activity while lowering the overall therapeutic dose. Results. Nirmatrelvir combined with molnupiravir, GS-441524, or ivermectin at suboptimal concentrations show increased antiviral activity compared to single treatment. No triple combinations showed improved inhibition of SARS-CoV-2 replication beyond what was observed for double treatments. Conclusions. In general, we observed that the addition of a third compound is not beneficial for antiviral activity, while various double combinations exhibit increased antiviral activity over single treatment. [ABSTRACT FROM AUTHOR]

Background: Neutralizing antibodies targeting the SARS-CoV-2 Spike protein reduce COVID-19-related risk of hospitalization, particularly in high-risk individuals. The COCOPREV-R study aimed to evaluate and compare clinical outcomes in high-risk SARS-CoV-2 patients treated with dual monoclonal antibody therapies and to identify associated virological factors. Methods: The COCOPREV-R study retrospectively collected real-world data from high-risk patients receiving Bamlanivimab/Etesevimab or Casirivimab/Imdevimab dual monoclonal antibody therapies (22 February 2021 to 15 June 2021). Results: The study included 1004 patients with COVID-19, of whom 691 received Bamlanivimab/Etesevimab and 313 received Casirivimab/Imdevimab. The alpha variant represented 90.1% of those for whom data were available. The risk of hospitalization within 30 days was lower with Bamlanivimab/Etesevimab (12.7%, CI 95% [9.9–16.3%]) compared to Casirivimab/Imdevimab (28.4%, CI 95% [22.7–35.1%) (p < 0.001). The 30-day mortality rates were comparable between both groups (p = 0.982). Analysis of SARS-CoV-2 PCR negativity showed no difference between the two treatment groups (95.2% [93.0–96.9%] and 93.5% [89.1–96.6%] until day 30, p = 0.851 for Bamlanivimab/Etesevimab and Casirivimab/Imdevimab, respectively). Among persistently positive samples with available sequencing results (n = 43), Spike protein changes occurred only in Bamlanivimab/Etesevimab (42.9%) vs. Casirivimab/Imdevimab (0.0%) groups. Q493R (25.0%) and E484K (12.5%) were the most common mutations selected by Bamlanivimab/Etesevimab in follow-up samples. Other factors (immunodepression, comorbidities, and age) did not appear to be associated with the occurrence of Spike protein mutations. Conclusions: A higher rate of hospitalization was seen with Casirivimab/Imdevimab (RONAPREVE®) in comparison with Bamlanivimab/Etesevimab treatment, but with the emergence of Spike mutations only in the Bamlanivimab/Etesevimab group. [ABSTRACT FROM AUTHOR]

Introduction Olfactory dysfunction (OD) has emerged as a notable symptom among coronavirus disease 2019 (COVID-19) patients, with its prevalence varying among different populations. Recognizing the need to provide therapeutic solutions for these individuals, the present study seeks to comprehensively review the current evidence on potential underlying mechanisms and treatment modalities to manage OD in COVID-19 patients. Objective To review the recent evidence on treatments for OD in COVID-19. From the beginning of the study until August 2nd, 2023, we conducted a systematic search on four electronic databases, PubMed, Scopus, Embase, and Web of Science, to find relevant publications. Data Synthesis In the present study, 37 articles were selected for data extraction and included in the final review. The total number of patients was of 3,560 (2,098 female and 1,462 male subjects). The predominant disorders reported were hyposmia, anosmia, and parosmia. In most of the studies, the pre and postintervention assessments were the same, except for one study, in which the pre-intervention assessment of the disorder was through the SST, Sniffin' Sticks Test (SST), and the post-intervention assessment was through the Visual Analog Scale (VAS) and the 22-item Sinonasal Outcome Test (SNOT-22). The findings suggest olfactory training (OT), ivermectin, palmitoylethanolamide, luteolin, and systemic corticosteroids, in combination with topical corticosteroids, are potential therapies for COVID-19 patients with olfactory impairment. Conclusion Although the review suggested several medications for OD treatment, further research must delve into the specific impact of OT, a non-pharmacological modality, regarding the mitigation of OD. By continuing to investigate and refine these therapeutic approaches, we can better support COVID-19 patients and improve their quality of life while navigating the challenges posed by OD. [ABSTRACT FROM AUTHOR]

At the beginning of the pandemic, SARS-CoV-2 infection represented a great medical burden worldwide, as targeted and effective therapeutic options were lacking. This resulted in the revival of existing molecules and the increasing popularity of over-the-counter nutritional supplements. Among the latter, lactoferrin has been investigated as an adjuvant in COVID-19 therapy with conflicting results, mainly depending on different study designs. Considering that lactoferrin is one of the main components of human breast milk with anti-microbial and anti-inflammatory activity, it is conceivable that such bioactive molecule could be effective in supporting anti-SARS-CoV-2 infection therapy, especially in infants and pregnant women, two subpopulations that have been poorly evaluated in the existing clinical trials. This narrative review is intended to offer insight into the existing literature on lactoferrin's biological functions and protective effects against COVID-19, with a special focus on pregnant women and their infants. [ABSTRACT FROM AUTHOR]

This paper describes a scoping review of China's academic resource databases, relevant official websites, news reports and public accounts spanning a period from the end of 2019 to the end of 2022, to investigate the challenges in scientific integrity and ethical soundness of research conducted during and immediately after the COVID-19 pandemic in China. By conducting the scoping review with keywords related to the research questions in Chinese, relevant data were extracted and classified into four categories: challenges in research, challenges in ethics review, challenges in publishing academic work, and research ethics guidelines during and after the pandemic. The paper points out that problematic studies and findings increased with the escalation in medical research projects during the pandemic in China. The situation faced by researchers was more difficult than before the pandemic. The mode of informed consent, and ethics review and oversight systems also underwent changes. In addition, Traditional Chinese Medicine as an alternative medical treatment for COVID-19, attracted attention from the research community and became a topic of discussion. We conclude that the various challenges and concerns identified indicate a need for a proper and timely response system be formulated in preparation for possible future occurrences of new pandemics or other critical situations. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic touched off an unprecedented search for vaccines and treatments. Without question, the development of vaccines to prevent COVID-19 was an enormous scientific accomplishment. Further, the RECOVERY and Solidarity trials identified effective treatments for COVID-19. But all was not success. The urgent need for COVID-19 prevention and treatment fueled an embrace of risks—to research participants and to the reliability of the science itself—as allegedly necessary costs to speed scientific progress. Scientists and (even) ethicists supported overturning longstanding norms protecting healthy volunteers in human challenge trials to speed vaccine development, but these trials led to no vaccines. Physicians, with the approval of research ethics committees, designed hundreds of unblinded, single-center clinical trials at high risk of bias to speed the identification of new treatments. But these clinical trials led to no treatments. The lesson for future pandemics is that the acceptance of greater risks to participants or science does not reliably lead to progress. We are better served by science that upholds the highest ethical and methodological standards. [ABSTRACT FROM AUTHOR]

Introduction: Hemoadsorption, an extracorporeal apheresis technique, is reportedly used in severe COVID-19 patients. However, limited evidence from randomized clinical trials supports this practice. Methods: In this single-center study, severe COVID-19 patients requiring ICU admission were randomly assigned (1:1) to receive HA-330 hemoadsorption in combination with standard treatment or standard therapy alone. Both groups received tocilizumab intravenously if their clinical conditions worsened within 24–48 h. The primary outcome was mortality from any cause within 28 days after randomization. Secondary outcomes included mechanical ventilator-free days, daily C-reactive protein levels, oxygenation (defined by PaO2/FiO2 ratio), daily sequential organ failure assessment score, and severity score of lung infiltration on chest X-rays (CXR RALE score). Results: A total of 28 patients underwent randomization, with 14 (50%) receiving HA-330 hemoadsorption. Only 9 out of 14 patients (64.3%) in the control group experienced clinical worsening and were subsequently administered intravenous tocilizumab. At 28 days, the mortality rate was significantly lower in the intervention group (28.57% vs. 78.57%, p = 0.021), with a hazard ratio of death of 0.26 (95% CI = 0.08–0.81; p = 0.021). All of secondary outcomes were comparable in both groups. Conclusion: Based on our pilot randomized trial, the early application of HA-330 hemoadsorption in patients with severe COVID-19 may establish a favorable outcome in term of mortality. These data provide the initial proof of concept for conducting a large-scale study in the future. [ABSTRACT FROM AUTHOR]

Introduction: The main objective of this study was to evaluate the impact of hemoadsorption on the elimination of inflammatory mediators. Methods: A prospective, bicenter, observational cohort study was conducted between March 2020 and February 2022 to explore the immunomodulatory response, demographic and clinical characteristics of individuals with COVID-19 admitted to the ICU with severe acute respiratory failure and in need of CRRT with Oxiris® with or without AKI. Results: Sixty-four patients were analyzed. Statistically significant differences were observed between exposed and unexposed groups, in relation to the reduction in D-dimer levels −15,614 (24,848.9) versus −4,136.5 (9,913.47) (p 0.031, d: 1.59, 95% CI: −21,830, −1,126). An increase in PCT was observed 0.47 (2.08) versus −0.75 (2.3) (p 0.044 95% CI: 0.03, 2.44). No differences were found in a decrease in CRP −4.21 (7.29) versus −1.6 (9.02) (p 0.22) nor in the rest of inflammatory parameters fibrinogen, IL-6, ferritin, lymphocytes, and neutrophils. Subgroup analysis in patients exposed to therapy also showed a significant decrease in D-dimer of 55% from baseline: 6,000 (1,984.5–27,750) pre-therapy versus 2,700 (2,119.5–6,145) (95% CI: −23,000, −2,489) post-therapy with a strong effect size (p 0.001, d: 0.65). Conclusion: The hemoadsorptive therapy in COVID-19 was associated with a significant decrease in D-dimer parameters without showing decreases in the rest of the clinical, inflammatory parameters and severity scales analyzed. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has prompted the medical systems of many countries to develop effective treatments to combat the high rate of infection and death caused by the disease. Within the array of proteins found in SARS-CoV-2, the 3 chymotrypsin-like protease (3CLpro) holds significance as it plays a crucial role in cleaving polyprotein peptides into distinct functional nonstructural proteins. Meanwhile, RNA-dependent RNA polymerase (RdRp) takes center stage as the key enzyme tasked with replicating the viral genomic RNA within host cells. These proteins, 3CLpro and RdRp, are deemed optimal subjects for QSAR modeling due to their pivotal functions in the viral lifecycle. In this study, SMILES-based QSAR classification models were developed for a dataset of 2377 compounds that were defined as either active or inactive against 3CLpro and RdRp. Pharmacophore (PH4) and QSAR modeling were used for the virtual screening on 60.2 million compounds including ZINC, ChEMBL, Molport, and MCULE databases to identify new potent inhibitors against 3CLpro and RdRp. Then, a filter was established based on typical molecular characteristics to identify drug-like molecules. The molecular docking was also performed to evaluate the binding affinity of 156 AND 51 potential inhibitors to 3CLpro and RdRp, respectively. Among the 15 hits identified based on molecular docking scores, M3, N2, and N4 were identified as promising inhibitors due to their good synthetic accessibility scores (3.07, 3.11, and 3.29 out of 10 for M3, N2, and N4 respectively). These compounds contain amine functional groups, which are known for their crucial role in the binding interactions between drugs and their targets. Consequently, these hits have been chosen for further biological assay studies to validate their activity. They may represent novel 3CLpro and RdRp inhibitors possessing drug-like properties suitable for COVID-19 therapy. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic disrupted routine health care and antenatal and birth services globally. The Shoklo Malaria Research Unit (SMRU) based at the Thailand-Myanmar border provides cross border antenatal care (ANC) and birth services to marginalised pregnant women. The border between the countries entered lockdown in March 2020 preventing cross-border access for women from Myanmar to Thailand. SMRU adapted by opening a new clinic during the COVID-19 pandemic in Myanmar. This study explored the impact of the COVID-19 pandemic and response on access to ANC and pregnancy outcomes for marginalised pregnant women in the border regions between Thailand and Myanmar. Methods: A retrospective review of medical records of all pregnancies delivered or followed at antenatal clinics of the SMRU from 2017 to the end of 2022. Logistic regression was done to compare the odds of maternal and neonatal outcomes between women who delivered pre-COVID (2017–2019) and women who delivered in the COVID-19 pandemic (2020–2022), grouped by reported country of residence: Thailand or Myanmar. Results: Between 2017 and the end of 2022, there were 13,865 (5,576 resident in Thailand and 8,276 in Myanmar) marginalised pregnant women who followed ANC or gave birth at SMRU clinics. Outcomes of pregnancy were known for 9,748 women with an EGA ≥ 28 weeks. Unknown outcome of pregnancy among women living in Thailand did not increase during the pandemic. However, there was a high (60%) but transient increase in unknown outcome of pregnancy for women with Myanmar residence in March 2020 following border closure and decreasing back to the baseline of 20–30% after establishment of a new clinic. Non-literate women were more likely to have an unknown outcome during the pandemic. There was no statistically significant increase in known stillbirths or maternal deaths during the COVID pandemic in this population but homebirth was over represented in maternal and perinatal mortality. Conclusion: Decreasing barriers to healthcare for marginalised pregnant women on the Thailand-Myanmar border by establishment of a new clinic was possible in response to sudden border closure during the COVID-19 pandemic and most likely preventing an increase in maternal and perinatal mortality. [ABSTRACT FROM AUTHOR]

Introduction: The monoclonal antibody therapies bamlanivimab (BAM) + etesevimab (ETE) received emergency use authorization (EUA) from the US Food and Drug Administration (February 9, 2021) for treatment of mild-to-moderate COVID-19. The EUA of BAM + ETE was revoked (December 14, 2023) due to the high prevalence of BAM + ETE-resistant variants of SARS-CoV-2. Efficacy and safety of 700/1400 mg and 2800/2800 mg BAM + ETE are well established and published; however, efficacy and safety of 350/700 mg BAM + ETE have not been disclosed to date. Methods: This portion of phase 3, BLAZE-1 trial (J2X-MC-PYAB) enrolled patients (between June 17, 2020 and April 9, 2021) with mild-to-moderate COVID-19 within 3 days of laboratory diagnosis of SARS-CoV-2 infection. In total, 354 patients with at least one risk factor for severe COVID-19 were enrolled, randomized (2:3), and infused with placebo (N = 141) or 350/700 mg BAM + ETE (N = 213), over ~ 8 min. Primary endpoint was to assess proportion of patients with persistently high SARS-CoV-2 viral load (PHVL) (log viral load > 5.27) 7 days after infusion. Results: Patients were aged (mean) 53 years, 49.7% female, and 82.7% White. Seven days after drug infusion, 10.8% (95% confidence interval: 6.6, 15.0; p < 0.001) of BAM + ETE-treated patients and 34.8% (26.9, 42.6) of placebo-treated patients had PHVL, and the viral load change from baseline (least square mean [standard error]) was − 3.50 (0.15; p < 0.001) in BAM + ETE-treated patients versus − 2.51 (0.19) in placebo-treated patients. The majority of treatment-emergent adverse events were considered mild or moderate in severity (BAM + ETE: 6.6%; placebo: 14.2%). No deaths were reported. Conclusions: Consistent with previous studies, patients treated with BAM + ETE (350/700 mg) had a significantly lower proportion of PHVL and greater reduction in viral load compared with placebo. The overall safety profile is consistent with higher doses of BAM + ETE. Infusions of over ~ 8 min did not result in meaningful increase in incidence of TEAEs compared to higher doses of BAM + ETE administered over 30–60 min. Trial Registration: Clinical trial.gov identifier, NCT04427501. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin D, known for its role in bone health, is now being explored for its immunomodulatory effects. This study aimed to evaluate the impact of vitamin D supplementation on mortality in coronavirus disease 2019 (COVID-19) patients through a systematic review and meta-analysis of randomized controlled trials. Methods: A comprehensive search was conducted across PubMed, Scopus, Web of Science, and preprint servers for eligible trials up to July 8, 2024. Two investigators independently screened the records and assessed the risk of bias using the Cochrane Risk of Bias Tool. Trials were eligible if they compared vitamin D with control interventions in adults with COVID-19. Data extraction and analysis were carried out independently, employing a random-effects model to estimate pooled odds ratios for mortality. Results: Nineteen randomized controlled trials with 2495 participants were included. The meta-analysis showed a significant reduction in all-cause mortality with vitamin D supplementation (pooled OR 0.72, 95% CI 0.53–0.98; I2 = 20%). Subgroup analysis for severe COVID-19 cases also indicated significant mortality reduction (pooled OR 0.57, 95% CI 0.35–0.92; I2 = 18%). Conclusion: Vitamin D supplementation appears to reduce mortality in COVID-19 patients, especially in severe cases. These findings highlight the potential benefits of vitamin D as an adjunct treatment in COVID-19, though further large-scale trials are needed to confirm these effects and determine optimal dosing. [ABSTRACT FROM AUTHOR]

In severe COVID-19 cases, an exacerbated inflammatory response triggers a cytokine storm that can worsen the prognosis. Compounds with both antiviral and anti-inflammatory activities show promise as candidates for COVID-19 therapy, as they potentially act against the SARS-CoV-2 infection regardless of the disease stage. One of the most attractive drug targets among coronaviruses is the main protease (MPro). This enzyme is crucial for cleaving polyproteins into non-structural proteins required for viral replication. The aim of this review was to identify SARS-CoV-2 MPro inhibitors with both antiviral and anti-inflammatory properties. The interactions of the compounds within the SARS-CoV-2 MPro binding site were analyzed through molecular docking when data from crystallographic structures were unavailable. 18 compounds were selected and classified into five different superclasses. Five of them exhibit high potency against MPro: GC-376, baicalein, naringenin, heparin, and carmofur, with IC50 values below 0.2 μM. The MPro inhibitors selected have the potential to alleviate lung edema and decrease cytokine release. These molecules mainly target three critical inflammatory pathways: NF-κB, JAK/STAT, and MAPK, all previously associated with COVID-19 pathogenesis. The structures of the compounds occupy the S1/S2 substrate binding subsite of the MPro. They interact with residues from the catalytic dyad (His41 and Cys145) and/or with the oxyanion hole (Gly143, Ser144, and Cys145), which are pivotal for substrate recognition. The MPro SARS-CoV-2 inhibitors with potential anti-inflammatory activities present here could be optimized for maximum efficacy and safety and be explored as potential treatment of both mild and severe COVID-19. [ABSTRACT FROM AUTHOR]

The primary aim of this investigation is to shed light on potential targets within the main protease Mpro, spike protein of SARS-CoV-2, and Angiotensine converting enzyme 2 (ACE2) for the exploration of novel inhibitors derived from therapeutic natural compounds originating from Atriplex halimus (AH). Many constituents were discerned within AH extracts through comprehensive gas chromatography/mass spectrometry (GC/MS). Notably, compounds, such as oleocanthal and methyl stearate, exhibited promising attributes across various biological activities, including inhibition of key proteins associated with SARS-CoV-2. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) settings were evaluated to explore the potential safety and viability of these compounds for pharmaceutical application, affirming their non-interference with human physiology and thus suggesting their suitability for pharmaceutical use. Catechin, epigallocatechin, and methyl stearate were discovered to be the compounds with the highest affinity to the studied protein showing a great potential to be inhibitors to COVID-19. Consequently, this discovery highlights Atriplex halimus as a promising candidate for utilization in combating the virus. In our study, several compounds from Atriplex halimus showed a significant inhibition activity against SARS-COV-2 Mpro and Spike protein, which promotes Atriplex halimus as a potential agent that can be used in the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19), a kind of respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily spreads through the respiratory tract from human to human. Its extensive and rapid spread has led to a global pandemic, causing great harm to human health and economic development all over the world. Current known evidence indicates that SARS-CoV-2 has evolved accumulating multiple mutations, with altered infectivity and viral replication capacity. A better understanding of the complications of COVID-19 and its relationship with underlying diseases is crucial for the prevention and treatment of SARS-CoV-2. This case series reviewed case data of our 4 recent patients with severe or critical COVID-19, including treatment plan, status of pulmonary infection and their microbiology workup with metagenomic next-generation sequencing with bronchoalveolar lavage fluid. This report shed light on the significance of rapid and accurate clinical diagnosis and treatment on COVID-19. [ABSTRACT FROM AUTHOR]

Objective: To determine the occurrence of breakthrough COVID-19 infections (BIs) in patients with systemic lupus erythematosus (SLE) compared with patients with other rheumatic autoimmune diseases (rAIDs), patients with non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs). Methods: The study was based on data from 7035 fully vaccinated respondents to the online COVAD questionnaire with SLE (N = 852), rAIDs (N = 3098), or nrAIDs (N = 414), and HCs (N = 2671). BI was defined as COVID-19 infection occurring in individuals vaccinated with ≥ 2 doses (or 1 dose of J&J) ≥ 14 days after vaccination and not after 6 months since the last vaccine dose. Data were analysed using linear and logistic regression models. Results: A total of 91/852 (10.7%) SLE patients reported at least one BI. The frequency of BIs in SLE patients was comparable to that among HCs (277/2671; p = 0.847) and patients with nrAID (39/414; p = 0.552) but higher than that among patients with other rAIDs (235/3098; p = 0.005). No demographic factors or treatments were associated with BIs in SLE patients (p ≥ 0.05 for all). Joint pain was more frequent in SLE patients than in HCs (odds ratio [OR]: 3.38; 95% confidence interval [CI]: 1.89–6.04; p < 0.001) or nrAID patients (OR: 2.44; 95% CI: 1.04–5.75; p = 0.041). Patient with SLE did not report a higher frequency of hospitalisation or need for advanced treatment for COVID-19 infection compared with disease controls and HCs, respectively. Conclusion: COVID-19 vaccination conferred similar protection against COVID-19 infection in terms of frequency and severity in patients with SLE to that reported by healthy individuals. [ABSTRACT FROM AUTHOR]

Previous research reported inconsistent results on the efficacy of molnupiravir in treating COVID-19. Moreover, efficacy was not assessed in the intended-use population (IUP), as defined by the FDA. Therefore, we aimed to evaluate the effectiveness and safety of molnupiravir for the treatment of COVID-19 in the IUP. We performed a retrospective cohort study on all IUP in Israel's Clalit Health Services from January 16, 2022, to February 16, 2023. The effectiveness outcome was the incidence of hospitalization or death due to COVID-19, and the safety outcome was the incidence of all-cause mortality within 35 days of SARS-CoV-2 infection. Cox-proportional hazard models were used to analyse the data after 1:5 propensity-score matching. A total of 49 515 patients met the eligibility criteria. Of them, 3957 molnupiravir-treated patients were matched to 19 785 untreated patients. In molnupiravir-treated patients, 70 out of 3957 (5.1 per 10 000 person per day) experienced COVID-19-related hospitalization or death, compared with 699 out of 19 785 untreated patients (10.4 per 10 000 person per day); RR: 0.50 (95% CI, 0.39–0.64). All-cause mortality was also lower in the treated group, with 41 out of 3957 (3.0 per 10 000 person per day) experiencing mortality compared with 414 out of 19 785 untreated patients (6.1 per 10 000 person per day); RR: 0.50 (0.36–0.68). In a real-world cohort of IUP, molnupiravir therapy was associated with a significant reduction in hospitalizations or deaths due to COVID-19 and all-cause mortality. [ABSTRACT FROM AUTHOR]

[Background] As the COVID-19 pandemic progressed from Januaiy 2020, the incidence of influenza infections fell drastically through measures such as the avoidance of non-essential outings and the "Three Cs" (closed spaces, crowded places, and close-contact settings). In May 2023, COVID-19 was reclassified to Class 5 and movement restrictions were eased, which was followed by an upsurge in influenza infections. This study examined the treatment statuses of COVID-19 and influenza using insurance pharmacy prescriptions. [Methods] We investigated prescriptions for COVID-19 and influenza medications filled at Nihon Chouzai pharmacies within Tokyo between April 2022 and March 2024, by analyzing medications targeting both diseases to reveal concurrent infections. [Results] We examined prescriptions from 11,307 COVID-19 patients, 34,337 influenza patients, and 19 patients with concurrent infections. The highest monthly number of COVED-19 patients was 1,712 (August 2023), with four peaks observed throughout the study period; the highest number of influenza patients was 5,876 (December 2023). Antipyretics/analgesics were the most common medication used for both diseases (approximately 90% of patients). [Discussion] The incidence of influenza was higher than COVID-19, and their incidences peaked at different times. Concurrent infections showed low incidence (n=19), which was similar (albeit with different values) to other reports. However, co payments for COVID-19 treatments were 15,000-30,000 JPY after the cessation of government subsidies during the study period. Some patients may forgo dispensation for financial reasons, thereby affecting prescription numbers. This issue arises for both concurrent infections and single infections, and is a limitation of studies that use insurance pharmacy prescriptions. [ABSTRACT FROM AUTHOR]

Cuprotosis related genes (CRGs) have been proved to be potential therapeutic targets for coronavirus disease 2019 (COVID-19) and cancer, but their immune and molecular mechanisms in COVID-19 infection in Diffuse Large B-cell Lymphoma (DLBC/DLBCL) patients are rarely reported. Our research goal is first to screen the key CRGs in COVID-19 through univariate analysis, machine learning and clinical samples. Secondly, we determined the expression and prognostic role of key CRGs in DLBCL through pan-cancer analysis. We validated the expression levels and prognosis using multiple datasets and independent clinical samples and validated the functional role of key CRGs in DLBCL through cell experiments. Finally, we validated the expression levels of CRGs in COVID-19 infected DLBCL patients samples and analyzed their common pathways in COVID-19 and DLBCL. The results show that synuclein-alpha (SNCA) is the common key differential gene of COVID-19 and DLBCL. DLBCL cells confirm that high expression of SNCA can significantly promote cell apoptosis and significantly inhibit the cycle progression of DLBCL. High expression of SNCA can regulate the binding of major histocompatibility complexes (MHCs) and T cell receptor (TCR) by regulating immune infiltration of Dendritic cells, effectively enhancing T cell-mediated anti-tumor immunity and clearing cancer cells. In conclusion, SNCA may be a potential therapeutic target for COVID-19 infection in DLBCL patients. Our study provides a theoretical basis for improving the clinical treatment of COVID-19 infection in DLBCL patients. [ABSTRACT FROM AUTHOR]