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While the general population regained a certain level of normalcy with the end of the global health emergency, the risk of contracting COVID-19 with a severe outcome is still a major concern for people with compromised immunity. This paper reviews the impact of COVID-19 on people with immunocompromised status, identifies the gaps in the current management landscape, and proposes actions to address this unmet need. Observational studies have demonstrated that people with immune dysfunction have a higher risk of COVID-19-related hospitalization and death, despite vaccination, than the general population. More research is needed to define the optimal prevention and treatment strategies that are specific to people with immunocompromised status, including novel vaccination strategies, monoclonal antibodies that provide passive immunity and complement suboptimal vaccination responses, and improved and safer antiviral treatment for COVID-19. Preventive measures beyond vaccination alone are urgently needed to protect this vulnerable population. [ABSTRACT FROM AUTHOR]

As South Africa faced the new dawn of COVID-19 pandemic, questions were raised regarding the utilization of African traditional medicine as a treatment of the illness. Madagascar was viewed by African people as a pioneer to regard and declare Artemisia as treatment for COVID-19 and developed products known as Africa following its breakthrough in traditional herbal cure for COVID-19 known as COVID Organics or CVO to be used by their citizens and the rest of African states. In July 2020, the World Health Organization (WHO) and the Africa Centres for Disease Control and Prevention formed a Regional Expert Committee on Conventional Medicine for COVID-19 in an attempt to enhance research and development of traditional medicines such as CVO, aiming to test traditional therapies and provide independent advice on their safety and efficacy. However, six months after its formation, it appeared that this attempt to regulate has failed to gain traction: None of the proposed remedies progressed beyond phase II clinical trials. Using existing secondary sources such as articles, government documents and media releases, this paper aims to look at the response from South African government on utilization of African Traditional Medicine as COVID-19 treatment. A special attention is given to South African government's response to the treatment proposed by the state of Madagascar and its way forward towards using traditional medicine as treatment to COVID-19. [ABSTRACT FROM AUTHOR]

Background: Chloroquine (CQ) is an antimalarial drug that was first synthesized by Hans Andersag, a German scientist, in 1934. Chloroquine has been widely researched and used over the years. The rapid development in the fields of modern science and technology has also contributed to the increase in interest in chloroquine. Hence, it is necessary to comprehensively summarize the research trends to understand the breakthroughs made in the field. Methods: The required data was compiled by analyzing the Web of Science Core Collection (WoSCC) database. The search period for studying global research trends in chloroquine research was set from 2012 to 2021 to ensure a comprehensive analysis over an extended timeframe. Data retrieval was performed on April 4, 2022, focusing on articles and reviews published in English. The retrieval words were: (TS = (chloroquine)) OR (TS = (aralen)). A total of 1,091 reviews and 7,259 articles were retrieved and analyzed. The data obtained from WoSCC was captured and analyzed using VOS viewer (version 1.6.16) and Citesspace (version 5.8.R5). Results: The number of literature reports on chloroquine published in the past 10 years has shown an annual increase. Among the countries, the United States has contributed the highest number of papers and ranks first in terms of both H-index and citation count. The League of European Research Universities is one of the largest research-focused university networks, and Malaria Journal stands out as a prominent journal publishing articles relevant to the field of study. A paper authored by Gautret and Philippe in 2020 achieved the highest citation score globally. The biosynthesis of chloroquine, mechanisms of drug resistance, and drug combinations are receiving growing attention. Conclusion: The research area of chloroquine has been significantly influenced by the American and China. The progress of chloroquine research is further propelled by fruitful collaborations among various countries. Researchers have extensively studied the anti-malarial effect, drug resistance mechanism, and autophagy of chloroquine for the development of a treatment method for COVID-19 based on chloroquine. Bibliometric analysis can be employed to identify hotspots, new directions, and frontiers in the field of chloroquine research. [ABSTRACT FROM AUTHOR]

While the general population regained a certain level of normalcy with the end of the global health emergency, the risk of contracting COVID-19 with a severe outcome is still a major concern for people with compromised immunity. This paper reviews the impact of COVID-19 on people with immunocompromised status, identifies the gaps in the current management landscape, and proposes actions to address this unmet need. Observational studies have demonstrated that people with immune dysfunction have a higher risk of COVID-19-related hospitalization and death, despite vaccination, than the general population. More research is needed to define the optimal prevention and treatment strategies that are specific to people with immunocompromised status, including novel vaccination strategies, monoclonal antibodies that provide passive immunity and complement suboptimal vaccination responses, and improved and safer antiviral treatment for COVID-19. Preventive measures beyond vaccination alone are urgently needed to protect this vulnerable population. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has significantly affected both the global economy and human health. COVID-19 is a single-stranded RNA virus that spreads through the inhalation of viral droplets. Its genome encodes four structural proteins: the envelop protein, spike protein, membrane protein, and nucleocapsid protein. The virus's capsid is a protein shell that contains a positive RNA strand that allows it to take control of human cell machinery. Currently, the only treatments for COVID-19 are preventative measures and immunization. Some of the anti-COVID and anti-cancer medications used to combat this virus include Camptothecin Polymer, Hyaluronic Acid-curcumin, and Hydroxychloroquine. Graphs are used extensively in chemical investigation to provide a mathematical model of molecules. The selection of graph invariants, formerly known as molecular structure descriptor's, is the mathematical modelling of chemical compounds' physio-chemical, pharmacologic, and toxicological aspects. This paper presents a new technique to compute topological indices for three types of chemical networks for a few anti-COVID and anti-cancer medications. Our findings suggest that these indices show a strong association with the acentric factor and entropy, which make them effective in QSPR and QSAR analysis with high accuracy. [ABSTRACT FROM AUTHOR]

Coronavirus disease-19 (COVID-19) has disproportionately affected certain demographics in England, exacerbating existing health disparities. Effective therapeutics are a critical line of defence against COVID-19, particularly for patients at elevated risk for severe disease. Surveillance systems were established to monitor the usage of COVID-19 therapeutics in hospital and community settings and to inform stewardship. Three antiviral therapies—nirmatrelvir plus ritonavir (Paxlovid®), remdesivir (Veklury®), and molnupiravir (Lagevrio®)—and two neutralising monoclonal antibody therapies (nMAbs)—sotrovimab (Xevudy®) and casirivimab with imdevimab (Ronapreve®)—were in use in England between July 2020 and April 2023. This paper aims to illuminate trends in the utilisation of COVID-19 therapeutics treatment in both hospital and community settings, stratified by the Index of Multiple Deprivation (IMD) in England. Chapter 3 of the English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) Report 2022 to 2023 also discusses the epidemiological surveillance of these five directly acting antiviral COVID-19 therapeutics' use in England between 2022 and 2023. [ABSTRACT FROM AUTHOR]

Since the outbreak of COVID-19 few years ago, the increasing of the number of medical waste has become a huge issue because of their harmful impact to environment. A major concern associated to the limitation of technologies for dealing with medical waste, especially conventional technologies, are overcapacities since pandemic occurs. Moreover, the outbreak of new viruses from post COVID-19 should become a serious attention to be prevented not only environmental issues but also the spreading of viruses to new pandemic near the future. The high possibility of an outbreak of new viruses and mutation near the future should be prevented based on the experience associated with the SARS-CoV-2 virus in the last 3 yr. This review presented information and strategies for handling medical waste during the outbreak of COVID-19 and post-COVID-19, and also information on the current issues related to technologies, such as incineration, pyrolysis/gasification, autoclaves and microwave treatment for the dealing with high numbers of medical waste in COVID-19 to prevent the transmission of SARS-CoV-2 virus, their advantages and disadvantages. Plasma technology can be considered to be implemented as an alternative technology to deal with medical waste since incinerator is usually over capacities during the pandemic situation. Proper treatment of specific medical waste in pandemics, namely face masks, vaccine vials, syringes, and dead bodies, are necessary because those medical wastes are mediums for transmission of the SARS-CoV-2 virus. Furthermore, emission controls from incinerator and plasma are necessary to be implemented to reduce the high concentration of CO2, NOx, and VOCs during the treatment. Finally, future strategies of medical waste treatment in the perspective of potential outbreak pandemic from new mutation viruses are discussed in this review paper. Implications: Journal of the air and waste management association may consider our review paper to be published. In this review, we give important information related to the technologies, managements and strategies for handling the medical waste and control the transmission of SARS-CoV-2 virus, starting from proper technology to control the high number of medical waste, their pollutants and many strategies for controlling the spreading of SARS-CoV-2 virus. Moreover, this review also describes some strategies associated with control the transmission not only the SARS-CoV-2 virus but also the outbreak of new viruses near the future. [ABSTRACT FROM AUTHOR]

Niclosamide is a well-established anthelmintic drug included in the WHO's essential list of medicines. Recently, it has been repurposed for the treatment of COVID-19. This article delves into the solvate formation of niclosamide. The anhydrous forms of niclosamide (polymorphs I and II) seem to have an adequate ratio of donor to acceptor groups and these are well utilized for hydrogen bonding with a high crystal packing index (>70%). Nevertheless, niclosamide has been shown to incorporate solvent molecules into its crystal structure. So far, two hydrate polymorphs and five solvates have been reported in the literature with their crystal structures. We noticed that niclosamide has a high tendency for solvates/hydrates over anhydrous forms in our crystallization attempts and this has prompted us to investigate the solvate formation more in detail to find out possible reasons/driving forces for it. We have observed six new solvates of niclosamide, of which two are polymorphic forms of niclosamide with N,N-dimethylacetamide (1 : 1 and 2 : 2), two are variable stoichiometry solvates with dioxan (1 : 0.5 and 2 : 1.5) and two are 1 : 1 solvates with dimethylsulfoxide and dimethylformamide solvents. Single crystal and powder X-ray diffraction measurements were carried out for deeper structural insights on how solvent molecules are accommodated in the crystals. Thermal and computational studies were carried out and correlated with the structural details to understand the influence of solvents on the crystal stability and desolvation process. Solvent molecules have played an important role in altering the hydrogen bonding pattern of niclosamide and overall molecular arrangements inside the crystal. The strength of the hydrogen bonding is found to be the key factor that is responsible for solvate formation in niclosamide. Both anhydrous forms and solvates are sustained by O–H⋯O hydrogen bonding, but the bonding is relatively stronger in solvates. As a result, niclosamide shows a higher preference for solvates over anhydrous forms despite the latter having a better packing coefficient. These results may find their applications in crystal engineering for better understanding of pharmaceutical hydrates or solvates. [ABSTRACT FROM AUTHOR]

The focus of this paper is on COVID-19, the December 2019 dated respiratory epidemic or infection that has ravaged most, if not all, of the world's 253 "countries" (consisting of 194 independent nation-states, 55 dependent-states, Antarctica, and 3 other territories). Readers of this paper should be aware of at least three facts. First, as of January 2022, the submission date of this paper, COVID-19 continues to impact the world, although to a much lesser extent, given the protection afforded by the mRNA vaccines, the boosters, and the antiviral medications (e.g., oseltamivir, penciclovir, acyclovir, Paxlovid, etc.). Second, the paper should be regarded as being inconclusive in both its outlook and its list of references; it provides, at best, an intermediary account of the continuing COVID-19 pandemic. Third, like the Spanish Flu of 1918, it is speculated that the COVID-19 pandemic will not endure beyond three years and will conclude as an endemic problem by, hopefully, early 2023. Therefore, the paper is partitioned into three sections which, respectively, address the infection's three phases: epidemic (initial infection), pandemic (worldwide infection) and endemic (pervasive but nonlife-threatening infection) phases. The lessons learned from the range of decisions made throughout the COVID-19 phases should help to inform and better prepare the world for future pathogens and deadly diseases. [ABSTRACT FROM AUTHOR]

Background: To investigate the efficacy of different doses of corticosteroids in treating severe coronavirus disease 2019 (COVID-19) pneumonia. Methods: Between May 01, 2023, and June 20, 2023, 48 patients with severe COVID-19 pneumonia were treated at the Department of Respiratory and Critical Care Medicine of Jinan Fourth People's Hospital. The observation group (21 patients) received standard care and high-dose corticosteroids, (high-dose group). The control group (27 patients) received standard care and low-dose corticosteroids (low-dose group). We collected baseline data and recorded inflammatory marker levels after 3 days of treatment, body temperature recovery time, length of stay, and 28-day all-cause mortality. The results of outpatient follow-up were recorded after 1 month. Results: There were no significant differences in 28-day mortality and length of stay. The number of days it took for body temperature to return to normal in the high-dose group was less than in the low-dose group. The high-dose group had significantly more reduced inflammatory factors (C-reactive protein (CRP), interleukin-6 (IL-6). A total of 20 discharged patients were given 8–16 mg of methylprednisolone, depending on chest computed tomography (CT) and clinical symptoms after 1 month; in all discharged patients using oral corticosteroids, CT features improved. Conclusion: High-dose corticosteroids had a significantly positive effect on the reduction of inflammatory factors and shortening body temperature recovery time. In the treatment of severe COVID-19 pneumonia, early administration of high-dose, short-course corticosteroids should be implemented. Highlights: The highlights of the paper are: 1. High-dose corticosteroid can shorten the recovery time of body temperature. 2. High-dose corticosteroid can better reduce inflammatory factors (CRP IL-6). 3. Oral hormones in discharged patients with severe COVID-19 pneumonia are beneficial. 4. Initial dosage and course of corticosteroid might be varied case by case. [ABSTRACT FROM AUTHOR]

The work presented in this paper makes multiple scientific contributions with a specific focus on the analysis of misinformation about COVID-19 on YouTube. First, the results of topic modeling performed on the video descriptions of YouTube videos containing misinformation about COVID-19 revealed four distinct themes or focus areas—Promotion and Outreach Efforts, Treatment for COVID-19, Conspiracy Theories Regarding COVID-19, and COVID-19 and Politics. Second, the results of topic-specific sentiment analysis revealed the sentiment associated with each of these themes. For the videos belonging to the theme of Promotion and Outreach Efforts, 45.8% were neutral, 39.8% were positive, and 14.4% were negative. For the videos belonging to the theme of Treatment for COVID-19, 38.113% were positive, 31.343% were neutral, and 30.544% were negative. For the videos belonging to the theme of Conspiracy Theories Regarding COVID-19, 46.9% were positive, 31.0% were neutral, and 22.1% were negative. For the videos belonging to the theme of COVID-19 and Politics, 35.70% were positive, 32.86% were negative, and 31.44% were neutral. Third, topic-specific language analysis was performed to detect the various languages in which the video descriptions for each topic were published on YouTube. This analysis revealed multiple novel insights. For instance, for all the themes, English and Spanish were the most widely used and second most widely used languages, respectively. Fourth, the patterns of sharing these videos on other social media channels, such as Facebook and Twitter, were also investigated. The results revealed that videos containing video descriptions in English were shared the highest number of times on Facebook and Twitter. Finally, correlation analysis was performed by taking into account multiple characteristics of these videos. The results revealed that the correlation between the length of the video title and the number of tweets and the correlation between the length of the video title and the number of Facebook posts were statistically significant. [ABSTRACT FROM AUTHOR]

This article is an editorial that explores the experiences of mental health professionals in psychiatric settings. It highlights the various stressors faced by these professionals and the negative impact on their well-being. The article emphasizes the need for attention to the health and well-being of mental health professionals and the lack of available data on their experiences. The editorial includes five papers that discuss different aspects of this topic, such as the impact of childhood adversity on the well-being of frontline psychiatry staff and the implementation of feedback models in psychiatric residency programs. The research aims to identify risk factors and effective strategies for supporting the mental health of mental health professionals and improving their work. [Extracted from the article]

Background: The global scientific community has been quick to respond to health crisis unleashed by Covid-19 pandemic with intensified investments in R&D and thereby it gave new impetus to Covid-19 research. The world has come to witness unprecedented increase in research publications on control and treatment of Covid-19 pandemic. Like any other region in the world, South Asia too has been the worst-hit region and it too witnessed increase in Covid-related research studies. Systematic reviews of such literature and bibliometric studies are used nowadays as tools to identify and analyze key and significant South Asian contribution to the subject. The present study aims to assess and quantify the contribution and impact of Covid-19 research made by a group of select four South Asian countries. Methods: Publications data on Covid 19 covering the period between December 2019 and 8.7.2021 was sourced from the Scopus database. VOSviewer 1.6.14 software was applied to generate network maps, assess hot topics in the area and describe collaboration patterns in research between different countries. Results: A total of 18,64,275 publications reflecting the global research output on Covid-19 were retrieved from the Scopus database. The publications data of select four South Asian countries - Pakistan, Bangladesh, Nepal and Sri Lanka - was also retrieved. Comparatively the data size of select four South Asian countries was small, limited to 4012 documents, and accounting for a 2.15% share of the global research output on Covid-19 virus. Pakistan published the most number of Covid-19 publications (n = 2246, 55.58%), followed by Bangladesh (n = 1203, 29.99%), Nepal (n=512, 12.76%) and Sri Lanka (n=202, 5.03%). The United States as the collaborating partner in most number of publications contributed by South Asian countries (n = 609, 25.41%), followed by the United Kingdom (n = 496, 20.69%), China (n=453, 18.90%), Saudi Arabia (n=441, 18.40%) and India (n=426, 17.77%). Covid-19 treatment type was the most studied topic in the contributions made by South Asian countries accounting for a 16.45% share, followed by epidemiology (15.63%), risk factors (5.835), clinical studies (4.81%), etc. Conclusion: This paper finds that the quantity and quality of research pursued by a select group of four South Asian countries in the domain of Covid 19 studies has so far been small and insignificant. There is an urgent need on the part of select group of South Asian counties to improve their productivity and qualitative performance at the national, institutional, and individual author level. [ABSTRACT FROM AUTHOR]

Competing risks data are commonly encountered in randomized clinical trials and observational studies. This paper considers the situation where the ending statuses of competing events have different clinical interpretations and/or are of simultaneous interest. In clinical trials, often more than one competing event has meaningful clinical interpretations even though the trial effects of different events could be different or even opposite to each other. In this paper, we develop estimation procedures and inferential properties for the joint use of multiple cumulative incidence functions (CIFs). Additionally, by incorporating longitudinal marker information, we develop estimation and inference procedures for weighted CIFs and related metrics. The proposed methods are applied to a COVID‐19 in‐patient treatment clinical trial, where the outcomes of COVID‐19 hospitalization are either death or discharge from the hospital, two competing events with completely different clinical implications. [ABSTRACT FROM AUTHOR]

The authors collaborated closely with elders, knowledge keepers and indigenous community members to design an online training intervention to educate public health staff in indigenous protocols and cultural safety protocols. User-centred design was utilized in every stage of the design process to better understand and assess user needs and to adapt the design to these needs. [Extracted from the article]

We highlighted in this current paper similar prolonged respiratory presentation with COVID-19 pneumonia in four severely immunocompromised patients currently being treated with anti-CD20 monoclonal antibodies (mAbs), such as ocrelizumab and rituximab, for multiple sclerosis or rheumatoid polyarthritis. Real-time reverse transcription-polymerase chain reaction on a nasopharyngeal swab specimen was negative in all patients. SARS-CoV-2 infection was confirmed from bronchoalveolar lavage fluid. A high titer of post-vaccine COVID-19 convalescent plasma was administered with complete recovery in all patients. [ABSTRACT FROM AUTHOR]

Background: A new coronavirus was first identified in Wuhan, China in December 2019. Since the times of the 1918 influenza pandemic, malnutrition has been known as a risk factor for severity and mortality from viral pneumonia. Similarly, the recently identified SARS-Cov2 infection (COVID-19) and related pneumonia may be closely linked to malnutrition. Therefore, this study will contribute to new knowledge and awareness of the recording and evaluation of each COVID-19 patient's nutritional status by assessing the effect of malnutrition on ICU admission and death of COVID-19 patients in developing countries. Method: We conducted a prospective cohort study in adult COVID-19 patients admitted to selected COVID-19 Isolation and Treatment Centers, Addis Ababa, Ethiopia. Baseline data of the patients were collected using interviewer-administered structured questionnaire and data on the adverse outcomes of follow up were extracted from follow up chart. The main clinical outcomes (ICU admission and death) were captured every week of follow up. We ran a multivariate Cox's regression analysis to determine the relationship between malnutrition at admission and its effect on ICU admission and death. Results: A total of 581 COVID-19 patients were enrolled. From the total of recruited patients, 346 (59.6%) were males and 235 (40.4%) were females. The mean age of the respondents was 55 years (16.45) years. The Cox proportional hazard model controlled for sex, age group, number of co-morbidities, and number of medications found that malnutrition at admission was associated with ICU admission and death. When compared to well-nourished patients, the rate of ICU admission was significantly associated and found to be higher among underweight [(adjusted hazard ratio (AHR) = 10.02, 95% CI: (8.64–12.10)] and overweight [(AHR = 7.7, 95% CI: (6.41–9.62)] patients. The rate of survival probability was significantly associated and was found to be better among well-nourished patients (AHR = 0.06, 95% CI : (0.01–0.44) when compared with malnourished COVID-19 patients. Conclusion: Malnutrition at the time of admission was shown to increase the risk of ICU admission and mortality among COVID-19 patients. Therefore, it is vital to evaluate patients' nutritional condition early in their admission and provide timely intervention to minimize the effects on patients and the healthcare system. [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]

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]

Background: Precision medicine has led to the development of targeted treatment strategies tailored to individual patients based on their characteristics and disease manifestations. Although precision medicine often focuses on a single health outcome for individualized treatment decision rules (ITRs), relying only on a single outcome rather than all available outcomes information leads to suboptimal data usage when developing optimal ITRs. Methods: To address this limitation, we propose a Bayesian multivariate hierarchical model that leverages the wealth of correlated health outcomes collected in clinical trials. The approach jointly models mixed types of correlated outcomes, facilitating the "borrowing of information" across the multivariate outcomes, and results in a more accurate estimation of heterogeneous treatment effects compared to using single regression models for each outcome. We develop a treatment benefit index, which quantifies the relative benefit of the experimental treatment over the control treatment, based on the proposed multivariate outcome model. Results: We demonstrate the strengths of the proposed approach through extensive simulations and an application to an international Coronavirus Disease 2019 (COVID-19) treatment trial. Simulation results indicate that the proposed method reduces the occurrence of erroneous treatment decisions compared to a single regression model for a single health outcome. Additionally, the sensitivity analyses demonstrate the robustness of the model across various study scenarios. Application of the method to the COVID-19 trial exhibits improvements in estimating the individual-level treatment efficacy (indicated by narrower credible intervals for odds ratios) and optimal ITRs. Conclusion: The study jointly models mixed types of outcomes in the context of developing ITRs. By considering multiple health outcomes, the proposed approach can advance the development of more effective and reliable personalized treatment. [ABSTRACT FROM AUTHOR]

The inhibition of heat shock protein 90 (HSP90), a molecular chaperone, has been proposed to be a potential novel treatment strategy for Coronavirus disease 2019 (COVID-19). In contrast to other studies, our data demonstrated that RGRN-305, a HSP90 inhibitor, exacerbated the cytopathic effect and did not reduce the viral shedding in VeroE6-hTMPRSS2 cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Likewise in a murine model of SARS-CoV-2, transgenic mice treated orally with RGRN-305 exhibited reduced survival by the end of the experiment (day 12) as 14% (1/7) survived compared to 63% (5/8) of those treated with drug-vehicle. Animal weight was not reduced by the RGRN-305 treatment. Interestingly, we demonstrated that inhibition of HSP90 by RGRN-305 significantly dampened the inflammatory response induced by SARS-CoV-2 spike protein in human macrophage-like cells (U937) and human lung epithelial cells (A549). Measured by quantitative real-time PCR, the mRNA expression of the proinflammatory cytokines TNF, IL1B and IL6 were significantly reduced. Together, these data suggest that HSP90 inhibition by RGRN-305 exacerbates the SARS-CoV-2 infection in vitro and reduces the survival of mice infected with SARS-CoV-2, but exhibits strong anti-inflammatory properties. This data shows that while RGRN-305 may be helpful in a 'cytokine storm', it has no beneficial impact on viral replication or survival in animals as a monotherapy. Further animal studies with HSP90 inhibitors in combination with an anti-viral drug may provide additional insights into its utility in viral infections and whether HSP90 inhibition may continue to be a potential treatment strategy for COVID-19 disease. [ABSTRACT FROM AUTHOR]

Introduction: When Coronavirus Disease-19 (COVID-19) struck the world in December 2019, initiatives started to investigate the efficacy of convalescent plasma, a readily available source of passive antibodies, collected from recovered patients as a therapeutic option. This was based on historical observational data from previous virus outbreaks. Methods: A scoping review was conducted on the efficacy and safety of convalescent plasma and hyperimmune immunoglobulins for COVID-19 treatment. This review included the latest Cochrane systematic review update on 30-day mortality and safety. We also covered use in pediatric and immunocompromised patients, as well as the logistic challenges faced in donor recruitment and plasma collection in general. Challenges for low resource countries were specifically highlighted. Results: A major challenge is the high donation frequency required from firsttime donors to ensure a safe product, which minimizes the risk of transfusiontransmitted infectious. This is particularly difficult in low- and middle-income countries due to inadequate infrastructure and insufficient blood product supplies. High-certainty evidence indicates that convalescent plasma does not reduce mortality or significantly improve clinical outcomes in patients with moderate to severe COVID-19 infection. However, CCP may provide a viable treatment for patients unable to mount an endogenous immune response to SARS-CoV-2, based on mostly observational studies and subgroup data of published and ongoing randomized trials. Convalescent plasma has been shown to be safe in adults and children with COVID-19 infection. However, the efficacy in pediatric patients remains unclear. Discussion: Data on efficacy and safety of CCP are still underway in ongoing (randomized) studies and by reporting the challenges, limitations and successes encountered to-date, research gaps were identified to be addressed for the future. Conclusion: This experience serves as a valuable example for future pandemic preparedness, particularly when therapeutic options are limited, and vaccines are either being developed or ineffective due to underlying immunosuppression. [ABSTRACT FROM AUTHOR]

The Food and Drug Administration (FDA) authorized the administration of ritonavir (RIT)-boosted nirmatrelvir (NMV) on May 25, 2023, for the treatment of mild to moderate COVID-19 in patients who are at high risk of developing severe COVID-19. In accordance with sustainability and environmental friendliness, simple, eco-friendly, and sustainable spectrophotometric methods were established for concurrently estimating RIT and NMV in newly launched copackaged pills. The suggested solutions for resolving the spectral overlap between RIT and NMV involve the following mathematical methods: the first derivative method (1D), second derivative method (2D), and dual-wavelength zero-order method (DWZ). When ethanol was used as a green dilution solvent, the linearity range was adjusted (10–250 µg/mL) for both drugs. The procedures resulted in a high correlation coefficient (not less than 0.9996) and satisfactory levels of detection and quantification. Additionally, method validation was performed in accordance with International Council for Harmonization norms. Moreover, a detailed ecological and sustainability evaluation protocol was established to confirm the greenness and whiteness of the methods. Finally, the proposed method, along with previously reported methods for analysing NMV and RIT, were reviewed analytically and ecologically. [ABSTRACT FROM AUTHOR]

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]

Background/Objectives: Long COVID covers many cardio-pulmonary symptoms, worsening individuals' health status. Health resort treatment applies balneological factors, physical medicine modalities, climate actions, and exercises that may be beneficial for COVID-19 survivors. This study aimed to assess the severity of the cardiopulmonary symptoms in people qualified for health resort treatment and its efficacy in this group of patients. Methods: Medical records of 239 people attending health resort treatment were analysed. A total of 122 people (71 women and 51 men) with a mean age of 64.35 years ± 8.66 years were enrolled in the analysis. The cardiopulmonary symptoms of long COVID were assessed twice: before and after health resort treatment. Results: Persisting COVID-19 symptoms do not differentiate between women and men. Health resort treatment reduces symptoms severity in both sexes. Age does not mediate the efficacy of health resort treatment. Conclusions: The persistent symptoms of COVID-19 are of low intensity in people qualified for health resort treatment and are independent of gender. Health resort treatment effectively mitigates dyspnoea, tightness of chest, and sputum in long COVID patients, so it should be implemented into the standard treatment course for COVID-19 survivors as a continuation of therapy. [ABSTRACT FROM AUTHOR]

The approval of pharmaceuticals in response to the COVID-19 pandemic is a global concern, and during emergencies, emergency approval or authorization systems that enable the rapid use of unapproved drugs to maintain national health are essential. However, there is limited research comparing these systems across countries and their effects. This cross-sectional study examined such systems in Japan (JP), Europe (EU), the United Kingdom (UK), and China (CN) for pharmaceuticals (n = 23) authorized under Emergency Use Authorization (EUA) in the United States (US) between December 2019 to July 2023. As of the end of July 2023, JP had granted approval or permission for 14 drugs (60.9%), EU for 14 (60.9%), UK for 12 (52.2%), and CN for three (13.0%). An examination of the developmental status of the 23 drugs revealed that JP had 6 drugs (26.1%), the EU had 3 drugs (8.7%), the UK had 5 drugs (21.7%), and CN had 16 drugs (69.6%) yet to be developed. The US had significantly more granted permissions and developed drugs, while CN the least. The UK had a significantly shorter period for approval than the US and the shortest overall. The EU had the shortest period from the issuance of EUA to approval dates. Although not statistically significant, JP had the longest duration until unapproved drugs could be used. Pharmaceuticals granted usage permission under the EUA in JP, the EU, and the UK were developed or on the market in over 70% of cases, whereas in CN, more than two-thirds were yet to be developed. This suggests that CN may not actively utilize pharmaceuticals from other countries for COVID-19 treatment and may rely on its own. When comparing the emergency approval and permission systems of each country, the most significant difference was in the type of system granting approval. [ABSTRACT FROM AUTHOR]

Background: The need for patient engagement in health research has been increasingly acknowledged and accepted in recent years. However, implementation is still limited due to lack of evidence on its value and lack of guidance on how to implement patient engagement. This study aims to provide insight into the contribution of patient engagement in the RECOVAC project, which studied COVID-19 vaccination in kidney patients, and formulate concrete practice-based action perspectives for patient engagement. Methods: We used a qualitative participatory mixed methods approach, based on the Patient Engagement Monitoring and Evaluation (PEME) framework. Patient engagement and data collection were based on the Reflexive Monitoring in Action (RMA) approach. Data collection included participant observations, open ended questionnaires and interactive reflection sessions. Qualitative analysis was done via a thematic approach. Results: We have described the process of patient engagement systematically, provided insight in its value and found that there is a need for clear aims, expectations and preparations from the start of the engagement process. We have shown that reflection throughout the process is of utmost importance and the same applies to clear communication between researchers and patient representatives. By being part of the consortium patient representatives had direct access to information, straight from the source, on for example the vaccination schedule and medication availability and had indirect influence on decisions made by the National Institute for Public Health and the Environment (RIVM) on preventive measures and treatment against COVID-19. Having experienced patient representatives is important, otherwise training needs to be provided. We also found that patient engagement had impact on conduct and outcomes of research activities itself and may have impact on future research and patient engagement activities in general. Conclusion: Patient engagement has changed the course of the project. Concrete practice-based action perspectives have been formulated, which are already being implemented by the Dutch Kidney Patients Association (NVN). Studying patient engagement in a high pace project with high public interest has resulted in lessons learned and will help prepare and implement patient involvement in future research projects. Clinical trial registration: The RECOVAC studies in which the patient engagement took place are registered at clinicialtrial.gov (NCT04741386 registration date 2021-02-04, NCT04841785 registration date 2021-03-22 and NCT05030974 registration date 2021-08-20). Plain English Summary: This article is about the extensive engagement of patients in a scientific research project and what that engagement adds to the project. Although researchers acknowledge the importance of engagement of patients in research projects, it is not happening very often, Because there is not enough scientific evidence on the value of patient engagement and not enough guidance for researcher on how to implement it in their research. We used the Patient Engagement Monitoring and Evaluation (PEME) framework and qualitative participatory mixed methods research to provide insight into patient involvement in the RECOVAC project, which studied COVID-19 vaccination in kidney patients. We also formulated practical guidance for researchers who want to engage patients in their research. We describe the process of patient engagement in the RECOVAC project; what went well and what could be improved. We found that it is important to prepare well, keep reflecting on the engagement process throughout the project with all stakeholders of the project, communicate clearly and have experienced patient representatives involved or have training available for them. Patient engagement had impact on the conduct and outcome of the research activities itself and on activities outside of the project (e.g., doctors changing their conversations with their patients). We can conclude that involving patients changed the project and its outcomes to better fit with the needs of patients. A guideline has been made and is already implemented by the Dutch Kidney Patients Association. The lessons learned from this project will help researchers involve patients in their future projects. [ABSTRACT FROM AUTHOR]

Background and Objectives: There is little information on changes in the process and outcomes of intensive tobacco dependence treatment during the COVID-19 pandemic. The following characteristics were evaluated: interest in treatment, the number of face-to-face or telephone follow-ups, the duration of pharmacotherapy use, and the success rate. The aim of our study was to compare the number of patients who entered tobacco dependence treatment programmes and evaluate the one-year success rate in patients three years before and three years after the COVID-19 pandemic. Materials and Methods: A single-site retrospective cohort study using data from patients treated at the Centre for Tobacco Dependence in Prague, Czech Republic, between 2017 and 2022 (n = 2039) was performed. The one-year abstinence rate was validated by measuring carbon monoxide in exhaled air (6 ppm cut-off). Patients were divided into two groups: the group for which treatment was initiated in 2017–2019 (i.e., before the COVID-19 pandemic, BC; n= 1221) and the group for which treatment was initiated in 2020–2022 (i.e., during the COVID-19 pandemic, DC; n = 818). Results: No significant differences in the success rate of tobacco dependence treatment were found between the two groups (BC group, 40.5% (494/1221) vs. DC group, 42.2% (345/818)) (χ2 (1, N = 2.039) = 0.6, p = 0.440). Furthermore, differences were not found in sex, education level, age at first cigarette, the duration of pharmacotherapy use, or the number of in-person visits. In contrast, there was an increase in the number of telephone contacts between the groups (18.7% (SD = 17.5%) vs. 32.9% (SD = 18.2%), p < 0.001). Conclusions: The number of patients who started treatment during the COVID-19 pandemic decreased by one-third compared to that during the 3-year period before the pandemic. The overall treatment success rate did not change significantly even with the increase in the number of telephone visits with the therapist. [ABSTRACT FROM AUTHOR]

The term long COVID (LC) effectively describes the broad long-term disease burden of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections, encompassing individual suffering and significant socioeconomic impacts. However, its general use hampers precise epidemiological research, diagnostics and therapeutic strategies. Misinterpretations occur, for example, when population surveys are compared to studies using health record data, because both refer to these data as LC. This also emphasizes the need for different terminology. The National Institute for Health and Care Excellence (NICE) rapid guideline differentiates ongoing symptomatic COVID-19 from post-COVID conditions, yet real-world observations challenge these two subgroup definitions. We propose refining the term LC into three subgroups: ongoing symptomatic COVID-19, SARS-CoV-2 induced or exacerbated diseases and post-acute COVID condition. This stratification aids targeted diagnostics, treatment and epidemiological research. Subgroup-specific documentation using the International Classification of Diseases, Tenth Revision (ICD-10) codes ensures accurate tracking and understanding of long-term effects. The subgroup of post-acute COVID condition again includes various symptoms, syndromes and diseases like post-exertional malaise (PEM), dysautonomia or cognitive dysfunctions. In this regard, differentiation, especially considering PEM, is crucial for effective diagnostics and treatment. [ABSTRACT FROM AUTHOR]

Objective: COVID-19 is caused by the SARS-CoV-2 virus. In this study, around 300 herbal compounds were screened virtually to find the best anti-COVID-19 structures. Materials and Methods: An extensive search in electronic databases was done. Around 300 herbal compounds, which were previously proven to be antiviral structures, were extracted from articles and considered our primary database. Then, molecular docking studies were performed to find the best inhibitors of the main SARS-COV-2 proteins, including spike protein (PDB 7BWJ), RNA-dependent RNA polymerase (PDB 6M71) and main protease (PDB 5R7Z). Results: The molecular docking and dynamics studies revealed that fangchinoline as an alkaloid could bind to the main protease of the virus more potent than lopinavir (-42.26 vs. -30.9 kJ/mol). Fangchinoline can be orally active based on drug-like properties. According to the molecular dynamic study, the complex between the fangchinoline and SARS-CoV-2 main protease is stable. chebulagic acid is a benzopyrene tannin that could inhibit RNAdependent RNA polymerase (RdRp) better than remdesivir (-43.9 vs. -28.8 kJ/mol). The molecular dynamic study showed that chebulagic acid-RdRp interaction is stable and strong. Furthermore, suramin could neutralize different variants of COVID-19 spike proteins (wild type, and alpha and beta variants). However, suramin is not orally active but it is a potential inhibitor for different coronavirus spike proteins. Conclusion: According to the promising in silico results of this study, fangchinoline, chebulagic acid and suramin could be introduced as potential lead compounds for COVID-19 treatment. We are hopeful to find a reliable remedy shortly through natural compounds. [ABSTRACT FROM AUTHOR]

Background: Qingfei Paidu Decoction (QFPDD) has played an important role in the prevention and treatment of COVID-19 infection in China. The present study aims to perform an econometric analysis and visualization of the literature on the treatment of COVID-19 with QFPDD in the Chinese databases and English databases. Methods: Six databases including such as Chinese databases CNKI, VIP, CBM, WANFANG as well as English databases PubMed, Web of Science were searched for publications related to the prevention and treatment of COVID-19 with QFPDD. The institutions, authors, keywords of each publication were cisualized using the software of CiteSpace. Results: A total of 187 literature on the prevention and treatment of novel coronavirus infection with QFPDD were included, of which 145 (77.5%) were in Chinese and 42 (22.5%) were in English. Those publications were written by 926 authors from 383 institutions. There were 78 theoretical studies (41.7%), 63 clinical studies (33.7%), and 46 basic studies (24.6%). The cooperative institutions with the core of "Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences" and "Shanghai University of Chinese Medicine Cross Academy of Science" have been formed, and two core teams with "Wang Yanping" and "Zhang Weidong" have been formed. The keyword analysis showed that the research mainly focuses on pathologic pathogenesis, clinical efficacy, adverse reactions, integrated Chinese and western medicine therapy, network pharmacology research. Conclusion: QFPDD has attracted worldwide attention, mechanism research and clinical research may become a future development trend. Therefore, in-depth basic research and clinical studies with large samples and multi-center cooperation should be carried out to provide high-level evidence-based evidence for the prevention and treatment of COVID-19 with QFPDD. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) represents an important but limited treatment for patients with severe COVID-19. We assessed the effects of an educational intervention on a person's ECMO care preference and examined whether patients and providers had similar ECMO preferences. Methods: In the Video+Survey group, patients watched an educational video about ECMO's purpose, benefits, and risks followed by an assessment of ECMO knowledge and care preferences in seven scenarios varying by hypothetical patient age, function, and comorbidities. Patients in the Survey Only group and providers didn't watch the video. Logistic regression was used to estimate the probability of agreement for each ECMO scenario between the two patient groups and then between all patients and providers. Results: Video+Survey patients were more likely (64% vs. 17%; p = 0.02) to correctly answer all ECMO knowledge questions than Survey Only patients. Patients in both groups agreed that ECMO should be considered across all hypothetical scenarios, with predicted agreement above 65%. In adjusted analyses, patients and providers had similar predicted agreement for ECMO consideration across six of the seven scenarios, but patients showed greater preference (84% vs. 41%, p = 0.003) for the scenario of a functionally dependent 65-year-old with comorbidities than providers. Discussion and conclusions: An educational video increased a person's ECMO knowledge but did not change their ECMO preferences. Clinicians were less likely than patients to recommend ECMO for older adults, so advanced care planning discussion between patients and providers about treatment options in critically ill patients with COVID-19 is critical. [ABSTRACT FROM AUTHOR]

Background: The profound impact of coronavirus disease (COVID-19) has led to an increased demand for sustainable pandemic governance practices. This study explored emerging hybrid governance practices that provide robust evidence on how to address the complex challenges of pandemics effectively. South Korea, which was severely affected by COVID-19, has implemented a novel governance approach using a whole-of-nation (WoN) model. This hybrid pandemic governance approach, which integrates both whole-of-government and whole-of-society approaches, has enabled synergistic and cohesive multi-sectoral coordination among all stakeholders (public authorities, private enterprises, and civil society) to address multifaceted challenges collectively and strengthen their resilience capacity. This study investigated South Korea's WoN practices and their embedded context and identified key governance enablers facilitating this approach. Methods: This study employed a case study design based on an extensive analysis of policy and program documents, drawing on South Korea's publicly available data from January 1, 2020 to March 30, 2023. It assessed six system-level collaborative pandemic governance practices and key enablers, all of which were intended to fortify the country's pandemic response. Results: The primary areas of the country's WoN governance practices for COVID-19 control were (i) whole-of-government policy-making and response, (ii) COVID-19 testing system, (iii) digital surveillance of COVID-19, (iv) COVID-19 triage and treatment system, (v) domestic vaccine production, and (vi) community engagement. Key governance enablers for implementing the WoN model were establishing a legal foundation, ensuring decisive and strong governance and leadership, increasing public investment, applying a whole-of-health approach with augmented investment in public health, enhancing crisis communication, and mobilizing local leaders and civil society organizations in the national public health response. Conclusions: In exploring innovative approaches to pandemic governance for increased efficacy, responsiveness, and impact, the WoN approach emerged as highly relevant. This example of emerging practice allows policy-makers to re-evaluate their governance strategies and initiatives to improve multi-agency partnerships across the country in their pandemic-preparedness planning. [ABSTRACT FROM AUTHOR]

Background: The 2019 coronavirus (COVID-19) outbreak was declared a global pandemic in March 2020. It quickly spread across all continents, causing significant social, environmental, health, and economic impacts. During the pandemic, there has been consideration of repurposing and repositioning of medications, such as corticosteroids, for the treatment of hospitalised COVID-19 patients. Objective: To assess and summarise corticosteroid regimens used for hospitalised COVID-19 patients, focusing on dosage, route of administration, and clinical outcome from clinical trials. Methods: PubMed and Embase databases and the grey literature were searched to identify randomised controlled trials (RCTs) that evaluated the efficacy of corticosteroids in hospitalised patients with COVID-19 between January 2020 and January 2023. This scoping review was conducted in line with the PRISMA extension for scoping reviews (PRISMA-ScR) checklist. Key findings: A total of 24 RCTs were eligible for inclusion. There was variation in the steroid regimens used for treatment across COVID-19 trials. Despite the heterogeneity of included RCTs, the overall results have shown the benefits of improving lung function and a lower all-cause mortality rate in hospitalised COVID-19 patients treated with systematic corticosteroids. Conclusions: Corticosteroids have proven to be an effective treatment for COVID-19 patients in critical condition. However, comparative effectiveness studies should be conducted to assess the efficacy and safety of optimal corticosteroid treatment at the population level. Moreover, the global burden of long COVID is significant, affecting millions with persistent symptoms and long-term health complications. Thus, it is also necessary to evaluate the optimal steroid regimen for long COVID treatment. [ABSTRACT FROM AUTHOR]

The JN.1 variant of COVID‐19 has emerged as the dominant strain worldwide since the end of 2023. As a subclade of the BA.2.86 variant, JN.1 harbors a unique combination of mutations inherited from the BA.2.86 lineage, notably featuring the novel L455S mutation within its receptor‐binding motif. This mutation has been linked to increased transmissibility and enhanced immune evasion capabilities. During the rise of JN.1, evidence of resistance to various monoclonal antibodies and reduced cross‐neutralization effects of the XBB.1.5 vaccine have been observed. Although the public health threat posed by the JN.1 variant appears relatively low, concerns persist regarding its evolutionary trajectory under immune pressure. This review provides a comprehensive overview of the evolving JN.1 variant, highlighting the need for continuous monitoring and investigation of new variants that could lead to widespread infection. It assesses the efficacy of current vaccines and therapeutics against emerging variants, particularly focusing on immunocompromised populations. Additionally, this review summarizes potential vaccine advancements and clinical treatments for COVID‐19, offering insights to optimize prevention and treatment strategies. This review thoroughly evaluates the JN.1 variant's impact on public health and its implications for future vaccine and therapeutic development, contributing to ongoing efforts to mitigate the risk of virus transmission and disease severity. [ABSTRACT FROM AUTHOR]

To illustrate the challenges encountered when gathering rapidly synthesized evidence in response to the coronavirus disease 2019 (COVID-19) pandemic. In this article, we describe the challenges encountered when we performed a systematic literature review (SLR) of randomized controlled trials (RCTs) on the efficacy and safety of treatments for severe COVID-19. The methods of the SLR are described in full, to show the context of our objectives. Then we use the results of the SLR to demonstrate the problems of producing synthesized evidence in this setting. Various challenges were identified during this SLR. These were primarily a result of heterogeneity in the study methodology of eligible studies. Definitions of the patient populations and outcome measurements were highly variable and the majority of studies demonstrated a high risk of bias, preventing quantitative synthesis of the collated evidence. Consolidating evidence from RCTs evaluating COVID-19 interventions was problematic. Guidance is needed for scenarios with high rapid output in primary research. [ABSTRACT FROM AUTHOR]

This review paper provides a comprehensive analysis of the diagnostics and treatment options available for COVID-19. The paper begins with an introduction that sets the context for understanding the subsequent sections. Section 2 presents an in-depth examination of various diagnostic approaches, including chemical and biological diagnostics, along with a detailed discussion on the transmission dynamics of the SARS-CoV-2 virus. Section 3 focuses on the treatment of COVID-19, highlighting the efficacy of antiviral therapies such as remdesivir, monoclonal antibodies, and combination therapy. Section 4 provides a critical review of different antiviral treatments, including Molnupiravir, the updated information on Remdesivir in 2021, Hydroxychloroquine and chloroquine, Lopinavir/ritonavir, and Ivermectin, analyzing their effectiveness and potential limitations. Lastly, Section 5 explores the use of anti-SARS-CoV-2 neutralizing antibody products as a promising treatment strategy. This review paper consolidates current research findings and clinical evidence, making it an essential resource for researchers, clinicians, and policymakers involved in managing COVID-19 cases and developing effective diagnostic and treatment strategies. [ABSTRACT FROM AUTHOR]

Ozone therapy (OT), a medical procedure, has been showing good results during the coronavirus disease (COVID-19). We aimed to build an evidence and gaps map (EGM) of OT in the COVID-19 ranking the articles found according to levels of evidence and outcomes. The EGM brings bubbles of different sizes and different colors according to the articles. The OT intervention used was major or minor autohemotherapy, rectal insufflation and ozonized saline solution. EGM was based on 13 clinical studies using OT for COVID-19 involving a total of 271 patients. We found 30 outcomes related to OT in COVID-19. Our EGM divided the outcomes into six groups: 1-clinical improvement; 2-hospitalization; 3-inflammatory, thromboembolic, infectious, or metabolic markers; 4-radiological aspects, 5-viral infection and 6-adverse events. Major autohemotherapy was present in 19 outcomes, followed by rectal insufflation. Improvement in clinical symptoms of COVID-19, improvement of respiratory function, improvement of oxygen saturation, reduction in hospital internment, decrease in C-reactive protein, decrease in ferritin, decrease in lactate dehydrogenase, decrease in interleukin 6, decrease in D-dimer, radiological improvement of lung lesions and absence of reported adverse events were related in the papers. The most commonly used concentrations of OT in major autohemotherapy and in rectal insufflation were 40 µg/mL and 35 µg/mL, respectively. Here, we bring the first EGM showing the efficacy and safety of OT in the treatment of COVID-19. OT can be used as integrative medical therapy in COVID-19 at a low cost and improve the health conditions of the patients. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has seen dramatic demand surges for hospital care that have placed a severe strain on health systems worldwide. As a result, policy makers are faced with the challenge of managing scarce hospital capacity to reduce the backlog of non-COVID patients while maintaining the ability to respond to any potential future increases in demand for COVID care. In this paper, we propose a nationwide prioritization scheme that models each individual patient as a dynamic program whose states encode the patient's health and treatment condition, whose actions describe the available treatment options, whose transition probabilities characterize the stochastic evolution of the patient's health, and whose rewards encode the contribution to the overall objectives of the health system. The individual patients' dynamic programs are coupled through constraints on the available resources, such as hospital beds, doctors, and nurses. We show that the overall problem can be modeled as a grouped weakly coupled dynamic program for which we determine near-optimal solutions through a fluid approximation. Our case study for the National Health Service in England shows how years of life can be gained by prioritizing specific disease types over COVID patients, such as injury and poisoning, diseases of the respiratory system, diseases of the circulatory system, diseases of the digestive system, and cancer. This paper was accepted by Chung-Piaw Teo, optimization. Funding: G. Forchini acknowledges funding from Jan Wallanders and Tom Hedelius Foundation and the Tore Browaldh Foundation, funding from MRC Centre for Global Infectious Disease Analysis [Reference MR/R015600/1], jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth and Development Office (FCDO), under the MRC/FCDO Concordat agreement, part of the EDCTP2 program supported by the European Union; and acknowledges funding by Community Jameel. D. Rizmie acknowledges partial funding from the MRC Centre for Global Infectious Disease Analysis [Reference MR/R015600/1]. J. C. D'Aeth acknowledges funding from the Wellcome Trust [Reference 102169/Z/13/Z]. S. Moret acknowledges partial support from the Swiss National Science Foundation (SNSF) under [Grant P2ELP2_188028]. S. Ghosal was funded by the Imperial College President's PhD Scholarship. F. Grimm was funded by the Health Foundation as part of core staff member activity. This research was funded in whole, or in part, by the Wellcome Trust [Grant 102169/Z/13/Z]. Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2023.4679. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), can manifest itself in several ways, including coagulopathy and thrombosis. These complications can be the first and sometimes only manifestations of SARS‐CoV‐2 infection and can occur early or late in the course of the disease. However, these symptoms are more prevalent in hospitalized patients with venous thromboembolism, particularly those admitted to intensive care units. Moreover, various forms of arterial and venous thrombosis, or micro‐ or macro‐vasculature embolisms, have been reported during the current pandemic. They have led to harmful consequences, such as neurological and cardiac events, nearly all resulting from the hypercoagulable state caused by this viral infection. The severe hypercoagulability observed in patients with COVID‐19 accounts for most cases of the disease that become critical. Therefore, anticoagulants seem to be one of the most vital therapeutics for treating this potentially life‐threatening condition. In the current paper, we present a thorough review of the pathophysiology of COVID‐19‐induced hypercoagulable state and the use of anticoagulants to treat SARS‐CoV‐2 infections in different patient groups, as well as their pros and cons. [ABSTRACT FROM AUTHOR]

The replication of biological systems by mechanical and electronic devices is referred to as bionics. The bionics industry has grown along four primary application areas, in addition to hearing, vision, orthopedics, and a small, dispersed group of implants that enhance cardiac and neurological functions. The SARS‐CoV‐2 virus is the infectious disease known as coronavirus disease (COVID‐19). The virus‐infected people require assistance to better understand the situation caused by COVID‐19 and to bring some easy, efficient, and effective solutions. One of the solutions mentioned for the early stages involves wearable sensors with temperature sensors for early Covid‐19 identification and photos delivered to an AI‐enabled smartphone, robotic sensor, or robot itself. In severe situations, lung X‐ray images are captured by robotic and remote sensors, and the lungs are given the right medication to finish off the virus. The paper presents the study on the overview, applications of artificial intelligence, and deep learning from the bionics point of view. Deep learning and machine learning will be used for reducing the Covid‐19 outbreak. Wearable sensors provide important data by having temperature‐embedded sensors in several physical devices that reveal details about the environment and body that are connected. Covid‐19 probability prediction is aided by smartphones with artificial intelligence and machine learning capabilities. Case history, doctor notes, chest X‐ray reports, details on the sites of breakouts, and other criteria can help forecast the severity of Covid‐19 when it is in its severe phases and direct the administration of medication to a specific area of the lungs. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to rapid vaccine development and large global vaccination schemes. However, patients with immune-mediated kidney disease, chronic kidney diseases and kidney transplant recipients show high non-response rates to vaccination despite more than three vaccinations and, consequently, reduced viral clearance capacity when infected while receiving certain immunosuppressants, carrying an elevated risk for coronavirus disease 2019 (COVID-19)-related morbidity and mortality. SARS-CoV-2 evolution has been characterized by the emergence of novel variants and spike mutations contributing to waning efficacy of neutralizing antibodies. To this end, the therapeutic field expands from vaccination towards a combined approach of immunization, pre-exposure prophylaxis and early post-exposure treatment using direct-acting antivirals and neutralizing monoclonal antibodies to treat early in the disease course and avoid hospitalization. This expert opinion paper from the Immunonephrology Working Group of the European Renal Association (ERA-IWG) summarizes available prophylactic and/or early treatment options (i.e. neutralizing monoclonal antibodies and direct-acting antivirals) of SARS-CoV-2-infected patients with immune-mediated kidney disease, chronic kidney disease and kidney transplant recipients. [ABSTRACT FROM AUTHOR]

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Background: Chronic rhinosinusitis is regarded as a chronic airway disease. According to WHO recommendations, it may be a risk factor for COVID‐19 patients. In most CRSwNP cases, the inflammatory changes affecting the nasal and paranasal mucous membranes are type‐2 (T2) inflammation endotypes. Methods: The current knowledge on COVID‐19 and on treatment options for CRS was analyzed by a literature search in Medline, Pubmed, international guidelines, the Cochrane Library and the Internet. Results: Based on international literature, on current recommendations by WHO and other international organizations as well as on previous experience, a panel of experts from EAACI and ARIA provided recommendations for the treatment of CRS during the COVID‐19 pandemic. Conclusion: Intranasal corticosteroids remain the standard treatment for CRS in patients with SARS‐CoV‐2 infection. Surgical treatments should be reduced to a minimum and surgery preserved for patients with local complications and for those with no other treatment options. Systemic corticosteroids should be avoided. Treatment with biologics can be continued with careful monitoring in noninfected patients and should be temporarily interrupted during the course of the COVID‐19 infection. [ABSTRACT FROM AUTHOR]

Graph Neural Network (GNN) architecture is a state-of-the-art model, which can obtain complete node embedding features and rich data information by aggregating the information of nodes and neighbors. Therefore, GNNs are widely used in electronic shopping, drug discovery (especially for the treatment of COVID-19) and other fields, promoting the explosive development of machine learning. However, user interaction, data sharing and circulation are highly sensitive to privacy, and centralized storage can lead to data isolation. Therefore, Federated Learning with high efficiency and strong security and privacy enhancement technology based on secure aggregation can improve the security dilemma faced by GNN. In this paper, we propose an Efficient Secure Aggregation for Federated Graph Neural Network(ESA-FedGNN), which can efficiently reduce the cost of communication and avoid computational redundancy while ensuring data privacy. Firstly, a novel secret sharing scheme based on numerical analysis is proposed, which employs Fast Fourier Transform to improve the computational power of the neural network in sharing phase, and leverages Newton Interpolation method to deal with the disconnection and loss of the client in reconstruction phase. Secondly, a regular graph embedding based on geometric distribution is proposed, which optimizes the aggregation speed by using data parallelism. Finally, a double mask is adopted to ensure privacy and prevent malicious adversaries from stealing model parameters. We achieve O (log N log (log N)) improvements compared to O N 2 in state-of-the-art works. This research helps to provide security solutions related to the practical development and application of privacy-preserving graph neural network technology. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has spread and become a substantial public health concern worldwide. The COVID-19 Treatment Guidelines Panel recommends COVID-19 vaccination as soon as possible for everyone who is eligible according to the CDC's Advisory Committee on Immunization Practices. As of March 2023, there are three Food and Drug administration (FDA)-authorized antiviral treatments available to treat people who have mild or moderate symptoms of COVID-19 infection and have risk factors for severe illness. The Special Issue "COVID-19 Prevention and Treatment" published in I Life i (ISSN 2075-1729), belonging to the section "Epidemiology", collects a series of research and review articles related to better design routes of prevention and treatment for COVID-19. [Extracted from the article]

This paper examines a patient with borderline mental capacity, where the healthcare team is conflicted about how to proceed. This case demonstrates the complicated intersection between undue influence and mental capacity, allowing us to explore how the law is applied in clinical practice. Patients have the right to decline or accept medical treatments offered to them. In Singapore, family members perceive a right to be involved in the decision-making process for sick and elderly patients. Elderly patients, dependent on mainly family members for care and support, sometimes submit to their overbearing influence resulting in decisions that fail to protect the patients' own best interests. However, the clinicians' own well-intentioned influence, driven by a desire for the best medical outcome can also be undue, and neither influence should seek to be a substitution for the patient's decision. Following Re BKR [2015] SGCA 26, we are now obliged to examine how mental capacity can be affected by undue influence. A lack of capacity can be found when a patient fails to appreciate the presence of undue influence or is susceptible to undue influence due to their mental impairment causing their will to be overborne. This then paves the way for the health care team to decide based on best interests, because the patient is determined to be lacking in mental capacity. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) can lead to pulmonary fibrosis due to the inflammatory process in the lung, resulting in a series of respiratory consequences. Patients with underlying systemic diseases or pre‐existing pulmonary diseases are particularly at risk of severe respiratory distress and persistent pulmonary abnormalities. Pirfenidone, a well‐known anti‐fibrotic agent recognized for its therapeutic effect on idiopathic pulmonary fibrosis, could be a feasible option in severe COVID‐19 cases given the similar pathophysiological features shared with interstitial lung diseases. In this paper, we share our experience of early administration of pirfenidone in combination with tofacitinib in a 61‐year‐old female patient with severe COVID‐19 pneumonia. Pirfenidone was initiated because of persistent dependence on high‐flow oxygen support and even the requirement for mechanical ventilation due to disease progression after initial standard COVID‐19 treatment. The patient was successfully extubated 15 days after the initiation of pirfenidone, and 13 days after extubation, she was completely weaned off supplemental oxygen. A series of chest radiographs and computed tomography scans demonstrated notable improvements in her lung condition. We propose a strategy of using pirfenidone plus tofacitinib as a rescue therapy in the management of patients with severe COVID‐19. [ABSTRACT FROM AUTHOR]