Treatment Of Coronavirus Disease 2019 Patients Research Articles

543 The link between preexisting hypertension and COVID-19 severity in a hamster model

OBJECTIVES/GOALS: Hypertension is a major risk factor for coronavirus disease 2019 (COVID-19) severity. Our goal was to determine if hypertension worsens lung pathology induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters. METHODS/STUDY POPULATION: Male hamsters (7-8 weeks old) were infused with angiotensin II (AII; 200 ng/kg/min via osmotic minipump) for 4 weeks to induce hypertension. During the last week of the infusion, the hamsters were inoculated intranasally with vehicle (V) or SARS-CoV-2 (S; 1 x 105 plaque forming units/ml). Half of the hamsters were sacrificed 1 day post-inoculation (dpi-1) and the other half on dpi-6. Two scoring systems were applied to lung tissue sections stained with hematoxylin and eosin to determine the degree and severity of lung pathology: the first system assessed all pertinent alterations in the lungs, while the second system only assessed the pathology related to the pulmonary vasculature. Lung histopathology scores were calculated as the sum of the airway and lung alveolar scores in arbitrary units (AU). RESULTS/ANTICIPATED RESULTS: Studies revealed that the SARS-CoV-2-infected hamsters exhibited a 76-fold higher total airway score compared to vehicle controls [(AU): V, 0.25 ± 0.1; S, 19.00 ±1.35; p<0.05; n=4]. Total lung alveolar scores (27-fold) [(AU): V, 0.30 ± 0.11; S, 8.0 ± 4.1; p<0.05; n=4] and total vascular scores (17-fold) [(AU): V, 0.35 ± 0.2; S, 6.0 ±1.4; p<0.05; n=4] were also markedly higher compared to controls on dpi-1. AII increased blood pressure, which was sustained through the 4-week infusion period. Under these conditions, body weight slightly dropped by 4.5%. Ongoing studies are assessing the effect of hypertension on the % of airway, alveoli and vessels affected, airway and alveolar severity, and bronchiolar epithelial and type II pneumocyte hyperplasia. DISCUSSION/SIGNIFICANCE: Establishing the hypertensive hamster as a small animal model of COVID-19 will facilitate investigations into why preexisting hypertension is a risk factor for disease severity. These studies could lead to the development of novel therapeuticsfor treating COVID-19 patients with hypertension.

Two new and effective food-extracted immunomodulatory agents exhibit anti-inflammatory response activity in the hACE2 acute lung injury murine model of COVID-19.

The coronavirus disease 2019 (COVID-19) spread rapidly and claimed millions of lives worldwide. Acute respiratory distress syndrome (ARDS) is the major cause of COVID-19-associated deaths. Due to the limitations of current drugs, developing effective therapeutic options that can be used rapidly and safely in clinics for treating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections is necessary. This study aims to investigate the effects of two food-extracted immunomodulatory agents, ajoene-enriched garlic extract (AGE) and cruciferous vegetables-extracted sulforaphane (SFN), on anti-inflammatory and immune responses in a SARS-CoV-2 acute lung injury mouse model. In this study, we established a mouse model to mimic the SARS-CoV-2 infection acute lung injury model via intratracheal injection of polyinosinic:polycytidylic acid (poly[I:C]) and SARS-CoV-2 recombinant spike protein (SP). After the different agents treatment, lung sections, bronchoalveolar lavage fluid (BALF) and fresh faeces were harvested. Then, H&E staining was used to examine symptoms of interstitial pneumonia. Flow cytometry was used to examine the change of immune cell populations. Multiplex cytokines assay was used to examine the inflammatory cytokines.16S rDNA high-throughput sequencing was used to examine the change of gut microbiome. Our results showed that AGE and SFN significantly suppressed the symptoms of interstitial pneumonia, effectively inhibited the production of inflammatory cytokines, decreased the percentage of inflammatory cell populations, and elevated T cell populations in the mouse model. Furthermore, we also observed that the gut microbiome of genus Paramuribaculum were enriched in the AGE-treated group. Here, for the first time, we observed that these two novel, safe, and relatively inexpensive immunomodulatory agents exhibited the same effects on anti-inflammatory and immune responses as neutralizing monoclonal antibodies (mAbs) against interleukin 6 receptor (IL-6R), which have been suggested for treating COVID-19 patients. Our results revealed the therapeutic ability of these two immunomodulatory agents in a mouse model of SARS-CoV-2 acute lung injury by promoting anti-inflammatory and immune responses. These results suggest that AGE and SFN are promising candidates for the COVID-19 treatment.

Assessing the Impact of COVID-19 on Incident Reporting and Elucidating the Characteristics of Incident Reports for COVID-19 Patients at the Critical Care Center of a Tertiary-Care Teaching Hospital in Japan.

The global coronavirus disease 2019 (COVID-19) pandemic has necessitated the establishment of new medical care systems worldwide. Medical staff treating COVID-19 patients perform their care duties in highly challenging and psychologically demanding situations, raising concerns about their impact on patient safety. Therefore, this study aimed to investigate and characterize incident reports related to COVID-19 patients to clarify the impact of COVID-19 on patient safety. The study included data from 557 patients admitted to the Critical Care Center of a tertiary-care teaching hospital in Osaka, Japan, from April 2020 to March 2021. The patients were divided into two groups: COVID-19 (n = 106) and non-COVID-19 (n = 451) and compared based on various characteristics, incident reporting rates, and the content of incident reports. The findings indicated a significantly higher rate of patients with incident reports in the COVID-19 group compared to the non-COVID-19 group (49.1% vs. 24.4%, P < 0.001). In addition, quantitative text analysis revealed that the topic ratio, consisting of "respiration," "circuit," "settings," "connection," "nursing," "ventilator," "control," "tape," "Oxylog®," and "artificial nose" was significantly higher in the incident reports of the COVID-19 group (P = 0.003). In conclusion, COVID-19 patients are more susceptible to adverse incidents and may face a higher risk of patient safety issues. The characteristic topics in incident reports involving COVID-19 patients primarily revolved around ventilator-related issues. In the future, the methodology used in the current study may be utilized to identify incident characteristics and implement appropriate countermeasures in the event of unknown patient safety issues.

Stigma and inequality in the management of coronavirus disease-2019 (COVID-19)- patients among healthcare providers in Saudi Arabia and associated beliefs: A cross sectional study

BackgroundStigma and discrimination (SAD) can greatly impact the management of Coronavirus Disease-19 (COVID-19) patients. Studies examining SAD in managing COVID-19 patients in Saudi Arabia (SA) are limited. This study examined the discrimination and inequality in treating COVID-19 patients and the associated beliefs among healthcare workers (HCWs) during the pandemic. MethodsThis was a cross sectional study using an online self-administrated questionnaire by 414 HCWs from September 2022 to January 2023. ResultsOf the 414 participants, 53.4% aged 18–30 years, were males (53.4%), mostly Saudi (82.1%), and residents of western SA (90.8%). Almost one-third of the participants (32.1%) were physicians, and 23.7% were pharmacists. 53.1% of the HCWs had work experience < 5 years, 49.3% either had a current/previous COVID-19 infection and 10.1% (n = 42) reported treating ≥ 2000 COVID-19 patients. Most of the participants had not received training on avoiding discrimination against COVID-19 patients (n = 246; 59.4%) and denied receiving any incentives from their institution (n = 294; 71%) or community (n = 248; 59.9%) during the pandemic. Less than 20% of the HCWs had observed some sort of discrimination in providing care for COVID-19 patients. The responses significantly differed by nationality, educational level, specialty, workplace and COVID-19 infection status (P < 0.05). Approximately, 20% of the participants held negative beliefs about COVID-19 patients and these responses varied significantly by nationality, work experience, workplace, gender, and age (p < 0.05). Cross-tabulation and regression analyses showed some differences by gender, workplace, specialty and COVID-19 infection status. ConclusionsThere was a low prevalence of negative beliefs about COVID-19 patients and a low prevalence of discriminatory behaviors in providing care for these patients in SA. Training and governmental regulations could further lower the prevalence of SAD against COVID-19 patients.

Time-course changes in mental distress and their predictors in response to the coronavirus disease 2019 (COVID-19) pandemic: A longitudinal multi-site study of hospital staff.

The coronavirus disease 2019 (COVID-19) pandemic provides a unique opportunity studying individual differences in the trajectory of mental distress to relatively homogeneous stressors by longitudinally examining time-course changes between pandemic waves. For 21 months, we tested the effects of COVID-19 waves on mental health among 545 staffs at 18 hospitals treating COVID-19 patients in Shizuoka Prefecture, Japan. Contrary to increasing new infected cases as waves progressed, initially elevated psychological distress (K6) and fear of COVID-19 (FCV-19S) were decreased among waves (K6: B = -.02, 95% confidence interval [CI] = -.03 to -.01; FCV-19S: B = -.10, 95% CI = -.16 to -.04). This initial increase and subsequent decrease in K6 and FCV-19S were more prominent in individuals with high trait anxiety (K6: B = 1.55, 95% CI = 1.18 to 1.91; FCV-19S: B = 4.27, 95% CI = 2.50 to 6.04) and in occupations other than physicians or nurses. The current study revealed time-course changes in psychological distress and fear regarding COVID-19 in each pandemic wave and across waves, and indicated the usefulness of trait anxiety and occupation as predictors of mental health outcomes.

Expression of ACE2, TMPRSS2, and SARS-CoV-2 nucleocapsid protein in gastrointestinal tissues from COVID-19 patients and association with gastrointestinal symptoms

BackgroundAlthough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect the gastrointestinal (GI) tract in coronavirus disease 2019 (COVID-19) patients, the mechanism of GI tract injury is largely unknown. We aimed to study the potential factors that cause COVID-19 GI symptoms. MethodsWe investigated the expression and co-localization of angiotensin converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), SARS-CoV-2 nucleocapsid protein (NP), and the severity of inflammation in GI tissues from COVID-19 patients (n = 19) by immunofluorescence and histopathologic staining, and then studied their associations with GI symptoms. ResultsInfected stomach tissues showed significantly higher ACE2 expression than uninfected ones, while infected duodenum tissues showed significantly higher TMPRSS2 expression than uninfected ones. The expression of TMPRSS2 exhibited a moderate correlation with viral NP across different GI tissues, while no significant association was observed between ACE2 and viral NP. Some GI symptoms such as diarrhea and nausea, were related to the expression level of ACE2, TMPRSS2 or the severity of inflammation. Furthermore, age and elevated aspartate transaminase were major risk factors for disease progression. ConclusionsACE2 and TMPRSS2 were essential proteins in the SARS-CoV-2 infection of GI tract, while TMPRSS2 rather than ACE2 may play a more important role. GI symptoms may derive from the host receptor expression level and pro-inflammatory response in COVID-19 patients after viral infection of GI tissues, and further exacerbate the disease. So targeting TMPRSS2 and inflammation may represent an effective strategy for treating COVID-19 patients with GI symptoms.

Update on Remdesivir in the Treatment of Novel Coronavirus Pneumonia

Worldwide epidemic prevention and control remain under significant stress due to the global novel coronavirus disease 2019 (COVID-19) pandemic and the ongoing emergence of variants like Omicron. The total confirmed COVID-19 cases globally as of now topped 620 million, while the total number of fatalities exceeded 6.6 million. The screening, drug discovery, and clinical development of novel treatments are still the hottest subjects in the treatment of COVID-19, and scientists throughout the world are dedicated to identifying prospective therapeutic agents to treat COVID-19 patients, including the new uses of old medications. Remdesivir, a COVID-19 therapeutic medication developed by Gilead Sciences, exerts antiviral effects by suppressing the RNA-dependent RNA polymerase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Remdesivir has maintained high inhibitory activity against all existing SARS-CoV-2 variants, including the Omicron variant. We systematically retrieved Web of Science, CNKI, PubMed, and Clinicaltrials.gov to gather information related to Remdesivir on COVID-19 treatment. In this review, we summarized and reviewed the drug targets for COVID-19 management, especially the mechanism of action and research progress of Remdesivir. More importantly, the outcome of current clinical trials of Remdesivir alone and when combined with other drugs for COVID-19 management was analyzed, and the limitations and clinical significance of each clinical trial were evaluated. From this review, we can understand the development progress of Remdesivir for COVID-19 management, deepens the current understanding of Remdesivir research status, and gives us some inspiration for better drug use in COVID-19 management.

Contribution of 15 Years (2007-2022) of Indo-US Training Partnerships to the Emergency Physician Workforce Capacity in India.

Indo-US Masters in Emergency Medicine (MEM) certification courses are rigorous three-year emergency medicine (EM) training courses that operate as a partnership between affiliate hospitals or universities in the United States with established EM training programs and local partner sites in India. Throughout their 15 years of operation, these global training partnerships have contributed to the EM workforce in India. Our objective in this study was to describe Indo-US MEM program graduates, their work environments, and their contribution to the growth of academic EM and to the coronavirus disease 2019 (COVID-19) response. An electronic survey was created by US and Indian MEM course stakeholders and distributed to 714 US-affiliated MEM program graduates. The survey questions investigated where graduates were working, their work environments and involvement in teaching and research, and their involvement in the COVID-19 response. We consolidated the results into three domains: work environment and clinical contribution; academic contribution; and contribution to the COVID-19 response. The survey response rate was 46.9% (335 responses). Most graduates reported working within India (210, 62.7%) and in an emergency department (ED) setting (304, 91.0%). The most common reason for practicing outside of India was difficulty with formal MEM certificate recognition within India (97, 79.5%). Over half of graduates reported dedicating over 25% of their work hours to teaching others about EM (223, 66.6%), about half reported presenting research projects at conferences on the regional, national, or international level (168, 50.5%), and almost all graduates were engaged in treating COVID-19 patients during the pandemic (333, 99.4%). Most graduates agreed or strongly agreed that they were satisfied with their overall MEM training (296, 88.4%) and confident in their ability to practice EM (306, 91.6%). Indo-US MEM graduates have made a notable contribution to EM in India through clinical service delivery, teaching, and research, even more essential in the context of the COVID-19 pandemic. The roles of these graduates should be acknowledged and can contribute further to expand EM specialty and systems development across India.

The effects of Alpha-2a and Beta-1a Interferons on the Coronavirus disease 2019 prognosis.

The pandemic coronavirus disease 2019 (COVID-19) has been associated with substantial mortality worldwide. Efforts have continued to find an effective treatment for COVID-19. In vitro activity of interferon (IFN) subtypes has been shown against the SARS-CoV and MERS-CoV. Furthermore, the superiority of IFN-β over IFN-α2b and IFN-α2a has been demonstrated in MERS treatment. Early studies showed a low plasma level of IFNs in the peripheral blood or lungs of patients with severe COVID-19. This study assessed the effects of IFN-alpha-2a and -beta-1a on the prognosis of patients with covid-19 infection. We conducted a triple-blind randomized clinical trial on adult patients with moderate to severe COVID-19 from April 2021 to June 2021. The patients were diagnosed based on clinical and laboratory findings and randomly assigned into four groups (A, B, C, and D) using the envelope allocation method. Patients in group A received IFN β-1a; group B received IFN β-1a placebo; group C received IFN α-2a, and group D was treated with IFN α-2a placebo. All patients concomitantly received the national protocol medications as well. A total of 95 eligible patients were randomly assigned into groups. National Early Warning Score 2 (NEWS2) index showed significant differences between groups only on the first day of admission (p-value = 0.001). CT scan scores on the first and tenth days slightly improved, although they were not statistically significant. Duration of hospitalization and hospital discharge did not significantly differ among all treated groups (Table 1). Mortality rates showed no significant statistical difference between the groups. However, viral clearance significantly accelerated in the patients receiving IFN β-1a or IFN α-2a (p < 0.05). It seems that IFN α-2a and IFN β-1a are ineffective in treating COVID-19 patients. Further randomized clinical trials with large sample sizes are needed to estimate the effects of IFN α-2a or IFN β-1a on the outcomes of COVID-19 disease.

Paxlovid for Treating COVID-19 Patients: A Case-Control Study From Two Hospitals in the Eastern Province of Saudi Arabia.

Background Coronavirus disease 2019 (COVID-19) is an infectious disease that shortly progressed into an unprecedented pandemic spreading all over the world and causing millions of deaths. Many new COVID-19-specific therapies were suggested for the treatment of the patients at increased risk of progression to severe disease, especially those who were unvaccinated and those with a likely inadequate vaccine response. One of the preferred therapies in this setting is Paxlovid, a combination of the oral protease inhibitors nirmatrelvir and ritonavir. Paxlovid was authorized by the Saudi Ministry of Healthfor the treatment of mild to moderate COVID-19. This study aimed to report the effects of Paxlovid on the mortality of the COVID-19 patients at Dammam Medical Complex (DMC) and Qatif Complex Hospital (QCH), two hospitals in the Eastern Provence of Saudi Arabia, and compare the results with the international data. Methods The study was a retrospective study that included all the COVID-19 patients who were treated with Paxlovid at DMC and QCH between January and December 2022. Those patients were compared with control COVID-19 patients who did not receive Paxlovid. The patients were included irrespective of their COVID-19 vaccination status. All the patients were managed according to the Saudi Ministry of Health guidelines. They were followed up through the infectious disease virtual clinics and were monitored for ICU admissions and death of any cause for three months following their COVID-19 infections. Results A total of 92 COVID-19 patients were included. The patients consisted of 47 male and 45 female patients (51.09% and 48.91%, respectively). The mean ± standard deviation for the patients' age was 55.58±19.25 years. Twenty-eight patients were given Paxlovid (30.43%). Eighteen patients (19.57%) died. The use of Paxlovid was associated with lower ICU admissions (0.0% vs. 18.75%, P value <0.05) and with lower deaths (3.57% vs 26.56%, P value <0.05) but the Paxlovid group included less immunocompromised patients (7.14% vs. 60.94%, P value <0.001), cancer patients (0.0% vs. 42.19%, P value <0.001), and chronic kidney disease patients (7.14% vs. 29.69%, P value <0.05) than the control group. Conclusion This study suggests that Paxlovid is highly effective in reducing the risk of severe COVID-19 or mortality. However, larger studies with better qualities are needed for a full assessment of the role of Paxlovid in COVID-19 management in Saudi Arabia.

Antithrombotic therapy in the management of hospitalised patients with COVID-19.

Hospitalised patients with coronavirus disease 2019 (COVID-19) are at a significantly higher risk of having thromboembolic events while in hospital and in the immediate post-hospital discharge period. Based on early data from observational studies, multiple high quality randomised controlled trials have been conducted worldwide to evaluate optimal thromboprophylaxis regimens to reduce thromboembolism and other COVID-19-related adverse outcomes in hospitalised patients. The International Society on Thrombosis and Haemostasis has published evidence-based guideline recommendations using established methodology for the management of antithrombotic therapy of COVID-19 patients, both in-hospital and in the immediate post-hospital discharge period. A good clinical practice statement supplemented these guidelines based on topics for which there was no or limited high-quality evidence. This review summarises the main recommendations of these documents to serve as a quick access tool for hospital doctors to use in their everyday practice when treating COVID-19 patients.

Exploring the Potential of Broadly Neutralizing Antibodies for Treating SARS-CoV-2 Variants of Global Concern in 2023: A Comprehensive Clinical Review.

In the aftermath of the coronavirus disease 2019 (COVID-19) pandemic, the world is still seeing outbreaks of COVID-19 infections as of 2023, especially in populations that have been adequately vaccinated. This situation across the globe gives rise to important questions regarding the efficacy of current treatments and the real rate of mutations in the COVID-19 virus itself which can make the currently available treatments and vaccines obsolete. We have tried to answer a few of those questions and put forth some new questions of our own. Our efforts in this paper were directed towards understanding the utilization of broadly neutralizing antibodies as a treatment for COVID-19 infection with a particular focus on the Omicron variant and other newer variants. We gathered our data from three major databases: PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials (CENTRAL). We have screened 7070 studies from inception till March 5, 2023, and gathered 63 articles that were relevant to the topic of interest. Based on the existing medical literature regarding the topic of interest and also based on our own personal and clinical experience treating COVID-19 patients across the multiple waves in the United States and India since the beginning of the pandemic, we haveconcluded that broad neutralizing antibodies could be an effective optionfor treatment and prophylaxis for current and future outbreaks of COVID-19 including the Omicron variant and newer variants. Further research, including clinical trials, is required to tailor optimal dosages, prevent adverse reactions/side effects, and develop treatment strategies.

Dietary phytochemicals against COVID‐19: A focus on thymoquinone

Dietary phytochemicals against COVID‐19: A focus on thymoquinone

Cellular and Molecular Mechanisms of Pathogenic and Protective Immune Responses to SARS-CoV-2 and Implications of COVID-19 Vaccines.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has devastated the world with coronavirus disease 2019 (COVID-19), which has imparted a toll of at least 631 million reported cases with 6.57 million reported deaths. In order to handle this pandemic, vaccines against SARS-CoV-2 have been developed and billions of doses of various vaccines have been administered. In the meantime, several antiviral drugs and other treatment modalities have been developed to treat COVID-19 patients. At the end of the day, it seems that anti-SARS-CoV-2 vaccines and newly developed antiviral drugs may be improved based on various new developments. COVID-19 represents a virus-induced, immune-mediated pathological process. The severity of the disease is related to the nature and properties of the host immune responses. In addition, host immunity plays a dominant role in regulating the extent of COVID-19. The present reality regarding the role of anti-SARS-CoV-2 vaccines, persistence of SARS-CoV-2 infection even three years after the initiation of the pandemic, and divergent faces of COVID-19 have initiated several queries among huge populations, policy makers, general physicians, and scientific communities. The present review aims to provide some information regarding the molecular and cellular mechanisms underlying SARS-CoV-2 infection.

Network-based drug repurposing for the treatment of COVID-19 patients in different clinical stages

In the severe acute respiratory coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need to develop effective treatments. Through a network-based drug repurposing approach, several effective drug candidates are identified for treating COVID-19 patients in different clinical stages. The proposed approach takes advantage of computational prediction methods by integrating publicly available clinical transcriptome and experimental data. We identify 51 drugs that regulate proteins interacted with SARS-CoV-2 protein through biological pathways against COVID-19, some of which have been experimented in clinical trials. Among the repurposed drug candidates, lovastatin leads to differential gene expression in clinical transcriptome for mild COVID-19 patients, and estradiol cypionate mainly regulates hormone-related biological functions to treat severe COVID-19 patients. Multi-target mechanisms of drug candidates are also explored. Erlotinib targets the viral protein interacted with cytokine and cytokine receptors to affect SARS-CoV-2 attachment and invasion. Lovastatin and testosterone block the angiotensin system to suppress the SARS-CoV-2 infection. In summary, our study has identified effective drug candidates against COVID-19 for patients in different clinical stages and provides comprehensive understanding of potential drug mechanisms.

Exploration and verification of COVID-19-related hub genes in liver physiological and pathological regeneration.

Objectives An acute injury is often accompanied by tissue regeneration. In this process, epithelial cells show a tendency of cell proliferation under the induction of injury stress, inflammatory factors, and other factors, accompanied by a temporary decline of cellular function. Regulating this regenerative process and avoiding chronic injury is a concern of regenerative medicine. The severe coronavirus disease 2019 (COVID-19) has posed a significant threat to people's health caused by the coronavirus. Acute liver failure (ALF) is a clinical syndrome resulting from rapid liver dysfunction with a fatal outcome. We hope to analyze the two diseases together to find a way for acute failure treatment. Methods COVID-19 dataset (GSE180226) and ALF dataset (GSE38941) were downloaded from the Gene Expression Omnibus (GEO) database, and the "Deseq2" package and "limma" package were used to identify differentially expressed genes (DEGs). Common DEGs were used for hub genes exploration, Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) was used to verify the role of hub genes in liver regeneration during in vitro expansion of liver cells and a CCl4-induced ALF mice model. Results: The common gene analysis of the COVID-19 and ALF databases revealed 15 hub genes from 418 common DEGs. These hub genes, including CDC20, were related to cell proliferation and mitosis regulation, reflecting the consistent tissue regeneration change after the injury. Furthermore, hub genes were verified in vitro expansion of liver cells and in vivo ALF model. On this basis, the potential therapeutic small molecule of ALF was found by targeting the hub gene CDC20. Conclusion We have identified hub genes for epithelial cell regeneration under acute injury conditions and explored a new small molecule Apcin for liver function maintenance and ALF treatment. These findings may provide new approaches and ideas for treating COVID-19 patients with ALF.

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Anti-C5a Antibody BDB-001 for Severe COVID-19: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Clinical Trial in Healthy Chinese Adults.

Severe Coronavirus Disease 2019 (COVID-19) progresses with inflammation and coagulation, due to an overactive complement system. Complement component 5a (C5a) plays a key role in the complement system to trigger a powerful "cytokine and chemokine storm" in viral infection. BDB-001, a recombinant human immunoglobulin G4 (IgG4) that specially binds to C5a, has the potential to inhibit the C5a-triggered cytokine storm in treating COVID-19 patients and other inflammation diseases. Here, we have explored its safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy adults. This trial is registered with http://www.chinadrugtrials.org.cn/(CTR20200429 ). Thirty-two enrolled participants were randomized into three single-dose cohorts (2, 4, and 8mg/kg) and 1 multi-dose cohort (4mg/kg), and received either BDB-001 or placebo (3:1) double-blindly. The safety and tolerability after administration were evaluated for 21days for single-dose cohorts and 28days for the multi-dose cohort. The pharmacokinetics of BDB-001 in plasma and pharmacodynamics as free C5a in plasma were analyzed. The incidence of drug-related adverse events (AEs) was low, and all AEs were mild or moderate: neither AEs≥3 (NCI-Common Terminology Criteria For Adverse Events, CTCAE 5.0) nor serious adverse events (SAEs) were found. The area under the concentration-time curve from time zero to 480h (AUC0-480h), that from time zero to infinity (AUCinf), and peak plasma concentration ©max) increased dose-dependently from 2 to 8mg/kg in the single-dose cohorts and were characterized by a nonlinear pharmacokinetics of target-mediated drug disposal (TMDD). The accumulation index by AUC0-tau after five administrations (4mg/kg) from the multi-dose cohort was 6.42, suggesting an accumulation effect. Furthermore, inhibition of C5a at the plasma level was observed. The results of this phase I study supported that BDB-001 is a potent anti-C5a inhibitor with safety, tolerability, and no immunogenicity. TRIALREGISTRATION NUMBER: CTR20200429.

Efficacy and Safety of Favipiravir in Treating COVID-19 Patients: A Meta-Analysis of Randomized Control Trials.

This meta-analysis was conducted with the aim to assess the safety and efficacy of favipiravir in treating patients with coronavirus disease 2019 (COVID-19). It was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a thorough search of online databases including PubMed, EMBASE, and the Cochrane Library from their inceptions to November 30, 2022, using the following search terms: "Favipiravir" AND "COVID-19". We included randomized control trials (RCTs) that were conducted to determine the efficacy and safety of favipiravir for COVID-19. Efficacy outcomes assessed in this meta-analysis included time to viral clearance in days, time to clinical improvement in days, need for supplementary oxygen, and requirement of ICUadmission. For safety outcomes, we compared overall adverse events and serious adverse events that had occurred during the treatment between the patients in the treatment group and the control group.Eight studies involving 1,448 patients were included in this meta-analysis. The results showed that no significant differences were found between the two groups in terms of time to viral clearance, time to clinical improvement, and the need for supplementary oxygen andICU admission. In terms of safety, no significant differences were found between the two groups in relation to adverse events and serious adverse events.The current study found that favipiravir did not exert any beneficial impact on reducing ICU admission, the need for oxygen therapy, and time to viral clearance. However, a slight benefit was reported with regard to the time for clinical improvement, but it was insignificant between the two study groups.

Cost of Treating Coronavirus Disease 2019 (COVID-19) Patients in Hospitals and Influencing Factors: A Systematic Literature Review

Background: Increasing beds for COVID-19 patients is not a simple matter for hospitals because hospitals cannot directly increase the number of existing beds due to limited facilities, infrastructure, equipment, and resources. Careful calculations are needed in terms of preparing the room and treating COVID patients, especially the estimated costs needed to treat COVID patients in the hospital. This expenditure is important so that it can be an illustration of the hospital how much expenditure is needed. This study aimed to determine the number of costs incurred for treating COVID-19 patients in hospitals and the factors that influence these costs.&#x0D; Methods: This study was conducted by systematic literature review using the PRISMA statement conducted May-June 2021. An article search was conducted on Pubmed, Scopus, Proquest, and Google Scholar with the inclusion criteria, namely research related to the cost of treating COVID-19 patients in hospitals and the factors that influence the amount of these costs.&#x0D; Results: A systematic search obtained six articles. Studies vary greatly in study design and perspective included in the cost category. Estimated costs for COVID-19 care range from $63/day to $2,990/day. Factors that affect the cost of care include age, previous medical history, degree of infection or severity of COVID-19, length of stay, place of care, and need for a ventilator.&#x0D; Conclusion: There is a considerable economic burden associated with the incident of COVID-19. Several factors affect the cost of COVID-19, namely the length of the treatment period and the need for intensive rooms and ventilators.

A comprehensive review on pharmacologic agents, immunotherapies and supportive therapeutics for COVID-19.

The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the approved and potential therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary for COVID-19.