Coronavirus Disease 2019 Therapy Research Articles

Totality of Evidence of the effectiveness of repurposed therapies for COVID-19: Can we use Real-World Studies alongside Randomised Controlled Trials?

Rapid and robust strategies to evaluate the efficacy and effectiveness of novel and existing pharmacotherapeutic interventions (repurposed treatments) in future pandemics are required. Observational 'Real-World Studies' (RWS) can report more quickly than randomised controlled trials (RCTs) and would have value were they to yield reliable results. Both RCTs and RWS were deployed during the COVID-19 pandemic. Comparing results between them offers a unique opportunity to determine the potential value and contribution of each. A learning review of these parallel evidence channels in COVID19, based on quantitative modelling, can help improve speed and reliability in the evaluation of repurposed therapeutics in a future pandemic. Analysis of all-cause mortality data from 249 observational RWS and RCTs across eight treatment regimens for COVID-19 showed that RWS yield more heterogeneous results, and generally over-estimate the effect size subsequently seen in RCTs. This is explained in part by a few study factors: the presence of RWS that are imbalanced for age, gender and disease severity, and those reporting mortality at 2 weeks or less. Smaller studies of either type contributed negligibly. Analysis of evidence generated sequentially during the pandemic indicated that larger RCTs drive our ability to make conclusive decisions regarding clinical benefit of each treatment, with limited inference drawn from RWS. These results suggest that when evaluating therapies in future pandemics, 1) large RCTs, especially platform studies, be deployed early; 2) any RWS should be large and should have adequate matching of known confounders and long follow-up; 3) reporting standards and data standards for primary endpoints, explanatory factors and key subgroups should be improved. In addition, 4) appropriate incentives should be in place to enable access to patient-level data; and 5) an overall aggregate view of all available results should be available at any given time.

Safety Profile and Clinical and Virological Outcomes of Nirmatrelvir-Ritonavir Treatment in Patients With Advanced Chronic Kidney Disease and Coronavirus Disease 2019.

Nirmatrelvir-ritonavir is currently not recommended in patients with an estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2. To determine the safety profile and clinical and virological outcomes of nirmatrelvir-ritonavir use at a modified dosage in adults with chronic kidney disease (CKD), a prospective, single-arm, interventional trial recruited patients with eGFR <30 mL/minute/1.73 m2 and on dialysis. Primary outcomes included safety profile, adverse/serious adverse events, and events leading to drug discontinuation. Disease symptoms, virological outcomes by serial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral polymerase chain reaction (PCR) tests, rapid antigen tests, and virological and symptomatic rebound were also recorded. Fifty-nine (69.4%) of the 85 participants had stage 5 CKD and were on dialysis. Eighty (94.1%) completed the full treatment course; 9.4% and 5.9% had adverse and serious adverse events, and these were comparable between those with eGFR < or >30 mL/minute/1.73 m2. The viral load significantly decreased on days 5, 15, and 30 (P < .001 for all), and the reduction was consistent in the subgroup with eGFR <30 mL/minute/1.73 m2. Ten patients had virological rebound, which was transient and asymptomatic. Among patients with CKD, a modified dose of nirmatrelvir-ritonavir is a well-tolerated therapy in mild COVID-19 as it can effectively suppress the SARS-CoV-2 viral load with a favorable safety profile. Virological and symptomatic rebound, although transient with low infectivity, may occur after treatment. Nirmatrelvir-ritonavir should be considered for use in patients with CKD, including stage 5 CKD on dialysis. Clinical Trials Registration. Clinical Trials.gov; identifier: NCT05624840.

COVID-19: Variants, Immunity, and Therapeutics for Non-Hospitalized Patients.

The continuing transmission of coronavirus disease 2019 (COVID-19) remains a world-wide 21st-century public health emergency of concern. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused greater than 600 million cases of COVID-19 and over 6 million deaths globally. COVID-19 continues to be a highly transmissible disease despite efforts by public health officials and healthcare providers to manage and control the disease. Variants identified in selected worldwide epicenters add to the complexity of vaccine efficacy, overage, and antibody titer maintenance and bioactivity. The identification of the SARS-CoV-2 variants is described with respect to evading protective efficacy of COVID-19 vaccines and breakthrough infections. Vaccines and other therapeutics have prevented millions of SARS-CoV-2 infections and thousands of deaths in the United States. We explore aspects of the immune response in a condensed discussion to understand B and T cell lymphocyte regulatory mechanisms and antibody effectiveness and senescence. Finally, COVID-19 therapies including Paxlovid, Remdisivir, Molnupiravir and convalescent plasma in non-hospitalized patients are presented with limitations for identification, collection, and distribution to infected patients.

Characteristics and Outcomes of Women With Mild and Moderate Forms of COVID-19 Giving Birth During the COVID-19 Pandemic.

We aim to investigate the clinical course and impact of mild and moderate forms of coronavirusdisease 2019 (COVID-19) infection on pregnant women. A retrospective cohort study was conducted on pregnant women who delivered in a hospital with confirmed COVID-19 infection. Demographic features, clinical characteristics, and perinataloutcomes were retrospectively evaluated. In total, 157 pregnant women with COVID-19 were hospitalized. In a total of 46 deliveries, three (6.5%) had comorbiditiesand six (13%) were symptomatic.Myalgia and cough were the leadingsymptoms. In total, 11 (23.8%) patients received COVID-19 therapy, 41 (90%) had mild disease, and five (10.9%) were transferred to the intensive care unit (ICU). Maternal mortality wasobserved in two(4.3%) cases. Of the patients, 15 (32.6) had pregnancy complications(preterm delivery) (n = 13, 28.2%), and the cesarean section rate was 91.3%. The course of COVID-19 was mild in the majority of cases. However, accompanyingcomorbid conditions may accelerate the return to severe form and cause death.

Anticoagulant therapy in COVID-19: A narrative review.

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 venous thromboembolism (VTE) patients, particularly those admitted to intensive care units (ICUs). 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 COVID-19 patients 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 article, 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.

The influence of COVID-19 on colorectal cancer was investigated using bioinformatics and systems biology techniques.

Coronavirus disease 2019 (COVID-19) is a global pandemic and highly contagious, posing a serious threat to human health. Colorectal cancer (CRC) is a risk factor for COVID-19 infection. Therefore, it is vital to investigate the intrinsic link between these two diseases. In this work, bioinformatics and systems biology techniques were used to detect the mutual pathways, molecular biomarkers, and potential drugs between COVID-19 and CRC. A total of 161 common differentially expressed genes (DEGs) were identified based on the RNA sequencing datasets of the two diseases. Functional analysis was performed using ontology keywords, and pathway analysis was also performed. The common DEGs were further utilized to create a protein-protein interaction (PPI) network and to identify hub genes and key modules. The datasets revealed transcription factors-gene interactions, co-regulatory networks with DEGs-miRNAs of common DEGs, and predicted possible drugs as well. The ten predicted drugs include troglitazone, estradiol, progesterone, calcitriol, genistein, dexamethasone, lucanthone, resveratrol, retinoic acid, phorbol 12-myristate 13-acetate, some of which have been investigated as potential CRC and COVID-19 therapies. By clarifying the relationship between COVID-19 and CRC, we hope to provide novel clues and promising therapeutic drugs to treat these two illnesses.

The triangle relationship between human genome, gut microbiome, and COVID-19: opening of a Pandora's box.

Since the pandemic started, the coronavirus disease 2019 (COVID-19) has spread worldwide. In patients with COVID-19, the gut microbiome (GM) has been supposed to be closely related to the progress of the disease. The gut microbiota composition and human genetic variation are also connected in COVID-19 patients, assuming a triangular relationship between the genome, GM, and COVID-19. Here, we reviewed the recent developments in the study of the relationship between gut microbiota and COVID-19. The keywords "COVID-19," "microbiome," and "genome" were used to search the literature in the PubMed database. We first found that the composition of the GM in COVID-19 patients varies according to the severity of the illness. Most obviously, Candida albicans abnormally increased while the probiotic Bifidobacterium decreased in severe cases of COVID-19. Interestingly, clinical studies have consistently emphasized that the family Lachnospiraceae plays a critical role in patients with COVID-19. Additionally, we have demonstrated the impact of microbiome-related genes on COVID-19. Specially, we focused on angiotensin-converting enzyme 2's dual functions in SARS-CoV-2 infection and gut microbiota alternation. In summary, these studies showed that the diversity of GMs is closely connected to COVID-19. A triangular relationship exists between COVID-19, the human genome, and the gut flora, suggesting that human genetic variations may offer a chance for a precise diagnosis of COVID-19, and the important relationships between genetic makeup and microbiome regulation may affect the therapy of COVID-19.

SARS-CoV-2 hijacks p38β/MAPK11 to promote virus replication.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, drastically modifies infected cells to optimize virus replication. One such modification is the activation of the host p38 mitogen-activated protein kinase (MAPK) pathway, which plays a major role in inflammatory cytokine production, a hallmark of severe COVID-19. We previously demonstrated that inhibition of p38/MAPK activity in SARS-CoV-2-infected cells reduced both cytokine production and viral replication. Here, we combined quantitative genetic screening, genomics, proteomics, and phosphoproteomics to better understand mechanisms underlying the dependence of SARS-CoV-2 on the p38 pathway. We found that p38β is a critical host factor for SARS-CoV-2 replication in multiple relevant cell lines and that it functions at a step after viral mRNA expression. We identified putative host and viral p38β substrates in the context of SARS-CoV-2 infection and found that most host substrates have intrinsic antiviral activities. Taken together, this study reveals a unique proviral function for p38β and supports exploring p38β inhibitor development as a strategy toward creating a new class of COVID-19 therapies. IMPORTANCE SARS-CoV-2 is the causative agent of the COVID-19 pandemic that has claimed millions of lives since its emergence in 2019. SARS-CoV-2 infection of human cells requires the activity of several cellular pathways for successful replication. One such pathway, the p38 MAPK pathway, is required for virus replication and disease pathogenesis. Here, we applied systems biology approaches to understand how MAPK pathways benefit SARS-CoV-2 replication to inform the development of novel COVID-19 drug therapies.

National Trends in Anticoagulation Therapy for COVID-19 Hospitalized Adults in the United States: Analyses of the National COVID Cohort Collaborative.

Anticoagulation (AC) utilization patterns and their predictors among hospitalized coronavirus disease 2019 (COVID-19) patients have not been well described. Using the National COVID Cohort Collaborative, we conducted a retrospective cohort study (2020-2022) to assess AC use patterns and identify factors associated with therapeutic AC employing modified Poisson regression. Among 162 842 hospitalized COVID-19 patients, 64% received AC and 24% received therapeutic AC. Therapeutic AC use declined from 32% in 2020 to 12% in 2022, especially after December 2021. Therapeutic AC predictors included age (relative risk [RR], 1.02; 95% confidence interval [CI], 1.02-1.02 per year), male (RR, 1.29; 95% CI, 1.27-1.32), non-Hispanic black (RR, 1.16; 95% CI, 1.13-1.18), obesity (RR, 1.48; 95% CI, 1.43-1.52), increased length of stay (RR, 1.01; 95% CI, 1.01-1.01 per day), and invasive ventilation (RR, 1.64; 95% CI, 1.59-1.69). Vaccination (RR, 0.88; 95% CI, 84-.92) and higher Charlson Comorbidity Index (CCI) (RR, 0.98; 95% CI, .97-.98) were associated with lower therapeutic AC. Overall, two-thirds of hospitalized COVID-19 patients received any AC and a quarter received therapeutic dosing. Therapeutic AC declined after introduction of the Omicron variant. Predictors of therapeutic AC included demographics, obesity, length of stay, invasive ventilation, CCI, and vaccination, suggesting AC decisions driven by clinical factors including COVID-19 severity, bleeding risks, and comorbidities.

A Tale of Two Proteases: MPro and TMPRSS2 as Targets for COVID-19 Therapies.

Considering the importance of the 2019 outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting in the coronavirus disease 2019 (COVID-19) pandemic, an overview of two proteases that play an important role in the infection by SARS-CoV-2, the main protease of SARS-CoV-2 (MPro) and the host transmembrane protease serine 2 (TMPRSS2), is presented in this review. After summarising the viral replication cycle to identify the relevance of these proteases, the therapeutic agents already approved are presented. Then, this review discusses some of the most recently reported inhibitors first for the viral MPro and next for the host TMPRSS2 explaining the mechanism of action of each protease. Afterward, some computational approaches to design novel MPro and TMPRSS2 inhibitors are presented, also describing the corresponding crystallographic structures reported so far. Finally, a brief discussion on a few reports found some dual-action inhibitors for both proteases is given. This review provides an overview of two proteases of different origins (viral and human host) that have become important targets for the development of antiviral agents to treat COVID-19.

Interaction of Biochemical Processes between Chronic Obstructive Pulmonary Disease (COPD), Pulmonary Arterial Hypertension (PAH), and Coronavirus Disease 2019 (COVID-19).

Both pulmonary arterial hypertension (PAH) and chronic obstructive pulmonary disease (COPD) are risk factors for coronavirus disease 2019 (COVID-19). Patients with lung injury and altered pulmonary vascular anatomy or function are more susceptible to infections. The purpose of the study is to ascertain whether individuals with COPD or PAH are affected synergistically by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data sources for the construction of a protein-protein interaction (PPI) network and the identification of differentially expressed genes (DEGs) included three RNA-seq datasets from the GEO database (GSE147507, GSE106986, and GSE15197). Then, relationships between miRNAs, common DEGs, and transcription factor (TF) genes were discovered. Functional analysis using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and other databases, as well as the forecasting of antiviral medications for COPD and PAH patients infected with SARS-CoV-2, were also performed. Eleven common DEGs were found in the three datasets, and their biological functions were primarily enriched in the control of protein modification processes, particularly phosphorylation. Growth factor receptor binding reflects molecular function. KEGG analysis indicated that co-DEGs mainly activate Ras, and PI3K-Akt signaling pathways and act on focal adhesions. NFKB1 interacted with HSA-miR-942 in the TF-miRNA-DEGs synergistic regulatory network. Acetaminophen is considered an effective drug candidate. There are some connections between COPD and PAH and the development of COVID-19. This research could aid in developing COVID-19 vaccines and medication candidates that would work well as COVID-19 therapies.

Nanotechnologies for the Diagnosis and Treatment of SARS-CoV-2 and Its Variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the global coronavirus disease 2019 (COVID-19) pandemic, has caused well over 750 million infections and 6.8 million deaths. Rapid diagnosis and isolation of infected patients are the primary aims of the concerned authorities to minimize the casualties. The endeavor to mitigate the pandemic has been impeded by the emergence of newly identified genomic variants of SARS-CoV-2. Some of these variants are considered as serious threats because of their higher transmissibility and potential immune evasion, leading to reduced vaccine efficiency. Nanotechnology can play an important role in advancing both diagnosis and therapy of COVID-19. In this review, nanotechnology-based diagnostic and therapeutic strategies against SARS-CoV-2 and its variants are introduced. The biological features and functions of the virus, the mechanism of infection, and currently used approaches for diagnosis, vaccination, and therapy are discussed. Then, nanomaterial-based nucleic acid- and antigen-targeting diagnostic methods and viral activity suppression approaches that have a strong potential to advance both diagnostics and therapeutics toward control and containment of the COVID-19 pandemic are focused upon.

Bioinformatics Approach to Identify the Influences of COVID-19 on Ischemic Stroke

As severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is becoming more infectious and less virulent, symptoms beyond the lungs of the Coronavirus Disease 2019 (COVID-19) patients are a growing concern. Studies have found that the severity of COVID-19 patients is associated with an increased risk of ischemic stroke (IS); however, the underlying pathogenic mechanisms remain unknown. In this study, bioinformatics approaches were utilized to explore potential pathogenic mechanisms and predict potential drugs that may be useful in the treatment of COVID-19 and IS. The GSE152418 and GSE122709 datasets were downloaded from the GEO website to obtain the common differentially expressed genes (DEGs) of the two datasets for further functional enrichment, pathway analysis, and drug candidate prediction. A total of 80 common DEGs were identified in COVID-19 and IS datasets for GO and KEGG analysis. Next, the protein–protein interaction (PPI) network was constructed and hub genes were identified. Further, transcription factor–gene interactions and DEGs–miRNAs coregulatory network were investigated to explore their regulatory roles in disease. Finally, protein-drug interactions with common DEGs were analyzed to predict potential drugs. We successfully identified the top 10 hub genes that could serve as novel targeted therapies for COVID-19 and screened out some potential drugs for the treatment of COVID-19 and IS.

Efficacy of convalescent plasma therapy for COVID-19 in Japan: An open-label, randomized, controlled trial

BackgroundConvalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19). Despite its use for treating several viral infections, we lack comprehensive data on its efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MethodsWe conducted a multicenter, open-label, randomized controlled trial of convalescent plasma therapy with high neutralizing activity against SARS-CoV-2 in high-risk patients within five days after the onset of COVID-19 symptoms. The primary endpoint was the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs from days 0–5. ResultsBetween February 24, 2021, and November 30, 2021, 25 patients were randomly assigned to either convalescent plasma (n = 14) or standard of care (n = 11) groups. Four patients discontinued their allocated convalescent plasma, and 21 were included in the modified intention-to-treat analysis. The median interval between the symptom onset and plasma administration was 4.5 days (interquartile range, 3–5 days). The primary outcome of the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs did not significantly differ between days 0–5 (1.2 log10 copies/mL in the convalescent plasma vs. 1.2 log10 copies/mL in the standard of care (effect estimate, 0.0 [95% confidence interval, −0.8–0.7]; P = 0.94)). No deaths were observed in either group. ConclusionsThe early administration of convalescent plasma with high neutralizing activity did not contribute to a decrease in the viral load within five days compared with the standard of care alone.

Therapeutics for COVID-19.

Vaccines and monoclonal antibody treatments to prevent severe coronavirus disease 2019 (COVID-19) illness were available within a year of the pandemic being declared but there remained an urgent need for therapeutics to treat patients who were not vaccinated, were immunocompromised or whose vaccine immunity had waned. Initial results for investigational therapies were mixed. AT-527, a repurposed nucleoside inhibitor for hepatitis C virus, enabled viral load reduction in a hospitalized cohort but did not reduce viral load in outpatients. The nucleoside inhibitor molnupiravir prevented death but failed to prevent hospitalization. Nirmatrelvir, an inhibitor of the main protease (Mpro), co-dosed with the pharmacokinetic booster ritonavir, reduced hospitalization and death. Nirmatrelvir-ritonavir and molnupiravir received an Emergency Use Authorization in the United States at the end of 2021. Immunomodulatory drugs such as baricitinib, tocilizumab and corticosteroid, which target host-driven COVID-19 symptoms, are also in use. We highlight the development of COVID-19 therapies and the challenges that remain for anticoronavirals.

2022 Looking Back at COVID-19 and Stem Cell Therapy

The global epidemic of Corona Virus Disease 2019 (COVID-19) has been raging since its outbreak in 2019, placing enormous strain on healthcare systems all over the world. The best course of action is to prevent COVID-19 in the future, despite the fact that its virological characteristics and pathogenesis have been largely understood. And all current treatment options probably include two types: one is active immunization and the other is passive immunization. Among them, passive immunity includes supportive therapy as well as neutralizing antibodies, and small molecule drugs and other treatments are used as supportive therapy, which only slows down the symptoms and prevents complications, and then waits for the body's immune system to heal itself. On the other hand, stem cell therapy is one type of active immunity. Typically, doctors use mesenchymal stem cells (MSC) to treat patients with severe or life-threatening disorders because of their potent immunomodulatory, anti-inflammatory, and tissue healing abilities. The remarkable developments in COVID-19 stem cell therapy during the past three years are outlined in this article, along with the current state of affairs. And it was found that although stem cell therapy has been successful in stages, it still has many limitations.

Common Coagulopathies Associated With COVID-19 Patients.

The coronavirus disease 2019 (COVID-19) outbreak, which first appeared in the Chinese province of Hubei city of Wuhan, has been spreading internationally since December 2019. The World Health Organization (WHO) declared the coronavirus illness from 2019 to be a pandemic on March 11, 2020. Patients hospitalised with severe coronavirus or comorbid conditions (like cardiovascular disease and obesity) are linked to a worse prognosis. The rise in D-dimer and its relationship to prognosis are the most often documented aberrations in coagulation/fibrinolysis in COVID-19. However, the D-dimer assessment's utility is not limitless. Since the coagulation/fibrinolytic state might occasionally change over a short period of time, routine exams are also advantageous in understanding the relevance of the inquiry. Both thrombotic and hemorrhagic diseases should be taken into consideration, despite the fact that the pathophysiology of disseminated intravascular coagulation (DIC) linked with coronavirus disease 19 differs significantly from that of septic disseminated intravascular coagulation. Coagulation as well as fibrinolysis indicators are used to make the diagnosis of COVID-19 thrombosis, which encompasses both macro- and micro-thrombosis. Compared to bacterial-sepsis-associated coagulopathy/DIC, COVID-19 has a lower prevalence of prolonged prothrombin time, activated partial thromboplastin time, and decreased antithrombin activity. However, the causes of coagulopathy remain poorly understood. Hypoxia, endothelial injury, dysregulated immunological responses mediated by inflammatory cytokines, and lymphocyte cell death are thought to be implicated. While blood loss tends to be rare, it is uncertain if COVID-19 suffers from thrombosis or whether the current recommendations for regular venous thromboembolic dose are appropriate. It is important to decide on the COVID-19 therapy phases. Antiviral therapy, cytokine storm therapy, and thrombosis therapy are the steps. Future advancements are predicted, such as a therapy that combines heparin and nafamostat.

Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory effects. Here, an integrative pharmacological strategy was applied to identify the antiviral and anti-inflammatory bioactive compounds from Q-14. Overall, a total of 343 chemical compounds were initially characterized, and 60 prototype compounds in Q-14 were subsequently traced in plasma using ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Among the 60 compounds, six compounds (magnolol, glycyrrhisoflavone, licoisoflavone A, emodin, echinatin, and quercetin) were identified showing a dose-dependent inhibition effect on the SARS-CoV-2 infection, including two inhibitors (echinatin and quercetin) of the main protease (Mpro), as well as two inhibitors (glycyrrhisoflavone and licoisoflavone A) of the RNA-dependent RNA polymerase (RdRp). Meanwhile, three anti-inflammatory components, including licochalcone B, echinatin, and glycyrrhisoflavone, were identified in a SARS-CoV-2-infected inflammatory cell model. In addition, glycyrrhisoflavone and licoisoflavone A also displayed strong inhibitory activities against cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4). Crystal structures of PDE4 in complex with glycyrrhisoflavone or licoisoflavone A were determined at resolutions of 1.54Å and 1.65Å, respectively, and both compounds bind in the active site of PDE4 with similar interactions. These findings will greatly stimulate the study of TCMT-NDRD against COVID-19.

Facilitating oral COVID-19 therapy utilization through a pharmacy consult service

BackgroundTwo oral therapies, nirmatrelvir/ritonavir (Paxlovid) and molnupiravir (Lagevrio), are now available for the treatment of coronavirus disease 2019 (COVID-19). Treatment guidelines recommend using these agents for nonhospitalized adults with mild to moderate COVID-19 who are at high risk of disease progression. Despite guideline recommendations, therapy is frequently underutilized, resulting in lost opportunity to prevent severe outcomes including death. ObjectiveThis study aimed to describe the implementation of a pharmacy consult service for oral COVID-19 therapy within the ambulatory care setting. Practice descriptionUpon receipt of a positive COVID-19 test result, providers were encouraged to place a pharmacy consult for review. Information required within the consult submission served as a simple guide for determining eligibility for therapy. Once submitted, the pharmacist would identify which oral COVID-19 medication and dosage was most appropriate. In addition, for nirmatrelvir/ritonavir, the pharmacist would provide clear and concise instructions on how to manage any significant drug-drug interactions identified. Upon consult completion, the provider would order the appropriate therapy. Practice innovationWe depict an interdisciplinary approach to facilitate oral COVID-19 therapy utilization at a health care system level. EvaluationVeterans with a positive COVID-19 test from January 10, 2022, to July 10, 2022, were identified. A chart review was then used to collect relevant patient demographics and outcomes. The primary outcome was the eligibility for and subsequent prescribing of oral COVID-19 therapy. ResultsOf the 245 positive COVID-19 cases, 172 (70%) were eligible for oral COVID-19 therapy. Of those eligible, 118 (68.6%) were offered therapy and 95 (80.5%) accepted. Nirmatrelvir/ritonavir was the predominant agent used with 16% requiring renal dosage adjustment. Pharmacists identified 167 significant drug-drug interactions with nirmatrelvir/ritonavir encompassing 42 unique medications. Fourteen of the interactions warranted the utilization of molnupiravir. ConclusionThe utilization of a pharmacy consult service has facilitated interdisciplinary team collaboration and ultimately empowered the utilization of oral COVID-19 therapy.

Cell-Based Biomaterials for COVID-19 Prevention and Therapy.

Coronavirus disease 2019 (COVID-19) continues to threaten human health, economic development and national security. Although many vaccines and drugs have been explored to fight against the major pandemic, their efficacy and safety still need to be improved. Cell-based biomaterials, especially living cells, extracellular vesicles and cell membranes, offer great potential in preventing and treating COVID-19 owing to their versatility and unique biological functions. In this review, we describe the characteristics and functions of cell-based biomaterials and their biological applications in COVID-19 prevention and therapy. We first summarize the pathological features of COVID-19, providing enlightenment on how to fight against COVID-19. Next, we focus on the classification, organization structure, characteristics, and functions of cell-based biomaterials. Finally, we comprehensively describe the progress of cell-based biomaterials in overcoming COVID-19 in different aspects, including the prevention of viral infection, inhibition of viral proliferation, anti-inflammation, tissue repair, and alleviation of lymphopenia. At the end of this review, a look forward to the challenges of this aspect is presented. This article is protected by copyright. All rights reserved.