Treatment Of COVID-19 Research Articles

The Impact of Antidepressants on COVID-19 and Post-Acute COVID-19 Syndrome: A Scoping-Review Update

On May 20, 2024, this systematic scoping review in PUBMED identified 1016 articles related to AD and COVID-19, Long COVID and SARS-COV-2. These included 10 retrospective "large scale" studies (> 20000 chart reviews), 8 prospective clinical trials (plus 4 regarding Long COVID), 11 placebo-controlled randomized (RCT) (plus 2 regarding Long COVID) and 15 meta-analyses. COVID-19: Retrospective studies with cohorts taking AD primarily for psychiatric comorbidities or chronic pain conditions directly prior to SARS-COV-2 infection described that this substance class (most studied: Selective Serotonin Re-Uptake Inhibitors (SSRI) and Selective Serotonin Noradrenaline Re-Uptake Inhibitors (SSNRI)) were associated with (i) significantly fewer SARS-COV-2 infections and (ii) a milder course of COVID-19 ("COVID-19 protection"). Ten of the 11 RCTs found regarding COVID-19 tested fluvoxamine, as this old AD appeared suitable as a prophylactic agent against severe COVID-19, taking into account its in vitro potency against the progression of intracellular sepsis cascades. Therefore, most (12 out of 15) meta-analyses also referred to fluvoxamine. They found (iii) a significant (40-70% reduction) in mortality, intubation and hospitalization rates when fluvoxamine was used as an add-on to standard therapy for mild to moderate COVID-19. When this AD was used in the early stages of the disease, it was more successful than when it was given later in advanced, severe COVID-19 (e.g. severe pneumonia, final sepsis stages). A dose dependency was observed: 2x50 mg fluvoxamine over 15 days was less effective than 2x100 or even 3x100 mg with an adverse event profile still at the placebo level. Direct comparisons with drugs approved for COVID-19 do not yet exist. A first indirect meta-analytical comparison showed an advantage of paxlovid or molnupiravir versus fluvoxamine against the development of severe COVID-19: risk reduction of 95% (I2 = N/A, but only one study) or 78% (I2=0) versus 5+-5% (I2=48). However, an add-on of fluvoxamine was still significantly more efficacious than symptom-oriented standard therapy alone. Long COVID: A common Long COVID phenotype with dominant anxiety and depression symptoms, which responds to AD, relaxation therapy and/or psychotherapy, has now been identified. Casuistics report positive effects of AD on fatigue, cognitive and autonomic dysfunctions. A first large prospective open-label RCT has just shown significantly more favourable courses, less viral load and less pro-inflammatory cytokines in the treatment of mild to moderate COVID-19 with fluvoxamine versus standard treatment, also with regard to the subsequent development of neuropsychiatric and pulmonary Long COVID or fatigue. Overall, there is promising evidence of a preventive effect of AD (especially fluvoxamine) against progression to severe COVID-19 and against the development of Long COVID. It is likely, that the entire AD substance class could be effective here. This assumption is based on the results of retrospective large scale studies, but awaits verification by better controlled studies. The potential effectiveness/efficacy (currently low and moderate confidence of the evidence for the entire substance class and specifically fluvoxamine, respectively) of fluvoxamine as an add-on against COVID-19 and possibly also directly against Long COVID could stimulate similar projects in other infectious diseases that also have the potential to pose a lasting threat to the health of those affected. We consider the evidence to date to be sufficient to be able to emphasize a possible positive effect of these substances in the psychoeducation of patients with COVID-19 or Long COVID who are already receiving AD for other conditions - especially also against the symptoms associated with the viral disease or its consequences. In regions where neither vaccines nor antiviral agents currently approved for the prevention or treatment of COVID-19 are available, AD and in particular fluvoxamine would be a cost-effective alternative to protect against a severe course, even if this AD appears to have a smaller effect against COVID-19 than the currently approved antiviral agents, but with presumably better tolerability. A direct comparative clinical trial with approved antiviral agents is still pending and should be positive to further open the door for a guideline-based recommendation of fluvoxamine (or perhaps even AD) for COVID-19 or its aftermath.

Mechanistic Insights into Targeting SARS-CoV-2 Papain-like Protease in the Evolution and Management of COVID-19

Mechanistic Insights into Targeting SARS-CoV-2 Papain-like Protease in the Evolution and Management of COVID-19

Maintaining and Improving Virtual Call Centers for Public Health: The CUNY Recovery Corps Experience.

In the early stages of the COVID-19 pandemic in New York City, individuals who tested positive, exposed contacts, and their families faced significant challenges in accessing essential resources for successful quarantine and isolation. These resources included alternative housing, food access, grocery delivery, missed wage assistance, transportation for household members, medical care, and more. The City University of New York (CUNY) Recovery Corps emerged as an innovative virtual resource navigation service to connect New Yorkers to essential resources and later to vaccinations, treatment, and services for Long COVID. The program prioritized reaching people living in underserved and under-resourced neighborhoods. Over 3years, it made a substantial impact, reaching 374728 New Yorkers and connecting 135147 to crucial resources. Implementing a successful virtual navigation center amidst a global pandemic posed unique challenges. It required well-established systems to provide services, manage staff, build community, and both assure and improve service quality. Continuous quality assurance and process improvement efforts resulted in a nearly 10-point increase in successful client-resource connections program-wide, with individual navigators showing improvements of up to 20%. Staff-led initiatives, such as population-specific resource guides and incentive awards, boosted morale and cohesion. Providing continuous professional development opportunities and requested training including trauma-informed care, self-care, and strategies for managing grief contributed to staff retention and improved client interactions. The CUNY Recovery Corps provides a blueprint for setting up navigation services for emergency response and supporting health and social services. The current paper delves into the intensive quality improvement efforts, program management infrastructure, and staff support that made this program a success. By applying these lessons on establishing and maintaining a virtual call center prioritizing the client's well-being and staff strengths, policymakers and social service leaders can effectively address various health and social service needs proactively rather than rebuilding after each disaster.

Analysis of the course and outcomes of COVID-19 at different stages of the pandemic in hemodialysis patients

The purpose of this study was a comparative analysis of the characteristics of the course and outcomes of COVID-19 in HD patients at different stages of the pandemic, focusing on the of the use of immunomodulatory therapy.Materials and methods. The retrospective study included 897 HD patients with COVID-19 (mean age 60.7 years, M 58.5%) who were hospitalized at Moscow City Hospital № 52. Group 1 (n=720) consisted of patients infected between the end of March 2020 and April 2021, group 2 (n=177) included patients hospitalized in May-December 2021. Each of group was divided into 2 subgroups based on treatment approaches. Subgroup 1a (n=231) included patients of the initial period of the pandemic who did not receive adequate immunomodulatory therapy, while Subgroup 1b (n=489) included patients of the late stage, were treated with IL-6 receptor blockers and corticosteroids. In group 2, 108 patients in Subgroup 2a received similar therapy, while 69 patients in Subgroup 2b were treated with neutralizing monoclonal antibodies in the early stages of the disease.Results. Mortality rates in Group 1 and Group 2 was 20.1% and 14.7%, respectively (p<0.09). The incidence of unfavorable outcome was highest in Subgroup 1a and lowest in Subgroup 2b (31.2% vs 5.8%, p<0.01). Mortality in Subgroups 1b and 2a was comparable (14.9% and 20.4%), despite more severe initial lung damage according to CT data in Subgroup 2a. In these patients, immunomodulators was more frequently combined with therapeutic plasma exchange (TPE). Independent risk factors for an unfavorable outcome were the progression of pulmonary pathology, with the transformation of stages CT 1-2 to CT 3-4, and a high comorbidity index.Conclusions. The use of immunomodulatory drugs imprtoved the effectiveness of COVID-19 treatment in patients with CKD5D. In severe cases, the most favorable outcomes were achieved with a combination of immunobiological drugs, corticosteroids, and TPE. An even more significant reduction in mortality was observed following the introduction of neutralizing monoclonal antibodies into clinical practice. Independent predictors of unfavorable outcome of COVID-19 in HD patients were a high comorbidity index and the progression of CT 1-2 into CT 3-4.

Bacterial co-infection in COVID-19: a call to stay vigilant.

Co-infection with diverse bacteria is commonly seen in patients infected with the novel coronavirus, SARS-CoV-2. This type of co-infection significantly impacts the occurrence and development of novel coronavirus infection. Bacterial co-pathogens are typically identified in the respiratory system and blood culture, which complicates the diagnosis, treatment, and prognosis of COVID-19, and even exacerbates the severity of disease symptoms and increases mortality rates. However, the status and impact of bacterial co-infections during the COVID-19 pandemic have not been properly studied. Recently, the amount of literature on the co-infection of SARS-CoV-2 and bacteria has gradually increased, enabling a comprehensive discussion on this type of co-infection. In this study, we focus on bacterial infections in the respiratory system and blood of patients with COVID-19 because these infection types significantly affect the severity and mortality of COVID-19. Furthermore, the progression of COVID-19 has markedly elevated the antimicrobial resistance among specific bacteria, such as Klebsiella pneumoniae, in clinical settings including intensive care units (ICUs). Grasping these resistance patterns is pivotal for the optimal utilization and stewardship of antibiotics, including fluoroquinolones. Our study offers insights into these aspects and serves as a fundamental basis for devising effective therapeutic strategies. We primarily sourced our articles from PubMed, ScienceDirect, Scopus, and Google Scholar. We queried these databases using specific search terms related to COVID-19 and its co-infections with bacteria or fungi, and selectively chose relevant articles for inclusion in our review.

Molecular mechanisms of thalidomide effectiveness on COVID-19 patients explained: ACE2 is a new ΔNp63α target gene

COVID-19 pandemic is caused by the SARS-CoV-2 virus, whose internalization and infection are mediated by the angiotensin-converting enzyme 2 (ACE2). The identification of novel approaches to tackle this step is instrumental for the development of therapies for the management of COVID-19 and other diseases with a similar mechanism of infection. Thalidomide, a drug sadly known for its teratogenic effects, has potent immunomodulatory and anti-inflammatory properties. Treatment with this drug has been shown to improve the immune functions of COVID-19 patients and proposed for the management of COVID-19 in clinical practice through drug repositioning. Here, we investigated the molecular details linking thalidomide to ACE2 and COVID-19, showing that in conditions mimicking SARS-CoV-2-associated cytokine storm, the transcription factor ΔNp63α and ACE2 are stabilized, and IL-8 production is increased. In such conditions, we found p63 to bind to and regulate the expression of the ACE2 gene. We previously showed that ΔNp63α is degraded upon thalidomide treatment and now found that treatment with this drug—or with its analogue lenalidomide—downregulates ACE2 in a p63-dependent manner. Finally, we found that thalidomide treatment reduces in vitro infection by pseudo-SARS-CoV-2, a baculovirus pseudotyped with the SARS-CoV-2 spike protein. Overall, we propose the dual effect of thalidomide in reducing SARS-CoV-2 viral re-entry and inflammation through p63 degradation to weaken SARS-CoV-2 entry into host cells and mitigate lung inflammation, making it a valuable option in clinical management of COVID-19.Key messagesThalidomide treatment results in p63-dependent ACE2 downregulation.ACE2 is a p63 transcriptional target.Thalidomide reduces the “cytokine storm” associated to COVID-19.Thalidomide prevents viral re-entry of SARS-CoV-2 by p63-dependent ACE2 downregulation.Thalidomide is a modulator of SARS-CoV-2 or other ACE2-dependent infections.ACE2 is modulated by a pharmacological substance.

In Silico Evaluation of HIV Protease and RNA Polymerase Inhibitors as Potential COVID-19 Therapeutics.

The COVID-19 coronavirus, also known as the acute respiratory syndrome coronavirus, emerged as a significant global health concern. First identified in Wuhan, China, in December 2019, the virus rapidly spread to over 187 countries due to its high transmissibility. Until an effective treatment or vaccine is developed, preventive measures remain the only mandatory strategy to curb person-to-person transmission. The study aimed to explore potential therapeutic options for COVID-19 by repurposing existing drugs. Specifically, the objective was to evaluate a library of clinically approved or investigational antiviral compounds through docking studies to identify candidates with high binding affinity to COVID-19 proteins. The study employed molecular docking techniques using the Maestro interface (Schrodinger Suite, LLC, NY) to assess the interaction of selected compounds with various COVID-19 protein targets. A total of 15 compounds were analyzed for their binding potential to multiple forms of the virus's proteins. The docking studies revealed that several compounds, particularly HIV protease inhibitors and RNA-dependent RNA polymerase inhibitors, demonstrated strong binding affinities to key COVID-19 enzymes. These interactions suggest their potential as therapeutic candidates for COVID-19 treatment. The findings from this drug repurposing study highlight the potential of certain existing antiviral agents in the treatment of COVID-19. The identified compounds could serve as promising candidates for further investigation in the ongoing battle against the coronavirus pandemic.

Exploring Alternative Health Facebook Groups in the COVID-19 Pandemic: An Automated Content Analysis Through Structural Topic Modeling.

Alternative health (AH) has an important role in public health across cultures, as the World Health Organization acknowledges. Using structural topic modeling, we analyzed 25,561 posts from public Facebook groups that contained AH-related content during the COVID-19 pandemic over 3 years. Thirty-one topics emerged, and they were categorized into six major themes, including (1) sharing information regarding AH treatment for COVID-19, (2) spiritual and mental healing in the pandemic, (3) news and information about COVID-19, (4) commercial content related to AH treatment, (5) COVID-19 precautions suggestions, and (6) caution against treating AH as a cure-all. We found that these Facebook groups served as digital spaces for AH content by playing a dual role: (1) disseminating information on COVID-19 and AH for both laypeople and experts and (2) providing spiritual connections and commercial content to alleviate anxiety during the pandemic. While accurate information and social support were shared, a notable part of commercial messages and AH treatments offered for COVID-19 included misleading and unverified claims. Findings shed light on the nature and extent of misleading AH content and why engagement with AH media may contribute to increased belief in health misinformation. We further discuss the complexity and diversity of content on AH media.

Use of Supplementary Medicines/Nutrients and Disease Behaviours during the COVID-19 Pandemic

Objective: The study was conducted to reveal which type of supplementary people used against COVID-19 disease and determine their behaviours/ideas related to the disease. Materials and Methods: This study is a cross-sectional was conducted between April and May 2021. It was limited to people over the age of 18, and the snowball sampling method was used along with a questionnaire form. Results: Of the individuals participating in the study, 74.4% were in the 18-33 age group, 72.6% were female, 64.6% were single, 65.8% had bachelor's degrees and associate degrees, 49.5% were actively working, and 63.13% had 1-10 years of work experience. Of the participants, 72.1% did not catch COVID-19. Medicines or supplementary nutrients are used mainly by individuals in the 34-49 age group (51.7%). Conclusion: The most used supplementary medicines and nutrients were antiviral and anti-flu medicines and paracetamol, vitamins C, D, B, iron, omega-3, green tea, honey, thyme, ginger, lemon, spicy teas, turmeric, and fruit tea. The use of non-medicine complementary methods has increased while studies on the treatment of COVID-19 are ongoing. Among these methods, there is a tendency to mostly use supplementary medicines, nutrients, vitamins, and herbal products, respectively.

Enhanced complement activation and MAC formation accelerates severe COVID-19

Emerging evidence indicates that activation of complement system leading to the formation of the membrane attack complex (MAC) plays a detrimental role in COVID-19. However, their pathogenic roles have never been experimentally investigated before. We used three knock out mice strains (1. C3−/−; 2. C7−/−; and 3. Cd59ab−/−) to evaluate the role of complement in severe COVID-19 pathogenesis. C3 deficient mice lack a key common component of all three complement activation pathways and are unable to generate C3 and C5 convertases. C7 deficient mice lack a complement protein needed for MAC formation. Cd59ab deficient mice lack an important inhibitor of MAC formation. We also used anti-C5 antibody to block and evaluate the therapeutic potential of inhibiting MAC formation. We demonstrate that inhibition of complement activation (in C3−/−) and MAC formation (in C3−/−. C7−/−, and anti-C5 antibody) attenuates severe COVID-19; whereas enhancement of MAC formation (Cd59ab−/−) accelerates severe COVID-19. The degree of MAC but not C3 deposits in the lungs of C3−/−, C7−/− mice, and Cd59ab−/− mice as compared to their control mice is associated with the attenuation or acceleration of SARS-CoV-2-induced disease. Further, the lack of terminal complement activation for the formation of MAC in C7 deficient mice protects endothelial dysfunction, which is associated with the attenuation of diseases and pathologic changes. Our results demonstrated the causative effect of MAC in severe COVID-19 and indicate a potential avenue for modulating the complement system and MAC formation in the treatment of severe COVID-19.

COVID-19’s effects on symptoms associated with benign prostatic hyperplasia

PurposeThe objective of this study was to identify the relationship between COVID-19 and lower urinary tract symptoms in patients with benign prostatic hyperplasia.Materials and methodsData from forty outpatients who had recovered from COVID-19 and had previously been diagnosed with and treated medically for benign prostatic hyperplasia were assessed. Pre- and post-COVID-19 assessments were also conducted for prostate volume, total serum PSA concentration, and lower urinary tract symptoms. Hospitalizations related to COVID-19, the time interval between COVID-19 recovery and urologist referrals, and comorbidities were considered. Independent Student’s t-tests or chi-square tests were used to compare changes in all variables. For the Spearman rank correlation analysis, only variables with a univariate analysis of p < 0.10 were included in the multiple regression models, with the significance threshold set at two-tailed p < 0.05.ResultsAfter COVID-19, there was an increase in IPSS (12.87 ± 3.76), total serum PSA (1.56 ± 0.87), and prostate volume (10.68 ± 11.73). Multiple linear regression analysis of the independent predictors of IPSS increase revealed pre-COVID-19 IPSS with intermittency and straining as leading symptoms and bladder catheterization during COVID-19. Pre-COVID-19 frequency and nocturia status were found to be independent predictors of increased blood volume, hospital treatment for COVID-19, and bladder catheterization. A weak stream, UTI, and hypertension were found to be independent predictors of a PSA increase. The time from COVID-19 recovery to urologist referral was shorter in patients with post-COVID-19 IPSS increase (p < 0.05).ConclusionDetermining the predictors of the effects of COVID-19 on worsening BPH symptoms is essential for continued monitoring and treatment.

The last COVID-19 lockdown in Bhutan: a referral hospital’s response to a community outbreak of the Omicron variant

This viewpoint outlines the COVID-19 management strategies Central Regional Referral Hospital (CRRH) adopted in Bhutan during the Omicron variant outbreak. The hospital in the high-risk region provided healthcare and public health services to its catchment area during the lockdowns imposed in Bhutan. Specifically, we discuss the hospital’s role in outbreak management, surveillance, isolation, patient care, and non-clinical services. Key strategies including community-based surveillance, isolation in hotel facilities, telemedicine and community engagement are highlighted. We briefly outlined lessons learned from the experience, such as the importance of community involvement and innovative approaches to healthcare delivery during pandemics.

MMFA-DTA: Multimodal Feature Attention Fusion Network for Drug-Target Affinity Prediction for Drug Repurposing Against SARS-CoV-2.

The continuous emergence of novel infectious diseases poses a significant threat to global public health security, necessitating the development of small-molecule inhibitors that directly target pathogens. The RNA-dependent RNA polymerase (RdRp) and main protease (Mpro) of SARS-CoV-2 have been validated as potential key antiviral drug targets for the treatment of COVID-19. However, the conventional new drug R&D cycle takes 10-15 years, failing to meet the urgent needs during epidemics. Here, we propose a general multimodal deep learning framework for drug repurposing, MMFA-DTA, to enable rapid virtual screening of known drugs and significantly improve discovery efficiency. By extracting graph topological and sequence features from both small molecules and proteins, we design attention mechanisms to achieve dynamic fusion across modalities. Results demonstrate the superior performance of MMFA-DTA in drug-target affinity prediction over several state-of-the-art baseline methods on Davis and KIBA data sets, validating the benefits of heterogeneous information integration for representation learning and interaction modeling. Further fine-tuning on COVID-19-relevant bioactivity data enhances model predictions for critical SARS-CoV-2 enzymes. Case studies screening the FDA-approved drug library successfully identify etacrynic acid as the potential lead compound against both RdRp and Mpro. Molecular dynamics simulations further confirm the stability and binding affinity of etacrynic acid to these targets. This study proves the great potential and advantages of deep learning and drug repurposing strategies in supporting antiviral drug discovery. The proposed general and rapid response computational framework holds significance for preparedness against future public health events.

Evaluation of the feasibility and efficacy of point-of-care antibody tests for biomarker guided management of COVID-19.

Biomarker guided therapy could improve management of COVID-19 inpatients. Although some results indicate that antibody tests are prognostic, little is known about patient management using point-of-care (POC) antibody tests. COVID-19 inpatients were recruited to evaluate 2 POC tests: LumiraDX and RightSign. Ease of use data was collected. Blood was also collected for centralized testing using established antibody assays (GenScript cPass). A nested case-control study assessed if POC tests conducted on stored specimens were predictive of time to sustained recovery, mortality, and a composite safety outcome. While both POC tests exhibited moderate agreement with the GenScript assay (both agreeing with 89% of antibody determinations), they were significantly different from the GenScript assay. Treating the GenScript assay as the gold standard, the LumiraDX assay had 99.5% sensitivity and 58.1% specificity while the RightSign assay had 89.5% sensitivity and 84.0% specificity. The LumiraDX assay frequently gave indeterminant results. Both tests were significantly associated with clinical outcomes. Although both POC tests deviated moderately from the GenScript assay, they predicted outcomes of interest. The RightSign test was easier to use and was more likely to detect those lacking antibody compared to the LumiraDX test treating GenScript as the gold standard.

Plasma Adsorption with the MTx.100 Column in Critically Ill COVID-19 Patients: A Prospective Study and Propensity Score Analysis.

Early in the COVID-19 pandemic, patients with severe disease admitted to the intensive care unit (ICU) had a high incidence of mortality. We aimed to investigate whether plasma adsorption with the MTx.100 Column could improve survival. We performed a prospective, single-arm, multicenter, Emergency Use Authorization (EUA) trial in patients admitted to the ICU with severe COVID-19 who were worsening despite standard therapy. The primary outcome was all-cause mortality on day 28. Outcomes were analyzed using both a pre-specified performance goal (PG), and a propensity score-matched (PSM) analysis from the highest enrolling center, in which patients treated with the standard of care (SOC) plus the MTx.100 Column (n = 70) were compared to a contemporaneous cohort treated at the same center with SOC only (n = 244). Between May 21, 2020, and November 2, 2021, 107 patients with severe COVID-19 (mean age 58.1) at 7 US centers were enrolled and had at least one plasma adsorption treatment initiated. All-cause mortality on day 28 was 37.4% (40/107), an improvement over the prespecified PG (88.1%, p < 0.0001). There were no serious adverse events attributable to the MTx.100 Column or plasmapheresis. Improvements in most metabolic and inflammatory markers were also noted. The PSM analysis showed that survival odds were three times higher for MTx.100 Column-treated patients (95% CI: 1.56-5.88) than for those treated with SOC only. The MTx.100 Column treatment in severe COVID-19 resulted in a lower mortality than SOC by both pre-specified PG and PSM analysis. clinicaltrials.gov (NCT04358003).

Clinical rebound after treatment with nirmatrelvir/ritonavir in COVID-19

BackgroundNirmatrelvir/ritonavir (NM/r) is a safe and effective oral antiviral therapeutic used for treatment of mild-to-moderate COVID-19. Case reports described a clinical rebound syndrome whereby individuals experience a relapse of symptoms shortly after completing successful treatment. There is a lack of information on frequency of COVID-19 rebound after NM/r in routine clinical care, contributing factors, and clinical outcomes.MethodsWe reviewed electronic medical records to verify COVID-19 diagnosis, symptoms, and treatment with NM/r from January-June 2022. We defined COVID-19 clinical rebound as clear improvement in symptoms followed by recurrence or worsening of symptoms within 30 days of a five-day course of NM/r.ResultsWe studied 268 adults with median age 57 (IQR 47, 68), 80% White race, 85% non-Hispanic ethnicity, 55% female, 80% vaccinated and boosted against SARS-CoV-2, and 68% with any co-morbidity. Sixteen (6.0%) of studied patients were determined to have COVID-19 clinical rebound. The median time from starting NM/r to rebound was 11 days (IQR 9, 13). Notable demographic and clinical factors with higher proportion (not statistically significant) among COVID-19 rebound patients were female sex (75% rebound vs. 54.5% no rebound), Black race (12.5% rebound vs. 4.9% no rebound), presence of at least one co-morbidity (81.3% rebound vs. 67.5% no rebound), and lack of prior SARS-CoV-2 infection (100% rebound vs. 92.9% no rebound). Only one patient (6.25%) was hospitalized after COVID-19 rebound.ConclusionsCOVID-19 clinical rebound after treatment with NM/r is mild with favorable outcomes and more common than previously reported from real-world clinical care studies.

Assessment of Supplementation with Different Biomolecules in the Prevention and Treatment of COVID-19.

Consequences of the disease produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to an urgent search for preventive and therapeutic strategies. Besides drug treatments, proposals have been made for supplementation with biomolecules possessing immunomodulatory and antioxidant properties. The objective of this study was to review published evidence on the clinical usefulness of supplementation with vitamin D, antioxidant vitamins (vitamin A, vitamin E, and vitamin C), melatonin, lactoferrin and natural products found in food (curcumin, luteolin, ginger, allicin, magnesium and zinc) as supplements in SARS-CoV-2 infection. In general, supplementation of conventional treatments with these biomolecules has been found to improve the clinical symptoms and severity of the coronavirus disease (COVID-19), with some indications of a preventive effect. In conclusion, these compounds may assist in preventing and/or improving the symptoms of COVID-19. Nevertheless, only limited evidence is available, and findings have been inconsistent. Further investigations are needed to verify the therapeutic potential of these supplements.

Molecular Investigations of Novel Pyrano[2,3-c]Pyrazole Congeners as Potential HCoV-229E Inhibitors: synthesis, Molecular Modeling, 3D QSAR, and ADMET Screening

The ongoing global pandemic caused by viral pathogens like SARS-CoV-2 (COVID-19) underscores that viral transmission is not confined by geographical boundaries. Thus, the development of novel antiviral therapies is critical to mitigate this crisis. Pyranopyrazoles have gained significant attention in medicinal chemistry due to their bioactive properties. In this study, we present a new series of pyranopyrazoles and their annulated derivatives, which were assessed for antiviral activity using a validated QSAR model and tested for their inhibitory effects against the viral 3CLpro enzyme. The findings were corroborated by various in silico techniques, including molecular docking, molecular dynamics simulations, and DFT calculations. Additionally, ADME studies were conducted to evaluate the pharmacokinetics and pharmacodynamics of the novel lead compound 2. These investigations identified a series of metabolically stable pyranopyrazoles and their annulated derivatives as effective inhibitors of the SARS-CoV-2 3CLpro enzyme, offering a promising therapeutic option for COVID-19. We believe that pyranopyrazoles warrant further evaluation and chemical optimization for potential use in COVID-19 treatment.

Aptamer-based Strategies for COVID-19 Detection and Treatment: A Systematic Review Study

Background: Aptamer-based strategies have emerged as promising tools for the detection and treatment of COVID-19, offering advantages such as high specificity, sensitivity, and versatility. This systematic review aims to evaluate the effectiveness and innovation of aptamer-based approaches for COVID-19 detection and treatment. Methods: Following the guidelines of the Cochrane Handbook for Systematic Reviews and the PRISMA 2020 guidelines, a systematic search was conducted across multiple databases up to 2024. The search included studies that utilized aptamers for the diagnosis or therapy of COVID-19. Screening and selection of studies were performed independently by two reviewers, with any disagreements resolved by a third reviewer. Data were extracted regarding study characteristics, aptamer details, and outcomes. Results: In our systematic review, 98 studies from an initial pool of 1541 records met the inclusion criteria for analysis. Aptamers, single-stranded DNA or RNA molecules with unique threedimensional (3D) structures, were extensively explored for COVID-19 detection and treatment. Various aptamer-based assays, including electrochemical sensors, surface plasmon resonance (SPR) biosensors, and lateral flow assays, demonstrated high sensitivity and specificity in detecting SARSCoV- 2 in clinical samples such as saliva, nasal swabs, and wastewater. Several aptamer structures targeting viral proteins like the spike and nucleocapsid proteins were employed. Nucleic Acid Amplification Techniques (NAATs) utilizing aptamers, such as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based and Loop-mediated Isothermal Amplification (LAMP) assays, showed exceptional sensitivity in detecting viral genetic material. Aptamer-based therapeutic approaches showed potential by blocking viral protein activity or serving as delivery vehicles for therapeutic agents like small interfering RNAs (siRNAs). Despite their advantages, aptamer technologies face limitations such as susceptibility to nuclease degradation and rapid renal clearance, highlighting the need for further optimization. Conclusion: Aptamer-based strategies present promising avenues for COVID-19 detection and treatment. These approaches offer advantages such as high sensitivity, specificity, and rapid detection, making them valuable tools in combating the COVID-19 pandemic. Further research and development are warranted to optimize aptamer-based strategies for widespread application in clinical settings.

Hyphenating sustainability with chemometrics in chromatographic analysis of COVID combo therapy, nirmatrelvir and Molnupiravir, in presence of their overlapping degradation products; blue-green dual evaluation tools

Our manuscript managed to hyphenate the novelty and sustainability in one method. A novel combination of molnupiravir (MNP) and nirmatrelvir (NTV) was found to be a potential symbiotic therapy against SARS-CoV-2. Yet, there is no analytical method published for either determination or stability investigation of this combination simultaneously. So, the proposed HPLC technique focused on determination of MNP and NTV in presence of their degradation products. The sustainability was achieved in our method by using chemometrics tools to quantify NTV in presence of its co-eluted degradation product (NTV-D) without excessive time and solvent usage for separation (run time 5 min.). Moreover, the linearity parameters of both MNP and NTV, including correlation coefficient, LOD and LOQ, have been enhanced significantly after chemometrics treatment through convolution of the resultant derivative curves using trigonometric Fourier function. For example, LOQ of MNP decreased from 3.53 to 0.31 µg/mL and for NTV, LOQ decreased from 4.98 to 2.10 µg/mL after chemometrics treatment. The stability results of the proposed method indicates that no interaction or change in stability behavior of both drugs when co-administered with each other. Thus, this can be used as an empirical basis to initiate clinical trials of this combination for the treatment of COVID-19 patients.Additionally, in order to determine the impact of chemometric methods in minimizing analysis time and reducing solvent, energy, and waste consumption, our chemometric methodology is evaluated in terms of greenness and blueness (dichromic assessment) using AGREE and BAGI, respectively. Besides, the method sustainability using Hexagon was evaluated.