Treatment Of COVID-19 Infection Research Articles

Hospital-based proton therapy implementation during the COVID pandemic: early clinical and research experience in a European academic institution

IntroductionA rapid deploy of unexpected early impact of the COVID pandemic in Spain was described in 2020. Oncology practice was revised to facilitate decision-making regarding multimodal therapy for prevalent cancer types amenable to multidisciplinary treatment in which the radiotherapy component searched more efficient options in the setting of the COVID-19 pandemic, minimizing the risks to patients whilst aiming to guarantee cancer outcomes.MethodsA novel Proton Beam Therapy (PBT), Unit activity was analyzed in the period of March 2020 to March 2021. Institutional urgent, strict and mandatory clinical care standards for early diagnosis and treatment of COVID-19 infection were stablished in the hospital following national health-authorities’ recommendations. The temporary trends of patients care and research projects proposals were registered.Results3 out of 14 members of the professional staff involved in the PBR intra-hospital process had a positive test for COVID infection. Also, 4 out of 100 patients had positive tests before initiating PBT, and 7 out of 100 developed positive tests along the weekly mandatory special checkup performed during PBT to all patients. An update of clinical performance at the PBT Unit at CUN Madrid in the initial 500 patients treated with PBT in the period from March 2020 to November 2022 registers a distribution of 131 (26%) pediatric patients, 63 (12%) head and neck cancer and central nervous system neoplasms and 123 (24%) re-irradiation indications. In November 2022, the activity reached a plateau in terms of patients under treatment and the impact of COVID pandemic became sporadic and controlled by minor medical actions. At present, the clinical data are consistent with an academic practice prospectively (NCT05151952). Research projects and scientific production was adapted to the pandemic evolution and its influence upon professional time availability. Seven research projects based in public funding were activated in this period and preliminary data on molecular imaging guided proton therapy in brain tumors and post-irradiation patterns of blood biomarkers are reported.ConclusionsHospital-based PBT in European academic institutions was impacted by COVID-19 pandemic, although clinical and research activities were developed and sustained. In the post-pandemic era, the benefits of online learning will shape the future of proton therapy education.

Ginsenosides, potential TMPRSS2 inhibitors, a trade-off between the therapeutic combination for anti-PD-1 immunotherapy and the treatment of COVID-19 infection of LUAD patients.

Background: Acting as a viral entry for coronavirus to invade human cells, TMPRSS2 has become a target for the prevention and treatment of COVID-19 infection. Before this, TMPRSS2 has presented biological functions in cancer, but the roles remain controversial and the mechanism remains unelucidated. Some chemicals have been reported to be inhibitors of TMPRSS2 and also demonstrated other pharmacological properties. At this stage, it is important to discover more new compounds targeting TMPRSS2, especially from natural products, for the prevention and treatment of COVID-19 infection. Methods: We analyzed the correlation between TMPRSS2 expression, methylation level, overall survival rate, clinical parameters, biological process, and determined the correlation between TMPRSS2 and tumor-infiltrating lymphocytes in the tumor and adjacent normal tissue of adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) respectively by using various types of bioinformatics approaches. Moreover, we determined the correlation between TMPRSS2 protein level and the prognosis of LUAD and LUSC cohorts by immunohistochemistry assay. Furthermore, the cancer immunome atlas (TCIA) database was used to predict the relationship between the expression of TMPRSS2 and response to programmed cell death protein 1 (PD-1) blocker immunotherapy in lung cancer patients. Finally, the putative binding site of ginsenosides bound to TMPRSS2 protein was built from homology modeling to screen high-potency TMPRSS2 inhibitors. Results: We found that TMPRSS2 recruits various types of immunocytes, including CD8+, CD4+ T cells, B cells and DCs both in LUAD and LUSC patients, and the correlation between TMPRSS2 expression and CD8+ and CD4+ T cells are stronger in LUAD rather than in LUSC, but excludes macrophages and neutrophils in LUAD patient cohorts. These might be the reason that higher mRNA and protein levels of TMPRSS2 are associated with better prognosis in LUAD cohorts rather than in LUSC cohorts. Furthermore, we found that TMPRSS2 was positively correlated with the prognosis in patient nonresponse to anti-PD-1 therapy. Therefore, we made an inference that increasing the expression level of TMPRSS2 may improve the anti-PD-1 immunotherapy efficacy. Finally, five ginsenosides candidates with high inhibition potency were screened from the natural chemical library to be used as TMPRSS2 inhibitors. Conclusion: All these may imply that TMPRSS2 might be a novel prognostic biomarker and serve as a potential immunomodulator target of immunotherapy combination therapies in LUAD patients nonresponse to anti-PD-1 therapy. Also, these findings may suggest we should pay more attention to LUAD patients, especially those infected with COVID-19, who should avoid medicating TMPRSS2 inhibitors, such as ginsenosides to gain prophylactic and therapeutic benefits against COVID-19.

The effect of thrombosis-related laboratory values on mortality in COVID-19 infection.

COVID-19 may cause thrombosis in both venous and arterial systems. Familiarity with the signs and symptoms of thrombosis and its treatment is essential in treating COVID-19 infection and its complications. D-Dimer and mean platelet volume (MPV) are measurements related to the development of thrombosis. This study investigates whether MPV and D-Dimer values could be used to determine the risk of thrombosis and mortality in the COVID-19 early stages. 424 patients who were COVID-19 positive, according to the World Health Organization (WHO) guidelines, were randomly and retrospectively included in the study. Demographic and clinical characteristics such as age, gender, and length of hospitalization were obtained from the digital records of participants. Participants were divided into living and deceased groups. The patients' biochemical, hormonal, and hematological parameters were analyzed retrospectively. White blood cells (WBC), neutrophils, and monocytes were significantly different in the two groups (p-value <0.001), and their values were lower in the living group than in the deceased group. MPV median values did not differ according to prognosis (p-value = 0.994). While the median value was 9.9 in the survivors, it was 10 in the deceased. Creatinine, procalcitonin, ferritin, and the number of hospitalization days in living patients were significantly lower than in patients who died (p-value <0.001). Median values of D-dimer (mg/L) differ according to prognosis (p-value <0.001). While the median value was 0.63 in the survivors, it was found as 438 in the deceased. Our results did not show any significant relationship between the mortality of COVID-19 patients and their MPV levels. However, a significant association between D-Dimer and mortality in COVID-19 patients was observed.

Trial Sequential Analysis and Updated Meta-Analysis of Fluvoxamine on Clinical Deterioration in Adult Patients with Symptomatic COVID-19 Infection

Preliminary meta-analyses suggested that fluvoxamine was effective in treating COVID-19 infection. However, the reliability of this evidence has not yet been examined. MEDLINE, CENTRAL, EMBASE, PsycINFO, and ClinicalTrials.gov were searched to identify any randomized controlled trials (RCTs) from the inception of the databases to 5 February 2023. We used trial sequential analysis (TSA) to examine the reliability of the current existing evidence on the benefits of fluvoxamine on COVID-19 infection. The primary outcome was clinical deterioration, as defined in the original study (reported as odds ratio (OR), with 95% confidence intervals), and the secondary outcome was hospitalization. In the TSA, we used the relative risk reduction thresholds of 10, 20, and 30%. The updated meta-analysis of the five RCTs showed that fluvoxamine was not associated with lower odds of clinical deterioration when compared with a placebo (OR: 0.81; 0.59-1.11). The effect of fluvoxamine lay within the futility boundary (i.e., lack of effect) when using a 30% relative risk reduction threshold. The effect estimates lay between the superiority and futility boundary using the 10% and 20% threshold, and the required size of information was not reached for these two thresholds. The effect of fluvoxamine on the odds of hospitalization was not statistically significant (0.76; 0.56-1.03). In conclusion, there is no reliable evidence that fluvoxamine, when compared to a placebo, reduces the relative risk of clinical deterioration among adult patients with COVID-19 infection by 30%, and a relative risk reduction of 20% or 10% is still uncertain. The role of fluvoxamine as a COVID-19 treatment cannot be justified.

Metabolic Activation of PARP as a SARS-CoV-2 Therapeutic Target-Is It a Bait for the Virus or the Best Deal We Could Ever Make with the Virus? Is AMBICA the Potential Cure?

The COVID-19 pandemic has had a great impact on global health and is an economic burden. Even with vaccines and anti-viral medications we are still scrambling to get a balance. In this perspective, we have shed light upon an extremely feasible approach by which we can control the SARS-CoV-2 infection and the associated complications, bringing some solace to this ongoing turmoil. We are providing some insights regarding an ideal agent which could prevent SARS-CoV-2 multiplication. If we could identify an agent which is an activator of metabolism and is also bioactive, we could prevent corona activation (AMBICA). Some naturally occurring lipid molecules best fit this identity as an agent which has the capacity to replenish our host cells, specifically immune cells, with ATP. It could also act as a source for providing a substrate for host cell PARP family members for MARylation and PARylation processes, leading to manipulation of the viral macro domain function, resulting in curbing the virulence and propagation of SARS-CoV-2. Identification of the right lipid molecule or combination of lipid molecules will fulfill the criteria. This perspective has focused on a unique angle of host-pathogen interaction and will open up a new dimension in treating COVID-19 infection.

AUTOMATIC DETECTION OF COVID-19 AND VIRAL PNEUMONIA IN X-RAY IMAGES USING DEEP LEARNING APPROACH

The early detection and treatment of COVID-19 infection are necessary to save human life. The study aims to propose a time-efficient and accurate method to classify lung infected images by COVID-19 and viral pneumonia using chest X-ray. The proposed classifier applies end-to-end training approach to classify the images of the set of normal, viral pneumonia and COVID-19-infected images. The features of the two infected classes were precisely captured by the extractor path and transferred to the constructor path for precise classification. The classifier accurately reconstructed the classes using the indices and the feature maps. For firm confirmation of the classification results, we used the Matthews correlation coefficient (MCC) along with accuracy and F1 scores (1 and 0.5). The classification accuracy of the COVID-19 class achieved was about ([Formula: see text])% with MCC score ([Formula: see text]). The classifier is distinguished with great precision between the two nearly correlated infectious classes (COVID-19 and viral pneumonia). The statistical test suggests that the obtained results are statistically significant as [Formula: see text]. The proposed method can save time in the diagnosis of lung infections and can help in reducing the burden on the medical system in the time of the pandemic.

Ephedrae Herba: A Review of Its Phytochemistry, Pharmacology, Clinical Application, and Alkaloid Toxicity.

Ephedrae Herba (Ephedra), known as "MaHuang" in China, is the dried straw stem that is associated with the lung and urinary bladder meridians. At present, more than 60 species of Ephedra plants have been identified, which contain more than 100 compounds, including alkaloids, flavonoids, tannins, sugars, and organic phenolic acids. This herb has long been used to treat asthma, liver disease, skin disease, and other diseases, and has shown unique efficacy in the treatment of COVID-19 infection. Because alkaloids are the main components causing toxicity, the safety of Ephedra must be considered. However, the nonalkaloid components of Ephedra can be effectively used to replace ephedrine extracts to treat some diseases, and reasonable use can ensure the safety of Ephedra. We reviewed the phytochemistry, pharmacology, clinical application, and alkaloid toxicity of Ephedra, and describe prospects for its future development to facilitate the development of Ephedra.

6-Shogaol Exhibits Anti-viral and Anti-inflammatory Activity in COVID-19-Associated Inflammation by Regulating NLRP3 Inflammasomes.

Recent global health concern motivated the exploration of natural medicinal plant resources as an alternative target for treating COVID-19 infection and associated inflammation. In the current study, a phytochemical, 6-shogaol [1-(4-hydroxy-3-methoxyphenyl)dec-4-en-3-one; 6-SHO] was investigated as a potential anti-inflammatory and anti-COVID-19 agent. In virus release assay, 6-SHO efficiently (94.5%) inhibited SARS-CoV2 replication. When tested in the inflammasome activation model, 6-SHO displayed mechanistic action by regulating the expression of the inflammasome pathway molecules. In comparison to the existing drugs, remdesivir and hydroxy-chloroquine, 6-SHO was not only found to be as effective as the standard anti-viral drugs but also much superior and safe in terms of predicted physicochemical properties and clinical toxicity. Comparative molecular dynamics simulation demonstrated a stable interaction of 6-SHO with NLRP3 (the key inflammasome regulator) in the explicit water environment. Overall, this study provides important cues for further development of 6-SHO as potential anti-inflammatory and anti-viral therapeutic agents.

COVID-19-Associated Misinformation Across the South Asian Diaspora: Qualitative Study of WhatsApp Messages.

South Asians, inclusive of individuals originating in India, Pakistan, Maldives, Bangladesh, Sri Lanka, Bhutan, and Nepal, comprise the largest diaspora in the world, with large South Asian communities residing in the Caribbean, Africa, Europe, and elsewhere. There is evidence that South Asian communities have disproportionately experienced COVID-19 infections and mortality. WhatsApp, a free messaging app, is widely used in transnational communication within the South Asian diaspora. Limited studies exist on COVID-19-related misinformation specific to the South Asian community on WhatsApp. Understanding communication on WhatsApp may improve public health messaging to address COVID-19 disparities among South Asian communities worldwide. We developed the COVID-19-Associated misinfoRmation On Messaging apps (CAROM) study to identify messages containing misinformation about COVID-19 shared via WhatsApp. We collected messages forwarded globally through WhatsApp from self-identified South Asian community members between March 23 and June 3, 2021. We excluded messages that were in languages other than English, did not contain misinformation, or were not relevant to COVID-19. We deidentified each message and coded them for one or more content categories, media types (eg, video, image, text, web link, or a combination of these elements), and tone (eg, fearful, well intentioned, or pleading). We then performed a qualitative content analysis to arrive at key themes of COVID-19 misinformation. We received 108 messages; 55 messages met the inclusion criteria for the final analytic sample; 32 (58%) contained text, 15 (27%) contained images, and 13 (24%) contained video. Content analysis revealed the following themes: "community transmission" relating to misinformation on how COVID-19 spreads in the community; "prevention" and "treatment," including Ayurvedic and traditional remedies for how to prevent or treat COVID-19 infection; and messaging attempting to sell "products or services" to prevent or cure COVID-19. Messages varied in audience from the general public to South Asians specifically; the latter included messages alluding to South Asian pride and solidarity. Scientific jargon and references to major organizations and leaders in health care were included to provide credibility. Messages with a pleading tone encouraged users to forward them to friends or family. Misinformation in the South Asian community on WhatsApp spreads erroneous ideas regarding disease transmission, prevention, and treatment. Content evoking solidarity, "trustworthy" sources, and encouragement to forward messages may increase the spread of misinformation. Public health outlets and social media companies must actively combat misinformation to address health disparities among the South Asian diaspora during the COVID-19 pandemic and in future public health emergencies.

Role of Molnupiravir in the Treatment of COVID-19

Background: Molnupiravir is a ribonucleoside analog and exhibits its antiviral mechanism by inhibiting replication. Preclinical studies have been reported that support the role of Molnupiravir towards the prophylaxis, cure, and prevention of SARS-CoV-2 infection. In addition to it, clinical studies have confirmed its activity against the most common variants of SARS-CoV-2. Objective: The manuscript aims to demonstrate the rationale behind the clinical use of Molnupiravir in the treatment of COVID-19 infection at the early stage of the onset of symptoms specific to five days. Methodology: A thorough literature search has been carried out using various suitable keywords to extract details on the antiviral mechanism, preclinical, and clinical use of Molnupiravir, its safety, tolerability, dosage, duration of treatment, etc. Results: The reported studies demonstrate the antiviral action of Molnupiravir by viral error catastrophe mechanism which results in the inhibition of the viral multiplication activity when it enters inside the host cells. The manuscript delivers complete detail regarding pharmacokinetic and pharmacological actions, usage, and various preclinical and clinical studies reported for this newly evaluated drug for the treatment of COVID-19 infection. Conclusion: The study concludes Molnupiravir has the potential in the treatment of COVID-19 infection. When used along with vaccines, it would be a low-cost, valuable, and incredible asset as an oral anti-COVID drug for saving human life.

COVID-19 и хроническая гастроэнтерологическая патология: особенности течения, тактика ведения, исходы

National and international clinical guidelines provide detailed information on the diagnosis and treatment of COVID-19 infection, but long-term damage to multiple organs and systems associated with the disease, especially in patients with aggravated premorbid history, is still barely understood. The digestive system appears to be a sensitive target for SARS-CoV-2, and there is evidence of long-term persistence of the virus in the gastrointestinal (GI) tract without its detection in the respiratory system. A quarter to half of COVID-19 patients have GI symptoms, which are associated with a more severe disease course. The virus can affect any part of the digestive system, and people with underlying GI diseases are at greatest risk for adverse outcomes. The probability of having a post-infectious pathology is evident, but of practical interest is the impact of current or past COVID-19 infection on the course of gastrointestinal pathology. Some patients with chronic GI diseases are more likely to develop COVID-19 disease. In these patients, it is difficult to diagnose the infectious process, and there is a risk of a more severe course and adverse outcomes of COVID-19. In this regard, the management of comorbid patients requires certain adjustments to standard treatment regimens for novel coronavirus infection. Key words: COVID-19, gastrointestinal pathology, children, post-COVID syndrome

Analysis of Interaction Between Odorant Receptors and Flexible Spike of SARS CoV-2- Key to Loss of Smell.

The development of a vaccine for SARS-CoV-2 is primarily focused on the structure of the spike (S) protein. The heavy glycosylation of S with flexible hinges at the stalk shields from antibody attachment. This study deciphers the flexible nature of hinges responsible for binding the odorant receptor on neurons responsible for the loss of smell in COVID-19 patients. The 3D structure via EPIK in Maestro, protein docking with ligands via Maestro protein analysis tool, and molecular dynamic simulation at 30 ns run using DESMOND was prepared. The data of the study strongly suggest that strong and stable bond formation results from the reaction between R:14: Trp and Phe at the residue, targeting the flexible hinges of SARS-CoV-2. The difference in the conformational structure of the S protein and its binding with the odorant receptor in COVID-19 is the prime factor for the loss of smell and taste in patients, as supported by the concept of Antigen (epitope) Antibody interaction by the stable formation of a hydrogen bond among odorant receptor and the S protein. The flexibility of structural proteins determines the binding potential of antibodies or other defense proteins produced to participate in the antigen-antibody reaction. Molecular and atomic details potentiate the design and screening of small molecules that can inhibit the fusion at entry level or odorant receptors and potentially be used in the prevention and treatment of infection, particularly when formulated as nasal drops, paving a new approach for pharmacologists in the treatment of COVID-19 infection.

Inhibition of the Mechanistic Targets of Rapamycin Beyond Transplant Immunosuppression: A Mini-Review

It has been about thirty years since identifying the target of rapamycin and using mTOR inhibitors in organ transplantation. There was a promise that they would replace calcineurin inhibitors with fewer nephrotoxic effects and better graft survival. Unfortunately, with time, the enthusiasm for using them in transplantation decreased due to the unpleasant profile of adverse events and limited evidence of tangible clinical benefit. With more understanding of physiology and judicious clinical application, new venues for mTOR inhibitors emerged. The mTOR pathway regulates primary cellular functions, including cell growth, metabolism, proliferation, and survival, and is critical for autophagy induction. Thus, as a master regulator, mTOR inhibitors emerged as anticancer therapies. In addition, such action proved beneficial for native or post-transplant malignancies. Signaling through components of the mTOR pathway is an essential regulator of normal cardiac growth and pathological hypertrophy. mTOR inhibitors are effective in reducing left ventricular thickness and mass. It could be an add-on benefit in kidney transplant recipients with high cardiovascular risk or attenuate cardiac allograft vasculopathy in heart transplant recipients. The mTOR inhibitors may help manage viral infections like cytomegalovirus, human herpesvirus 8-related Kaposi sarcoma, and possibly the BK virus. Furthermore, the mTOR pathway is modulated in many RNA viruses. Based on these facts, the idea of using mTOR inhibitors to treat COVID-19 infection has been evaluated. Accordingly, a new therapeutic role for mTOR inhibitors for treating COVID-19 infection t has emerged through reducing viral replication, and autophagocytosis, improving T cells function and preventing cytokine storm. This paper will review these applications of mTOR inhibitors beyond the horizon of transplant immunosuppression.

Hyperbaric Oxygen Therapy : A new Evolving Future Perspective for Management of Mucormycosis and COVID 19 in Children in Developing Countries

The SARS COVID-19 virus has arisen as a major hazard to mankind, posing harm to the whole world population. During the second COVID wave, mucormycosis has emerged as one of the deadliest and most devastating illnesses. Mucormycosis is strongly associated with diabetes, prolonged use of steroids, prolonged hospitalisation and immunocompromised states. Children have also been affected by this badly. Hyperbaric oxygen therapy is a non-invasive, cost-effective and painless therapy where 100% oxygen is given to patients under high atmospheric pressure in small tents or chambers. It helps in tissue regeneration and angiogenesis. Hyperbaric oxygen has proved to be effective in the treatment of oculo-rhino-cerebral mucormycosis. Various studies have proved its role in the management of mucormycosis and acute respiratory distress syndrome associated with COVID-19 infection. The advantages of hyperbaric oxygen are same in children as in adults with minimum side effects. Hyperbaric oxygen therapy can be one of the good adjunctive therapies in the management of mucormycosis. It is found to be safe in the treatment of COVID-19 infection, but data is still limited on its use and further studies are needed. This article is all about its use, its efficacy, and future perspectives in the management of mucormycosis and COVID-19 in view of the arrival of the third COVID wave in developing countries like India.

Neuropsychiatric dimensions of COVID-19 - literature review

SARS-CoV-2 infection leads to severe multiple organ failure. The immune system is stimulated by activating the inflammatory mechanism and by releasing inflammatory cytokines. COVID-19 is able to penetrate the central nervous system, inducing neuritis and neurodegeneration. In our study, we analyzed the latest available articles. We focused on the subject of COVID-19 infection and consequences of neuroinflammation. For this study, we searched the literature available in Pubmed and Google Scholar databases using keywords. There is evidence of a common background of COVID-19 complications and neurological diseases such as Parkinson's or Alzheimer's disease. This type of complication is more frequently observed in serious cases of COVID-19, with a more intense immune response, with higher levels of CRP, ferritin and D-dimers. Organic changes in conjunction with environmental stress caused by the experience of severe illness, fear of becoming ill and social limitations, lead to neuropsychiatric pathologies, including major depressive disorders and post-traumatic stress. The neuropsychiatric implications of COVID-19 represent a severe clinical problem that deserves special attention in the treatment of COVID-19 infection. There is a need to monitor the neuropsychiatric consequences of COVID-19, in order to completely understand the impact of SARS-CoV-2 infection. This knowledge is necessary to be able to confront the public health crisis created by the COVID-19 pandemic.

Prophylactic Effect of Chloroquine and Hydroxychloroquine on COVID-19 Treatment

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19), which has threatened human health and public safety.&#x0D; Objectives: Hydroxychloroquine (HCQ) is an anti-malaria drug with controversial antiviral properties. Some in vitro studies have approved its antiviral effects. Many efforts have been made to prevent and treat COVID-19, but effective drugs for complete eradication of COVID-19 have not been found yet and all available drugs are supportive.&#x0D; Methods: We tried to review some new aspects of HCQ efficacy in the prevention and treatment of COVID-19 infection. Also, some data from recent clinical trials were studied. It has been shown that HCQ may improve some symptoms of patients, but in severe or critical stages, it did not have significant therapeutic effects and did not reduce the rate of mortality.&#x0D; Results: In this review article, we explained some results of recent studies, including clinical trials on the effects of HCQ on the prevention and treatment of COVID-19 infection. Some studies have revealed HCQ’s beneficial effects in outpatients, and some data showed its hazardous impacts on the heart. The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID.&#x0D; Conclusion: It was suggested that the dose of HCQ administration must be adjusted and monitored correctly; furthermore, the levels of some myocardial biomarkers, such as troponin must be measured in mild to moderate, severe, and critical infection. Also, combination therapy with other drugs, such as azithromycin may have better anti-inflammatory and antiviral effects.

Pharmacogenomics deliberations of 2-deoxy-d-glucose in the treatment of COVID-19 disease: an in silico approach

The outbreak of COVID-19 caused by the coronavirus (SARS-CoV-2) prompted number of computational and laboratory efforts to discover molecules against the virus entry or replication. Simultaneously, due to the availability of clinical information, drug-repurposing efforts led to the discovery of 2-deoxy-d-glucose (2-DG) for treating COVID-19 infection. 2-DG critically accumulates in the infected cells to prevent energy production and viral replication. As there is no clarity on the impact of genetic variations on the efficacy and adverse effects of 2-DG in treating COVID-19 using in silico approaches, we attempted to extract the genes associated with the 2-DG pathway using the Comparative Toxicogenomics Database. The interaction between selected genes was assessed using ClueGO, to identify the susceptible gene loci for SARS-CoV infections. Further, SNPs that were residing in the distinct genomic regions were retrieved from the Ensembl genome browser and characterized. A total of 80 SNPs were retrieved using diverse bioinformatics resources after assessing their (a) detrimental influence on the protein stability using Swiss-model, (b) miRNA regulation employing miRNASNP3, PolymiRTS, MirSNP databases, (c) binding of transcription factors by SNP2TFBS, SNPInspector, and (d) enhancers regulation using EnhancerDB and HaploReg reported A2M rs201769751, PARP1 rs193238922 destabilizes protein, six polymorphisms of XIAP effecting microRNA binding sites, EGFR rs712829 generates 15 TFBS, BECN1 rs60221525, CASP9 rs4645980, SLC2A2 rs5393 impairs 14 TFBS, STK11 rs3795063 altered 19 regulatory motifs. These data may provide the relationship between genetic variations and drug effects of 2-DG which may further assist in assigning the right individuals to benefit from the treatment.

Tixagevimab-Cilgavimab: COVID-19 Pre-Exposure Prophylaxis.

Tixagevimab-cilgavimab is the only nonvaccine drug currently authorized in the United States for the prevention of COVID-19 infection in individuals who are moderately to severely immunocompromised or unable to receive COVI.

Integrating in silico and in vivo approach for investigating the role of polyherbal oil in prevention and treatment of COVID-19 infection

Currently, there are no FDA approved antiviral drugs available to treat COVID-19 patients. Also, due to emergence of new SARS-CoV-2 variants, the protective efficacy of vaccines could be reduced, hence it is urgent to have alternative treatments for combating the SARS-CoV-2 infection. Since, there is a long-standing history of herbal medicine in the treatment of respiratory diseases. In the present study, we investigated two polyherbal oil blend viz. Sudarshan AV and Elixir AV (SAV and EAV) in inhibiting SARS-COV-2. From GC-MS analysis of polyherbal oils (SAV and EAV) a total of 11 active compounds were selected, on the basis of their abundance and activity. Further, from the molecular docking studies, we found an inhibitory effect of these compounds on viral envelope and membrane, spike proteins whilst an agonistic effect with human host receptor angiotensin-converting enzyme 2 (ACE2) implicating the crucial role of the individual compound in resistance of SARS-CoV-2.Since, the in-silico results suggest that polyherbal oil (SAV and EAV) contributes in preventing the entry of SARS-CoV-2 into the human body, we further investigated the efficacy of polyherbal formulated essential oil (FEO; SAV & EAV) in prevention and treatment of COVID-19 in hamster model. The male golden Syrian hamsters (n = 23) were divided into 5 groups i.e., Group 1: Control (n = 3); Group 2: Infected (n = 5); Group 3: Infected + Remdesivir (n = 5); Group 4: Infected + FEO (n = 5) and Group 5: Prophylactic FEO + Infected (n = 5). In both treatment and prophylactic groups, the FEO's significantly reduced the lung injury investigated histo-pathologically and viral load expression measured by real time PCR in comparison to infected hamsters. Furthermore, cytokines expression analysis clearly highlighted the efficacy of FEO's due to its anti-inflammatory activity and overall protection in treatment groups. In conclusion, the FEO (SAV & EAV) seem to be potent in both prevention and treatment of COVID-19 and related lung injury.

Urban monitoring of antimicrobial resistance during a COVID-19 surge through wastewater surveillance

During the early phase of the COVID-19 pandemic, infected patients presented with symptoms similar to bacterial pneumonias and were treated with antibiotics before confirmation of a bacterial or fungal co-infection. We reasoned that wastewater surveillance could reveal potential relationships between reduced antimicrobial stewardship, specifically misprescribing antibiotics to treat viral infections, and the occurrence of antimicrobial resistance (AMR) in an urban community. Here, we analyzed microbial communities and AMR profiles in sewage samples from a wastewater treatment plant (WWTP) and a community shelter in Las Vegas, Nevada during a COVID-19 surge in December 2020. Using a respiratory pathogen and AMR enrichment next-generation sequencing panel, we identified four major phyla in the wastewater, including Actinobacteria, Firmicutes, Bacteroidetes and Proteobacteria. Consistent with antibiotics that were reportedly used to treat COVID-19 infections (e.g., fluoroquinolones and beta-lactams), we also measured a significant spike in corresponding AMR genes in the wastewater samples. AMR genes associated with colistin resistance (mcr genes) were also identified exclusively at the WWTP, suggesting that multidrug resistant bacterial infections were being treated during this time. We next compared the Las Vegas sewage data to local 2018–2019 antibiograms, which are antimicrobial susceptibility profile reports about common clinical pathogens. Similar to the discovery of higher levels of beta-lactamase resistance genes in sewage during 2020, beta-lactam antibiotics accounted for 51 ± 3 % of reported antibiotics used in antimicrobial susceptibility tests of 2018–2019 clinical isolates. Our data highlight how wastewater-based epidemiology (WBE) can be leveraged to complement more traditional surveillance efforts by providing community-level data to help identify current and emerging AMR threats.